MXPA00011994A - Cell adhesion-inhibiting antinflammatory compounds - Google Patents

Abstract

Compounds having Formula (I) are useful for treating inflammation. Also disclosed are pharmaceutical compositions comprising compouns of Formula (I), and methods of inhibiting/treating inflammatory diseases in a mammal.

Description

ANTI-INFLAMMATORY COMPOUNDS THAT INHIBIT CELL ADHESION TECHNICAL FIELD The present invention relates to compounds that are useful for treating inflammatory diseases, to pharmaceutical compositions comprising these methods and to methods for inhibiting inflammation in a mammal.

BACKGROUND OF THE INVENTION Inflammation results from a cascade of events that includes vasodilation accompanied by increased vascular permeability and fluid exudation and plasma proteins. This interruption of vascular integrity precedes or coincides with an infiltration of inflammatory cells. Inflammatory mediators generated at the site of the initial lesion serve to recruit inflammatory cells to the site of damage. These mediators (chemokines such as IL-8, MCP-1, MIP-1 and RANTES, complement fragments and lipid mediators) have chemotactic activity for leukocytes and solicit the inflammatory cells to the inflamed lesion. These chemotactic mediators that cause circulating leukocytes to be localized at the site of inflammation require that the cells cross the vascular endothelium at a precise location. This leukocyte recruitment is carried out by a process called cell adhesion.

Cell adhesion occurs through a series of coordinately regulated stage that allows the leukocytes to first adhere to a specific region of the vascular endothelium and then cross the endothelial barrier to migrate to the inflamed tissue (Springer, TA, 1994, Traffic Signs for Lymphocyte Recirculation and Leukocyte Emigration; The Multistep Paradigm, Cell 76: 301-314; Lawrence, MB and Springer, TA, 1991, Leukocytes' Roll on a Selectin at Physiologic Flow Rates: Distinction from and Prerequisite for Adhesion Through Integrins, Cell 65: 859 -873; von Adrián, U., Chambers, JD, McEnvoy, LM, Bargatze, RF, Arfos, KE and Butcher, EC, 1991, Two-Step Model of Leukocyte-Endothelial Cell Interactions in Inflammation, Proc. Nati. Acad. Sci. USA 88: 7538-7542; and Ley, K., Gaehtgens, P., Fennie, C, Singer, MS, Lasky, LH and Rosen, SD, 1991, Lectin-Like Cell Molecule Adhesion 1 Mediates Rolling in Mesenteric Venules in vivo, Blood 77: 2553-2555). These steps are mediated by the families of adhesion molecules such as integrin, members of the Ig supergene family, and selectins that are expressed on the surface of circulating leukocytes and vascular endothelial cells. The first stage consists of winding the leukocyte along the lining of the vascular endothelial cell in the region of inflammation. The winding step is mediated by an interaction between the leukocyte surface oligosaccharides (such as Lewis-S Sialylated Slex antigen) and a selectin molecule expressed on the surface of the endothelial cell in the region of inflammation. The selectin molecule it is usually not expressed on the surface of endothelial cells but is preferably induced by the action of inflammatory mediators such as TNF-a and interleukin-1. Winding reduces the velocity of the circulating leukocyte in the region of inflammation and allows the cells to adhere more firmly to the endothelial cell. Firm adhesion is carried out by the interaction of integrin molecules that occur on the surface of the coiling leukocytes and their counter-receptors, the Ig superfamily molecule, on the surface of the endothelial cell. The Ig superfamily molecules or CAMs (Cell Adhesion Molecules) are either expressed or not expressed at low levels in normal vascular endothelial cells. CAMs, such as selectins, are induced by the action of inflammatory mediators such as TNF-alpha and IL-1. The final event in the adhesion process is the extravasation of the leukocyte through the endothelial cell barrier and the migration of the leukocyte along the chemotactic gradient to the site of inflammation. This transmigration is mediated by the conversion of the leukocyte integrin from a low avidity state to a high avidity state. The adhesion process lies in the induced expression of selectins and CAM's on the surface of vascular endothelial cells to mediate the coiling and firm adhesion of leukocytes to the vascular endothelium. The induced expression of e-selectin and CAM's is mediated by the transcription factor NFkB. NFkB is a family of dimeric transcription factors made of monomers containing the Reí domain of 300 amino acids. These factors can bind to DNA, interact with each other and bind to an inhibitory molecule ending in IkB (Vermaa, IM, Stevenson, JK, Schwarz, EM, Antwerp, DV and Miyamoto, S, 1995, Rel / NFIB / lkB Family: Intimate Tales of Association and Dissociation, Genes Dev. 9: 2723-2735; and Baldwin, AS 1996, The NFkB and IkB proteins: New Discoveries and Insights, Annu., Rev. Immunol., 14: 649-681). NFkB is found in the cytoplasm in complex with IkB. Activation of NFkB occurs in response to inflammatory mediators such as TNF-α, IL-1 and lipopolysaccharide. The activation of NFkB requires the phosphorylation of IkB followed by ubiquitinylation of the IkB molecule and subsequent degradation by proteosomes. The release of NFkB from the association with IkB results in translocation of the dimer to the nucleus where it can be associated with specific DNA sequences. The e-selectin and CAM's gene contains NFkB recognition sequences upstream of their coding regions. The NFkB bound to DNA that acts with other proteins in the transcription complex directs the expression of the CAM genes and e-selectin among others controlled by this transcription factor. The present invention describes the compounds that inhibit the expression of e-selectin and ICAM-1 relative to VCAM-1. These compounds are useful for the treatment or prophylaxis of diseases caused by the expression of adhesion molecules. These diseases include those in which leukocyte trading plays a role, inflammatory diseases Chronic and markedly acute, autoimmune diseases, tumor metastasis, allograft rejection and reperfusion injury.

SUMMARY OF THE INVENTION In one embodiment of the present invention, the compounds represented by the structural Formula I are described: or a pharmaceutically acceptable salt or premedication thereof, wherein the symbol - represents a single bond or a double bond, provided that when a bond is a double bond, the adjacent link is a unique link; E, F, and G are independently selected from (1) carbon, (2) nitrogen, and • (3) N + -O-, provided that at least one of E, F or G is nitrogen or N + -O ", and further provided that at least one of E, F or G is carbon, Y and Z are independently selected from (1) carbon, (2) nitrogen, 25 (3) oxygen, and (4) S (O), where t is an integer 0-2, provided that at least one of Y or z is other than carbon; LA is selected from r - '(1) a covalent bond, • 5 (2) -O-, (3) -S (O) t-, (4) -NR6- wherein R6 is selected from (a) hydrogen , (b) alkyl of one to ten carbons optionally substituted with 1 or 2 substituents independently selected from, (i) aryl and (ii) cycloalkyl of three to ten carbons, (c) alkanoyl wherein the alkyl part is one at ten 15 carbons, and (d) cycloalkyl of three to ten carbons, (5) -C (W) - wherein W is selected from (a) O and (b) S and 20 (6) alkenylene; XA is selected from (1) halo, (2) alkyl of one to ten carbons optionally substituted with 1, 2 or 3 substituents independently selected from 25 (a) oxo. (b) cycloalkyl of three to ten carbons, (c) -CO2R7, wherein R7 is selected from (i) hydrogen and (ii) alkyl of one to ten carbons optionally substituted with 1, or 2 substituents independently selected from aryl and cycloalkyl of three to ten carbons, (d) -NR8R9 wherein R8 and Rg are selected independently of (i) hydrogen, * (ii) alkyl of one to six carbons optionally substituted with 1 or 2 substituents independently selected from 15-OH aryl, heterocycle, cycloalkyl of three to ten carbons, and -N RARB wherein RA and RB are selected • independently of hydrogen and alkyl of one to six carbons optionally substituted with 1 or 2 substituents selected from -OH, (iii) alkanoyl wherein the alkyl part is from one to ten carbons, (iv) cycloalkyl of three to ten carbons, (v) alkoxy, (vi) heterocycle, and (vii) aryl, wherein (vi) and (vii) are substituted with 1 or 2 substituents independently selected from alkyl of one to six carbons and halo, (e) -C (W) R? o where W is previously defined and Rio is selects from (i) hydrogen, (ii) alkyl of one to ten carbons optionally substituted with 1 or 2 substituents independently selected from aryl and cycloalkyl of three to ten carbons, (iii) -NR8R9, and (iv) -OR7) (f) -OH, • 20 (g) aryl, and (h) heterocycle, wherein (g) and (h) can be optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from 25 (i) alkyl from one to twenty carbons, (ii) -NR8R9, (iii) alkoxy of one to ten carbons, (iv) thioalkoxy of one to ten carbons, (v) halo • 5 (vi) perfluoroalkyl of one to three carbons, (vii) alkenyl of two to ten carbons, (viii) alkyl of one to ten carbons optionally substituted with 1 or 2 substituents independently selected from alkoxy of one to ten carbons and -OH, (ix) -CO2R7, (x) aryl, and (xi) -CHO, 15 (3) cycloalkyl of three to ten carbons, (4) aryl, (5) heterocycle wherein (4) and (5) can be optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from • 20 (a ) alkyl of one to twenty carbons, (b) alkyl of one to ten carbons substituted with 1, 2 or 3 substituents independently selected from (i) -ORn wherein Rn is selected from hydrogen-C (W) R12 wherein R 2 is selected from alkyl of one to ten carbons, cycloalkyl of three to ten carbons, aryl, and heterocycle, and • heterocycle optionally substituted with 1, 2, 3 or 4 substituents independently selected from -OH and alkyl of one to six carbons optionally substituted with 1 or 2 substituents selected from -. 10 -OH, (ii) alkoxy of one to ten carbons optionally substituted with 1 or 2 substituents independently selected from alkoxy and alkoxyalkoxy, (iii) spiroalkyl of three to ten carbons, and (iv) halo, (c) alkoxy of one to ten carbons optionally substituted with 1 or 2 substituents independently • 20 selected from (i) alkoxy, and (ii) alkoxyalkoxy, (d) thioalkoxy of one to ten carbons, (e) halo, 25 (f) perfluoroalkyl of one to three carbons, (g) two to ten carbon alkenyl optionally substituted with 1 or 2 substituents independently selected from (i) -C (W) R? o and • "% 5 (ii) -C (W) R? 2 (h) -CO2R7 (i) -NR8R9, (j) aryl (k) -C (W) R12, 10 (I) -CHO, (m) -C (O) NR8R9, • (n) -CN, (o) optionally substituted heterocycle with 1 or 2 substituents independently selected from 15 (i) alkyl of one to ten carbons and (ii) perfluoroalkyl of one to three carbons, (p) -C (W) R10, (q) ethylenedioxy, and (r) -OCF3 , • 20 (6) -OR7, (7) hydrogen, and (8) -NR8R9; LB is selected from (1) a 25 (2) -O- covalent bond, (3) -S (O) t-, (4) -NR6- (5) -C (W) -, and (6) -C (= NR? 3) - wherein R13 is selected from (a) hydrogen , (b) -NO2, (c) -CN, and (d) -OR? wherein R 4 is selected from (i) hydrogen (ii) aryl, and (iii) alkyl of one to ten carbons optionally substituted with 1 or 2 substituents independently selected from aryl and -C (O) Ri 5 wherein R 15 is selected of hydrogen, -OH, alkoxy, and NRARB; is selected from (1) hydrogen (2) alkyl of one to ten carbons optionally substituted with 1, 2 or 3 substituents independently selected from (a) -CO2R7, (b) -NR8R9) (c) -C (W) NR8R9, (d) heterocycle, (e) aryl optionally substituted with 1 or 2 substituents independently selected from 5 (i) alkyl of one to ten carbons, (ii) -NO2, and (iii) -N RARB, (f) -OR16 wherein Rie is selected from (i) hydrogen and 10 (ii) -C (W) NRARB, and (g) -NRAC (W) NR8R9, • (3) two-alkenyl six carbons optionally substituted with 1 or 2 substituents independently selected from (a) -C (W) NRARB, 15 (b) -CO2R7 > and (c) heterocycle, (4) -NR17R18 wherein R17 and R18 are independently selected from (a) hydrogen, (b) alkyl of one to ten carbons optionally substituted with 1, 2 or 3 substituents independently selected from (i) -OH, (ii) -C (W) R10, 25 (iii) -NRAC (= NR13) NRBR? 9 wherein RA, RB and R13 are previously defined and R 9 is selected from hydrogen, alkyl of one to ten carbons, and -NO 2, (iv) heterocycle, (v) aryl, (vi) halo, and (vii) -NRARB, (c) alkoxy 10 ( d) aryl optionally substituted with 1, 2 or substituents independently selected from • (i) halo, (ii) alkyl of one to ten carbons, (iii) alkoxy of one to ten carbons, and 15 (iv) perfluoroalkyl of one to three carbons, (e) heterocycle, (f) -N RARB, (9) -C (O) R2o wherein R2o is selected from (i) hydrogen, • (ii) alkyl of one to ten carbons, (ii) -OR12, and (h) cycloalkyl of three to ten carbons, and (i) -OH, 25 (5) alkoxy, (6) -OH, (7) -NRAC (= NR13) NRBR? 9, (8) -C (W) NR8R9, (9) aryl • 5 (10) heterocycle, wherein (9) and (10) they may be optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from (a) halo, (b) alkyl of one to ten carbons optionally substituted with 1, 2 or 3 substituents independently selected from • (i) halo, (ii) alkoxy of one to ten carbons, (iv) -OH, (v) -CO2R7, (vi) -C (W) NRARB, and (v? I) aryl, (C) -NRARB, 20 (d) alkoxy of one to ten carbons, (e) ) thioalkoxy of one to ten carbons, (f) perfluoroalkyl of one to three carbons, (g) -OH, (h) -C (W) NR8R9, 25 (i) -CO2R7, (j) -NRAC (W) OR2? wherein RA is previously defined and R2 is selected from (i) alkyl of one to ten carbons optionally substituted with 1 or 2 substituents selected from ^ and 5 aryl and cycloalkyl of three to ten carbons, (ii) aryl, and (ii) cycloalkyl of three to ten carbons (k) alkenyl or two to ten carbons, 10 (I) heterocycle, (m) aryl, ( n) -NO2, (11) -CN, (12) -CHO, 15 (13) halo, and (14) -B (ORA) (ORB); provided that when Ri, R2, R3, R and R5 are hydrogen or absent, -LA- is a covalent bond, and -LB- is a covalent bond, then one of XA and XB is different from hydrogen; and • Ri, R2, R3, R and Rs are absent or independently selected from (1) hydrogen, (2) alkyl of one to six carbons optionally substituted with 1 or 2 substituents independently selected from 25 (a) -OC ( O) R22, where R22 is selected from (i) alkyl, (ii) alkoxy, and (b) alkoxy, • 5 (c) -OH, (d) -NRARB, (e) heterocycle, and (f) aryl, (3) -CO2R7, 10 (4) -C (O) NRARB, (5) -SR23 wherein R23 is selected from • (a) hydrogen, (b) alkyl of one to six carbons, (c) aryl optionally substituted with 1 or 2 substituents selected from (i) alkyl of one to six carbons and (ii) ) halo, (6) -NRARB, (7) halo, ^ 20 (8) alkoxy, (9) perfluoroalkyl of one to three carbons, (10) -OH, and (1 1) heterocycle, provided that when E, F , and Y be carbon, G is nitrogen, Z is sulfur, -LA- is a covalent bond and XA is halo, Ri is different from - CO2R7. In another embodiment of the invention, methods are described for treating diseases which comprises administering an effective amount of a compound having the Formula I. In yet another embodiment of the invention, pharmaceutical compositions containing the compounds of Formula I are described.

DETAILED DESCRIPTION OF THE INVENTION Definition of Terms The term "alkanoyl" as used herein refers to an alkyl group attached to the molecular group of origin through a carbonyl group. The term "alkenyl" as used herein is refers to a branched or straight monovalent chain group of 2-12 carbon atoms containing at least one carbon-carbon double bond derived from alkene by removal of one hydrogen atom. The term "alkenylene" as used herein refers to a bivalent straight or branched chain group of 2-10 carbon atoms containing a carbon-carbon double bond derived from an alkene by the removal of two hydrogen atoms . The term "alkoxy" as used herein refers to an alkyl group attached to the molecular group of origin through an oxygen atom.

The term "alkoxyalkoxy" as used herein refers to an alkoxy group attached to the molecular group of origin through another alkoxy group. The term "alkoxycarbonyloxy" as used in the # 5 present refers to an alkoxy group, as defined herein, appended to the molecular part of origin through a carbonyloxy group, as defined herein. The term "alkoxycarbonyloxymethylene" as used herein refers to an alkoxycarbonyloxy group, as defined herein, appended to the parent molecular part through a methylene group, as defined herein. • The term "alkyl" as used herein refers to a straight or branched chain group of 1-20 carbon atoms derived from an alkane by removal of a hydrogen atom. The term "alkylcarbonyl" as used herein refers to an alkyl group, as defined herein, appended to the molecular part of origin through a carbonyl group. The term "alkylcarbonyloxy" as used in ia F 20 present refers to an alkyl group, as defined herein, appended to the molecular part of origin through a carbonyloxy group, as defined herein. The term "alkylcarbonyloxymethylene" as used herein refers to an alkylcarbonyloxy group, as defined in present, appended to the molecular part of origin through a group of methylene, as defined herein. The term "alkylene" denotes a bivalent group derived from a branched or straight chain hydrocarbon of from 1 to 10 carbon atoms. Representative examples of alkylene, • 5 include, but are not limited to, -CH2-, -CH CH2-, -CH2CH2CH2-, - CH2CH2CH2CH2-, CH2CH (CH3) CH2- and the like. The term "amino" as used herein refers to a group -NR80Rs? , wherein R80 and Rei are independently selected from hydrogen and alkyl. The term "aminocarbonyl" as used herein refers to an amino group, as defined herein, appended to the molecular part of origin through a carbonyl group, as defined herein. The term "aminocarbonyloxy" as used herein refers to an aminocarbonyl group, as defined herein, appended to the parent molecular part through an oxy group, as defined herein. The term "aminocarbonyloxymethylene" as used herein refers to an aminocarbonyloxy group, as defined herein, appended to the parent molecular part through a methylene group, as defined herein. The term "aryl" refers to a mono-o or bicyclic carbocyclic ring system having one or two aromatic rings. The aryl group can also be fused to a ring cyclohexane, cyclohexene, cyclopentane or cyclopentene. The groups aryl of this invention can be optionally substituted. The term "carbonyl" as used herein refers to a group -C (O) -. The term "carbonyloxy" as used herein is • 5 refers to a carbonyl group, as defined herein, appended to the molecular part of origin through an oxy group, as defined herein. The term "cycloalkyl" as used herein refers to a saturated, monovalent cyclic hydrocarbon group of 3-12 carbon atoms derived from a cycloalkane by the removal of a single hydrogen atom. The term "ethylenedioxy" as used herein refers to a group -O (CH2) 2O- wherein the oxygen atoms of the ethylenedioxy group are attached to the molecular part of origin through a carbon atom forming a carbon atom. 5-membered ring or the oxygen atoms of the ethylenedioxy group are attached to the molecular part of origin through two adjacent carbon atoms forming a six-membered ring. The terms "halo" or "halogen" as used in the • 20 present refer to F, Cl, Br or I. The term "heterocycle" represents a 4, 5, 6 or 7 member ring containing one, two or three heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur. The 4 and 5 member rings have zero to two double bonds and the 6 and 7 member rings have zero to three double bonds. The term "heterocycle" also includes bicyclic, tricyclic and tetracyclic groups in which any of the above heterocyclic rings are fused to one or two rings independently selected from an aryl ring, a ring of • 5-cyclohexane, a cyclohexene ring, a cyclopentane ring, a cyclopentene ring or another monocyclic heterocyclic ring. Heterocycles include acridinyl, benzimidazolyl, benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, biotinyl, cinolinyl, dihydrofuryl, dihydroindolyl, dihydropyranyl, dihydrothienyl, dithiazolyl, furyl, homopiperidinyl, imidazolidinyl, imidazolinyl, imidazolyl, indolyl, isoquinolyl, isothiazolidinyl, isothiazolyl, isoxazolidinyl, isoxazolyl, morfoiinilo, oxadiazolyl, oxazolidinyl, oxazolyl, oxadiazolyl, piperazinyl, piperidinyl, pyranyl, pirazoiidinilo, pyrazinyl, pirazoiilo, pyrazolinyl, pyridazinyl, pyridyl , pyrimidinyl, Pyrimidyl, pyrrolidinyl, pyrrolinyl, pyrrolyl, quinolinyl, quinoxaloyl, tetrahydrofuryl, tetrahydroisoquinolyl, tetrahydroquinolyl, tetrazoyl, thiadiazolyl, thiazolidinyl, thiazolyl, thienyl, thiomorpholinyl, triazolyl and the like. Heterocyclics also include bicyclic groups • 20 bridges where a heterocyclic group is bridged by an alkylene group such as JL > and the similar. The heterocyclics also include compounds of the formula wherein X * is selected from -CH2-, -CH2O- and -O-, and Y * is selected from -C (O) - and - (C (R ") 2) v-, where R" is hydrogen or • alkyl of one to four carbon atoms and v is 1 -3. These heterocyclics include 1,3-benzodioxolyl, 1,4-benzodioxanyl and the like. The heterocyclic groups of this invention can be optionally substituted. The term "oxo", as used herein, refers to a = O. The term "oxy", as used herein, refers to • to -O-. The term "methylene", as used herein, refers to a -CH2- group. The term "perfluoroalkyl", as used herein, refers to an alkyl group in which all hydrogen atoms have been replaced by fluoride atoms. The term "phenyl", as used herein, refers to a monocyclic carbocyclic ring system having a ^ 20 aromatic ring. The aryl group can also be fused to a ring of cyclohexane or cyclopentene. The phenyl groups of this invention can be optionally substituted. The term "pharmaceutically acceptable prodrugs" as used herein represents those prodrugs of the compounds of the present invention that they are, within the scope of sound medical judgment, suitable for use in contact with human and lower animal tissues with undue toxicity, irritation, allergic response, and the like, of measure equal to reasonable benefit / risk ratio, and effective for its proposed use, as well as the amphoteric ion forms, where possible, of the compounds of the invention. The term "prodrug", as used herein, represents compounds that are rapidly transformed in vivo to the parent compound of the above formula, for example, by hydrolysis in the blood. A full discussion is provided in T. Higuchi and V. Stella, Prodrugs as Novel Delivery Systems. Vol. 14 of A. C.S. Symposium Series, and in Edward B. Roche, ed., Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press 1987, both of which incorporated herein by reference The term "spiroalkyl" as used herein refers to an alkylene group wherein two carbon atoms of the alkylene group are attached to a carbon atom of the molecular group of origin thus forming a carbocyclic ring from three to eleven atoms • 20 carbon. The term "tautomer" as used herein refers to a proton change from one atom of a molecule to another atom of the same molecule where two or more structurally distinct compounds are in equilibrium with each other. The term "thioalkoxy" as used herein is refers to an alkyl group attached to the molecular group of origin through a sulfur atom. The compounds of the present invention can exist as stereoisomers wherein chiral or asymmetric centers are presented. These compounds are designated by the symbols "R" or "S", depending on the configuration of the substituents around the chiral carbon atom. The present invention contemplates various stereoisomers and mixtures thereof. Stereoisomers include enantiomers and diastereomers, and mixtures of enantiomers or diastereomers are designated (+). The individual stereoisomers of the compounds of the present invention can be prepared synthetically from commercially available starting materials containing chiral or asymmetric centers or by the preparation of racemic mixtures followed by resolution well known to those of ordinary skill in the art. These resolution methods are exemplified by (1) attachment of a mixture of enantiomers to a chiral auxiliary, separation of the resulting mixture of diastereomers by recrystallization or chromatography and release of the optically pure product from the auxiliary or (2) direct separation of the mixture from Optical enantiomers in chiral chromatographic columns. Geometric isomers may exist in the compounds of the present invention. The present invention contemplates the various geometric isomers and mixtures thereof resulting from the installation of substituents around a double bond of carbon-carbon installation of substituents around a carboxylic ring. Substituents around a carbon-carbon double bond are designated as being in the Z or E configuration where the term "Z" represents • 5 substituents on the same side of the carbon-carbon double bond and the term "E" represents substituents on opposite sides of the carbon-carbon double bond. The installation of substituents around a carbocyclic ring is designated as cis or trans in d, where the term "cis" represents substituents on the same side of the plane of the ring and the term "trans" represents substituents on opposite sides of the plane of the ring. Mixtures of compounds • wherein the substituents are placed on the same side as on opposite sides of the ring plane are designated cis / trans. Tautomers may also exist in the compounds of the present invention. The present invention contemplates tautomers due to proton changes from one atom to another atom of the same molecule generating two different compounds that are in equilibrium with each other. The compounds of the present invention include, but • 20 are not limited to methyl 2 - [(6-ethylthieno [2,3-d] pyrimidin-4-yl) thio] acetate, 6-ethyl-4 - [(4-methylphenyl) thio] thieno [2,3 -d] pyrimidine, 6-ethyl-4- (2-pyridinylthio) thieno [2,3-d] pyrimidine, 6-ethyl-4 - [(2-methylethyl) thio] thieno [2,3-d] pyrimidine, 25 6-ethyl-4 - [(phenylmethyl) thio] thieno [2,3-d] pyrimidine, 6-Ethyl-4 - [(5-methyl-1,3,4-thiadiazol-2-yl) thio] thieno [2,3-d] pyrimidine, ethyl 6-ethyl-4 - [(4-methylphenyl) thio] ] thieno [2,3-d] pyrimidine-6-carboxylate, 6-ethyl-N- (phenylmethyl) thieno [2,3-d] pyrimidin-4-amine, 6-ethyl-N- (5-methyl-1 , 3,4-thiadiazol-2-yl) thieno [2,3-d] pyrimidine-4-amine, 4 - [(5-amino-1,3,4-thiadiazol-2-yl) thiol-6-ethyl) -2- (phenylmethyl) thieno [2,3-d] pyrimidine, 4-chloro-6-ethyl-2- (phenylmethyl) thieno [2,3-d] pyrimidine, 4 - [(5-amino-1,3,4-thiadiazol-2-yl) thio] -6-ethyl -2- (phenylmethyl) thieno [2,3-d] pyrimidine, 7-methyl-4 - [(4-methylphenyl) thio] thieno [3,2-d] pyrimidine, 7-methyl-4 - [(5- methyl-1,3,4-thiazol-2-yl) thio] thieno [3,2-d] pyrimidine, 7-methyl-4 - [[5- (methylthio) -1,4,4-thiadiazole- 2-yl) thio] thieno [3,2-d] pyrimidine, 4 - [(5-amino-1, 3,4-thiadiazol-2-yl) thio] -7-methylthieno [3,2-d] pyrimidine , 7-methyl-N - [(4- (methylthio) phenyl] thieno [3,2-d] pyrimidin-7-amine, 7-methyl-4 - [(4-methylphenyl) thio] thieno [3,2- d] pyrimidine-6-carboxamide, methyl 4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridine-2-carboxylate, 4-t (4-methylphenyl) thio] thieno acid [2,3- c] pyridine-2-carboxylic acid, 4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridine-2-carboxamide, 4- (2-pyridinylthio) thieno [2,3-c] pyridine-2 -carboxamide, 4 - [(4-chlorophenyl) thio] thieno [2,3-c] pyridine-2-carboxamide, N-methoxy-N-methyl-4 - [(4-methylphenyl) thio] thieno [2,3 -c] pyridine-2-carboxamide, N-methoxy-4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridine-2-carboxamide, N- (4-chlorophenyl) -4 - [(4 -methyl phenyl) thio] t-ene [2,3-c] pyridine-2-carboxamide, 4 - [(4-methylphenyl) thio] thieno (2,3-c] pyridine-2-carboxboxyIdehyde, 4 - [(4- methylphenyl) thio] thieno [2,3-c] pyridine-2-carboxaldehyde, O-methyloxime, 4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridine-2-carboxaldehyde, O- (phenylmethyl) oxime, 2 - [[[4 - [(4-methylphenyl) thio] t-ene [2,3-c] pyridin-2-ylmethylene] aminojoxyacetic acid, 4 - [(4-methylphenyl) thio] thieno (2,3-c] pyridine-2-carboxaldehyde, O-phenyloxime, 4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridine-2- carboxaldehyde, oxime, 2 - [[[4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridin-2-ylmethylene] -amino] oxy] acetamide, (E) -3 - [(4- methylphenyl) thio] thieno [2,3-c] pyridin-2-yl] -2-propenamide, 5 1 - [4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridin-2 -yl] ethanone, 2-benzoyl-4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridine, 2-ethyl-4 - [(4-methylphenyl) thio] thieno [2,3-c] ] pyridine, 1- [4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridin-2-yl] ethanone, oxime, N- (2,3-dihydroxypropyl) -4 - [(4- R-ethylphenyl) thio-Jethylene [2,3-c] pyridine-2-carboxamide, 4 4 - [(4-methylphenyl) thio] t-ene [2,3-c] pyridine-2-carboxylic acid, hydrazide, F N2-4 - [(4-methylphenyl) thio] thienot2,3-c] pyridin-2-ii] carbonyl] -N6 - [(nitroamino) iminomethyl] -L-lysine, methyl ester, N- (aminoiminomethyl) -4- [ (4-methylphenyl) thio] thieno [2,3-c] pyridine-2-carboxamide, 4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridine-2-carbothioamide, 15 4 - [( 4-methylphenyl) thio] thieno [2,3-c] pyridine, m ethyl 4 - [(2-methoxy-2-oxoethyl) thio] thieno [2,3-c] pyridine-2-carboxylate, 4 - [(2-amino-2-oxoethyl) thio] thieno [2,3-c] ] pyridine-2-carboxamide, 4 - [(4-bromophenyl) th] thieno [2,3-c] pyridine-2-carboxamide, 4- (phenylthio) thieno [2,3-c] pyridine-2- carboxamide, • 20 4 - [[4- (trifluoromethyl) phenyl] thio] thieno [2,3-c] pyridine-2-carboxamide, 4 - [(2-methylphenyl) thio] thieno [2,3-c] pyridine -2-carboxamide, 4 - [(3-methylphenyl) thio] thieno [2,3-c] pyridine-2-carboxamide, 4 - [(3,4-dimethylphenyl) thio] thieno (2,3-c) pyridine -2-carboxamide, 4 - [(3,5-dimethylphenyl) thio] thieno [2,3-c] pyridine-2-carboxamide, 4 - [(2,4-dimethylphenyl) thio] -thieno [2,3-c] pyridine-2-carboxamide, 4 - [(2-methyl-3-furaniI) thio] thieno [2,3-c] pyridine-2-carboxamide, 4 - [[(4-chlorophenyl) methyl] thio] thieno [2,3-c] pyrid Na-2-carboxamide, 4 - [(3,4-dichlorophenyl) thio] thieno [2,3-c] pyridine-2-carboxamide, 4 - [(4-methoxyphenyl) thio] thieno [2,3-c] ] pyridine-2-carboxamide, • 4- (cyclohexylthio) thien [2,3-c] pyridine-2-carboxamide, 4 - [(4-methylphenyl) thio] -N- [3- (4-morpholinyl ) propyl] thieno [2,3-c] pyridine-2-carboxamide, trifluoromethylacetate salt, 4 - [(4-methylphenyl) sulfinyl] thieno [2,3-c] pyridine-2-carboxamide, methyl 4 - [( 4-methylphenyl) sulfinyl] thieno (2,3-c] pyridine-2-carboxylate, 4- (4-methylphenoxy) thieno [2,3-c] pyridine-2-carboxamide, methyl 4- (4-methylphenoxy) thieno [2,3-c] pyridine-2-carboxylate, 4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, methyl 4- (4-chlorophenoxy) thieno [2, 3-c] pyridine-2-carboxylate, 4- [4- (trifluoromethyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 4- (4-octylphenoxy) thieno [2,3- c] pyridine-2-carboxamide, 4- [4- (1-methylethyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 4- (2-bromo-4-chloro) enoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-ethylphenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-ethenylphenoxy) thieno (2,3- c] pyridine-2-carboxamide, 4- [4- (1, 2-dihydroxyethyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 4-. { 2- (2-propenyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 4- [2- (2,3-dihydroxypropyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide 4- [4- (trifluoromethyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 1-oxide, 4-. { 3- (pentadecyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 4- (4-bromophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (3-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-t-butylphenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-chloro) -3-methylphenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-chloro-2-methylphenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-methoxyphenoxy) ) thieno [2,3-c] pyridine-2-carboxamide, ethyl 3 - [[2- (aminocarbonyl) thieno [2,3-c] pyridin-4-yl] oxy] benzoate, 4-phenoxythien [2,3 -c] pyridine-2-carboxamide, 4- (3-bromophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-fluorophenoxy) thieno [2,3-c] pyridine-2- carboxamide, 4- (3,5-dimethyphenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (3-chloro-4-methylphenoxy) thieno [2,3-c] pyridine-2- carboxamide, 4- (4-iodophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4- (methoxymethyl) phenoxy) thieno [2,3-c] pyridine-2-carboxamide, 2- ( aminocarbonyl) -4- (4-chlorophenoxy) thieno [2,3-c] pyridinium, iodide, 4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxylic acid, N- (4- ( 4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl) -O- (3-tetrahydrofuranyl) carbamate, 4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-methanol, (E) -3- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl]] -2-propenoic, 4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxaldehyde, (E) -3- [4- (4-chlorophenoxy) thieno [2,3-c] pyridine- 2-yl] -2-propenamide, 4-bromothieno [2,3-c] pyridine-2-.carboxamide, methyl 4-bromothieno [2,3-c] pyridine-2-carboxylate, 4-chlorothieno [2,3 -c] pyridine-2-carboxamide, 4- [4- (trifluoromethyl) phenyl] thieno [2,3-c] pyridine-2-carboxamide, methyl 4- [4- (trifluoromethyl) phenyl] thieno [2,3- c] pyridine-2-carboxylate, N-methyl-4- [4- (trifluoromethyl) phenyl] thieno [2,3-c] pyridine-2-carboxamide, 4-phenylethieno [2,3-c] pyridine-2-carboxamide, methyl 4-phenylthiene [2,3-c] pyridine-2-carboxylate, 4 - ([1,1 '-biphenyl] -4-lithium) thieno [2,3-c] pyridine-2-carboxamide, • 5 4- (5- formyl-2-furanyl) thieno [2,3-c] pyridine-2-carboxamide, ethyl 4 - [[2- (aminocarbonyl) thieno [2,3-c] pyridin-4-yl] oxy] benzoate, - [[2- (aminocarbonyl) thieno [2,3-c] pyridin-4-yl] oxy] benzoic acid, 4- (1-phenylethenyl) thieno [2,3-c] pyridine-2-carboxamide, methyl 4- (1-phenylethenyl) thieno [2,3-c] pyridine-2-carboxylate, 4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridine-2-methanol, 4- (4-chlorophenoxy) ) -N-methylthieno [2,3-c] pyridine-2-carboxamide, • 4- (4-chlorophenoxy) -N, N-dimethylthieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) ) -N, N-diethylthieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) -N-cyclopropyl-thieno [2,3-c] pyridine-2-carboxamide, 15 1 - [[4 - (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] carbonyl] pyrrolidine, 1 - [[4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] carbonyl ] p iperidine, 4 - [[4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] carbonyl] morpholine, 1-II4- (4-chlorophenoxy) thieno [2,3-c] pyridine- 2-yl] carbonyl] ^ .- methylpiperazine,, 1 - [[4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] carbonyl] -4-phenyl] piperazine, 1- [ [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] carbonyl] -4- (phenylmethyl) -piperazine, 1 - [[4- (4-chlorophenoxy) thieno [2,3-] c] pyridin-2-yl] carbonyl] -4- (2-pyridinyl) -piperazine, 4- (4-chlorophenoxy) -N- (2-hydroxyethyl) lthieno [2,3-c] pyridine-2-carboxamide, 4 - [[4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] carbonyl] -N- (1-methylethyl) -1- piperazineacetamide, trifluoroacetate salt, 4- ( 4-chlorophenoxy) -N- [1- (hydroxymethyl) ethyl] thieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) -N- [1 > 1-bis (hydroxymethyl) ethyl] thieno [2,3-c] pyridine-2-carboxamide, (D, L) -4- (4-chlorophenoxy) -N- (2-hydroxypropyl) thieno [2,3-c] ] pyridine-2-carboxamide, 4- (4-chlorophenoxy) -N- [2- (4-morpholinyl) ethyl] thieno [2,3-c] pyridine-2-carboxamide, F 4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-sulfonamide, 5 - 4 - [(4-methylphenyl) methyl] thieno [2,3-c] pyridine-2-carboxamide, methyl 4- [(4-methylphenyl) methyl] thieno [2,3-c] pyridine-2-carboxylate, 4- (4-morpholinyl) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, N-oxide, methyl (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxylic acid, N-oxide, 4- (4-chlorophenoxy) ) -2- (2-methoxyphenyl) thieno [2,3-c] pyridine, 4- (4-chlorophenoxy) thieno [2,3-c] pyridine, 4- (4-chlorophenoxy) -3-methylthieno [2, 3-c] pyridine-2-carboxamide, Methyl 4- (4-chlorophenoxy) -3-methylthieno [2,3-c] pyridine-2-carboxylate, 4- (4-chlorophenoxy) -3-hydroxythieno [2,3 -c] pyridine-2-carboxamide, 15-methyl-4- (4-chloro-phenoxy) -3-hydroxy-thieno [2,3-c] pyridine-2-carboxylate, 4- (4-chlorophenoxy) -3- ( 1-methylethoxy) thieno [2,3-c] pyridine-2-carboxamide, 3-bromo-4- (4-chlorophenoxy) thieno [2,3-c] pyridine, 4- (4-chlorophenoxy) thieno acid [2,3-c] pyridine-3-carboxylic acid, 4- (4-chlorophenoxy) thieno [2,3-c] pyridine-3-carboxamide, • 20 3-amino-4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, methyl 3-amino-4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxylate, 3-amino acid 4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxylic acid, 4 - [(4-methylphenyl) thio] thieno [2,3-b] pyridine, 4 - [(4-methylphenyl) ) thiojthieno [2,3-b] pyridine-2-carboxamide, 4-chloro-N- (4-chlorophenyl) thieno [2,3-b] pyridine-5-carboxamide, ethyl 4 - [(5-methyl-1, 3,4-thiadiazol-2-yl) thio] thieno [2,3-b] pyridine-5-carboxylate, 7 - [(4-methylphenyl) thio] thieno [3 , 2-b] pyridine-2-carboxamide, methyl 6 - [(4-methylphenyl) thio] thieno [2,3-b] pyridine-2-carboxylate, methyl 3-amino-6-chlorothieno [2, 3-b] pyridine-2-carboxylate, 5 6 - [(4-methylphenyl) thio] thieno (2,3-b] pyridine-2-carboxamide, 2-bromo-4 - [(4-methylphenyl) thio] thieno [3,2-c] pyridine, 4 - [(4-methylphenyl) thio] thieno [3,2-c] pyridine-2-carboxamide, 4 - [(4-methylphenyl) thio] thieno (3,2- c] pyridine-2-carbonitrile, 4- (4-Methylphenoxy) thieno (3,2-c] pyridine-2-carboxamide, 4- (4-Methylphenoxy) thieno [3,2-c] pyridine-9- carbonitop, 7- (4-methylphenoxy) oxazolo [5,4-c] pyridine-2-carboxamide, • methyl 7- (4-methylphenoxy) oxazolo [5,4-c] pyridine-2-carboxylate, 7- (4-methylphenoxy) [1,3] thiazole [5,4-c] pyridine-2-carboxamide, methyl 7- (4-methylphenoxy) [1,3] thiazolo [5,4-c] pyridine-2 -carboxylate, 7-7- (4-methylphenoxy) -3H-imidazo [4,5-c] pyridine-2-carboxamide, methyl 7- (4-methylphenoxy) -3H-imidazo [4,5-c] pyridine-2 -carboxylate, 4- (4-chlorophenoxy) thieno [2,3-d] pyridazine-2-carboxamide, 4- (4-cyranophenoxy) thieno [2,3-d] pyridazine-2-carboxylic acid, 7- (4-chlorophenoxy) thieno [3,2-c] pyridine-2-carbamide, • 7- (4-chlorophenoxy) thieno [3,2-c] pyridine-2-carboxylic acid, 4- ( 4-chlorophenoxy) thieno [2,3-c] pyridine-2-carbothioamide, 4- (4-chlorophenoxy) -N-ethyIthieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) - N- (2,3-dihydroxypropyl) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-bromophenoxy) -N- (2,3-dihydroxypropyl) thieno [2,3-c] pyridine- 2-carboxamide, N- (2-chloroethyl) -4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-bromophenoxy) -N- (2-hydroxyethyl) thieno [2,3-c] pyridine-2-carboxamide, 4- (2-bromo-4-chlorophenoxy) -N- (2-hydroxyethyl) thieno [ 2,3-c] pyridine-2-carboxamide, N- (2-hydroxyethyl) -4- [4- (trifluoromethyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, N- (2 -aminoethyl) -4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, Kr 5 4- (4-chlorophenoxy) -N-hydroxythieno [2,3-c] pyridine-2 -carboxamide, 4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carbohydrate, 4- (4-bromophenoxy) thieno [2,3-c] pyridine-2-carbohydrate, 4- [4 - (trifluoromethyl) phenoxy] thieno [2,3-c] pyridine-2-carbohydrazide, 4- (4-chlorophenoxy) -N-hydroxythieno [2,3-c] pyridine-2-carboxamide, 2- ( { [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] carbonyl}. Amino) acetic acid, N- (2-amino-2-oxoethyl) -4- (4-chlorophenoxy) ) thieno [2,3-c] pyridine-2-carboxamide, N- (2-amino-2-oxoethyl) -4- (4-bromophenoxy) thieno [2,3-c] pyridine-2-carboxamide, Acid ( 2S) -2- ( { [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] carbonyl}. Amino) -3-hydroxypropanoic, 15 N - [(1 S) -2-amino-1 - ( hydroxymethyl) -2-oxoetyl] -4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, (2R) -2- (. { [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] carbonyl) amino) -3-hydroxypropanoic acid (2R) -2- ( { [4- (4-chlorophenoxy)) thieno [2,3-c] pyridin-2-yl] carbonyl] amino) propanoic, 4- (4-chlorophenoxy) -N - [(1 R) -1-methyl-2- (methylamino) -2-oxoethyl ] thieno [2,3-c] pyridine-2-carboxamide, (2S) -2- ( { [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] carbonyl acid} amino) propanic, 4- (4-chlorophenoxy) -N - [(1S) -1-methyl-2- (methylamino) -2-oxoethyl] thieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) -N - [(1 R) -1 - (hydroxymethyl) -2- (methylamino) -2-oxoethyl] thieno [2,3-c] pyridine- 2-carboxamide, 4- (4-chlorophenoxy) -N - [(1S) -1- (hydroxymethyl) -2- (methylamino) -2-oxoethyl] thieno [2,3-c] pyridine-2-carboxamide, 4 - (3-pyridinyloxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-bromophenoxy) -N-methylthieno [2,3-c] pyridine-2-carboxamide, 4- (4-bromophenoxy) ) -N, N-dimethylthieno [2,3-c] pyridine-2-carboxamide, NN-dimethylM? -trifluoromethyl phenoxystyrene P.S-cjpyridine ^ -carboxamide, 4- (4-chloro-3-fluorophenoxy) -N-methyl triene . { 2,3-c] pyridine-2-carboxamide, 4- (4-chloro-3-fluorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-chloro-3-ethylphenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (3-fluorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (2,3-difluorophenoxy) thieno [2,3- c] pyridine-2-carboxamide, 4- (2) 3-difluorophenoxy) -N-methylthieno [2,3-c] pyridine-2-carboxamide, 4- (3-fluorophenoxy) -N-methylthieno [2,3- c] pyridine-2-carboxamide, N-methyl-4- (2,3,4-trifluorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (2,3,4-trifluorophenoxy) thieno [ 2,3-c] pyridine-2-carboxamide, N-methyl-4- [4- (trifluoromethyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 4- [3- (trifluoromethyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, N, N-dimethyl-4- (4-vinylphenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4- cyanophenoxy) -N-methylthieno [2,3-c] pyridine-2-carboxamide, 4- (4-cyanophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-aminophenoxy) thieno [2 , 3-c] pyridine-2-carboxamide, 4- [4- (acetylamino) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, N-methyl-4- [4- (4-morpholine L) feno xi] thieno [2,3-c] pyridine-2-carboxamide, 4- [4- (hydroxymethyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 4- [4- (hydroxymethyl) phenoxy] -N-methytieno [2,3-c] pyridine-2-carboxamide, 4- [4- (methoxymethyl) phenoxy] -N-methylthieno [2,3-c] pyridine- 2-carboxamide, 4-. { 4 - [(2-methoxyethoxy) methyl] phenoxy} thieno [2,3-c] pyridine-2-carboxamide, 4-. { 4 - [(2-methoxyethoxy) methyl] phenoxy} -N-methylthieno [2,3-c] pyridine-2-carboxamide, 4- (4-. {[2- (2-methoxyethoxy) ethoxy] methyl} phenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-. {[[2- (2-methoxyethoxy) ethoxy] methyl] phenoxy) -N-methyltiene [2,3-c] pyridine-2-carboxamide, -. { 4 - [(tetrahydro-2 H -pyran-2-yloxy) methyl] phenoxy} thieno [2,3-c] pyridine-2-carboxamide, N-methyl-4-. { 4 - [(Tetrahydro-2H-pyran-2-yloxy) methyl] phenoxy} thieno (2,3-c) pyridine-2-carboxamide, 4- { [2- (aminocarbonyl) thieno [2,3-c] pyridin-4-yl] oxy}. benzyl 2-furoate, • 4- [4- ( { [(2R, 4R, 5S, 6R) -4,5-Dihydroxy-6- (hydroxymethyl) tetrahydro-2H-pyran-2-yl] oxy} methyl) phenoxy] - Ñ-methylthieno [2, 3-c] pyridine-2-carboxamide, 4- (4-acetylphenoxy) -N-methylthieno [2,3-c] pyridine-2-carboxamide, 4- [4- (4-morpholinylcarbonyl) phenoxy] t eno [2,3-c] pyridine-2-carboxamide, N-methyl-4- [4- (4-morpholinylcarbonyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 4- [4 - ( { [2- (4-morpholinyl) ethyl] amino.} Carbonyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, N-methyl-4- [4- ( { [2- (4-morpholinyl) ethyl] amino.} Carbonyl) phenoxy] thieno [2,3-c] pyridine-2- • 20 carboxamide, 4-. { 4 - [(E) -3- (4-morpholinyl) -3-oxo-1-propenyl] phenoxy} thieno [2,3-c] pyridine-2-carboxamide, 4- [4 - ((E) -3- { I 2 - (4-morpholinyl) ethyl] amino.} - 3-oxo-1-propeni phenoxy] thieno [2,3-c] pyridine-2-carboxamide, N-methyl-4- [4 - ((E) -3- { [2- (4-morpholinyl) ethyl] amino.} - 3-oxo-1-propenyl) phenoxy] thieno [2,3- 25 c] pyridine-2-carboxamide, 4- (4- { (E) -3 - [(2,3-dihydroxypropyl) amino] -3-oxo-1-propenyl}. Phenoxy) thieno (2,3-c] pyridine-2-carboxamide 4- (4- { (E) -3 - [(2,3-dihydroxypropyl) amino] -3-oxo-1-propenyl} phenoxy) -N-methylthieno [2,3-c] pyridine -2-carboxamide, 4- [4 - ((E) -3- { [2- (1 H-imidazol-4-yl) ethyl] amino.} - 3-oxo-1 -propenyl) phenoxy] -N-methylthieno [2,3-c] pyridine-2-carboxamide, 4- { 4 - [(E) -3- (. {2- 2- [bis (2-hydroxyethyl) amino) -1-3 -oxo-1-propenyl] phenoxy.} - N-methylthieno [2,3-c] pyridine-2-carboxamide, 4- { 4 - [(E) -3- (. {2- [bis (2-hydroxyethyl) amino] ethyl.}. amino) -3-oxo-1-propenyl] thieno [2,3-c] pyridine-2-carboxamide, 4- [4- (1H-imidazol-1- il) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, N-methyl-4- [4- (1 H -pyrazol-1-yl) phenoxy] thieno [2,3-c] pyridine-2- carboxamide, N-methyl-4- [4- (1 H-1, 2,4-triazol-1-yl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, N-methyl-4. {4- [5- (trifluoromethyl) -1,4-oxadiazol-3-yl] phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 4- [4- (4 ) 5-dihydro-1H-imidazol-2-yl) phenoxy] -N-methylthieno [2,3-c] pyridine -2-carboxamide, N-methyl-4- [4- (2-thienyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 4 - ([1,1, -biphenl] -4-yloxy) -N-methylthieno [2) 3-c] pyridine-2-carboxamide, N-methyl-4- [4- (1-methyl-1 H-imidazol-5-yl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 4-. { 4- [1- (hydroxymethyl) cyclopropyl] phenoxy} -N-methylthieno [2,3-c] pyridine-2-carboxamide, 4- [4- (1- { [2- (2-ethoxyethoxy) ethoxy] methyl.}. Cyclopropyl) phenoxy] -N-methylthieno [2,3-c] pyridine-2-carboxamide, N- methyl-4- [4- (trifluoromethoxy) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, -. { 4- [4- (1- { [2- (2-ethoxyethoxy) ethoxylmethyl} - cyclopropyl) phenoxy] thieno [2,3- c] pyridin-2-yl} -1,3,4-oxadiazol-2-amine, 4- [4- (1,1-difluoro-2-hydroxyethyl) phenoxy] N-methylthieno [2,3-c] pyridine-2-carboxamide, F 4- (4- {-2 2 - (2-ethoxyethoxy) ethoxy] -1,1-difluoroethyl.} Phenoxy) -N-methylthieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) -6-. { [(2,2-dimethylpropanoyl) oxy] methyl) -2 - [(methylamino) carbonyl] thieno [2,3- c] pyridin-6-io, 4- (4-bromophenoxy) -6-. { [(212-dimethylpropanoyl) oxylmethyl} -2- [(methylamino) carbonyl] thieno [2,3-c] pyridin-6-io, 2- (aminocarbonyl) -4- (4-chlorophenoxy) -6-. { [(isopropoxycarbonyl) oxy] methyl} thieno [2,3-c] pyridin-6-io "• 4- (benzyloxy) thieno [2,3-c] pyridine-2-carboxamide, 4 - [(4-chlorophenyl) (hydroxy) methyl] thieno [2 , 3-c] pyridine-2-carboxamide, 4- (4-chlorobenzoyl) -N-methylthieno [2,3-c] pyridine-2-carboxamide, N4- (4-chlorophenyl) thieno [2,3-c] ] pyridine-2,4-dicarboxamide, [4- (4-bromophenoxy) thieno [2,3-c] pyridin-2-yl] methanol, 4- (4-bromophenoxy) thienot2,3-c] pyridine-2- carbaldehyde, oxime 4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carbaldehyde, 4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carbaldehyde O-methyloxime, • 20 1 - [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -1-ethanone O-methyloxime, 1 - [4- (4-chlorophenoxy) thieno [2,3-c] ] pyridin-2-yl] -1-ethanone O-methyloxime, oxime 1 - [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -1-ethanone, oxime 1 - [4 - (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -1-ethanone, 1- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] - 1-propanone, 25 oxime 1- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -1-propanone, 2- [4- (4-chlorophenoxy) thieno [2,3-c] pyridip-2-yl] -N-methoxy-N-methyl-2-oxoacetamide, 4- (4-chlorophenoxy) thieno [2,3- Cypyridine-2-carbonitrile, 4- (4-chlorophenoxy) -N'-hydroxythieno [2,3-c] pyridine-2-carboximidamide, • 4- (4-chlorophenoxy) -N'-cyanothieno [2,3- c] pyridine-2-carboximidamide, [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] (2-nitrophenyl) methanol, [4- (4-chlorophenoxy) thieno [2,3 -c] pyridin-2-yl] (2-nitrophenyl) methanone, (2-aminophenyl) [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] methanone, (2-aminophenyl) [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] methanol, 10 [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] (3- nitrophenyl) methanol, (3-aminophenyl) [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] methanone, (3-aminophenyl) [4- (4-chlorophenoxy) thieno [2, 3-c] pyridin-2-yl3methanol, 4- (4-bromophenoxy) -2-vinylthieno [2,3-c] pyridine, 1 - [4- (4-chlorophenoxy) thieno [2,3-c] pyridine- 2-yl] -1,2-ethanediol, 15 1 - [4- (4-bromophenoxy) thieno [2,3-c] pyridin-2-yl] -1,2-ethanediol, [4- (4-chlorophenoxy ) thieno [2,3-c] pyridin-2-yl] methanamine, [4- (4-chloro phenoxy) thieno [2,3-c] pyridin-2-yl] methyl carbamate, N-. { [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] methyl} urea, (E) -3- [4- (4-bromophenoxy) thieno [2,3-c] pyridin-2-yl] -2-propenamide, • 20 (E) -3- [4- (4-bromophenoxy ) thieno [2,3-c] pyridin-2-yl] -N-methyl-2-propenamide, 3- [4- (4-bromophenoxy) t-ene [2,3-c] pyridin-2-yl] -2,3-dihydroxy-N-methylpropanamide, 3- [4- (4-bromophenoxy) thieno [2,3-c] pyridin-2-yl] -2,3-dihydroxypropanamide, 4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-ylamine, 4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-ylformamide, 25 N- [4- (4-chlorophenoxy) thieno [2, 3-c] pyridin-2-yl] urea, N- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -N'-methylthiourea, 4- (4-chlorophenoxy) -N-methylthieno [2,3-c3pyridine-2-] sulfonamide, 4- (4-chlorophenoxy) -N- (2,3-dihydroxypropyl) thieno [2,3-c] pyridine-2-sulfonamide, 4- (4-chlorophenoxy) -N- (2-hydroxyethyl) thieno [ 2,3-c] pyridine-2-sulfonamide, 4- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] phenol, 3- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-ii] aniline, 4- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] aniline, 4- (4-chlorophenoxy) -2 - (5-Nitro-2-pyridinyl) thieno [2,3-c] pyridine, 6- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -3-pyridinamine, 5- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -2-pyridinamine, 5- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2 -yl] -1,4,4-oxadiazol-2-amine, • 5- [4- (4-bromophenoxy) thieno [2,3-c] pyridin-2-ii] -1,3,4-oxadiazole- 2-ylamine, 5- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-ylHH-1,2,4-triazoI-3-amine, 5- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -1,4,4-thiadiazol-2-amine, 4- (4-chlorophenoxy) -2- (5-methyl-1, 2,4-oxadiazole -3-il) thieno [2,3-c] piri dina, 5- { 4- [4- (trifluoromethyl) phenoxy] thieno [2,3-c] pyridin-2-yl} -1,3,4-oxadiazol-2-amine, 4- (4-chlorophenoxy) -2- [5- (methylsulfanyl) -1,3,4-oxadiazol-2-yl] thieno [2,3-c] pyridine, 4- (4-chlorophenoxy) -2- (2-methyl-2H-1,2,3,4-tetrazol-5-yl) thieno [2,3-c] pyridine, 5- [4- (4 chloro-phenoxy) thieno [2,3-c] pyridin-2-yl] -4-methyl-4H-1,2,4-triazole-3- • 20-amine, 4- (4-chlorophenoxy) -2- [5 - (trifluoromethyl) -1,2,4-oxadiazol-3-yl] thieno [2,3-c] pyridine, 5- [4- (4-chlorophenoxy) t-ene [2,3-c] pyridin-2 -yl] -1,2,4-oxadiazol-3-amine, 5- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -N-methyl-1,3 , 4-thiadiazol-2-amine, 4- (4-chlorophenoxy) -2- (1, 2,4-oxadiazol-3-yl) thieno [2,3-c] pyridine, 2- (1, 3,4-oxadiazol-2-yl) -4- [4- (trifluoromethyl) phenoxy] thieno [2,3-c] pyridine, 3- [4- (4-chlorophenoxy) thieno [2, 3-c] pyridin-2-yl] -1, 2,4-oxadiazol-5-amine, 2- (5-methyl-1, 3,4-oxadiazol-2-yl) -4- [4- (trifluoromethyl) ) phenoxy] thieno [2,3-cjpyridine, • 5-methyl 2- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -1,3-thiazole-4-carboxylate, - [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -1,3-thiazole-4-carboxamide, tert-butyl 2- [4- (4-chlorophenoxy) thieno [2] , 3-c] pyridin-2-yl] -1,3-thiazol-4-ylcarbamate, 2- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -1, 3 -thiazole-4-amine, 4- (4-chlorophenoxy) -2- (1,3-oxazol-2-yl) thieno [2,3-c] pyridine, 4- (4-chlorophenoxy) -2- ( 1H-imidazol-2-yl) thieno [2,3-c] pyridine, 4-chloro-3-methylthieno [2,3-c] pyridine-2-carboxamide, 3-amino-4-chlorothieno [2,3- c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) -N, 3-d-methylthieno [2,3-c] pyridine-2-carboxamide, 4- (4-bromophenoxy) -3-methylthieno [2 , 3-c] pyridine-2-carboxamide, 7-chloro-4- (4-chlorophenoxy) -3-methylthieno [2,3-c] pyridine-2-carboxamide, tert-butyl 2- (ami) nocarbonyl) -4- (4-chlorophenoxy) thieno [2,3-c] pyridine-3-carboxylate, N-methyW- (4-toluidino) thieno [2,3-c] pyridine-2-carboxamide, • 20 4 - (4-chloroanilino) -N-methylthieno [2) 3-c] pyridine-2-carboxamide, N-methyl-4- (4-morpholinyl) thieno [2,3-c] pyridine-2-carboxamide, 7- chloro-4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 7-chloro-4- (4-chlorophenoxy) -N-methyltiene [2,3-c] pyridine-2 -carboxamide, 7-chloro-4- (4-cyranophenoxy) -N- (2-hydroxyethyl) thieno [2,3-c] pyridine-2-carboxamide, 7-Bromo-4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 7-bromo-4- (4-chlorophenoxy) -N-methylthieno [2,3-c] pyridine-2-carboxamide, 4- (4-bromophenoxy) -7-chlorothieno [2,3-c] pyridine-2- carboxamide, 4- (4-bromophenoxy) -7-chloro-N-methylthieno [2,3-c] pyridine-2-carboxamide, 7-chloro-4- [4- (trifluoromethyl) phenoxy] thieno [2,3- c] pyridine-2-carboxamide, • 5-chloro-N-methyl-4- [4- (trifluoromethyl) phenoxy] thieno [2,3-c] pyrridine-2-carboxamide, 7-chloro-N- (2 -hydroxyethyl) -4- [4- (trifluoromethyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) -N, 7-dimethylthieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) -7-methoxy-thieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) -7-oxo-6,7-dihydrothieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) -N-methyl-7- (methylamino) thieno 2,3-c] pyridine-2-carboxamide, • 7- (4-methylphenoxy) [1, 3] thiazolo [5,4-c] pyridine-2-carboxamide, N-methyl-7- (4-methylphenoxy) [1,3] thiazolo [5], 4-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) furo [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) furo [2,3-c] p Ridin-2-carbothioamide, 4 - [(E) -2-phenylethenyl] thieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenyl) thieno [2,3-c] pyridine- 2-carboxamide, 4- [3- (trifluoromethyl) phenyl] thieno [2,3-c] pyridine-2-carboxamide, 4- (3-chlorophenyl) thieno [2,3-c] pyridine-2-carboxamide , • 4- (4-bromophenyl) thien [2,3-c] pyridine-2-carboxamide, 4- (3-aminophenyl) thieno [2,3-c] pyridine-2-carboxamide, 4- ( 315-dichlorophenyl) thieno [2,3-c] pyridine-2-carboxamide, 4- (2,4-dichlorophenyl) thieno [2,3-c] pyridine-2-carboxamide, 4- (3,4-dichlorophenyl) t-ene [2,3-c] pyridine-2-carboxamide, 4- (2,4-difluorophenyl) thieno [2,3-c] pyridine-2-carboxamide, . 4- (4-fluorophenyl) thieno [2,3-c] pyridine-2-carboxamide, and 4- (4-bromophenoxy) -5-chlorothieno [2,3-c] pyridine-2-carboxamide. The endothelial cells of the primary, clustered human umbilical vein (HUVEC's) (Clonetics) between passages 3 and 7 are • 5 placed in a 96-well plate (Costar), 100 μl / well, 5 × 10 4 cells / ml in Clonetics EBM / 2% FBS / EFG / Bovine brain extract / gentamicin in the absence of hydrocortisone. The next day, the compounds of the invention were added in 100 μL / well medium, and the plates were incubated at 37 ° C. 24 hours after the addition of the compound. TNF (Gibco / BRL) in 10 μL / well medium was added to a final concentration of 5 ng / mL, and the cells were incubated for 6 hours at 37 ° C. Then, the medium was removed, and the plates were rinsed once with D-PBS (Gibco / BRL) and treated with primary antibodies (Becton Dickinson, City), 100 μL / well in D-15 PBS / 2% BSA (Sigma ) /0.01% azide. The primary antibodies in an initial concentration of 1 mg / mL were used in the following dilutions: anti-ELAM-1, 1: 2000, anti-ICAM-1, 1: 2000 and anti-VCAM-1, 3000: Plates were stored overnight at 4 ° C, washed 3 times with D-BPS, and treated with secondary antibody (Jackson Labs), 100 μl / well 1: 8000 dilution HRP-IgG (H + L) of monoclonal anti-mouse conjugate in D-BPS / 2% BSA. Plates were incubated for a minimum of 1 hour at room temperature, rinsed 3 times with D-PBS and treated with 100 μL of ortho-phenylene diamine-2 HCl reagent per well. The plates developed approximately 15 minutes and neutralized with 100 μL / 1 N cavity of sulfuric acid. The Absorbency was read at 490 nm. The inhibitory potencies for representative compounds of the invention are shown in Table 1. Table 1 • fifteen • twenty • • fifteen F 20 i • 15 F 20 25 In this manner, the compounds of the present invention act as anti-inflammatory agents with potencies below 1 μM and are therefore useful for treating inflammatory diseases.

Pharmaceutical Compositions and Treatment Methods The present invention also provides pharmaceutical compositions comprising compounds of the present invention formulated together with one or more pharmaceutically acceptable, non-toxic vehicles. The pharmaceutical compositions can Formulated especially for oral administration in solid or liquid form, for parenteral injection or for rectal administration. • The pharmaceutical compositions of this invention can be administered to humans and other animals, orally, rectally, parenterally, intracisternally, intravaginally, intraperitoneally, topically (as by powders, ointments or drops), buccally or as a nasal or oral sprayer. The term "parenteral" administration as used herein refers to modes of administration which include intravenous, intramuscular, intraperitoneal, intrasternal, subcutaneous and intravenous injection and infusion. • 20 intraarticular. The pharmaceutical compositions of this invention for parenteral injection comprise sterile aqueous or non-aqueous pharmaceutically acceptable solutions, dispersions, suspensions or emulsions as well as sterile powders for reconstitution. in dispersions or sterile injectable solutions just before be used. Examples of vehicles, solvents, diluents or aqueous or non-aqueous vehicles including water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, and the like), and suitable mixtures thereof, vegetable oils (such as oil 5 olive) and injectable organic esters such as ethyl oleate. Proper fluidity can be maintained, for example, by the use of coating materials such as lecithin, by the maintenance of the required particle size in the case of dispersions, and by the use of surfactants. These compositions may also contain adjuvants such as preservatives, humectants, emulsifiers, and F dispersants. The prevention of the action of microorganisms can be ensured by the inclusion of various antifungal and antibacterial agents, for example, parebene, chlorobutanol, sorbic acid phenol, and the like. It may be desirable to include isotonic agents such as sugars, sodium chloride, and the like. Prolonged absorption of the injectable pharmaceutical form can be caused by the inclusion of agents that delay absorption such as aluminum monostearate and gelatin. In some cases, in order to prolong the effect of the drug, it is desirable to decrease the absorption of the intramuscular or subcutaneous injection drug. This can be accomplished by the use of a liquid suspension of amorphous or crystalline material with poor water solubility. The absorption speed of The medication then depends on its rate of dissolution, the which, in turn, may depend on the crystal size and crystal shape. Alternatively, the delayed absorption of a parenterally administered drug form is carried out upon dissolving or suspending the medicament in an oil vehicle. Injectable depot forms are made by forming microencapsule matrices of the drug in biodegradable polymers such as polylactide-polyglycolide. Depending on the proportion of drug for the polymer and the nature of the particular polymer employed, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly (orthoesters), and poly (anhydrides). Depot injectable formulations are also prepared by trapping the drug in liposomes or microemulsions that are compatible with body tissue. The injectable formulations can be sterilized, for example, by filtration through a bacterial retention filter, or by incorporating sterilization agents in the form of sterile solid compositions that can be dissolved or dispersed in sterile water or other sterile injectable medium just prior to use. . Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active compound is mixed with at least one pharmaceutically acceptable carrier or excipient, inert such as sodium citrate or dicalcium phosphate and / or a) fillers or extenders such such as starches, lactose, sucrose, glucose, mannitol and salicylic acid) b) binders such as, for example, carboxymethyl cellulose, alginates, gelatin, polyvinyl pyrrolidone, sucrose and acacia, c) humectants such as glycerol, d) disintegration such as agar-agar, calcium carbonate, tapioca or potato starch, alginic acid, certain silicates, and sodium carbonate, e) agents that retard the solution such as paraffin, f) absorption accelerators such as ammonium compounds quaternary, g) wetting agents such as, for example, cetyl alcohol and glycerol monostearate, h) absorbents such as kaolin and bentonite clay, and i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, lauryl sodium sulfate, and mixtures thereof. In the case of capsules, tablets and pills, the dosage form may also comprise regulating agents. Solid compositions of a similar type can also be used as fillings in soft and hard filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like. similar. The solid dosage forms of tablets, dragees, capsules, pills and granules can be prepared with coatings and shells such as enteric coatings and other coatings well known in the pharmaceutical formulating art. May optionally contain opacifying agents and can also be a composition that releases the active ingredient (s) only, or preferably, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of included compositions that may be used include waxes and polymeric substances. The active compounds may also be in micro-encapsulated form, if appropriate, with one or more of the above excipients. Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups and elixirs. In addition to the active compounds, the liquid dosage forms may contain inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing and emulsifying agents such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, acetate. ethyl, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethyl formate, oils (in particular, cottonseed, peanut, corn, germ, olive, castor, and sesame oils, glycerol, tetrahydrofuryl alcohol, polyethylene glycols, and sorbitan fatty acid esters and mixtures thereof In spite of the inert diluents, the oral compositions may also include adjuvants such as wetting agents, suspending and emulsifying agents, sweetening, flavoring and flavoring agents.The suspensions, in addition to the active compounds, they may contain suspending agents such as, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth and mixtures thereof. Compositions for rectal or vaginal administration are preferably suppositories which can be prepared by mixing the compounds of this invention with suitable non-irritating carriers or excipients such as cocoa butter, polyethylene glycol or a suppository wax which are solid at room temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active compound. The compounds of the present invention can also be administered in the form of liposomes. As is known in the art, liposomes are generally derived from phospholipids or other lipid substances. Liposomes are formed by mono- or multi-lamellar hydrated liquid crystals that are dispersed in an aqueous medium. Any lipid metabolizable and physiologically acceptable, non-toxic capable of forming liposomes can be used. The present compositions in liposome form may contain, in addition to a compound of the present invention, stabilizers, preservatives, excipients and the like. The preferred lipids are phospholipids and phosphatidyl (lecithin) hills, both natural and synthetic. Methods for forming liposomes are known in the art. See, for example, Prescott, E., Methods in Cell Biology, Volume XIV, Academic Press, New York, N.Y. (1976), p. 33 et seq.

The compounds of the present invention can be used in the form of pharmaceutically acceptable salts derived from inorganic or organic acids. Through "salt "Pharmaceutically acceptable t" are understood to mean those salts which are within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like and measure equal to a reasonable benefit / irrigation ratio. The pharmaceutically acceptable salts are known well in the matter. For example, S.M. Berger, et al., Discloses pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1977, 66: 1 et seq. The salts can be prepared in situ during the purification and final isolation of the compounds of the invention or separately by reacting a free base function with a suitable acid. Representative acid addition salts include, but are not limited to, acetate, adipate, alginate, citrate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphorrate, camphorsulfonate, digluconate, glycerophosphate, hemisulfate, heptanoate, hexanoate, fumarate, hydrochloride. , hydrobromide, hydroiodide, 2- • 20-hydroxyethanesulfonate (isethionate), lactate, maleate, methanesulfonate, nicotinate, 2-naphthalenesulfonate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, picrate, pivalate, propionate, succinate, tartrate, t? ocinate, phosphate, glutamate, bicarbonate, p-toluenesulfonate and undecanoate. Also, groups that contain basic nitrogen can be quaternized with such agents as alkyl halides lower such as butyl, propyl, ethyl and methyl iodides, bromides and chlorides; diakyl sulfates such as diamyl, dibutyl, diethyl and dimethyl sulfates; long chain halides such as iodides, bromides and chlorides of stearyl, myristyl, lauryl and decyl; halides of • 5 arylalkyl as phenethyl and benzyl bromides and others. Dispersible and oil-soluble products are obtained in this way. Examples of acids that can be employed to form pharmaceutically acceptable addition salts include such inorganic acids as hydrochloric acid, hydrobromic acid, sulfuric acid, and acid phosphoric and such organic acids as oxalic acid, maleic acid, succinic acid and citric acid. • The basic addition salts can be prepared in situ during the purification and final isolation of compounds of this invention by reacting a part containing carboxylic acid with a suitable base such as hydroxide, carbonate or bicarbonate of a pharmaceutically acceptable metal cation or with ammonium or a primary, secondary or tertiary organic amine. The pharmaceutically acceptable salts include, but are not limited to, cations based on alkali metals or alkaline earth metals such as • 20 salts of lithium, sodium, potassium, calcium, magnesium and aluminum and the like and non-toxic ammonium and quaternary ammonium cations including ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, diethylamine, ethylamine and the like. Other representative organic amines useful for the formation of salts of base addition include ethylenediamine, ethanolamine, diethanolamine, piperidine, piperizine and the like. Preferred salts of the compounds of the invention include phosphate, tris and acetate. Dosage forms for topical administration of a compound of the invention include powders, sprays, ointments and inhalants. The active compounds are mixed under sterile conditions with a pharmaceutically acceptable carrier and necessary preservatives, regulators or propellants that may be required. Ophthalmic formulation, eye ointments, powders and solutions are also contemplated as being within the scope of this invention. The current dose levels of active ingredients in the pharmaceutical compositions of this invention can be varied to obtain an amount of the active compound (s) which are effective to achieve the desired therapeutic response for a particular patient S, compositions and administration mode. The dose level selected will depend on the activity of the particular compound, the route of administration, the severity of the condition being treated, and the condition and prior medical history of the patient being treated. However, it is within the experience of the material to initiate dose of the compound at levels lower than those required to achieve the desired therapeutic effect and to gradually increase the dose until the desired effect is achieved. Generally dose levels of from about 1 5 to about 50, more preferably from about 5 to about 20 mg of active compound per kilogram of body weight per day are administered orally to a mammalian patient. If desired, the effective daily dose can be divided into multiple doses for administration purposes, for example, two to four doses per • separated by day.

Preparation of the Compounds of this Invention Abbreviations 10 The abbreviations that have been used in the descriptions of the schemes and the examples that follow are: BH3 SP for borane; BH3 DMS for borane dimethylsulfide compleko, BINAP for 2,2'-bis (diphenylphosphino) -1, 1'-bifin, BF3OEt2 for boron trifluoride diethyl ether complex, n-BuLi for n-butyllite, CCI for carbon tetrachloride, Cs2CO3 for cesium carbonate, DBU for 1, 8-diazabicyclo [5.4.0] undec-7-ene, DMA for N, N-dimethylacetamide, DIBAL for diisobutylaluminum hydride, DME for dimethoxyethane, DMF for N , N-dimethylformamide, DMSO for dimethylsulfoxide, DIPEA for diisopropylethylamine, DPPA for diphenylphosphoryl azide, EDCI of 20 EDC for 1-ethyl-3- [3- (dimethylamino) propyl] -carbodiimide hydrochloride, EtN3 for triethylamine, EtO2 for diethyl ether, EtOAc for ethyl acetate, EtOH for ethanol, K2CO3 for potassium carbonate, LiAIH for lithium aluminum hydride, LDA for lithium diisopropylamide, MeOH for methanol, NaOMe for methoxide sodium, NaOH for sodium hydroxide, HCl for hydrochloric acid, NMP for 1-methyl-2-pyrrolidinone, H2 / Pd for hydrogen and a palladium catalyst, iPrOH for isopropyl alcohol, PPh3 for triphenylphosphine, THF for tetrahydrofuran, THP for tetrahydropran, TFA for trifluoroacetic acid, and pyBOP for benzotriazole-1 - * • iloxitripirrolidinofosfanio hexafluorophosphate.

Synthetic Methods The compounds and processes of the present invention will be better understood in connection with the following synthetic schemes illustrating the methods by which the compounds of the invention can be prepared. In addition, all citations herein are incorporated by reference.

Scheme 1 Sfl 'K CO, * ^ > \\ DMG Scheme 1 shows the preparation of thieno [2,3-Jpyrimidines of esters of the general formula 1 by published methods. 4-Clothothieno [2,3-d] pyrimidines of the general formula 3 were substituted with thiols to provide 4-thioethers of the general formula 4 or substituted with amines to provide 4-aminothieno [2,3-d] pyrimidines of the formula general 5. Scheme 2 Scheme 2 shows the preparation of 2-carboxy-substituted thieno [2,3-d] pyrimidines. The pyrimidinones of the general formula 1 are reacted with phosphoryl chloride to produce 4-chloro-pyrimidines of the general formula 6, which were then substituted with thiols to provide thioethers of the general formula 7. Scheme 3 Scheme 3 shows the preparation of thieno [3,2- djpyrimidines derived from chloropyrimidines of the general formula 8. L substitution of the chlorides with thiols provided thioethers of the general formula 9, and the substitution of the chlorides with amines provided aminopyridines of the general formula 10. Scheme 4 11 11 12 25 Analogs having 2-carboxamide groups of the thieno [2,2-d] pyrimidine were prepared as shown in Scheme 4. Thiophene in position 2 was deprotonated with a strong base such as lithium diisopropylamide, and the corresponding carbanion was treated with carbon dioxide to provide acids of the general formula 1 1.

• The acids were converted into the corresponding amides of the general formula 12 through the intermediate acid chlorides. squema 5 17 Scheme 5 shows the preparation of 6-alkyl Substituted thieno [2,3-d] pyrimidines with alkylthio group in the pottion 4. Using known procedures, 2-aminothiophene 13 was acylated to provide amide 14 which was cyclized to provide thienopyrimidinone 15. The pyrimidinone was converted to chloride and in addition to thioether 17 by standard procedures. 25 Scheme 6 R SH. hasti 1 HOUR 'fc * The general process for preparing 2,4-disubstituted thieno [2,3-d] is shown in scheme 6. 3,5 commercially available dichloropyridine was treated with strong base such as lithium diisopropylamide in an anhydrous solvent at low temperature followed by the reaction with methyl format (or alternatively, dimethylformamide) to provide known pyridinat-4-carboxaldehyde 18. The aldehyde 18 is then substituted with an equivalent of lime (R1 = heterocyclic, substituted or unsubstituted alkyl or aryl) to produce chloroaldehyde of the general formula 19. The treatment of 19 with thioglycolate of methyl and a base such as cesium carbonate or potassium carbonate provided 4-thioether [2,3-c] -thienopyridine esters of the general formula 20. The esters were converted into the corresponding acids of the general formula 21 by basic hydrolysis, for example using lithium, sodium or * 5 potassium hydroxide in a mixture of water and tetrahydrofuran. The acids of the general formula 21 can also be converted to amides of the general formula 22 or 23 via the intermediate acid chlorides by first treating with oxalyl chloride or thionyl chloride, then with the amine of choice (R2, R3 may to be heterocyclic, substituted or unsubstituted alkyl or aryl).

F Alternatively, the acids 21 can be converted to amides 22 or 23 by other coupling methods, such as carbodiimide (for example, N-ethyl-N '- (3-dimethylamino) propyl carbodiimide hydrochloride (EDC)), mixed anhydrides (derivatives of chloride pivaloyl or treatment of chlorbutramybutyl), and active esters (for example, derivatives of N-hydroxysuccinimide, p-nitrophenol). • 24 27 OR 1 ÜOH NaOH. O 25 MeOH. EtOH, i-P'OH, - ^ i; ~ c OH or THF, H20 28 OR1 OR '(COCÍ); A f R3R3NH. . - .__- N. O CHJCIJ T -V \ (-1 29 3Q Scheme 7 illustrates the analogous preparation of substituted 4-ether-thienopyridines of the general formula 30. The aldehydes 18 were substituted with alcohols (R 1 = heterocyclic, substituted or unsubstituted aryl) under basic conditions (for example, potassium tert-butoxide or cesium carbonate in dimethylformamide or anhydrous tetrahydrofuran) to give pyridine ethers of the general formula 24, and then reacted with methyl thioglycolate to provide thieno [2,3-c] pyridine esters of the general formula 25. These esters can be converted into the corresponding primary amides of the general formula 26 by heating in methanolic ammonium solution. Alternatively, the esters of the general formula 25 can be reacted with mono or disubstituted amines in polar solvents such as dimethylformamide or methanol. The esters of the general formula 25 were hydrolysed with carboxylic acids of the general formula 28 by basic hydrolysis with sodium or lithium hydroxide in tetrahydrofuran or aqueous methanol. The acids were then converted to amides of the general formula 30 by reaction of the corresponding acid chlorides of the general formula 29 with amines. Alternatively, the acids were coupled to amines by coupling conditions of the standard peptide as described in Scheme 6 for amides 22 or 23.

Scheme 8 Similar methods can be used for the preparation of 4-bromothieno [2,3-c] pyridine 32, as shown in Scheme 8. 3,5-Dibromopyridine was converted to aldehyde 31 by the process described for the preparation of compound 18 in Scheme 6. The reaction of 31 with methyl thioglycolate, for example in the presence of cesium carbonate in DMF, yielded 4-bromothieno [2,3-c] pyridine ester 32. Bromide 32 was provided as starting material for the preparation of 4-aryl, heterocyclic, alkyl or alkene derivatives of the general formula 32 using Suzuki coupling methodology as shown. Bromide 32 can also be coupled with terminal alkylene to provide alkynyl derivatives (R1 = alkynyl) following the Sonogashira methodology (Sonogashira, K., Tohda, Y.; Hagihara, N. Tetrahedron Lett., 1975, 4467-70). The esters of the general formula 33 were converted into amides of the general formula 34 by the procedures described for 26, 27 or 30 in Scheme 7. Scheme 9 36 37 HH 'H 36 38 39 40 SR1 SR1 39 41 Scheme 9 shows the conversion of acids from the general formula 21 in aldehyde or acetone-derived compounds. For example, the aldehydes of the general formula 36 were produced by the reduction of the N-methyl-N-methoxylamides of the general formula 35. The amides of the general formula 35 are also reacted with Grignard reagents to produce non-symmetric ketones of the general formula 39. The aldehydes of the general formula 36 and Acetone of the general formula 39 were used for the production of oximes of the general formula 37 or 40 by the reaction with derivatives of hydroxylamine. The aldehyde of the general formula 36 was reacted with phosphoranos (or phosphonoacetate salts) to produce substituted 2-alkenyl derivatives of the general formula 38. The "• Acetones of the general formula 39 were reduced to the corresponding alkanes of the general formula 41 by treatment with hydrazine and strong base, such as potassium hydroxide.

Analogous derivatives at the 2-position of thienopyridine ethers of the general formula 28 in Scheme 7 would follow similar synthetic routes as described in Scheme 9. In this manner, the acids 28 can be converted into substitutions of aldehydes, ketones, oximes , alkenes or alkanes in position 2. 20 Scheme 10 34 42 The amides of general formula 34 (or 26, 27 or 30) can be converted to the corresponding thionoamides of the formula 34 per treatment with Lawesson's reagent as shown in Scheme 10. Scheme 1 1 As shown in Scheme 11, 4-sulfoxides of the general formula 43 were produced by the reaction of thioethers of the general formula 20 with an oxidant such as m-chloroperoxybenzoic acid under controlled conditions. Scheme 12 Do teim A K . . * • SC. O1H powder tie Cu N. X f 21, 28 44 45 Alternative functionality was introduced into position 2 of thienopyridines of general formula 44 by metalation of position 2, followed by reaction with appropriate electrophiles, as shown in Scheme 12. Acids of general formula 21 (LAXA =: thioalkoxy, alkoxy, alkyl, alkenyl, aryl, heterocyclic) were decarboxylated at elevated temperatures (optionally in the presence of copper powder) to provide 2-unsubstituted derivatives of the general formula 44. The compounds of the general formula 44 were deprotonated with strong organic bases such as n-butyllithium, and then reacted with electrophiles such as borates, cyanoformates, aldehydes, or trialkyltin chlorides according to standard procedures (Masakatsu, N .; Kazuhiro, N .; Ichiro, M .; Iwao, W. Chem. Lett., 1983, 6, 905-908). Scheme 13 • or 25 46 Scheme 13 illustrates an alternative method for the preparation of 2-carboxaldehydes of the general formula 36 or 47. The esters of the general formula 20 or 25 (R 1 = thioalkoxy, alkoxy, alkyl, Alkenyl, aryl, hetrocyclic) were reduced to the corresponding alcohols of the general formula 46 using calcium borohydride. The alcohols were then oxidized to the aldehydes using Swern conditions. The aldehydes were then reacted with Wittig reagents (for example, phosphorus to produce the derivatives • Acrylate 20 of the general formula 48 (Jung, M.E. and Kiankarami, M.J. Org, Chem. 1998, 63, 2968-2974).

* Scheme 14 27 or 30 l "(n Rr) 49 As shown in Scheme 14, the thienopyridines of the general formula 27 or 30 were alkylated on the pyridine nitrogen using alkyl iodides (or alkyl bromides or triflates) to produce the pyridinium salts of the general formula 49. For example R can be alkylcarbonyloxymethylene, aminocarbonyloxymethylene, alkoxycarbonyloxymethylene, or alkyl. Such derivatives can serve as a means of promoting the thienopyridine amides 27 or 30 Scheme 15 53 A variety of 2-aminothieno [2,3-c] pyridine derivatives was available starting from the 2-carboxylic acids of the general formula 21 or 28, as shown in Scheme 15, wherein R 1 may be thioalkoxy, alkoxy, alkyl, alkenyl, aryl, heterocyclic. Re-installation Curtius led to isocyanates of the general formula 50, which are reacted with alcohols (alkyl, aryl, heterocyclic, or dialkylaminoalkyl) to provide carbamates of the general formula 51. The isocyanates can be reacted with amines (ammonium, primary alkyl or secondary alkyl) to provide ureas of the general formula 52. Also, it can be reacted with arylmagnesium or alkyl halides, or alkyl lithium salts, to provide amides of the formula No. 53. Isocyanate 50 was hydrolyzed under aqueous conditions to produce 2-amino derivatives of general formula 54. Scheme 16 The amines of the general formula 54 were reacted with appropriate electrophiles to further derivatize this position. Thus, the reaction of 54 with alkylsulfonium or aryl chlorides (R2 = alkyl, aryl, heterocyclic) or sulfamoyl chlorides, (R2 = NH2, mono- or di-alkylamino) to give sulfonamides of the general formula 55. amino derivatives 54 were also reacted with chlorides of acyl (R2 = alkyl, heterocyclic or aryl) to produce amides of the general formula 53 as shown in Scheme 16. Scheme 17 The functionality present in the aryl rings attached at the 4-position of thieno [2,3-c] pyridines can be further reacted for the advantage, as illustrated in Scheme 17. For example, the styryl derivatives 56 were converted to 1 , 2-diol 57 by treatment with osmium tetroxide under standard conditions, the 4- (4-bromophenoxy) derivative 58 underwent easy substitution with boronic aryl acids under palladium catalysis under Suzuki conditions to provide biaryl derivatives of the formula 59. Alternatively, alkoxycarbonylation under palladium catalysis effectively provides esters of the general formula 61.

Scheme 19 B4 G5 H.

Nu = RS- RMHS, RC.? i, etc. 68 Scheme 19 shows the use of boronic acid derivatives to functionalize the 4-position of thieno [2,3-c] pyridines. The chemistry depicted can be applied to a wide range of analogs of aryl olefins for bromostyrene 62. In the case shown, bromostyrene 62 was converted to boronic acid 63 under standard conditions, and the boronic acid was coupled to 4-bromothienopyridine 32 under Suzuki conditions, provided the styryl analogue 64. Ester 64 was converted to amide 65 by the method previously described (Miyara, N and Suzuki, A. Chem. Rev. 1995, 95, 2457-2463). The olefin group can then be converted to the epoxide 66, which can undergo reactions with nucleophilic reagents in the less articulated position of the epoxide to produce analogs of the general formula 67. Alternatively, the steryl derivative 65 can be converted to the diol 68 by standard methods . Scheme 20 CuCN.2L «C.

E * = RCOCl. RX, RCMO, RSnCI, RüOR " Another method for the introduction of substituents at the 4-position of thieno [2,3-c] pyridines is shown in Scheme 20. Bromide 32 can be converted into the corresponding cuprate through the intermediate zinc bromide reagent, which can then be reacted with appropriate electrophiles (acid chlorides, zinc halides, aldehydes, ketones) to provide the substituted compounds of the general formula 69 (Zhu, L .; Wehmeyer, RM; Rieke, RDJ Org. Chem. 1991, 56, 1445-1453 ).

Scheme 21 Scheme 21 represents the preparation of 5-halo thienopyridine derivatives, as exemplified by the preparation of the 5-chloro-75 analogue. The formylation of lithiated 2,3,5-trichlorpyridine with methyl formate gave aldehyde 72. The displacement of chlorins 3 and 5 with excess 4-bromophenol and the reaction with methylthioglycolate gave 5-chlorothienopyridine 74 in low production, together with the main product 73. The 5-chloro isomer was treated with ammonium in methanol in a pressure tube to generate amide 75. It should be noted that this chemistry can be applied using a range of phenols or hydroxy heterocyclic compounds instead of 4-bromophenol. Scheme 22 The 2-position of thienopyridines is substituted with alkyl, acetyl, vinyl or aryl groups using the procedure shown in Scheme 22. The boronic acids of the general formula 76 prepared according to Scheme 12, were coupled to aryl halides under palladium catalysis to produce 2-aryl derivatives of the general formula 80. Scheme 23 Or ?? 3NHOCH3 aq) or < I oxal? fo io 89 90 or «or No .. '-: ^ - > 20 f? 7 91 Scheme 23 illustrates the preparation of 4-acyl derivatives of thieno [2,3-c] pyridines. Carboxylic acid 85 was converted to amide 86 through acid chloride, then hydroxyamide 86 experienced thionyl chloride mediated cyclization for Oxazolin 87 (Meyers, A.I., Stoianova, D.J. Org.Chem, 1997, 62, 5219-5221). The palladium-mediated alkoxycarbonylation of 87 yielded ester 88 (Heck, R.F., et al, J. Org. Chem. 1974, 39, 3318). The ester 88 can be converted to the Weinreb amide 89 by standard methods. The amide 89 was reacted with the appropriate Grignard reagents to provide the desired 4-acyl products of the general formula 90. The hydrolysis of the oxazoline and conversion of the resulting carboxylic acid to the amide yields the desired products of the general formula 91. Scheme 24 methyl 93 93 Scheme 24 represents a proposed method for the formation of substituted 4-hydroxy thieno [2,3-c] pyridine. The reaction of phenol 92 with dihydropyran under acidic conditions yields tetrahydropyranyl ether 93 (Grant, H.N., et al., Helv. Chim. Acta. 1963, 46, 41). The lithiation of 93 and the subsequent cooling with the format of methyl aldehyde 94. Displacement of the halide with methyl troglicolate and subsequent cyclization with cesium carbonate yields the ester 95. Removal of the tetrahydropyranyl ether with aqueous HCl gives hydroxypyridine 96, which can be converted to the amide as describes previously. Scheme 25 Scheme 25 proposes the use of the 4-hydroxy group for the introduction of functionality to position 4 of thieno [2,3-clpyridines. The 2-carboxylic acid group is first protected as oxazoline 99 (through intermediate amide 98), then the hydroxy group is converted to aryl triflate 100 by standard conditions. Triflate 100 can then be converted to N-methyl-N-methoxy amide 89 under conditions similar to those of bromide 87. It should be noted that 4-triflate 100 can serve as a coupling standard in a variety of transition metal-mediated couplings with suitable nucleophilic patterns (eg, boronic acids, boranes, alkyl or aryl-zinc reagents).

Diagram 26 1) ROH t BuOK TH - Compounds with amino substitutions at the 3-position of thieno [2,3-c] pyridines were prepared according to the procedures outlined in Scheme 26. The aldehyde 18 was converted to the cyanopyridine 107 by treatment with hydroxylamine under the conditions of dehydration. In a manner similar to reactions that include aldehyde 18, cyanopyridine 107 was substituted sequentially with phenols and methyl trioglycolate to provide 3-amino thieno [2,3-c] pyridines of the general formula 108. The esters of the general formula 105 they were then converted into amides of the general formula 109 by standard procedures.

Scheme 27 110 111 Scheme 27 illustrates the additional derivatives that can be derived from amino esters of the general formula 108 or amino amides of the general formula 109. For example, the amino amides of the general formula 109 can be treated with 1, 1 '- carbonyldiimidazole to produce cyclic amides of the general formula 1 10. The 3-amino group was acylated (for example, with acid chlorides and weak base, or by coupling with acids using carbodiimides) to give the diamides of the general formula 1 1 . The 3-amino group can be alkylated under reductive conditions using aldehydes and a reducing agent (such as triacetoxyborohydride), to provide alkylated amines of the general formula 1 12.

Scheme 28 CI - HF 114 115 Scheme 28 shows the preparation of compounds that share alkyl substituents in the 3-position of thieno [2,3-cjpyridines. Using chemistry similar to that described for compound 30, 3,5-dichloropyridine was deprotonated with strong base (e.g., lithium diisopropylamide), and then reacted with an acylating reagent (ester, N-methyl-N-methoxyamide, acyl pyrazole, or others) to provide acetone 1 13. Alternatively, the anion can be reacted with an aldehyde (e.g., acetamide) and subsequently the product can be oxidized (e.g., with tetrapropylammonium perruthenate) to provide 13-13 acetone. the underlined procedures for Example 30, the dichloroacetone is subsequently reacted with phenols and then with methyl thioglycolate to provide cyclic products of the general formula 1 14. The esters of the general formula 1 14 can be converted to various derivatives as outlined above. 117 118 R ^ X? 53SC R "R7 119 120 Scheme 29 describes a similar strategy used to obtain derivatives with alkoxy groups at the 3-position of thieno [2, 3-c] pyridines. Ester 16 is substituted and cycled to provide 3-hydroxy analogs of general formula 1 17. The hydroxy group can be left unsubstituted, leading to amides of the general formula 1 (or other derivatives). Alternatively, the hydroxy esters of the general formula 17 may be alkylated by standard procedures to produce 3-alkoxy derivatives of the general formula 1 19, followed by the formation of amide to provide compounds of the general formula 120.

Scheme 30 Ei Scheme 30 shows the procedure used for the transformation of a commercially available furo [2,3-bipyridine in amide 122.

Scheme 31 10 nBuLi GO? 44 123 124 125 3) Ag (OBz) 2 126 Scheme 31 proposes the preparation of thienopyridine derivatives containing an amide group in the 3-position. The thienopyridines of the general formula 44 are halogenated using electrophilic halide sources (eg, N-bromosuccinimide, 12), to produce 3-halothienopyridines of the general formula 123. Metal-halogen exchange, followed by retention with carbon dioxide, provides acids of the general formula 124. The acids are converted to amides of the general formula 125 by functional procedures, or they can be homologated in esters of the general formula 126 (for example, by the Arndt-Eisert method). The esters of the general formula 126 can then be converted to amides or other functionality by the methods described above. Scheme 32 127 128 1 OH H ^ O i P.O *? HO ' Scheme 32 describes the methods used for the preparation of a variety of thieno [2,3-b] pyridines starting from the known 4-doro-5-ester 127. The displacement of the chlorine of 127 proceeds with thiols in the presence of potum carbonate to provide 4-thioethers of the general formula 128. The ester 127 also hydrolyzed the acid 127, which was converted to amides of the general formula 130 by standard coupling conditions. Scheme 33 Do teimA Cu 128 131 powder 134 Scheme 33 shows the conversion of thioethers of general formula 128 to 2,4-disubstituted analogues. The corresponding acids of the general formula 131 can be thermally decarboxylated to provide the 5-unsubstituted analogs of the general formula 132. The compounds of the general formula 132 were treated with strong base (e.g., n-butylithium), and reacted with dioxide of carbon to provide 2-carboxylic acids of the general formula 133. The acids were then transformed into amides of the general formula 134 by previously described methods.

Scheme 34 138 13 » R * R "NH let me do coupling '' T * °? ' 139-10 140 • Scheme 34 illustrates the preparation of thieno [3,2-bjpyridines] Chloride 135 was transformed by a similar set of conditions to that described in Scheme 33 to produce acids of the general formula 1 39 and amides of the general formula 140. fifteen • twenty Scheme 35 145 14B 147 Scheme 35 represents the preparation of thieno [3,2-cjpyridines. Starting with thienopyridone 141, 4-oxo-4,5-dihydrothieno [3,2-c] pyridine-2-nitrile 144 was prepared according to the methods of the literature (Eloy, F.; Deryckere, A. Bul. Soc. Chim, Belg, 1970, 79, 301, Troxler, F, Wiskott, E. Patent of US 3,998,835). Treatment of thienopyridone 144 with phosphoryl chloride at 130 ° C gave chloride 145, which after thiol exposure under basic conditions gave thioethers of the general formula 146. hydrolysis of the nitrile group with phosphoric acid gave the corresponding amides of the formula general 147 Scheme 36 148 Scheme 36 shows that the ethers of the general formula 149 were prepared in an analogous manner as previously described in Scheme 35. Scheme 37 Scheme 37 shows the preparation of intermediate compounds of the general formula 151, useful for the preparation of 2-alternative derivatives. Treatment of 2-bromo-4-chlorothieno [3,2-cypyridine 150 with 1 equivalent of a lime gave 2-bromothieno [3,2-c] pyridines of the general formula 151.

Juema 38 157 158 159 160 Scheme 38 represents an example of the preparation of a related clof inhibitors based on a structure oxazolopyridine. 3-chloropyridine commercially available is oxidized in N-oxide 1 52 with peracetic acid, which is then nitrated in a mixture of concentric nitric, concentrated sulfuric and fuming sulfuric acids to give the 4-nitro derivative 153. The chlorine in 153 then moves with sodium salt of p-cresol, and the resulting biaryl ether 1 54 is hydrogenated (Raney nickel catalysis) to reduce both the group functional nitro as the N-oxide to give 155. the amino group of 155 is protected with an N-trimethylacetyl group, and the 5-hydroxyl group is introduced according to the procedure of 156, quenching with trimethyl borate, and oxidation of the ester of intermediate boronate followed by • hydrolysis with basic hydrogen peroxide to give hydroxypyridine 157. The amide is hydrolyzed with hydrochloric acid to give 158, which is condensed with oxalyl methyl chloride to give the oxazolopyridine 158. The methyl ester at 159 are then converted to the primary amide by treatment with ammonium in methanol to give the objective compound 160. fifteen * > twenty Scheme 39 tA. Qß * NH 1 Sß S '^. M *'? E? H O -.H A A Á.

HCO > < ? 39% 1 G4 165 Scheme 39 illustrates an example of the preparation of an inhibitor based on analogous thiazolopyridine. The scheme illustrates the use of para-cresol pyridine pyridine as the starting material, but the synthesis can be generalized to another aryl, heterocyclic or alkyl ethers. The dianion of 4- (N-trimethylacetyl) -amino-3- (4-methylphenoxy) -pyridine is cooled with tetramethylthiurane disulfide to introduce the 5-mercapto group into the substituted pyridine ring as dithiocarbamate 161. Subsequent deprotection of the amine under acidic conditions is followed by acylation of the free aniline 162 with oxalyl chloride methyl to provide the oxalamide 163. The bicyclic thiazolopyridine core 164 is then prepared by treatment with mild acid (e.g. formic acid under reflux). The ester functionality is converted to the corresponding amide 165 with a solution of an amine in methanol with heating, Scheme 40 168 1fi9 A related imidazopyridine cyan of compounds can be prepared from intermediates shown in Scheme 40. 5-Hydroxypyridine 157 can be converted to the corresponding aniline 166 by heating in ammonium hydroxide saturated with sulfur dioxide in a pressure vessel (Newman and Galt, J. Org. Chem. 1960, 25, 214). After removal of the pivaloyl group of 166 with hydrochloric acid, the resulting diaminopyridine 167 can be condensed with oxalyl methyl chloride to give imidazopyridine 168. The ester functionality can then be converted to amide 169 by treatment with ammonium in methanol, as described previously.

Scheme 41 172 173 ? 7¿ 17S 1 6 Scheme 41 is an illustration of the preparation of inhibitors containing thienopyridazine. The protected thiophene acid 170 was deprotonated with strong base (e.g., n-butyllithium), and reacted with a formylating agent. The resulting oxazoline aldehyde 171 was hydrolyzed and cyclized with hydrazine to provide the thienopyrazine dihydroxy 172. The hydroxy group was converted to chloride 173 by the action of phosphorus oxychloride and subsequent substitution by achoxides produced the ethers 174. The amide group is introduced in a manner analogous to that described above for the thienopyridines, providing amide 176.

Scheme 42 17B Syntheses of soluble glucosyl amide derivatives of water of the general formula 178 are shown in Scheme 42. The tributylphosphine-mediated coupling of thienopyridine carboxylic acids of the general formula 21 or 28 with 2,3,4,6- tetra-O-acetyl-D-glucopyranosilazide with the assistance of PyBOP softly coated the protected β-glucosyl amides of the general formula 177. No other isomers were detected in the reaction. Division of the acetyl groups with methyl amine gave compounds of the general formula 178.

Scheme 43 DH ? B 17S aocNi, ^ - .. HSCH¿CO¿CH_3 MH CHjOH * ^ or CHJC HCCNH tai 182 Scheme 43 underlines the preparation of 4- (4-yminophenoxy) thieno [2,3-c] pyridine-2-carboxamide using a modification of the path described in Scheme 7. A two-step sequence was adopted to assemble the thienopyridine nucleus in the synthesis of 182. Treatment of the dichloropyridine aldehyde with an equivalent of N-BOC-protected 4-hydroxyaniline provided the compound 179, which was cyclized to ester 180. The transformation to amide 181 followed after the previously described procedure, and the Boc group was removed by treatment with trifluoroacetic acid. It should be noted that aniline 182 also serves as an initial material for Sandmeyer reactions through the diazonium salt, in which the amino group can become a variety of functional groups, including halo, hydroxy, cyano, among other standard Sandmeyer products. Scheme 44 184 Scheme 44 exemplifies a general method for the preparation of 4-substituted aminophenoxythieno [2,3-c] pyridines using methodology described by Buchwald, et al. (Wolfe, John; Buchwald, Stepgen, L. J. Org. Chem. 1997, 62, 6066). Iodide 183, prepared by the previously described methods, was coupled with disubstituted amines (such as morpholine in the previous example) in the presence of bis (dibenzylideneacetone) dipalladium and BINAP to provide a substituted aniline 184.

Scheme 45 OH I rC rfS 18 t-SüO. THF T f A.'C: H2CI. ii) H.SCH? C02CHa OTr Cs- ^ Oa N ,. > - S OCH, 1B5 185 187 188 Scheme 45 describes the preparation of 4- (4-hydroxymethylphenyl) thieno [2,3-c] pyridine 188, using a modification of the pathway shown in Scheme 7. Starting with mono-tritylated 4-hydroxybenzyl alcohol, condensation with dichloroaldehyde 18, followed by cyclization with methyl thioglycolate, provided protected benzyl alcohol 188. Standard transformations provided alcohol 188.

Scheme 46 190 Scheme 46 describes the preparation of a protected benzyl alcohol 190, starting from mono-tetrahydropyran-protected hydroxybenzyl alcohol 189. Standard acid catalyzed hydrolysis of the HP group can also yield the benzyl alcohol analog 188. Scheme 47 O 18B 191 R = alkyl, ethyl or aluminum, as shown in Scheme 47, the benzyl alcohol 188 can be further derivatized in esters, using standard coupling methods, for example under conditions of carbodiimide shown above, or by the use of acid chloride. In addition, alcohol can be converted to carbamates (R = NH2, mono or disubstituted amino) by treatment with isocyanates or carbamoyl chlorides. Scheme 48 193 Benzyl alcohol glycosides 187 can be produced using the procedure outlined in Scheme 48. Treatment of 187 t tri-O-acetyl-D-glucal alcohol with stoichiometric scandium triflate provided stereospecifically protected glycoside 192, which was deprotected with amine methyl to give the free glycoside 193.

Scheme 49 199 Stille coupling of iodophenyl derivative 194 (or the corresponding bromophenyl analogs) with tributylethoxyvinyltin allowed the introduction of an acetyl group at the 4-position of the phenyl ether as shown in Scheme 49. The intermediate vinyl ether is hydrolysed during working conditions, thus providing derivative of acetophenone 1 95. The addition of methylmagnesium bromide to acetone 195 at -50 ° C did not give the product of expected addition, but instead the adduct of aldol 196 was isolated in 40% product. Palladium catalyzed carbonylation of methyl ester bromophenoxy 197 in aqueous medium afforded the acid 198 in modest product. Coupling mediated by PyBOP or EDC with amines (illustrated above with morpholine), followed by amination of 2-methyl ester, provided the diamides 199. Scheme 50 2D1 Scheme 50 describes the preparation of cinnamate ethers. The Heck reaction of the methyl ester bromophenoxy 197 with t-butyl acrylate using tritoliphosphine as the binder coated the cinnamate 200 in good product. Hydrolysis of t-butyl ester with trifluoroacetic acid, followed by PyBOP or EDC mediated coupling with an amine, and then amination of the methyl ester, gave diamide 201.

Scheme 51 ZQ4 Scheme 51 exemplifies the preparation of 4-heterocyclic phenoxythienopyrins. Treatment of para-c-anophenyl 202 derivative with hydroxyamine in a mixture of DMF and ethanol gave slightly hydroximidamide 203, which was heated with trifluoroacetic anhydride in pyridine to provide oxadiazole 204. The cyano derivative 202 was transformed into low imidazole 205 the conditions described above. The incorporation of other heterocyclics was carried out using Stille, Suzuki or Hecl conditions as exemplified by the Stille coupling of iodine compound 194 and tributyltinthiophene to provide compound 205A. The aryl coupling reactions described above can be applied to compounds with a variety of C2-substituents of the thienopyridine, in addition to the methyl amides exemplified in Scheme 51. Scheme 52 201. 307 2DB 209 210 The cyclopropylcarbinyl derivatives of the 4-phenyl ethers can be prepared according to the procedure described in Schemes 52 and 53. The commercially available phenoliccyclopropane carboxylic acid is converted into the corresponding alcohol 206 by reduction of LAH, after demethylation and selective protection of the hydroxymethyl group provides phenol 207. Using the procedure of Scheme 7, phenol 207 is condensed with dichloroaldehyde 18 and then methyl thioglycolate to produce thienopyridine 208. Standard transformations led to the desired compounds 209 and 210. Scheme 53 zr.6 .or. , C ...-. CO, * JaS ^ H3? 1R "" Or "DMF," i.pC H Ci '^ CO ^ Cl ..

OH 211 212 As shown in Scheme 53, alcohol 206 is it was alkylated to produce the polyether 211 phenol which is converted to cyclopropylcarbinyl polyether 212 using similar procedures described in Scheme 52. Such alkylation chemistry can be widely applied by the replacement of the diether tosylate shown with other alkyl halides or sulfonate esters . Scheme 54 . -Z \ A In Scheme 54, the difluoroacetic acid derivative 213 was synthesized by a copper-mediated coupling between iodide 194 and ethyl iododifluroacetate in the presence of phenol, which was found to markedly inhibit side reactions. The reduction of the ester 21 3 gave difluoroethyl alcohol 214. The alkylation of alcohol 214 with ethoxyethyl tosylate in the presence of sodium hydride and 15-crown-5 provided polyether 215. Scheme 55 HO, C- í, Oli C - .'-,., - O .., - . azodfcaibojdliito de dietilo 2. t i mato de methyl 36% -78 C 216 Rr, NH 719 .v.oOH. ieflujo Oh ÍÍ Ar - \, NHR 'R CHOH or IZOÍIKÍII b xilírto de .líetílo 220 I MF " 222 221 An alternative synthesis of 4-alkoxythieno [2,3-c] pyridines through phenolic alkylation strategy is outlined in Scheme 55. Mitsunobu alkylation of 5-chloro-3-hydroxypyridine provided Benzyl ether 216, which was deprotonated with an alkyl lithium base and the resulting anion was treated with methyl formate to produce the pyridine carboxaldehyde 217. The construction of the thienopyridine nucleus was carried out by condensation with methyl thioglycolate under preconditions described, leading to ester 218. This method can be applied to other alkyl ethers analogous to 216 to provide a variety of 4-alkoxy derivatives related to 218. The esters 218 were then converted to other active derivatives such as amides using previously procedures described. The benzyl ether 218 was hydrogenolyzed to phenol 219, which was converted to the corresponding amide 220 by standard procedures. Phenol 219 also serves as a standard in Mitsunoby reactions with a variety of primary or secondary alcohols, to provide alkyl ethers of general formula 221 (Huang, F., ef al, J. Med. Chem. 1998, 41, 4216-4223). The esters of the general formula 221 were converted to amides of the general formula 222 by treatment under standard reflux conditions with methanolic amine solutions.

Scheme 56 cv N * 227 Ci Cl X MgBr;? R. a "c DMSC. íClCOJ r t? . ci'iC, j A 23fl 231 * The thienopyridine analogs that share a 4-carbonyl group can be prepared by the procedures described in Scheme 56. The dichloropyridine aldehyde 1 8 was treated with methyl thioglycolate under conditions previously described to produce the 4-chlorothienopyridine ester 223. Ester exchange was carried out by base catalyzed hydrolysis in 224 acid., and the esterification of tert-butyl in 225 was carried out with trichloroacetimidiato O-t-butyl under catalysis of Lewis acid. Palladium-catalyzed carbotoxilation proceeded under conditions previously described to give diester 226. Reduction / oxidation reactions led to aldehyde 227, which was then condensed with arylmagnesium halide reagents (exemplified above with 4-chlorophenyl magnesium chloride) to produce alcohol 228. Ester 228 can be transformed into several 2-substituted thienopyridine analogs directly, and oxidized to the corresponding 4-keto derivative 230. The standard transformation of ester 230 into amide 231 completes the synthesis. It should be noted that the ester 226 can be selectively converted to amide derivatives by initial alkaline hydrolysis of the ethyl ether, coupling to an amine, then acidic hydrolysis of the tert-butyl ester, and finally coupling to another amine to produce 308.

Scheme 57 L / .X? l? To Cloiuio e oxalílo OCH :, C? ZA.:ÍRH | OH DMSO N s o »< Í: ethanol THF NZ -78 ° C? 0,? S 232 234 233 235 A variety of 2-substituted thieno [2,3-c] pyridines were accessible from 2-esters of the general formula 20 and 25. Scheme 57 exemplifies the products obtainable from hydroxymethyl derivatives of the general formula 232. reduction of calcium borohydride of esters of the general formula 20 or 25 provided alcohols of the general formula 232. Swern oxidation clearly provided aldehydes of the general formula 233. This versatile intermediate can be converted to olefins by standard Witting conditions, as exemplified for the preparation of 2-vinyl thienopyridyrams of the general formula 234 (Hibino, SJ Org. Chem. 1984, 49, 5006-5008). Further modification in dihydroxyethyl compound 235 was carried out through the use of catalytic osmium tetroxide with 4-methylmorpholine N-oxide as a stoichiometric oxidant.

Scheme 58 1 2 23S 240 Scheme 58 illustrates the conversion of aldehyde 233 to acrylate 236, which is carried out by Horner-Emmons condensation with trimethyl phosphonoacetate (Jung, M.E. and Kiankarami, M. J. Org. Chem. 1998, 63, 2968-2974). The disclosed methods can be extended into analogs that share a wide variety of C-4 substituents, including aryloxy, alkoxy, arylamino, aryl, alkyl. The derivatized esters 236 are then subjected to hydrolysis to provide acid 237. The carboxylic acid 237 was subjected to standard coupling conditions to produce amide 238. The Acrylates derived from the general formula 239 can be oxidized to the corresponding diols of the general formula 240 with catalytic osmium tetroxide in the presence of 4-methylmorpholine-N-oxide. Scheme 59 233 241 í-A ^ A. ~ p-lHo ofeno? í 1. Í ^ gX? Oxidation Swei n t 242 2? 3 Scheme 59 illustrates the use of aldehyde 233, with LAXA = aryioxy, as the starting material for the preparation of oxime derivatives of general formula 241. The underlined strategy is generally applied to analogues with a variety of LAXA substituents. The aldehydes of the general formula 233 were also reacted with organomagnesium reagents (or organolithium) to produce secondary alcohols which are oxidized in the corresponding acetones of the general formula 242 Oxidation is preferably carried out by standard Swern conditions (DMSO and oxalyl chloride in CH2Cl2 solution at low temperature, followed by treatment with tertiary amines such as ethyldiisopropyl amine), but other conditions (tetra-n-propyl perruthenate, manganese dioxide) may be employed. The acetones were then converted to oximes of the general formula 243 by previously described methods. Scheme 60 TGA? • AX? . • zNC.m tC «¡AX? N rv-! i; '- NHt piíidna K -. * S 2e 244 45 24B 24 »The preparation of 2-heterocyclic thienopyridines of the general formula 249 is illustrated in Scheme 60. The primary amides of the general formula 26 were treated with excess trifluoroacetic anhydride in pyridine to produce slightly nitriles of the general formula 244, which it serves as a convenient intermediate compound for the preparation of amidine and azole derivatives. In this way, the nitriles of the general formula 244 were converted to the amidoximes of the general formula 245 by the treatment with hydroxylamine hydrochloride and triethylamine. The reaction of amidoximes of the general formula 245 with acetyl chloride, trifluoroacetic anhydride, triethyl ortoformate or trichloroacetyl chloride in pyridine yielded the oxadiazoles of the general formula 246 with variations in X dictated by the choice of acylation / dehydration reagent. The trichloromethyl oxadiazoles of the general formula 246 (X = CCI3) were converted to 5-amino-1,4-oxadiazoles of the general formula 247 by heating with ammonium in a sealed tube. The nitriles of the general formula 244 were also converted to cyanoamidines of the general formula 248 when subjected to excess cyanamide in THF with DBU as the base. The 3-amino-1, 2,4-oxadiazoles of the general formula 249 were then generated by the treatment of cyanamides of the general formula 248 with hydroxylamine hydrochloride and triethylamine in methanol.

Scheme 61 252? £ 1 253 25G Scheme 61 represents the preparation of 2-arylcarbonylthienopyridines. The thienopyridines of the general formula 44 were deprotonated with an alkyl lithium base and condensed with nitrobenzaldehydes to produce the benzyl alcohols of the general formula 250. The reduction induced by tin (II) of the nitrophenyls to the anilines of the general formula 251 was followed by the oxidation of selective alcohol with pyrid'mio chlorochromate. The nitro benzyl alcohols of the general formula 250 were also converted to the corresponding ketones of the general formula 253 under Swern conditions (eg, oxalyl chloride / DMSO / CH2Cl2 at low temperature, followed by treatment with amino bases) .

Scheme 62 232 254 N OCN Tt-? KOCSÍ. HC H20,? Efiu¡ * 2sr, 255 Scheme 62 represents the preparation of 2-carbamateothienopyridines and 2-ureatienopyridines. The alcohols of the general formula 232 were converted to the amines of the general formula 254 by the reaction Mitsunobu with efhalimide, followed by deprotection with hydrazine. The amines of the general formula 254 were converted to the corresponding ureas of the general formula 255 by the reaction with potassium isocyanate under acidic conditions. Similarly, the alcohols of the general formula 232 were converted into the corresponding carbamates of the general formula 256. This chemistry is generally applicable to the use of substituted isocyanates or carbamoyl chlorides, leading to mono- or disubstituted ureas or carbamates.

Scheme 63 • 54 257 The burn 63 illustrates the preparation of 2-thioureatienopyridine, starting from 2-aminothienpyridines of the general formula 54. Reaction of 54 with substituted isothiocyanates in refluxing pyridine provided the thioureas of the general formula 257. 10 Scheme 64 • to 21 water to.%, -. Hr.fi;, at 44 CH¿ and 15 2ER 259 20 Scheme 64 exemplifies the synthesis of sulfonamides at position 2 of the thienopyridines. An improved process for the decarboxylation of thienopyridine-2-carboxylic acids is shown, wherein the acids of the general formula 21 were heated in diphenyl ether at 210 ° C to provide thienopyridines of the general formula 44 in high product. The compounds 44 were deprotonated with base strong, then treated with sulfur dioxide to produce intermediate sulfinic acids. The addition of N-chlorosuccinimide produced sulfonyl chlorides of the general formula 258, of which a variety of sulfonamides of the general formula 259 were prepared by the reaction with ammonium, primary or secondary amines in the presence of diisopropylethylamine in protic solvents such as methanol (Prugh, JD, et al., J. Med. Chem. 1991, 34, 1805-1818; Davidsen, SK et al., J. Med. Chem. 1998, 41, 74-95). Scheme 65 PGC? ÍDPr, F ^. Csl- "AX ??. R?,. Ll Í 79 -" T 1? - ^. NOxA OR 2U0 BFír-, -. 1 f JC N. ^ \ "-" - "" OH Scheme 65 provides the highlights of the synthesis of additional 2-arylthienopyridines with amino or hydroxy groups in the aril ring. Using the method of Scheme 24, the Suzuki coupling of boronic acids of the general formula 79 with nitro-substituted aryl iodides yielded biaryls of the general formula 260. The biaryls of the general formula 260 were reduced in the aminophenyl derivatives of the general formula 261 with tin chloride (ll). The methyl ethers of the general formula 262 were prepared from boronic acids 79 by coupling with methoxy iodobenzenes, and converted into the hydroxy derivatives of the general formula 263 through the use of boron tribromide to demethylate the methyl ethers . Scheme 66 266 Schemes 66-71 illustrate the synthesis for heterocycles of 5 additional members at position 2 of the thienopyridines. Scheme 66 underlines a method for producing 1, 3,4-oxadiazoles. The hydrazides of the general formula 264 were prepared by treating esters of the general formula 20 or 25 with hydrazine in methylene chloride. The hydrazides were converted to 5-amino-1, 3,4-oxadiazoles of the general formula 265 by reaction with cyanogen bromide. The hydrazides of the general formula 264 can be converted to substituted or 5-unsubstituted 1, 3,4-oxadiazoles of the general formula 266 by condensation with orthoesters under reflux conditions. Example 67 268 263 2nd Scheme 67 indicates a method for preparing 1, 3,4-triazoles of methyl esters of the general formula 20 or 25. Condensation with aminoguanidine under basic conditions (for example sodium methoxide in methanol) yielded the 2-amino-1 , 3,4 triazoles of the general formula 267. The non-specific methylation was carried out in 1, 3.4 triazoles of the general formula 267 using sodium hydride and methyl iodide, which provided mono-methyl triazoles of the formula 268, dimethyl triazoles of the general formula 269, and trimethyl triazoles of the general formula 270, which were separated chromatographically.

Scheme 68 272 Scheme 68 indicates a method for the preparation of 1,4-thiadiazoles of the general formula 272. Acid chlorides derived from acids of the general formula 21 or 28"were reacted with thiosemicarbazide or substituted thiosemicarbazides to give the acylated thiosemicarbazides intermediates of the general formula 271, which are cyclized under acid catalysis (for example methanesulfonic acid in reflux toluene) to provide thiadiazoles of the general formula 272. Scheme 69 264 273 L X? 274 Scheme 69 provides a method for the preparation of 1,4-oxadiazole-2-thiones and the alkylthio-substituted oxadiazoles derived from the general formula 274. The hydrazides of the general formula 264 were treated with carbon disulfide in potassium hydroxide in aqueous ethanol solution to give the cyclic thiocarbamates of the general formula 273. The thiocarbonyl group was alkylated in low product with alkyl halides to give the 1,4-oxadiazoles of alkylthio of the general formula 274. Scheme 70 244 775 CH2Na N. N r tfOi * A-s N "8 27S Scheme 70 shows the preparation of tetrazoles at position 2 of thienopyridines. The 2-cyano derivatives of the general formula 244 were converted to tetrazoles of the general formula 275 using trimethylsilyl azide in the presence of catalytic dibutyltin oxide. The tetrazoles were converted to the N-methyl derivatives of the general formula 276 by the use of a solution of diazomethane in methanol. Scheme 71 278 279 201 7R2 15 Scheme 71 illustrates the syntheses of thienopyridines of 2-oxazole and 2-imidazole. The chloroethyl amides of the general formula 277 are prepared by chlorination of the corresponding hydroxyethyl amides and then cyclized into oxazolines of the formula general 278 under basic catalysis (for example, diazabicyclo lodene in dichloromethane). The oxazolines of the general formula 278 can be converted to oxazoles of the general formula 278 by dehydrogenation according to the Meyers method (Meyers, A. I. et al., J. Amer. Chem. Soc. 1975, 97, 7383). The amides of aminoethyl of the general formula 280 are cyclized in the imidazolines of the general formula 281 by treatment with calcium oxide at elevated temperature in diphenyl ether. The imidazolines of the general formula 281 can be converted into imidazoles of the general formula 282 by methods of the literature (Hughey, J.L. et al. Synthesis [SYNTBF] 1980, (6), 489). Scheme 72 ?: or. ° s- a i '' / "- 7 ° ° $ 2 Oi? Dact? N S ein • <. 114 11f? In Scheme 72, an improved preparation of 3-alkyl-substituted thienopyridines of the general formula 1 is described. The aldehyde 18 was condensed with preformed potassium phenoxides to produce a mixture of mono- or disubstituted aryloxyaldehydes. This mixture was then reacted with the desired Grignard reagent, followed by a Swern oxidation of the resulting mixture of secondary alcohols to give the desired aryloxy acetone compounds. The mixture of aryloxy acetones is further reacted with methyl thioglycolate in the presence of cesium carbonate for provide the esters of trisubstituted 2,3,4-thieno [2,3-c] pyridine of the general formula 1 14. These esters are converted to the corresponding acids by hydrolysis with lithium hydroxide and then the acids are coupled with several amines , for example by carbodiimides, to give the desired amides of the general formula 1 1 5. Scheme 73 284? 8S TG? - i '.ci. T; TO 2B6 2B7 Scheme 73 provides a synthesis of 3-carboxythienopyridines. Using methodology analogous to that described for the preparation of 20 or 25, 3,5-dichloropyridine was treated with a strong base such as lithium diisopropylamide in anhydrous etheral at low temperature, followed by the addition of t-butyl chlorooxoacetate to provide 3,5-dichloropyridine 4-tert-butyl-2-acetoster 283. The ester 283 was then reacted with 1.25 equivalents of potassium phenoxides preformed at room temperature, to give the monoaryloxy derivatives as the main product. Without purification, the monoaryloxy esters were treated with methyl thioglycolate and base such as cesium carbonate or potassium t-butoxide to provide the desired thienopyridine diesters of the general formula 284. The diesters of the general formula 284 were then treated with methanolic amines to give the corresponding 3-tert-butyl ester amides of the general formula 285. The tert-butyl ester amides were converted to the corresponding acid amides of the general formula 287 by solvolysis with fluoroacetic acid. The diesters of the general formula 284 can also be converted to the acids of the general formula 286 by a similar solvolysis reaction. Scheme 74 Br HJFIÍNH '.H2NH aO'B- 32 NR.H? II MeCH Nf ^ "S n (! -co? O? Ta-ß N S O Prl7 (sh3) .., BIN? H T | i F. N? 7fi9 60" C Scheme 74 describes the use of 4-bromothienopyridine 32 to prepare 4-amino substituted thienopyridine derivatives. Ester 32 was converted to amides of general formula 288 by standard procedures, and then coupled to a variety of amines using palladium (O) catalysis, as described by Buchwald (J. Org. Chem. 1997, 62, 6066 -6068), yielding 4-amino derivatives of the general formula 289.

Scheme 75 j-'OX.-g. leflux 2d 2? Ü t- * 2 791 2! Í2 X'C Or x = c: f? ' O NR, R-, 236 2S7 Scheme 75 highlights the preparation and reactions of 7-chloro and 7-bromothienopyridine derivatives. The analogs are useful for preparing active derivatives as well as for serving as synthetic intermediates for a variety of 7-substituted thienopyridines. The esters of the general formula 25 are oxidized in pyridine-N-oxides of the general formula 290 with meta-chloroperbenzoic acid. The N-oxides were re-installed in the 7-halo derivatives of the general formula 291 upon heating in phosphoric oxychloride or phosphoric oxybromide. The resulting 7-halides could be converted to the amine derivatives of the general formula 292 by standard methods without reaction of the 7-chloro or 7-bromo moieties. However, under wrestling conditions, the chloro or bromo groups could be substituted with amines or alcohols to provide 7-amino derivatives of the general formula 293 and 7-alkoxy derivatives of the general formula 294, respectively. The esters of the general formula 294 were converted to amides of the general formula 295 using standard methods. The 7-hydroxy analogs of the general formula 296 were prepared from derivatives of 291 using acetic anhydride followed by hydrolysis with water. In addition, the 7-halo 291 derivatives, in particular the 7-bromo derivatives, were effective residues in Suzuki reactions with boronic aryl pacients, similar to those described in Schemes 1 and 65.

Scheme 76 .89 30D Scheme 76 describes the preparation of furopyridine analogs such as 299 (Example 327). By an analogous procedure to that of the 20 or 25 preparation, the dichloropyridinecarboxaldehyde 18 was reacted sequentially with a potassium phenoxide, then with ethyl glycolite, followed by cyclization under basic conditions, affording furopyridine ester 298 in low product. Standard hydrolysis and coupling conditions provided the amide 299. The amide was converted to thioamide 300 by treatment with Lawesson's reagent in hot toluene. Scheme 77 1. K -íCMefo leflux N- N A .. -., And -s. "c? NM, J) Natán *. EiC- i eflnjo 265 101 Ei Scheme 77 illustrates the preparation of N-alkyl 5-amino- 1, 3,4-oxadiazoles. Treatment of 265 in reflux trimethylorthoformate followed by reduction of the eneamine intermediate with sodium borohydride in refluxing ethanol gives N-alkylated 5-amino-, 1,4-oxadiazoles of the general formula 301. Scheme 78 227 302 NHj 303 304 Scheme 78 exemplifies the synthesis of substituted vinyl portions at the 4-position of thienopyridines. Treatment of aldehyde 227 with the appropriate diethylphosphonate in the presence of potassium bis (trimethylsilyl) amide gave 302. Compound 302 was then treated with sulfuric acid in methanol to yield methyl ester 303, followed by the formation of standard amide with ammonium and methane) to produce 4-vinyl-substituted thienopyridines of the general formula 304. The installation of a substituted vinyl can also be carried out by using Wittig phosphorane chemistry.

Scheme 79 228 305 3 I heard 307 Scheme 79 demonstrates the preparation of 4-substituted alkyl thienopyridines. The alcohol 228 was subjected to palladium on carbon in acetic acid to generate the methylene derivative 305. Treatment of 305 with sulfuric acid in methanol yields 306. The formation of the amide is carried out by treating 306 with ammonium in methane. ! to produce 307.

Esq uema 80 309 310 ?? °? -yA- 1; 311 Scheme 80 illustrates the preparation of thiazole derivatives at position 2 of thienopyridines. The thioamides of the general formula 309 are alkylated and cyclized with ethyl bromopyruvate to provide thiazole esters of the general formula 310. The standard amide formation leads to amides of the general formula 31 1. Other amines can be used to produce a variety of substituted amides. In addition, the esters of the general formula 310 can be converted to carbamates of the general formula 312 through the reinstallation of Curtius from the intermediate acid. The tert-butyl carbamates of the general formula 312 were converted to the primary amines of the general formula 313 by the action of fluoroacetic acid.

Scheme 81 Scheme 81 highlights an alternative method for preparing 3-substituted thienopyridines, wherein Ar = unsubstituted or substituted aryl, or heterocycle, and R = alkyl, alkoxy, alkyl substituted, aryl, arylalkyl. The aldehyde 18 is reacted with the appropriate organomagnesium halide, to give an intermediate secondary alcohol, which is oxidized in the corresponding acetone 314. The oxidation method was the Swern method, although other standard oxidations of this type can be employed (eg PCC , TPAP). The procedure then follows that described for 3-unsubstituted analogs, leading to ester 315. Ester 315 then serves as the starting material for the preparation of amides, or other heterocyclic derivatives in the 2-position of thienopyridines.

• Scheme 82 31 10 313 31 • Scheme 82 describes a method for producing cyclic derivatives between positions 2 and 3 of thienopyridines. The 3-methyl derivative 1 15 was treated with N-bromosuccinimide (or alternatively N-chlorosuccinimide) in carbon tetrachloride for Give bromomethyl (or chloromethyl) compound 316 (X = Br, Cl). Compound 316 can then be reacted with a primary amine, through alkylation and acylation, leading to tricyclic lactam 317. Compound 316 can also be reacted with substituted amines to produce the corresponding amides 319. The compounds and processes of the present invention they will be better understood in connection with the following examples which are proposed as an illustration of and not a limitation of the scope of the invention. Example 1 25 Methyl 2-α (6-ethyl-tienor-2,3-dl-pyrimidin-4-yl) thio-1-acetate Example 1A methyl 6-etl-3, 4-dihydro-4-oxothienor-2,3-d-pyrimidine-2-carboxylate The desired compound was prepared as described in J. Heterocyclic Chem. 1987, 24, 581-587. Example 1 B 6-Ethylthieno-2,3-dl-pyrimidin-4 (3H) -one Example 1 A (35 g, 140 mmol) and LiCl (6.5 g, 153 mmol) in DMSO (80 mL) and water (8 mL) it was heated at 150 ° C for 18 hours, cooled to room temperature, diluted with water, and extracted with ethyl acetate. The extract was dried (MgSO4), filtered, and concentrated to provide the designated compound. Example 1 C 4-Chloro-6-ethylthienof2,3-d1pyrimidine Example 1 B (3.97 g, 22.0 mmol) in POCI3 (22 mL) was heated to reflux for 2 hours, cooled, poured into ice, diluted with water, made basic with concentrated ammonium hydroxide and extracted with ethyl acetate. The extract was dried (MgSO4), filtered, and concentrated. The residue was purified by flash chromatography on silica gel with 10% ethyl acetate-hexane to provide the designated compound. Example 1 D Methyl 2-f (6-ethyl-2,3-dl-pyrimidin-4-ylthio) acetate Example 1 C (0.25 g, 126 mmol) in DMF (1.2 mL) (0.134 g, 1.26 mmol) was treated sequentially with methyl thioglycolate (0.1 34 g, 1.26 mmol), and potassium carbonate (0.174 g, 1.26 mmol), stirred at room temperature for 18 hours, cooled, poured into water diluted brine, and extracted with dichloromethane. The extract was rinsed with water and brine, dried (MgSO), filtered and concentrated. The residue was then triturated, rinsed with 10% ethyl acetate / hexanes to provide the main compound. mp 36-58 ° C; MS (DCI / NHg) m / z 269 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 1 .33 (t, 3 H), 2.99 (q, 2 H), 3.75 (s, 2 H), 4. 26 (s, 3H), 7.23 (s, 1 H), 8.76 (s, 1 H). EXAMPLE 2 6-Ethyl-4-f (4-methylphenyl.t¡ottienof2,3-dlpyrimidine, Example 1 C was processed as in Example 1 D but substituting thiocresol for methyl thioglycolate to provide this major compound. NH 3) m / z 286 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 1.32 (t, 3H), 2.38 (s, 3H), 2.99 (q, 2H), 7. 20 (s, 1 H), 7.33 (m, 2H), 7.52 (m, 2H), 8.63 (s, 1 H); Anal. Cale, for C? 5H14N2S2: C, 62.90; H, 4.93; N, 9.78. Found: C, 63.1 1; H; 4.82; N, 9.63. Example 3 6-ethyl-4- (2-pyridinylthio) thienof2,3-dlpyrimidine Example '1 C was processed as in Example 1 D but substituting 2-mercaptopyridine for methyl thioglycolate to provide the main compound. Mp 76.5-79 ° C; MS (DCI / NH3) m / z 274 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 1.31 (t, 3 H), 2.99 (q, 2 H), 7.18 (s, 1 H), 7.46 (d t, 1 H), 7.81 (d, 1 H), 7.90 (d t, 1H), 8.60 (m, 1H), 8.74 (s, 1H). EXAMPLE 4 6-ethyl-4-f (2-methyl-ethylthio1-tienof2.3-dlpyrimidine Example 1C was processed as in Example 1D but replacing isobutyl mercaptan with methyl thioglycolate to provide the main compound MS (DCI / NH3) m / z 253 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 1.08 (d, 6H), 1.39 (t, 3H), 2.03 (hep, 1H), 2.95 (q, 2H), 3.28 (d , 2H), 7.01 (s, 1H), 8.71 (s, 1H), Anal.Cal, for C12H16N2S2: C, 57.12; H, 6.38; N, 11.09.Found: C, 57.22; H, 6.29 N, 11.08. Example 5 6-ethyl-4-f (phenylmethyl) thio1-tienof2,3-dlpyrimidine Example 1C was processed as in Example 1D but substituting benzyl mercaptan for methyl thioglycolate to provide the main compound, mp 54-60 ° C; MS (DCI / NH3) m / z 287 (M + H) +; 1H NMR (300 MHz, DMSO-d6) d 1.30 (t, 3H), 2.96 (q, 2H), 4.65 (s, 2H), 7.16 (s, 1H), 7.21-7.36 (m, 3H), 7.46 (m, 2H), 8.83 (s 1H), Anal.Cal, for C15H14N2S2: C, 62.90; H, 4.93; N, 9.78. Found: C , 62.11; H, 4.94 N, 9.71 Example 6 6-ethyl-4-f (5-methyl-1.3l 4-thiadiazol-2-yl) thiolthienof2,3-dlpyrimidine Example 1 C was processed as in Example 1 D but substituting 5-methyl-1, 3,4-thiadiazole-2-thiol for methyl thioglycolate to provide the main compound, mp 132-135 ° C; MS 5 (DCI / NH3) m / z 295 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 1.35 (t, 3 H), 2.82 (s, 3 H), 3.05 (q, 2 H), 7.42 (s, 1 H), 8.88 (s, 1 H); Anal. Cale, for CnH10N4S3: C, 44.88; H, 3.42; N, 1 9.03. Found: C, 44.61; H, 3.47 N, 18.92. Example 7 ethyl 6-ethyl-4-r (4-methyphenyl) thiolthienof2,3-dlpyrimidine-6-carboxylate Example 1 A was processed as in examples 1 C and 2 and to provide the main compound, mp 87.5- 90 ° C; MS (DCI / NH3) m / z 359 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 1 .26 (t, 3 H), 1 .31 (t, 3 H), 2.39 (s, 3 H), 3.02 (q, 2 H), 4.27 (q, 2 H), 7.17 (s, 1 H), 7.33 (m, 2H), 7.57 (m, 2H); Anal. Cale, for C18H18N2? 2S2: C, 60.31; H, 5.06; N, 7.81. Found: C, 60.44; H, 4.88 N, 7.65. Example 8 6-Ethyl-N- (phenylmethyl) thienor 2,3-d-pyrimidin-4-amine Example 1 C (0.27 g, 1.37 mmol) in isopropanol (1.5 mL) was treated with benzylamine (0.19 mL, 1 .71 mmol) and sodium carbonate (0.24 g, 2.3 mmol), stirred at room temperature overnight, filtered, and concentrated. The residue was purified by chromatography Flash on silica gel with 25% ethyl acetate / hexanes to provide the main compound. mp 128-131 ° C MS (DCI / NH 3) m / z 270 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 1.30 (t, 3 H), 2.88 (q, 2 H), 4.72 (d, 2H), 7.20-7.40 (m, 6H), 8.26 (s, 1 H), 8.34 (t, 2H); Anal. Cale, for C? 5H15N3S2: C, 66.89; H, 5.61; N, 15.60. Found: C, 66.66; H, 5.43 N, 15.43. EXAMPLE 9 e-ethyl-N-td-methyl-IS-thiadiazole ^ -iDtienofS.S-dlpyrimidine ^ -amine A solution of Example 1 C (0.20 g, 1 .01 mmol) in isopropanol (2 mL) was treated with 2% ethyl acetate. -amino-5-methyl-1, 3,4-thiadiazole (0.15 g, 1.26 mmol) and sodium carbonate (0.18 g, 1.7 mmol), stirred at room temperature for 48 hours, treated with cesium carbonate (0.55 g, 1.7 mmol), stirred at reflux for 24 hours, concentrated, treated with water and extracted with dichloromethane. The extract was dried (MgSO4), filtered and concentrated. The residue was recrystallized with ethanol / water to provide the main compound. mp 277-280 ° C MS (DCI / NH 3) m / z 278 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 1 .33 (t, 3 H), 2.63 (s, 3 H), 2.96 (q, 1 H), 7. 81 (br s, 1 H), 8.65 (s, 1 H); Anal. cale, for Cn HnN5S2: C, 47.63; H, 4.00; N, 25.25. Found; C, 47.48; H, 3.68 N, 24.89. Example 10 4-f (5-amino-1,3,4-thiadiazol-2-yl) thiol-6-ethyl-2- (phenylmethyl) thienof2.3-dlpyrimidine. Example 1 0A 2-amino-5-ethylthiophene-3-carboxamide The designated compound was prepared as described in 5 J. Heterocyclic. Chem. 1987, 24, pp 581-587. Example 10B 5-ethyl-2-f (phenylacetyl) amino-3-thiophenecarboxamide Example 10A was processed as in Bull, Soc. Chim. France 1975, p 815 to provide the designated compound. Example 10C 6-Ethyl-2-phenylmethylthienof2.3-d1pyrimidin-4.3H.-one Example 10B was stirred in dioxane / water in the presence of 10% Na2COI3 to provide the designated compound. Example 1 0D% $ 4-chloro-6-etl-2- (phenylmethyl) thienor 2,3-dlpyrimidine Example 1 0C was processed as in Example 1 C to provide the designated compound. EXAMPLE 1 0E 4-f (5-amino-1,3,4-thiadiazol-2-yl) thio-1-6-ethyl-2- (phenylmethyl) tenoeno-2,3-d-pyrimidine Example 10D and 5-amino-1 , 3,4-thiadiazole-2-thiol were processed as in Example 1 D to provide the main compound. MS (DCI / NH3) m / z 386 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 1.31 (t, 3 H), 2.97 (q, 2 H), 4.17 (s, 2 H), 25 7.17-7.30 (m, 6 H), 7.70 (br s, 2 H ); Anal. cale, for C17H15N5S3: C, 52.96; H, 3.92; N, 18.17. Found; C, 53.1 0; H, 3.74 N, 18.03. Example 1 7-methyl-4-r (4-methylphenyl) thio1-tienof3,2-d1-pyrimidine • 5-methyl-7-chlorothieno [3,2-d] pyrimidine was processed as in Example 1 D but replacing p-thiocresol by methyl glycolate to provide the main compound. mp 103-107 ° C; MS (DCI / NH3) m / z 273 (M + H) +; 10 1 H NMR (300 MHz, DMSO-d 6) d 2.40 (s, 6H), 7.36 (m, 2H), 7.57 (m, • 2H), 8.04 (s, 1 H), 8.88 (s, 1 H); Anal. cale, for Ci5H12N2OS2: C, 61.73; H, 4.44; N, 10.28. Found; C, 61.73; H, 4.50 N, 10.21. Example 12 15 7-methyl-4-((5-methyl-1,3,4-thiadiazol-2-yl) thiothienof3.2-dlpyrimidine 3-Methyl-7-chlorothieno [3,2-d] pyrimidine and 5-methyl-1, 3,4-thiadiazole-2-thiol were processed as in Example 1 D to provide the main compound. mp 144-147 ° C; MS (DCI / NH3) m / z 281 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 2.44 (s, 3 H), 2.83 (s, 3 H), 8.20 (s, 1 H), 9.08 (s, 1 H); Anal. cale, for C 10 H 8 N 4 S 3: C, 42.84; H, 2.88; N, 19.98. Found; C, 42.72; H, 2.83 N, 19.64. 25 Example 13 7-methyl-4-ff5- (methylthio) -1.3.4-thiadiazol-2-yl) thio1tienof3.2-d1pyrimidine 3-Methyl-7-chlorothieno [3,2-d] pyrimidine and 5- (methylthio) -1 , 3,4-thiadiazole-2-thiol were processed as in Example 1 D to give the main compound. 5 mp 163-166 ° C; MS (DCI / NH3) m / z 313 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.45 (s, 3 H), 2.83 (s, 3 H), 8.22 (s, 1 H), 9.1 1 (s, 1 H); Anal. cale, for C? 0H8N4S4: C, 38.44; H, 2.58; N, 17.93. Found; 10 C, 38.46; H, 2.63 N, 17.82. Example 14 4-r (5-amino-1,3,4-thiadiazol-2-yl) thio-1-7-methyl-t-enof3.2-dlpyrimidine 3-Methyl-7-chlorothieno [3,2-d] pyrimidine and 5-amino -1, 3,4-thiadiazole-2-thiol were processed as in Example 1 D to provide the main compound, mp 221-232 ° C; MS (DCI / NH3) m / z 282 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 2.43 (s, 3 H), 7.80 (br s, 2 H), 8.15 (s, 1 H), 9.02 (s, 1 H); 20 Anal. cale, for C9H7N5S3: C, 38.42; H, 2.51; N, 24.89. Found; C, 38.41; H, 2.42 N, 24.97. Example 15 7-methyl-Nf- (4- (methylthio) phenynthienof3.2-dlpyrimidin-4-amine A solution of 3-methyl-7-chlorothieno [3,2-d] pyrimidine in ethanol was treated with 4- (methylmercapto) aniline, stirred at reflux for 45 minutes. minutes, cooled to room temperature, and filtered. The precipitate was recrystallized from ethane / water to provide the main compound, mp 212-225 ° C; MS (DCI / NH3) m / z 288 (M + H) +; 5 1 H NMR (300 MHz, DMSO-dβ) d 2.37 (s, 3 H), 2.48 (s, 3 H), 7.29 (m, 2 H), 7.76, (m, 2 H), 7.87 (br s, 1 H), 8.60 (s, 1 H), 9.63 (br s, 1 H); Anal. Cale, for C 14 H 13 N 3 S 2: C, 58.51; H, 4.56; N, 14.62. Found; C, 58.31; H, 4.49 N, 14.47. Example 16 10 7-methyl-4-((4-methylphenyl) thio1t en enof3,2-d1pyrimidine-6-carboxamide (Example 16A 7-Methyl-4-f (4-methylphenyl) thiothienof3.2-dlpyrimidine- 2-carboxylic acid A solution of LDA (0.1 m in THF, 9.6 mL) at -78 ° C was treated with Example 1 1 (0.26 g, 0.96 mmol), heated at 0 ° C for 1 15 h, poured into dry ice with Turbulence was cooled with NH CI saturated and extracted with 3: 1 chloroform / isopropanol The extract was concentrated, and the residue was purified by flash chromatography on silica gel with 7% methanol / dichloromethane to provide the a á-designated compound. Example 16B 7-methyl-4-f (4-methylphenyl) thio1t-inof3.2-dlpyrimidine-2-carboxamide A suspension of Example 16A in dichloromethane (3.3 mL) was treated sequentially with oxalyl chloride (0.03 mL, 0.33 mmol) and DMF (1 drop), and concentrated after the formation of acid chloride. The residue was suspended in THF (10 mL), transferred to a vigorously stirred solution of 1: 1 ammonium hydroxide / water (10 mL), and extracted with dichloromethane. The extract was dried (MgSO), filtered and concentrated. The residue was recrystallized from ethyl acetate / hexanes to provide the main compound. mp 243-246 ° C; MS (DCI / NH3) m / z 316 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.40 (s, 3 H), 2.58 (s, 3 H), 7.35 (m, 2H), 7.57 (m, 2H), 8.01 (br s, 2H), 8.93 (s, 1 H); Anal. Cale, for C15H13N3? S2: C, 57.12; H, 4.1 5; N, 13.32. Found; C, 56.81; H, 4.06 N, 13.25. Example 17 Methyl 4-r (4-methylphenyl) thio-thienof2,3-clpyridine-2-carboxylate Example 17a 3.5-dichloropyridine-4-carboxyaldehyde The diisorpropyl amine (15.6 mL, 0.1 1 1 mole) in dry THF (25 mL ) at 0 ° C was treated with n-BuLi (44.6 mL, 2.5 M in hexane, 0.1 1 1 mol) for 35 minutes, stirred for 30 minutes, cooled to -78 ° C, diluted with THF (100 mL), and a solution of 3,5-dichloropyridine (15.0 g, 0.101 mol) in THF (175 mL) was added slowly over 3.5 hours in order to maintain an internal temperature < -74 ° C. The solution was mixed at -78 ° C for 30 minutes, treated dropwise for 35 minutes with methyl formate (12.5 mL, 0.203 mmol) in THF (50 mL) maintaining an internal temperature of < -74 ° C, stirred -78 ° C for 1.4 hours, quickly cannulated in a cold ice solution of saturated NaHCO3 with vigorous stirring, divided with ethyl acetate (500 mL), extracted sequentially with saturated NaHCO3 (2x100 mL), salmiera (3x150 mL), dried MgSO4 and concentrated. The residue was purified by flash chromatography on silica gel with 10% acetone / hexane. MS (DCI / NH3) m / z 176, 178, 180 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 8.80 '(s, 2 H), 10.31 (s, 1 H). Example 17B 3 (4-methylphenylthio) -5-chloro-4-pyridinecarboxyaldehyde Example 17A (5.05 g, 28.7 mmol) in DMF (70 mL) was treated with co-thiocresol (3.56 g, 28.7 mmol) and potassium carbonate (4.36 g). g, 31.6 mmol), stirred for 0.5 hour at 0 ° C then for 1 hour at room temperature, poured into water, diluted with brine and extracted with dichloromethane. The extract was sequentially rinsed with water and brine, dried (MgSO4), filtered and concentrated to provide the designated compound. Example 17C Methyl 4-f (4-methylphenyl) thio1thienof2.3-clpyridine-2-carboxylate A solution of Example 17B was processed as in Example 1 D to provide the titled compound. mp 1 16-1 19 ° C; MS (DCI / NH3) m / z 316 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.28 (s, 3 H), 3.91 (s, 3 H), 7.20 (m, 2 H), 7 29 (m, 2 H), 8.00 (s, 1 H) , 8.44 (s, 1 H), 9.36 (s, 1 H); Anal. Cale, for C16H13NO2S2 0.25 H2O: C, 60.07; H, 4.25; N, 4.37. Found; C, 60.04; H, 4.08 N, 4.27.

Example 18 4-f (4-methylphenyl) thio1-tienof2.3-c1pyridine-2-carboxylic acid A suspension of Example 17C (2.0 g, 6.35 mmol) and LiOH-H2O (1.4 g, 32 mmol) in isopropanol (25 mL) and Water (15 mL) was heated at 75 ° C for 1 hour, cooled, treated with water, and rinsed with diethyl ether. The aqueous layer was cooled in an ice bath and adjusted to pH 2 with 10% HCl. The resulting solid was collected, rinsed with water, dried and recrystallized from ethane / water to provide the main compound. mp 272-274 ° C; MS (DCI / NH3) m / z 302 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.29 (s, 3 H), 7.20 (m, 2 H), 7.28 (m, 2 H), 7.92 (s, 1 H), 8.44 (s, 1 H), 9.34 ( s, 1 H); Anal. cale, for dsH ^ NsOSa: C, 59.78; H, 3.67; N, 4.64. Found; C, 59.48; H, 3.58 N, 4.54. Example 19 4-f (4-methylphenyl) thio1-tienor-2,3-clpyridine-2-carboxamide A suspension of Example 18 (0.535 g, 1.78 mmol) in dichloromethane (25 mL) at 0 ° C was treated sequentially with oxalyl chloride (0.34 g, 2.67 mmol) and DMF (1 drop), stirred at room temperature for 0.5 hour, and concentrated. The residue was suspended in THF, treated with THF (60 mL), water (30 mL) and concentrated NH OH (30 mL), and stirred for 0.5 hours. The THF layer was separated, rinsed with brine, partially dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography on silica gel with % methanol / dichloromethane and recrystallized from 95% ethanol to provide the main compound, mp 198-199 ° C; MS (DCI / NH3) m / z 301 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 2.29 (s, 3 H), 7.20 (m, 2 H), 7.30 (m, 2 H), 7.89 (br s, 1 H), 8.26 (s, 1 H), 8.35 (s, 1 H), 8.54 (br s, 1 h), 9.16 (s, 1 H); Anal. Cale, for C15H12N2OS2: C, 59.97; H, 4.02; N, 9.32. Found; C, 59.84; H, 4.12 N, 9.31. Example 20 4- (2-pyridinylthio) thienof2,3-clpyridine-2-carboxamide Example 17A was processed as in Examples 17B, 17C, 18 and 19 but substituting 2-mercaptopyridine for p-thiocresol in Example 17B to provide the compound principal. mp 239-242 ° C; MS (DCI / NH3) m / z 305 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 6.99 (d, 1 H), 7.17 (dd, 1 H), 7.65 (dt, 1 H), 7.85 (br s, 1 H), 8.18 (s, 1 H) ), 8.36 (m, 1 H), 8.49 (br s, 1 H), 8.69 (s, 1 H), 9.23 (s, 1 H); Anal. Cale, for C 13 H 9 N 3 OS 2: C, 54.34; H, 3.16; N, 14.47. Found; C, 54.10; H, 3.14 N, 14.62. Example 21 4-f (4-Chlorephenyl) thio1-tienof2,3-c1pyridine-2-carboxamide Example 17A was processed as in examples 17B, 17C, 18 and 19 but replacing 4-chlorothiophenol with p-thiocresol in the Example 17B to provide the main compound. mp 239-241 ° C; MS (DCI / NH3) m / z 321 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 7.31 (m, 2 H), 7.43 (m, 2 H), 7.89 (br s, 1 H), 8.24 (s, 1 H), 8.54 (br s, 1 H) 8.56 (s, 1 H), 9.38 (s, 1 H); Anal. Cale, for C14H9CIN2OS2: C, 54.42; H, 2.83; N, 8.73.

Found; C, 52.33; H, 2.80 N, 8.63. Example 22 N-Methoxy-N-methyl-4-f (4-methylphenyl) thio1-tienof2.3-clpyridine-2-carboxamide A solution of Example 18 (0.66 g, 22 mmol) in dichloromethane was treated sequentially with oxalyl chloride (0.29 g). mL, 3.3 mmol) and DMF (1 drop), stirred for 30 minutes, and concentrated.

The residue was suspended in THF, transferred to a solution of N, O-dimethylhydroxylamine hydrochloride (0.32 g, 3.3 mmol) and triethylamine (0.92 mL, 6.6 mmol) in 1: 1 THF water, and stirred for 5 minutes. The THF layer was separated, dried (MgSO), filtered and concentrated.

The residue was purified by flash chromatography on silica gel with 20% ethyl acetate / hexanes to provide the main compound. mp 103-107 ° C; MS (DCI / NH3) m / z 345 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.27 (s, 3 H), 3.34 (s, 3 H), 3.74 (s, 3H), 7.19 (m, 2H), 7.27 (m, 2H), 8.02 (s, 1 H), 8.46 (s, 1 H); Anal. Cale, for C? 7H1? N2? 2S2: C, 59.28; H, 4.68; N, 8.13. Found; C, 58.76; H, 4.58 N, 8.06.

Example 23 N-Methoxy-4-α (4-methylphenyl) thiolthienof2,3-c1pyridine-2-carboxamide Example 18 was processed as in Example 22 but replacing O-methylhydroxyl aminehydrochloride with N, O-dimethylhydroxylamine hydrochloride for provide the main compound, mp 200-203 ° C; MS (DCI / NH3) m / z 331 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 2.29 (s, 3 H), 3. 76 (s, 3 H), 7.20 (br, 1 H), 7.20 (m, 2 H), 7.30 (m, 2 H), 8.15 (s, 1 H), 8.4 (s, 1 H), 9.3 (s, 1 H); Anal. Cale, for C1 ßH14N2O2S2 0.25H2? C, 58.16; H, 4.27; N, 8.48. Found; C, 57.46; H, 4.1 N, 8.01. Example 24 N- (4-chlorophenyl) -4-f (4-methylphenyl) thio1-tienof2.3-c1pyridine-2-carboxamide A solution of Example 18 (0.1 g, 0.33 mmol) in dichloromethane was treated with oxalyl chloride ( 0.03 mL, 0.33 mmol) and DMF (1 drop), stirred at reflux for 20 minutes, and concentrated. The residue was suspended in (3: 1) benzene / dichloromethane (4 mL), treated with triethylamine (0.5 mL) and 4-chloroaniline (46 mg, 0.36 mmol), stirred at reflux overnight, and concentrated. The residue was treated with water and extracted with dichloromethane. The extract was dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography on silica gel with ethyl acetate / hexanes to provide the main compound. mp 208-21 1 ° C; MS (DCI / NH3) m / z 41 1 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.29 (s, 3 H), 7.23 (m, 2 H), 7.33 (m, 2 H), 7.47 (m, 2 H), 7.81 (m, 2 H), 8.34 (s, 1 H), 8.57 (s, 1 H), 9.31 (s, 1 H), 10.90 (br s, 1 H); Anal. Cale, for C12H15CIN2OS2: C, 61 .38; H, 3.68; N, 6.82. Found; C, 61.22; H, 3.67 N, 6.79. Example 25 4-R (4-methylphenyl) thiolthiene (2,3-c1pyridine-2-carboxyaldehyde A solution of Example 22 (3.33 g, 9.6 mmol) in THF at -5 ° C was treated dropwise with 1 M DIBA1 -H in THF (14.5 mL, 14.5 mmol), stirred for 45 minutes, poured into ice / HCl with constant stirring, and extracted with dichloromethane.The extract was dried (MgSO4), filtered and concentrated to give the title compound. NH 3) m / z 303 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 2.29 (s, 3 H), 7.22 (m, 2 H), 7.34 (m, 2 H), 8.40 (s, 1 H), 8.48 (s, 1 H), 9.38 (s, 1 H), 10.23 (s, 1 H), Anal.Cal, for C15HH NOS2: C, 63.13; H, 3.33; N, 4.91. Found; C , 62.81; H, 3.97 N, 5.01 Example 26 4-f (4-methylphenyl) thiolthienof2.3-clpyridine-2-carboxaldehyde O-methyloxime A solution of Example 25 (0.22 g, 0.76 mmol) in 1: 1 pyridine: ethanol (8 mL) was treated with methoxylamine hydrochloride (0.51 mL, 1.52 mmol), stirred at room temperature for 3 hours, concentrated, treated with water and extracted with dichloromethane. The extract was rinsed with 1 N HCl, dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography on silica gel with 20% ethyl acetate / hexanes to provide the main compound. mp 95-98 ° C; MS (DCI / NH3) m / z 315 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 2.28 (s, 3 H), 3.95 (s, 1.8 H), 4.08 (s, 1. 2H), 7.18 (m, 2H), 7.25 (m, 2H), 7.79 (s, 0.6H), 7.95 (s, 0.4H), 8.27 (s, 0.4H), 8.36 (s, 0.6H), 8.38 (s, 0.4H), 8.68 (s, 06H), 9.20 (s, 0.6H), 9. 30 (s, 0.4H); Anal. Cale, for C? 6H14N2OS2: C, 61.12; H, 4.49; N, 8.91. Found; C, 60.93; H, 4.55 N, 8.98. EXAMPLE 27 4-f (4-methylphenyl) thiolt-inof2,3-c1pyridine-2-carboxaldehyde. O- (phenylmethyl) oxime Example 25 and O-benzylhydroxylamine hydrochloride was processed as in Example 26 but for 18 hours instead of 3 hours to provide the main compound. mp 127-133 ° C; MS (DCI / NH3) m / z 391 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 2.27 (s, 3 H), 5.22 (s, 1. 2 H), 5.38 (s, 0. 8H), 7.15-7.26 (m, 4H), 7.31 -7.47 (m, 5H), 7.78 (s, 0.6H), 7.96 (s, 0.4 H), 8.31 (s, 0.4H), 8.36 (s, 0.6 H), 8.39 (s, 0.4H), 8.74 (s, 0.6H), 9. 20 (s, 0.6H), 9.30 (s, 0.4H); Anal. cale, for C22H18N2OS2: C, 67.66; H, 4.65; N, 7.17. Found; C, 67.45; H, 4.80 N, 7.13. Example 28 2-fff4-f (4-methylphenyl) thio1-tienof2.3-c1pyridin-2-ylmethylene-1-aminoloxylacetic acid Example 25 was processed as in Example 26 but replacing carboxymethoxylamine hemihydrochloride with methoxylamine hydrochloride to provide the main compound, mp 227-230 ° C; MS (DCI / NH3) m / z 359 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.28 (s, 3 H), 4.71 (s, 2 H), 7.1 9 (m, 2 H), 7.25 (m, 2 H), 7.84 (s, 1 H), 8.36 ( s, 1 H), 8.79 (s, 1 H), 9.20 (s, 1 H); Anal. Cale, for C? 7H14N2O3S2: C, 56.97; H, 3.94; N, 7.82. Found; C, 56.90; H, 4.10 N, 7.97. Example 29 4-f (4-methylphenyl) thio1thiene (2.3-c1pyridine-2-carboxaldehyde, O-phenyloxime Example 25 was processed as in Example 26 but replacing O-phenylhydroxylamine hydrochloride with methoxylamine-hydrochloride to provide the main compound, mp 94-97 ° C; MS (DCI / NH3) m / z 377 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.38 (s, 3H), 7.09-7.50 (m, 9H), 7.98 (s, 0.5H), 8.16 (s, 0.5H), 8.39 (s, 0.5H), 8.42 (s, 0.5H), 8.71 (s, 0.5H), 9.16 (s, 0.5H), 9.27 (s), s, 0.5H), 9.37 (s, 0.5), cale anal, for C2? H1ßN2OS2: C, 67.00, H, 4.28, N, 7.44, found, C, 67.14, H, 4.50 N, 7.57, Example 30 4 -f (4-methylphenyl) thio1-tienof2,3-c1pyridine-2-carboxaldehyde oxime Example 25 was processed as in Example 26 but substituting hydroxylamine hydrochloride for methoxylamine hydrochloride to provide the main compound, mp 209-210 ° C; MS (DCI / NH3) m / z 301 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.28 (s, 3 H), 7.18 (m, 2 H), 7.70 (s, 0.3 H), 7.87 (s, 0.7 H), 8.19 (s, 0.7 H), 8.35 (s, 0.3H), 8.38 (s, 0.7H), 8.56 (s, 0.3H), 9.17 (d, 0.3H), 9.27 (s, 0.7H); Anal. Cale, for C15H12N2OS2: C, 59.98; H, 4.03; N, 9.33. Found; C, 59.80; H, 4.08 N, 9.30. EXAMPLE 31 2-rrf4-f (4-methylphenyl) thio1-tienof2.3-clpyridine-2-methylalaminoloxpacetamide Example 28 was processed as in Example 19 to provide the main compound, mp 152-156 ° C; MS (DCI / NH3) m / z 358 (M + NH4) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.27 (s, 3 H), 4.52 (s, 0.6 H), 4.66 (s, 0.4 H), 7.19 (m, 2 H), 7.25 (m, 2 H), 7.32 ( br s, 1 H), 7.40 (br s, 1 H), 7.84 (s, 0.6H), 7.97 (s, 0.4H), 8.32 (s, 0.4H), 8.37 (s, 0.6H), 8.40 (s) s, 0.4H), 8.75 (s, 0.6H), 9.21 (s, 0.6H), 9.32 (s, 0.4H); Anal. cale, for C17H15N3? 2S2- (1.25H2O): C, 57.12; H, 4.23; N, 1 1 .76. Found; C, 56.19; H, 4.48 N, 10.94. Example 32 (E) -3-f (4-methylphenyl) thio1thienof2,3-clpyridin-2-p-2-propenamide Example 25 (0.23 g, 1.27 mmol) in chloroform (10 mL) was treated with carbamoylmethylenetriphenylphosphorane (0.41 g) 1.27 mmol), heated to reflux for 30 minutes, cooled and concentrated. The residue was purified by flash chromatography on silica gel with 2% methanol / dichloromethane to give the main compound, mp 171-174 ° C; MS (DCI / NH3) m / z 327 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.28 (s, 3 H), 6.64 (d, 1 H), 7.19 (m, 2 H), 7.25-7.37 (m, 3 H), 7.68-7.82 (m, 3 H) , 8.35 (s, 1 H), 9.19 (s, 1 H); Anal. cale, for C17H? 4N2OS2-H2O: C, 62.55; H, 4.32; N, 8.58. Found: C, 59.78; H, 4.50; N, 8.20. Example 33 1-f4-f (4-methylphenyl) thio1-tienof2.3-clpyridin-2-inetanone A solution of Example 22 in THF (25 mL) at 0 ° C was treated with magnesium methyl bromide (1.4M in toluene / THF, 1.85 mL, 2.6 mmol), warmed to room temperature, stirred overnight , treated with methylmagnesium bromide (1.4M in toluene / THFm 0.7 mL, 1.3 mmol) stirred for 1 hour, poured with constant turbulence over ice / NH4CI, and extracted with ethyl acetate. The extract was dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography on silica gel with 20% ethyl acetate / hexanes to provide the main compound, mp 134-138 ° C; MS (DCI / NH3) m / z 317 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 2.33 (s, 3 H), 2.71 (s, 3 H), 7.24 (m, 2 H), 7.38 (m, 2 H), 8.28 (s, 1 H), 8.31 (s) , 1 H), 9.29 (s, 1 H); Anal. cale, for C16H13NOS2: C, 64.19; H, 4.38; N, 4.68. Found: C, 64.1 1; H, 4.41; N, 4.61. Example 34 2-benzoyl-4-f (4-methylphenyl) thio1thienof2.3-c1pyridine Example 22 and phenyl lithium were processed as in Example 33 to provide the main compound. mp 103-107 ° C; MS (DCI / NH3) m / z 362 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 2.33 (2, 3 H), 7.26 (m, 4 H), 7.57 (m, 2 H), 7.71 (m, 4 H), 8.49 n (s, 1 H), 9.40 ( s, 1 H); Anal. cale, for C21H15NOS2- 1 .25H2O: C, 65.68; H, 4.59; N, 3.64.

Found: C, 65.67; H, 4.09; N, 3.46. Example 35 2-ethyl-4-f (4-methylphenyl) tio1tienof2.3-clpiridina A solution of Example 33 in ethylene glycol (10 mL) was treated with hydrazine hydrate (0.18 mL, 5.8 mmol), stirred at 160 ° C for 30 minutes, cooled to room temperature, treated with potassium hydroxide, stirred at 150 ° C for 45 minutes, cooled to room temperature, treated with water and extracted with ethyl acetate. The extract was rinsed with water, dried (MgSO), filtered and concentrated. The residue was purified by flash chromatography on silica gel with 10% ethyl acetate / hexanes to provide the main compound. MS (DCI / NH3) m / z 286 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 1.28 (t, 3 H), 2.26 (s, 3 H), 2.99 (q, 2 H), 7. 14-7.27 (m, 5H), 8.34 (s, 1 H), 9.1 1 (s, 1 H); Anal. cale, for C16H15NS2-0.25H2O: C, 67.33; Hi, 5.30; N, 4.91.

Found: C, 66.63; H, 5.38; N, 4.72. Example 36 1-f4-f (4-methylphenyl) thiolthieno-2,3-clpyridin-2-y-pytanone. oxime Example 33 and hydroxylamine hydrochloride were processed as in Example 26 to provide the main compound. mp 209-213 ° C; MS (DCI / NH3) m / z 315 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.22 (s, 1.5 H), 2.28 (s, 3 H), 2.32 (s, 1. 5H), 7.20 (m, 2H), 7.30 (m, 2H), 7.62 (s, 0.5H), 7.70 (s, 0.5H), 8.30 (s, 0.5H), 8.34 (s, 0.5H), 9.12 (s, 0.5H), 9.24 (s, 0.5H); Anal. cale, for Ci6H14N2OS2: C, 61.16; H, 4.49; N, 8.91. Found: C, 60.83; H, 4.61; N, 9.03. Example 37 N- (2,3-dihydroxypropyl) -4-f (4-rnetilfenil) tioltienof2,3-2-carboxamide c1piridina-A solution of Example 18 (2.5 g, 8.3 mmol) and N-hydroxysuccinimide (0.95 g, 8.3 mmol) in dichloromethane (35 mL) was treated with DCC (1882 g, 9.13 mmol) in methylene chloride (15 mL), stirred at room temperature for 18 hours and concentrated. The residue was dissolved in ethyl acetate, rinsed with water, dried (MgSO), filtered and concentrated. The residue was added to a solution of 3-amino-1,2-propane diol (0.144 g, 1.6 mmol) in 3: 1 dioxane / methanol (20 mL), stirred at room temperature for 18 hours, concentrated, dissolved in ethyl acetate, rinsed with water, dried (MgSO), filtered and concentrated. The residue was purified by flash chromatography on silica gel with 6% methanol / dichloromethane to provide the main compound, mp 120-122 ° C; MS (DCI / NH3) m / z 375 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 2.29 (s, 3 H), 3.19 (m, 1 H), 3.4 (m, 1 H), 3.65 (m, 1 H), 4.62 (t, 1 H) , 4.88 (d, 1 H), 7.20 (m, 2H), 7.30 (m, 2H), 8.38 (s, 1 H), 9.1 (s, 1 H), 9.28 (s, 1 H); Anal. cale, for C18H18N2O3S2 0.75H2O: C, 57.73; H, 4.84; N, 7.48. Found: C, 55.54; H, 5.23; N, 6.7. Example 38 4-r (4-methylphenyl) tio1tienof2,3-c1piridina-2-carboxylic acid, hydrazide Example 18 was processed as in Example 37 but substituting hydrazine for 3-amino-1, 2-propanediol to provide the title compound, m 176-178 ° C; MS (DCI / NH3) m / z 316 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 2.29 (s, 3 H), 4.68 (br s, 2 H), 7.20 (m, 2 H), 7.30 (m, 2 H), 8.2 (s, 1 H), 8.4 ( s, 1 H), 9.28 (s, 1 H), 10.4 (br s, 1 H); Anal. cale, for C15Hi3N3OS2-0.25H2 ?: C, 57.12; H, 4.15; N, 13.32. Found: C, 56.49; H, 4.19; N, 12.29. Example 39 N2-4-f (4-methylphenyl) thio1-tienof2.3-c] pyridin-2-incarbonip-N6-r (nitroamino) iminomethin-L-lysine. methyl ester N -? - Nitroarginine methyl ester hydrochloride and NaHCO3 were processed as in Example 37. The residue was purified by flash chromatography on silica gel with 5% methanol / dichloromethane to provide the main compound. mp 84-87 ° C; MS (DCI / NH3) m / z 517 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 1.60 (m, 2 H), 1.85 (m, 2 H), 2.29 (s, 3 H), 3.20 (m, 2 H), 3.68 (s, 3 H), 4.35 (t, 1 H), 4.48 (m, 1 H), 7.20 (m, 2H), 7.30 (m, 2H), 8.32 (s, 1 H), 8.48 (s, 1 H), 8.52 (br s) , 1 H), 9.30 (s, 1 H), 9.42 (d, 1 H); Anal. cale, for C22H2 N6O5S2-0.25H2O: C, 51.15; H, 4.68; N, 16.27. Found: C, 50.95; H, 4.89; N, 15.73. EXAMPLE 40 N- (aminoiminomethyl) -4-r (4-methylphenyl) thiolthienor 2,3-clpyridine-2-carboxamide A solution of guanidine hydrochloride (0.095 g, 1 mmol) in methanol was treated with potassium t-butoxide (0.1 12 g, 1 mmol), stirred at room temperature for 30 minutes, treated with Example 17 (0.1 g, 0.3 mmol), warmed to room temperature for 16 hours and concentrated. The concentrate was dissolved in ethyl acetate (100 mL), rinsed with water, dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography on silica gel with 6% methanol / dichloromethane to provide the main compound, mp 202-205 ° C; MS (DCI / NH3) m / z 343 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 2.29 (s, 3 H), 6.90 (br s, 2 H), 7.20 (m, 4 H), 7.80 (S, 1 H), 8.00 (br s, 2 H), 8.20 (s, 1 H), 8.40 (s, 1 H), 9.24 (s, 1 H). j ^ k Example 41 5 4-f (4-rnethylphenyl) thiojthienof2.3-c1pyridine-2-carbothioamide A solution of Example 19 (190 mg, 0.63 mmol) and Lawsesson's reagent (383 mg, 9.48 mmol) in toluene (15 mL) was warmed to room temperature for 5 hours and concentrated. The residue was purified by flash chromatography on silica gel with 4% methanol / dichloromethane to provide the compound ^ k main. mp 181 -183 ° C; MS (DCI / NH3) m / z 317 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.29 (s, 3 H), 7.20 (m, 2 H), 7.30 (m, 15 2 H), 8.18 (br s, 1 H), 8.32 (s, 1 H), 9.2 (s, 1 h), 10.1 (br s, 1 H), 10.2 (br s, 1 H); Anal. cale, for C15H? 2N2S3: C, 56.93; H, 3.82; N, 8.85. Found: C, 55.89; H, 3.83; N, 8.48. ^ Example 42 4-f (4-methylphenyl) thio1tienof2.3-c1pyridine Boiling Dowterm (2 mL) was treated sequentially with the Example 18 (0.6 g, 1.99 mmol) and copper powder (0.3 g), stirred for 5 minutes, cooled, diluted with hexanes, and purified by flash chromatography on silica gel with 15% ethyl acetate.

Ethyl / hexanes. The product was then recrystallized from hexanes to provide the main compound, mp 94-95 ° C; MS (DCI / NH3) m / z 258 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.27 (s, 3 H), 7.16 (m, 2 H), 7.23 (m, 2 H), 7.44 (d, 1 H), 8.20 (d, 1 H), 8.40 ( s, 1 H), 9.27 (s, 1 H); Anal. cale, for C14H11 NS2: C, 65.33; H, 4.30; N, 5.44. Found: C, 65.44; H, 4.20; N, 5.26. Example 43 Methyl 4-f (2-methoxy-2-oxoethyl) thio1t-enof2.3-clpridine-2-carboxylate Example 93A was processed as in Examples 17B and 17C, but replacing methyl thioglycolate with p-triocresol in Example 17B to provide the main compound. MS (DCI / NH3) m / z 298 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 3.59 (s, 3 H), 3.94 (s, 3 H), 4.04 (s, 2 H), 8.14 (s, 1 H), 8.55 (s, 1 H), 9.27 ( s, 1 H). Example 44 4-f (2-amino-2-oxoethyl) thio1-tienor-2,3-clpyridine-2-carboxamide Example 43 was dissolved in 2M methanolic ammonium and heated at 45 ° C in a sealed tube for 18 hours. The precipitate was filtered, rinsed with methanol-diethyl ether (1: 1) and dried under vacuum to provide the main compound. MS (APCI) m / z 268 (M + H) +; 1 H NMR (400 MHz, DMSO-d 6) d 3.81 (s, 2 H), 7.17 (br s, 1 H), 7.59 (br s, 1 H), 7.82 (br s, 1 H), 8.29 (br s, 1 H), 8.46 (s, 1 H), 8.52 (br s, 1 H), 9.14 (s, 1 H).

Example 45 4-R (4-bromophenyl) thio1t-enof2,3-cjpyridine-2-carboxamide Example 17A was processed as in Examples 17B and 17C, and 44, but substituting 4-bromothiophenol for p-thiocresol in Example 17B for provide the main compound. MS (DCI / NH3) m / z 365 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 7.20 (dt, 2 H), 7.53 (dt, 2 H), 7.87 (br s, 1 H), 8.21 (s, 1 H), 8.51 (br s, 1 H) , 8.54 (s, 1 H), 9.36 (s, 1 H); Anal. cale, for C 14 H 9 BrN 2 OS 2: C, 46.04; H, 2.48; N, 7.67. Found: C, 45.86; H, 2.30; N, 7.51. Example 46 4- (phenylthio) thienor 2,3-clpyridine-2-carboxamide Example 17A was processed as in Examples 17B, 17C, and 44, but substituting thiophenol for p-thiocresol in Example 17B to provide the main compound. MS (DCI / NH3) m / z 287 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 7.29-7.40 (m, 5H), 7.86 (br s, 1 H), 8.25 (s, 1 H), 8.46 (s, 1 H), 8.52 (br s, 1 H), 9.31 (s, 1 H); Anal. cale, for C l4H? oN2OS2: C, 58.72; H, 3.52; N, 9.28. Found: C, 58.62; H, 3.42; N, 9.48. Example 47 4-ff4- (trifluoromethyl) phenyltio1-tienor2.3-c1pyridine-2-carboxamide Example 17A was processed as in examples 17B, 17C, and 44, but substituting a, a, -trifluorothiocresol for p-thiocresol in Example 17B for provide the main compound.

MS (DCI / NH3) m / z 355 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 7.31 (d, 1 H), 7.65 (d, 2 H), 7.85 (br s, 1 H), 8.19 (s, 1 H), 8.50 (br s, 1 H ), 8.68 (s, 1 H), 9.44 (s, 1 H); Anal. cale, for C15H9F3N2? S2: C, 50.84; H, 2.56; N, 7.91. Found: C, 50.63; H, 2.44; N, 7.82. Example 48 4-f (2-methylphenyl) thio1thienof2,3-clpyridine-2-carboxamide Example 17A was processed as in Examples 17B and 17C, and 44, but substituting 2-methylthiophenol for p-thiocresol in Example 17B. The residue was purified by column chromatography, eluting with 5% methanol in dichloromethane to provide the main compound, mp 170-172 ° C; MS (DCI / NH3) m / z 301 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.41 (s, 3 H), 7.04 (dd, 1 H), 7.15 (dt, 1 H), 7.27 (dt, 1 H), 7.38 (br d, 1 H) , 7.86 (br s, 1 H), 8.20 (s, 1 H), 8.23 (s, 1 H), 8.53 (br s, 1 H), 9.28 (s, 1 H); Anal. cale, for C15H12N2OS2: C, 59.97; H, 4.03; N, 9.33. Found: C, 59.86; H, 4.16; N, 9.1 1. Example 49 4-f (3-methylphenyl) thio1-tienor-2,3-c1pyridine-2-carboxamide Example 17A was processed as in Examples 17B and 17C, and 44, but substituting 3-methylthiophenol for p-thiocresol in Example 17B. The residue was purified by flash chromatography with 5% methanol / dichloromethane to provide the main compound. mp 171 -173 ° C; MS (DCI / NH3) m / z 301 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 2.27 (s, 3 H), 7.06-713 (m, 2 H), 7.21 -7.27 (m, 2 H), 7.89 (br s, 1 H), 8.26 (s, 1 H), 8.42 (s, 1 H), 8.55 (br s, 1 H), 9.30 (s, 1 H); Anal. cale, for C15H12N2? S2 0.25H2 ?: C, 59.08; H, 4.13; N, 9.19. Found: C, 59.10; H, 4.16; N, 9.1 1. Example 50 4-f (3,4-dimethylphenyl) thiolthiene (2,3-c) pyridine-2-carboxamide Example 17A was processed as in examples 17B and 17C, and 44, but substituting 3,4-d-methylphenylphenol for p-thiocresol in Example 17B The residue was purified by flash chromatography with 5% methanol / dichloromethane to give the title compound, mp 192-194 ° C, MS (APCI) m / z 315 (M + H) +, 1H NMR (300 MHz, DMSO-dβ) d 2.09 (s, 3H), 2.1 1 8s, 3H), 7.05 (m, 2H), 7.19 (s, 1 H), 7.81 (br s, 1 H), 8.12 (d, 2h ), 8.49 (br s, 1 H), 9.15 (s, 1 H); Anal. cale, for C? ßH14N2? S2 0.25H2O: C, 60.25; H, 4.58; N, 8.78. Found: C, 60.34; H, 4.52; N, 8.75. Example 51 4-f (3,5-dimethyl-phenyl) thiolthienof2,3-clpyridine-2-carboxamide Example 17A was processed as in Examples 17B and 17C, and 44, but substituting 3,5-dimethylthioferroyl for p- thiocresol in the Example 17B. The residue was purified by flash chromatography, with 5% methanol / dichloromethane to provide the main compound. mp 177-179 ° C; MS (DCI / NH3) m / z 315 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.13 (s, 6H), 6.83 (s, 1 H), 6.92 (s, 1 H), 7.81 (br s, 1 H), 8.21 (s, 1 H), 8.30 (s, 1 H), 8.50 (br s, 1 H), 9.19 (s, 1 H); Anal. cale, for C16H? 4N2OS2: C, 61.12; H, 4.49; N, 8.91. Found: C, 60.82; H, 4.48; N, 8.75. Example 52 4-f (2,4-dimethylphenyl) thioltienor2,3-c1pyridine-2-carboxamide Example 1 7A was processed as in Examples 17B and 1 7C, and 44, but substituting 2,4-dimethylthiophenol for p-thiocresol in Example 17B. The residue was purified by flash chromatography, with 5% methanol / dichloromethane to provide the main compound. mp 193-195 ° C; MS (APCI) m / z 315 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.28 (s, 3 H), 2.38 (s, 3 H), 7.02 (d, 1 H), 7.13 (d, 1 H), 7.20 (s, 1 H), 7.91 (br s, 1 H), 8.05 (s, 1 H), 8.58 (br s, 1 H), 9.22 (s, 1 HOUR); Anal. cale, for C1 ßH? 4N2OS2-0.25H2O: C, 60.25; H, 4.58; N, 8.78.

Found: C, 60.40; H, 4.52; N, 8.72. Example 53 4-f (2-methyl-3-furanyl) thiolthienof2.3-cjpyridine-2-carboxamide Example 17A was processed as in examples 17B and 17C, and 44, but substituting 2-methyl-3-furantiol for p-thiocresol in he Example 17B. The residue was purified by flash chromatography, with 5% methanol / dichloromethane to provide the main compound. mp 236-239 ° C; MS (ESI) m / z 291 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.41 (s, 3 H), 6.68 (d, 1 H), 7.74 (d, 1 H 9, 7.93 (br s, 1 H), 8.19 (s, 1 H), 8.38 (s, 1 H), 8.60 (br s, 1 H), 9.15 (s, 1 H); Anal. cale, for C 13 H 10 N 2 O 2 S 2 0.25H 2 O: C, 52.95; H, 3.59; N, 9.50.

Found: C, 52.57; H, 3.41; N, 9.30. Example 54 4-ff (4-chlorophenyl) metiptioltienof2,3-clpiridine-2-carboxamide Example 17A was processed as in Examples 17B and 17C, and 44, but substituting 4-chlorobenzyl mercaptan for p-thiocresol in the Example 17B. The residue was purified by flash chromatography, with 5% methanol / dichloromethane to provide the main compound. mp 198-199 ° C; MS (APCI) m / z 335 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 4.40 (s, 2H), 7.31 (s, 4H), 7.86 (br s, 1 H), 8.26 (s, 1 H), 8.41 (s, 1 H), 8.52 (br s, 1 H), 9.15 (s, 1 H); Anal. cale, for C ^ HnCINsOSz: C, 53.80; H, 3.31; N, 8.37.

Found: C, 53.52; H, 3.18; N, 8.31. Example 55 4-r (3,4-dichlorophenol) thio1-tienof2.3-clpyridine-2-carboxamide Example 1 7A was processed as in examples 17B and 17C, and 44, but substituting 3,4-dichlorothiophenol for p-thiocresol in the Example 17B. The residue was purified by flash chromatography, with 5% methanol / dichloromethane to provide the main compound. MS (ESI) m / z 355 (M + H) +; H NMR (300 MHz, DMSO-dβ) d 7.10 (dd, 1 H), 7.55 (d, 1 H), 7.59 (d, 1 H), 7.91 (br s, 1 H), 8.21 (s, 1 H) ), 8.53 (br s, 1 H), 8.62 (s, 1 H), 9.41 (s, 1 H); Anal. cale, for C 14 H 8 Cl 2 N 2 OS 2: C, 47.33; H, 2.27; N, 7.89. Found: C, 47.34; H, 2.52; N, 8.05. Example 56 4-r (4-methoxyphenyl) thio1thienof2.3-c1pyridine-2-carboxamide Example 17A was processed as in Examples 17B and 17C, and 44, but substituting 4-methoxythiophenol for p-thiocresol in Example 17B. The residue was purified by flash chromatography, with 5% methanol / dichloromethane to provide the main compound, mp 219-221 ° C; MS (ESI) m / z 317 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 3.76 (s, 3 H), 6.99 (d, 2 H), 7.46 (d, 2 H), 7.89 (br s, 1 H), 8.17 (s, 1 H), 8.30 (s, 1 H), 8.54 (br s, 1 H), 9.18 (s, 1 H); Anal. cale, for C, 56.94; H, 3.82; N, 8.85. Found: C, 56.80; H, 3.78; N, 8.79. Example 57 4- (cyclohexylthio) thienor 2,3-clpyridine-2-carboxamide Example 17A was processed as in examples 17B and 17C, and 44, but replacing cyclohexyl mercaptan with p-thiocresol in the Example 17B. The residue was purified by flash chromatography, with 5% methanol / dichloromethane to provide the main compound. mp 205-207 ° C; MS (ESI) m / z 293 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 1 .14-1 .43 (br m, 6H), 1 .51 -1 .61 (br m, 1 H), 1 .66-1.78 (br m, 2H), 1.83-1.98 (br m, 2H), 7.90 (br s, 1 H), 8.33 (s, 1 H), 8.52 (s, 1 H), 8.57 (br s, 1 H) 9.22 (s, 1 H); Anal. cale, for C? 4H1 ßN2OS2: C, 57.50; H, 5.51; N, 9.58. Found: C, 57.53; H, 5.39; N, 9.51. Example 58 4-f (4-methylphenyl) thio1-N-f3- (4-morpholinyl) propynthienof2.3-c1pyridine-2-carboxamide. trifluoromethylacetate (salt) Example 17C (200 mg, 0.635 mmol) in 9: 1 4- (3-aminopropyl) morpholine / acetic acid (2 mL) was heated at 70 ° C for 4 hours, with acetonitrile (6 mL), and purified by reverse phase HPLC.

C-18 with a gradient of 20% acetonitrile / water at 100% CH3CN containing 0.1% trifluoroacetic acid to provide the main compound MS (APCI) m / z 428 (M + H) +; 1 H NMR (400 MHz, DMSO-d 6) d 1.95 (m, 2 H), 3.08 (m, 2 H), 3.18 (m, 2 H), 3.36 (m, 2 H), 3.43 (m, 2 H), 3.68 (m, 2 H). m, 4H), 7.20 (d, 2H), 7.28 (d, • 5 2H), 8.0 (br s, 1 H), 8.27 (s, 1 H), 8.34 (m, 1 H), 9.27 (m, 1 H). Example 59 4-R (4-methylphenyl) sulfinintienof2.3-c1pyridine-2-carboxamide Example 59A Methyl 4-f (4-methylphenyl) sulphiniptienof2.3-clpyridine-2-carboxylate A solution of example 17C (144 mg, 0.46 mmol) in dichloromethane (10 mL) at 0 ° C was treated with 3-chlorophenoxybenzoic acid • (57-86%, 82 mg), warmed to room temperature for 4 hours, treated with dichloromethane (50 mL), sequentially rinsed with 1 N NAOH, water, and brine, dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography on silica gel with 50% ethyl acetate / hexane to provide the main compound. MS (DCI / NH3) m / z 332 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.25 (s, 3 H), 3.84 (s, 3 H), 7.38 (d, 2H), 7.65 (d, 2H), 8.41 (s, 1 H), 9.0 (s, 1 H), 9.58 (s, 1 H). Example 59B 4-f (4-methylphenyl) sulphiniptienor 2,3-clpyridine-2-carboxamide Example 59A was processed as in Example 44 to provide the main compound. MS (DCI / NH3) m / z 317 (M + H) +; 25 1 H NMR (300 MHz, DMSO-dβ) d 2.31 (s, 3 H), 7.38 (d, 2 H), 7.79 (d, 2H), 7.94 (br s, 1 H), 8.43 (s, 1 H), 8.62 (br s, 1 H), 8.85 (s, 1 H), 9.43 (s, 1 H). Example 60 4- (4-methylphenoxy) t-inof2,3-c1pyridine-2-carboxamide Example 60A Methyl 4- (4-methylphenoxytieno (2,3-c1pyridine-2-carboxylate Example 17A was processed as in examples 17B and 17C, but substituting p-cresol for p-thiocresol in Example 17B to provide the main compound: mp 96-98 ° C; MS (DCI / NH3) m / z 317 (M + H) +, 300 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 2.32 (s, 3 H), 3.91 (s, 3 H), 7.05 (m, 2 H 9, 7.24 (m, 2 H), 7.95 (s, 1 H), 8.12 (s, 1 H), 9.17 (s, 1 H), Anal cale, for C1 ßH13NO3S: C, 64.19; H, 4.37; N, 4.67. Found: C, 64.05; H, 4.34; N, 4.52. Example 60B 4- (4-methyloxy) thienor-2,3-clpyridine-2-carboxamide Example 60A was processed as in Examples 18 and 19 to provide the main compound: mp 196-197 ° C; MS (DCI / NH3) m / z 285 (M + H) +, 302 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.31 (s, 3H), 7.04 (m, 2H), 7.25 (m, 2H) , 7.82 (br s, 1 H), 8.00 (s, 1 H), 8.21 (s, 1 H), 8.42 (br s, 1 H), 9.07 (s, 1 H); Anal cale, for C ^ H ^ NzOzS: C, 63.36; H, 4.2 5; N, 9.85. Found: C, 63.29; H, 4.28; N, 9.68. Example 61 4- (4-chlorophenoxy) thienof2,3-clpyridine-2-carboxamide Example 61 A Methyl 4- (4-chlorophenoxy) thienof2,3-clpridine-2-carboxylate A solution of 4-chlorophenol (2.63 g, 20.5 mmol) in THF (20 mL) at 0 ° C was treated dropwise with a tert-butoxide solution (1.0 M solution in THF, 20.4 mL, 20.5 mmol), stirred at 25 ° C for 1 hour , cooled to 0 ° C, treated with a solution of Example 17A (3.54 g, 20.23 mmol) in THF (40 mL), heated at 60 ° C for 0.5 hours, cooled to 0 ° C, treated with methylthioglycolate (1989 g; 22.25 mmol) and Cs2CO3 (6.59 g, 20.23 mmol), heated at 60 ° C for 0.25 hours, cooled to room temperature and filtered. The filtrate was diluted with ethyl acetate, rinsed sequentially with water and brine, dried (MgSO4), filtered and concentrated. Purification of the residue by flash chromatography on silica gel with 4% acetone / hexane provided the main compound, mp 99-100 ° C; MS (APCI) m / z 320 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 3.91 (s, 3 H, OCH 3), 7.14 (d, 1 H), 7.48 (d, 2 H), 7.95 (s, 1 H), 8.23 (s, 1 H) 9.23 (s, 1 H); 13 C NMR (100 MHz, DMSO-dβ) d 56.45 (OCH 3), 120.19 (CH), 123.06 (Ar-CH), 128.04 (Ar-CH), 131 .34 (C), 132-37 (Ar-CH) , 133.38 (Ar-CH), 136.40 (Ar-CH), 139.38 (C), 141.75 (C), 142.09 (C), 144.89 (Ar-CH), 150.91 (C), 158.64 (C), 164.95 (CO); Anal. cale, for C15H10CINO3S: C, 56.34; H, 3.15; N, 4.38. Found: C, 56.23; H, 3.16; N, 4.38. Example 61 B 4- (4-chlorophenoxy) thienof2,3-c1pyridine-2-carboxamide • Example 61A was processed as in Example 44 to provide the main compound, mp 176-177 ° C; MS (DCI / NH3) m / z 305 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 7.15 (m, 2 H), 7.50 (m, 2 H), 7.95 (b, 10 1 H), 8.25 (d, 2 H), 8.45 (b, 1 H) ), 9.15 (s, 1 H); Anal. cale ', for C14H9CIN2O2S 0.25H2O: C, 54.37; H, 3.10; N, 9.06.

• Found: C, 54.44; H, 2.74; N, 9.06. Example 62 4-f4- (trifluoromethyl) phenoxyptienor2.3-c1pyridine-2-carboxamide Example 17A was processed as in Example 61 but substituting 4- (trifluoromethyl) phene for 4-chlorophenol to give the main compound. MS (DCI / NH3) m / z 339 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 7.24 (d, 2 H), 7.77 (d, 2 H), 7.88 (br s, 20 1 H), 8.10 (s, 1 H), 8.33 (s, 1 H) , 8.45 (br s, 1 H), 9.24 (s, 1 H); Anal. cale, for C15H9F3N2O2S: C, 53.26; H, 2.68; N, 8.28. Found: C, 53.06; H, 2.55; N, 8.19. Example 63 4- (4-octylphenoxy) thienor-2,3-c1pyridine-2-carboxamide Example 17A and 4-octylphenol were processed as in Example 61 to provide the main compound. MS (DCI / NH3) m / z 383 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 0.88 (t, 3 H), 1.22-1.38 (m, 10 H), 1.62 (m, 2 H), 2.61 (t, 2 H), 6.05 (br s, 2H), 6.99 (d, 2H), 7.20 (d, 2H), 7.87 (s, 1 H), 8.07 (br s, 1 H), 8.92 (br s, 1 H); Anal. cale, for C22H2ßN2? 2S: C, 69.08; H, 6.85; N, 7.32. Found: C, 69.04; H, 6.82; N, 7.22. Example 64 4-f4- (1-methylethyl) phenoxyptiene-2,3-c1pyridine-2-carboxamide Example 17A and 4- (1-methylethyl) phenol were processed as in Example 61 to provide the main compound. MS (DCI / NH3) m / z 313 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 1.21 (d, 6H), 2.92 (septet, 1 H), 7.05, d, 2H), 7.30 (d, 2H), 7.82 (br s, 1 H) , 8.03 (s, 1 H), 8.21 (s, 1 H), 8.44 (br s, 1 H), 9.09 (s, 1 H). Example 65 4- (2-Bromo-4-chlorophenoxy) thienof2.3-c1pyridine-2-carboxamide Example 17A and 2-bromo-4-chlorophenol were processed as in Example 61 to provide the main compound. MS (DCI / NH3) m / z 383 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 7.18 (d, 1 H), 7.49 (br s, 1 H), 7.90 (br s, 1 H), 7.98 (s, 2 H), 8.23 (s, 1 H ), 8.49 (br s, 1 H), 9.14 (s, 1 H); Anal. cale, for C 14 H 8 BrCIN 2 O 2 S: C, 43.83; H, 2.10; N, 7.30. Found: C, 43.53; H, 1.97; N, 6.99. Example 66 4- (4-ethylphenoxy) thieno.2.3-c1pyridine-2-carboxamide Example 17A and 4-ethylphenol were processed as in Example 61 to provide the main compound. MS (DCI / NH3) m / z 299 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 1.19 (t, 3 H), 2.62 (q, 2 H), 7.05 (d t, 2 H), 7.26 (d t, 2 H), 7.81 (br s, 1 H), 8.07 ( s, 1 H), 8.21 (s, 1 H), 8.43 (br s, 1 H), 9.08 (s, 1 H); Anal. cale, for C 16 H 14 N 2 O 2 S CH 3 OH: C, 63.71; H, 4.69; N, 9.14. Found: C, 63.34; H, 4.51; N, 9.51. EXAMPLE 67 4- (4-ethenylphenoxy) thieno (2 3-c1pyridine-2-carboxamide Example 67A 4-Vinylphenol A solution of 4-vinylphenol in propylene glycol was treated with water and extracted with diethyl ether in order to remove the propylene glycol and provide the designated compound in diethyl ether Example 67B 4- (4-ethenylphenoxy) thieno (2,3-c) pyridine-2-carboxamide Example 17A and Example 67A were processed as in Example 61 to provide the main compound. MS (DCI / NH3) m / z 297 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 5.24 (d, 1 H), 5.79 (d, 1 H), 6.75 (dd, 1 H ), 7.10 (d, 2H), 7.54 (d, 2H), 7.87 (br s, 1 H), 8.12 (s, 1 H), 8.18 (s, 1 H), 8.45 (br s, 1 H), 9.13 (s, 1 H); Anal cale, for C ^ H ^ NsOzS O ^ dCHsOH: C, 64.13; H, 4.06; N, 9.20.

Found: C, 64.40; H, 4.12; N, 9.27. Example 68 4-f4- (1,2-dihydroxyethyl) phenoxyptienof2.3-c1pyridine-2-carboxamide A solution of Example 67B (35 mg, 0.1-1.8 mmol) in pyridine (5 mL) was treated with OsO4 (90 mg, 0.354 mmol ), stirred for 5 hours, treated with 10% aqueous NaHSO3, stirred for 5 hours, treated with brine, and extracted with ethyl acetate. The extract was dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography on silica gel with 1:10 methanol / dichloromethane to provide the main compound. MS (DCI / NH3) m / z 331 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 3.44 (t, 2 H), 4.55 (q, 1 H), 4.73 (t, 1 H), 5.27 (d, 1 H), 7.08 (d, 2 H), 7.39 (d, 2H), 7.85 (br s, 1 H), 8.03 (s, 1 H), 8.21 (s, 1 H), 8.47 (br s, 1 H), 9.10 (s, 1 H); Anal. cale, for C1ßH14N2O4S 0.25CH3OH: C, 57.68; H, 4.24; N, 8.28. Found: C, 57.92; H, 4.35; N, 8.24. Example 69 4-f2- (2-propenyl) phenoxyphenof2.3-clpyridine-2-carboxamide Example 17A and 2-allylphenol were processed as in Example 61 to provide the main compound. MS (DCI / NH3) m / z 31 1 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 3.43 (d, 2 H), 5.01 (m, 1 H), 5.05 (m, 1 H), 5.98 (m, 1 H), 7.00 (dd, 1 H), 7.27 (m, 2H), 7.39 (dd, 1 H), 7.82 (s, 1 H), 7.88 (br s, 1 H), 8.27 (s, 1 H), 8.49 (br s, 1 H), 9.05 (s, 1 H); Anal. cale, for C 17 H 14 N 2 O 2 S: C, 65.79; H, 4.55; N, 9.03. Found: C, 65.53; H, 4.37; N, 8.95. Example 70 4-r 2 - (2,3-dihydroxypropyl) phenoxyptienor 2,3-c 1pyridine-2-carboxamide Example 69 was processed as in Example 68 to provide the main compound. MS (DCI / NH3) m / z 345 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.60 (dd, 1 H), 2.88 (dd, 1 H), 3.29 (t, 1 H), 3.76 (m, 1 H), 4.55 (t, 1 H ), 4.63 (d, 1 H), 6.94 (dd, 1 H), 7.22 (m, 2H9, 7.45 (dd, 1 H), 7.84 (s, 1 H), 7.88 (br s, 1 H), 8.26 (s, 1 H), 8.46 (br s, 1 H), 9.04 (s, 1 H), cale anal, for C17H16N2O4S: C, 59.29; H, 4.68; N, 8.13, Found: C, 59.16; , 4.51; N, 8.06 EXAMPLE 71 4-f4- (trifluoromethyl-phenoxfltienor2,3-c1pyridine-2-carboxamide, 1-oxide) A solution of Example 62 (26 mg, 0.077 mol) in (1 mL) and dichloromethane (5 mL), at 0 ° C was treated with m-CPBA (80-85%, 30 mg, 0.14 mmol), stirred at 0 ° C for 1 hour and at room temperature for 10 hours.The precipitate that formed was collected by filtration and rinsed with dichloromethane HPLC analysis of the material (C-18, reverse phase) showed a mixture of desired sulfoxide and initial thiamphene in a ratio of 8: 1. The mixture was recrystallized from DMF / methanol / dichloromethane to provide the main compound (97.5% pure by analysis s HPLC) MS (HPCI / NH3) m / z 355 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 7.39 (d, 2 H), 7.79 (br s, 1 H), 7.81 (d, 2H), 8.02 (s, 1 H), 8.05 (d, 1 H), 8.36 (br s, 1 H), 9.02 (s, 1 H); Anal. cale, for C 15 H 3 F 3 N 3 S 0.25 CH 3 OH: C, 50.55; H, 2.57; N, 7.73.

Found: C, 50.55; H, 2.59; N, 7.69. Example 72 4-f3- (pentadecyl) phenoxy-1-tienor-2,3-clpyridine-2-carboxamide Example 17A and 3-pentadecylphenol were processed as in Example 61 to provide the main compound. MS (DCI / NH3) m / z 481 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 0.84 (t, 3H), 1 .20-1.28 (m, 24H), 1.54 (m, 2H), 2.57 (t, 2H), 6.92 (m , 1 H), 6.97 (t, 1 H), 7.03 (d, 1 H), 7.33 (t, 1 H), 7.85 (br s, 1 H), 8.03 (s, 1 H), 8.23 (s, 1 H), 8.44 (br s, 1 H), 9.09 (s, 1 H); Anal. cale, for C29H4oN2? 2S: C, 72.46; H, 8.39; N, 5.83. Found: C, 72.69; H, 8.18; N, 5.47. Example 73 Methyl 4- (4-Bromophenoxy) thienof2,3-clpyridine-2-carboxylate To a solution of 4-bromophenol (4.94 g, 25.55 mmol) in anhydrous tetrahydrofuran (10 mL) under nitrogen atmosphere was added dropwise a potassium t-butoxide solution (1 M solution in THF, 28.6 mL, 28.6 mmol). The reaction mixture was stirred at room temperature for 30 minutes, then a solution of Example 17A (2 g, 11.1 mmol) in anhydrous tetrahydrofuran. (20 mL) was added and refluxed for 8 hours. The reaction mixture was allowed to cool to 25 ° C, methyl thioglycolate (1.23 mL, 13.7 mmol) was added and refluxed for 15 minutes. The reaction mixture cooled was diluted with ethyl acetate (300 mL) and partitioned with a cold 1 N NaOH solution (3 x 75 mL). The organic layer was rinsed with brine (3x100 mL), dried (MgSO4), and the solvents were removed under reduced pressure to obtain the crude product (4.2 g). This was purified by flash chromatography on silica gel eluting with 10% acetone-hexane to obtain the main compound (1.81 g) in 44% product. 1 H NMR (300 MHz, DMSO-d 6) d 3.91 (s, 3 H), 7.10 (d, J = 9 Hz, 2 H), 7.59 (d J = 9 Hz, 2 H), 7.94 (s, 1 H), 8.25 ( s, 1 H), 9.24 (s, 1 H); MS (APCI) m / e 364; 366 (M + H) +; Example 74 4- (3-chlorophenoxy) thienof2,3-clpyridine-2-carboxamide Example 17A and 3-chlorophenol were processed as in Example 61 to provide the main compound. MS (DCI / NH3) m / z 305 (M + H) +; . 1 H NMR (300 MHz, DMSO-d 6) d 7.10 (m, 1 H), 7.30 (m, 2 H), 7.45 (b, 1 H), 7.95 (b, 1 H), 8.20 (d, 1 H), 8.30 (s, 1 H), 8.6 (b, 1 H), 9.30 (s, 1 H). Example 75 4- (4-t-butylphenoxy) thieno-2,3-clpyridine-2-carboxamide Example 17A and 4-tert-butylphenol were processed as in Example 61 to provide the main compound. MS (DCI-NH3) m / z 327 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 1 .3 (s, 9 H), 7.10 (d, 2 H), 7.45 (d, 2 H), 7.85 (br s, 1 H), 8.05 (s, 1 H) , 8.20 (s, 1 H), 8.45 (br s, 1 H), 9.1 (s, 1 H). Example 76 4- (4-Chloro-3-methylphenoxy) thienor-2,3-clpyridine-2-carboxamide Example 17A and 4-chloro-3-methylphenol were processed as in Example 61 to provide the main compound. MS (DCI / NH3) m / z 319 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.30 (s, 3 H), 6.95 (dd, 1 H), 7.20 (br, 1 H), 7.45 (d, 1 H), 7.20 (br, 1 H) , 8.15 (s, 1 H), 8.19 (s, 1 H), 8.45 (br s, 1 H), 9.15. (S, 1 H). Example 77 4- (4-chloro-2-methylphenoxy) thieno.2,3-clpyridine-2-carboxamide Example 17A and 4-chloro-2-methylphenol were processed as in Example 61 to provide the main compound. MS (DCI / NH3) m / z 319 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.30 (s, 3H), 6.95 (dd, 1 H), 7.30 (d, 1 H), 7.50 (d, 1 H), 7.85 (br s, 1 H) , 7.95 (s, 1 H), 8.25 (s, 1 H), 8.45 (br s, 1 H), 9.15 (s, 1 H). Example 78 4- (4-methoxyphenoxy) t-inof2.3-c1pyridine-2-carboxamide Example 17A and 4-methoxyphenol were processed as in Example 61 to provide the main compound. MS (DCI / NH3) m / z 301 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 3.78 (s, 3 H), 7.00 (d, 2 H), 7.15 (d, 2 H), 7.85 (b, 1 H), 7.90 (s, 1 H), 8.30 ( s, 1 H), 8.45 (b, 1 H), 9.05 (s, 1 H). Example 79 ethyl 3-ff2- (aminocarbonyl) thienof2.3-c1pyridine-4-ylmethylbenzoate Example 17A and ethyl 3-hydroxybenzoate were processed as in Example 61 to provide the main compound. MS (DCI / NH3) m / z 343 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 1.30 (t, 3 H), 4.30 (s, 3 H), 7.40 (dd, 1 H), 7.60 (m, 2 H), 7.80 (dd, 1 H), 7.85 (b, 1H), 8.15 (s, 1H), 8.20 (s, 1H), 8.42 (b, 1H), 9.17 (s, 1H). Example 80 4-phenoxythienof2,3-clpyridine-2-carboxamide Example 17A and phenol were processed as in Example 61 to provide the main compound. MS (DCI / NH3) m / z 271 (M + H) +; H NMR (300 MHz, DMSO-dβ) d 7.15 (dd, 2H), 7.20 (t, 1H), 7.45 (t, 2H), 7.85 (b, 1H), 8.10 (s, 1H), 8.20 (s, 1H), 8.45 (b, 1H), 9.15 (s, 1H). Example 81 4- (3-Bromophenoxy) thienof2,3-clpyridine-2-carboxamide Example 17A and 3-bromophenol were processed as in Example 61 to provide the main compound. MS (DCI / NH3) m / z 349, 351 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 7.07 (dt, 2Hz, 1H), 7.36-7.39 (m, 3H), 7.87 (br s, 1H), 8.15 (s, 1H), 8.20 (s, 1H) , 8.45 (br s, 1H), 9.17 (s, 1H); Anal. Cale, for C 14 H 9 N 2 O 2 S CH 3 OH: C, 47.26; H, 2.64; N, 7.35. Found: C, 47.26; H, 3.21; N, 7.29. Example 82 4- (4-fluorophenoxy) thienof2,3-clpyridine-2-carboxamide Example 17A and 4-fluorophenol were processed as in Example 61 to provide the main compound. MS (DCI / NH3) m / z 289 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 7.25 (m, 4H), 7.85 (b, 1 H), 8.05 (s, 1 H), 8.20 (s, 1 H), 8.42 (b, 1 H), 9.10 (s, 1 H). Example 83 4- (315-dimethylphenoxy) thienor 2,3-clpyridine-2-carboxamide Example 17A and 3,5-dimethylpheni were processed as in Example 61 to provide the main compound. MS (DCI / NH3) m / z 299 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 3.30 (s, 6H), 6.75 (s, 2H), 6.85 (s, 1 H), 7.80 (b, 1 H), 8.05 (s, 1 H), 8.18 (s, 1 H), 8.45 (b, 1 H), 9.10 (s, 1 H). Example 84 4- (3-Chloro-4-methylphenoxy) thienof2,3-clpyridine-2-carboxamide Example 17A and 3-chloro-4-methylphenol were processed as in Example 61 to provide the main compound. MS (DCI / NH3) m / z 319 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.35 (s, 3 H), 7.00 (dd, 1 H), 7.25 (d, 1 H), 7.45 (d, 1 H), 7.85 (b, 1 H), 8.15 (s, 1 H), 8.20 (s, 1 H), 8.45 (b, 1 H), 9.15 (s, 1 H). Example 85 4- (4-vodophenoxy) thien-2,3-c1pyridine-2-carboxamide Example 17A and 4-iodophenol were processed as in Example 61 to provide the main compound. MS (DCI / NH3) m / z 397 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 6.94 (d, 2 H), 7.74 (d, 2 H), 7.86 (br s, 1 H), 8.13 (s, 1 H), 8.17 (s, 1 H), 8.44 (br s, 1 H), 9.16 (s, 1 H); Anal. Cale, for C1 H9IN2O2S: C, 42.44; H, 2.29; N, 7.07. Found: C, 42.58; H, 2.27; N, 7.08. Example 86 4- (4- (methoxymethyl) phenoxy) thienof2,3-clpyridine-2-carboxamide Example 17A and 4- (methoxymethyl) phenol were processed as in Example 61 to provide the main compound, mp 168-168.5 ° C; MS (DCI / NH3) m / z 315 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 3.30 (s, 3 H), 4.41 (s, 2 H), 7.10 (d, 2 H), 7.37 (d, 2 H), 7.86 (s, 1 H), 8.08 (s) , 1 H), 8.19 (s, 1 H), 8.45 (br s, 1 H), 9.12 (s, 1 H). Example 87 2- (aminocarbonyl) -4- (4-chlorophenoxy) thienof2,3-clpyridinium, iodide Example 61 (0.1 1 g, 0.0033 mol) was treated with methyl iodide (0.2 mL, 0.0033 mmol) at reflux for 2 hours and filter. The precipitate was rinsed with ether, dried and recrystallized from acetonitrile to provide the main compound. MS (DCI / NH3) m / z 305 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 4.40 (s, 3 H), 7.40 (dd, 2 H), 7.65 (dd, 2 H), 8.25 (br s, 1 H), 8.55 (s, 1 H), 8.65 (s, 1 H), 8.70 (br s, 1 H), 9.70 (s, 1 H).

Example 88 4- (4-Chlorophenoxy) thienof2.3-c1pyridine-2-carboxylic acid Example 61 A (354 mg, 1.1 mmol), lithium hydroxide monohydrate (98 mg, 2.33 mmol) in 3: 1 methanol Water (4 mL) was stirred at room temperature for 20 hours, acidified with 90% formic acid (0.13 mL) and filtered to provide the main compound. MS (DCI / NH3) m / z 306.308 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 7.26 (m, 2 H), 7.47 (m, 2 H), 7.83 (s, 1 H), 8.23 (s, 1 H), 9.21 (s, 1 H); Anal. Cale, for C14H8CINO3S: C, 55.00; H, 2.64; N, 4.58. Found: C, 54.77; H, 2.60; N, 4.44. Example 89 N- (4- (4-chlorophenoxy) thienof2,3-c1pyridin-2-yl) -O- (3-tetrahydrofuranyl) carbamate A suspension of Example 88 (100 mg, 0.327 mmol) in toluene (2 mL) was treated with ethyldiisopropylamine (63 mg, 0.49 mmol) and diphenylphosphoryl acid (109 mg, 0.394 mmol) at 63 ° C, stirred for 1, treated with (+) - 3-hydroxytetrahydrofuran (130 mg, 1.47 mmol) at 1 10 ° C, stirred for 18 hours, and concentrated. The residue was purified by flash chromatography on silica gel with 30% ethyl acetate / hexane and recrystallized from ethyl acetate to provide the main compound, mp 194-201: MS (APCI) m / z 391 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 1.93-2.04 (m, 1 H), 2.13-2.28 (m, 1 H), 3. 29-3.34 (m, 1 H plus HOD), 3.70-3.86 (m, 4H), 5.33 (m, 1 H), 6.56 (s, 1 H), 7.02 (dt, 2H), 7.43 (dt, 2H) , 8.14 (s, 1 H), 8.91 (s, 1 H); Anal. Cale, for C? 8H15CIN2O4S: C, 55.32; H, 3.87; N, 7.17. Found: C, 55.08; H, 3.69; N, 7.05. F 5 EXAMPLE 90 4- (4-Chlorophenoxy) thienof2,3-clpyridine-2-methanol A solution of Example 61A (254 mg, 0.793 mmol) in absolute ethanol (4 mL) was treated with anhydrous CaCl2 (177 mg, 1 mL). .59 mmol), stirred for 1 hour, cooled to 0 ° C, treated with NaBH (123 mg, 3.25 mmol), stirred at 0 ° C for 4 hours and at room temperature for 18 hours, treated with water and extracted with dichloromethane . He F extract was rinsed with brine, dried (NaSO4), filtered and concentrated. The residue was purified on silica gel with 30% ethyl acetate / hexane to provide the main compound. 15 mp 90-91 ° C; MS (APCI) m / z 292, 294 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.2-2.65 (vbr s, 1 H), 4.97 (d, 2 H), 6.95 (dt, 2 H), 7.43 (m, 1 H), 7.31 (dt, 2 H) , 8.13 (s, 1 H), 8.89 (s, 1 H); Anal. Cale, for C14H, 0CINO2S: C, 57.64; H, 3.45; N, 4.80. 20 Found: C, 57.50; H, 3.58; N, 4.66. Example 91 (E) -3-f4- (4-chlorophenoxy) thieno acid [2,3-c1pyridin-2-in-2-propenoic acid Example 91 A 4- (4-chlorophenoxy) thienof2,3-clpyridine-2-carboxaldehyde 25 One DMSO solution (77 mg, 0.99 mmol) in 1.7 mL of dichloromethane at -78 ° C was treated dropwise with oxalyl chloride (109 mg, 0.86 mmol), stirred for 5 minutes, treated dropwise with Example 90 (123 mg, 0.420 mmol) in 2 mL of dichloromethane, stirred at -78 ° C for 1 hour, treated with ethyldiisopropylamine (326 mg, 2.53 • 5 mmol), warmed to -20 ° C, stirred for 1.5 hours and divided between 10 mL of dichloromethane and 5 mL of water and extracted. The extract was rinsed with water (5 mL) and brine (5 mL), dried (NaSO4) and filtered. The residue was rotoevaporated and dried under vacuum to provide the main compound. MS (APCI) m / z 290, 292 (M + H) +; EXAMPLE 91 B • (E) -3-f4- (4-chlorophenoxy) thieno.2,3-c1pyridin-2-ip-2-propenoate Example 91 A (138 mg, 0.42 mmol) and methyl triphenylphosphoranylidene acetate (210 mg, 0.628 mmol) in dichloroethane (2 mL) was stirred at 65 ° C for 3 hours and concentrated. The residue was purified by flash chromatography on silica gel with 25% ethyl acetate / hexane to provide the main compound. MS (APCI) m / z 346, 348 (M + Hf; 1 H NMR (300 MHz, DMSO-d6) d 3.83 (s, 3H), 6.43 (d, 1 H), 7.00 (dt, 2 H), 7.35 (dt, 2 H), 7.48 (s, 1 H), 7.84 (d, 1 H), 8.1 1 (s, 1 H), 8.88 (s, 1 H); Anal. Cale, for C17H17CINO3S: C, 59.05; H, 3.50; N, 4.05. Found: C, 58.82; H, 3.46; N, 3.86. Example 91 C 25 Acid (E) -3-f4- (4-chlorophenoxy) thienor-2,3-c1pyridin-2-in-2-propenoic acid Example 91 B was processed as in Example 88 to provide the main compound. MS (ESI) m / z 330, 332 (M + H) "; 1 H NMR (300 MHz, DMSO-d 6) d 6.46 (d, 1 H), 7.14 (dt, 2H), 7.46 (dt, 2H), 7.83 (s, 1 H), 7.92 (d, 1 H), 8.15 (s, 1 H), 9.10 (s, 1 H), Anal, Cale, for C17H17CINO3S: C, 59.05; H, 3.50; N, 4.05 Found: C, 58.82; H, 3.46; N, 3.86, Example 92 (E) -3-f4- (4-chlorophenoxy) thienor-2,3-clpyridin-2-yl-2-propenamide A solution of Example 91 C ( 51.5 mg, 0.155 mmol), N-hydroxybenzotriazole monohydrate (34.5 mg, 0.225 mmol), 4-methylmorpholine (47 mg, 0.464 mmol) and NH4CI (31.6 mg, 0.591 mmol) in DMF (1 mL) a 0 ° C was treated with EDC (45.0 mg, 0.235 mmol), stirred at 0 ° C for 4 hours and at room temperature for 10 hours, treated with chloroform (5 mL), rinsed sequentially with 1 M NaHCO3 and brine, dried ( Na2SO), filtered and concentrated The residue was purified by flash chromatography on silica gel with 5% methanol / dichloromethane to provide the main compound, mp 176-178 ° C; MS (ESI) m / z 331, 333 (M + H) +; 1 H NMR (300 MHz, CDCI3) d 5.60 (br s, 2H), 6.46 (d, 1 H), 7.01 (m, 2H), 7.35 (m, 2H), 7.46 (s, 1 H), 7.84 (d, 1 H), 8.1 1 (s, 1 H), 8.88 (s, 1 HOUR); Anal. Cale, for dßHuCINzOzS: C, 58.10; H, 3.35; N, 8.47. Found: C, 57.98; H, 3.24; N, 8.45.

Example 93 4-Bromothieno-2,3-c1pyridine-2-carboxamide Example 93A 3.5-Dibromopyridine-4-carboxaldehyde A solution of diisopropylamine (6.6 mL, 46.43 mmol) in THF (40 mL) at 0 ° C was treated with n-butyllithium in hexanes (2.50 M solution, 18.6 mL, 46.43 mmol) for 15 minutes, stirred at 0 ° C for 30 minutes, diluted with THF (200 mL), cooled to -78 ° C, treated with 3,5-dibromopyridine (10 g, 42.21 mmol) in THF (1 10 mL) for 95 minutes, stirred at -78 ° C for 2 hours, transferred to solution of Saturated, cold NaHCO3, stirred for 15 minutes, and extracted with diethyl ether. The extract was rinsed with brine, dried (MgSO), filtered and concentrated. The residue was purified by flash chromatography on silica gel with 10% acetone / hexane to provide the main compound. MS (DCI / NH3) m / z 266 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 8.91 (s, 2 H), 10.09 (s, 1 H). Example 93B Methyl 4-bromotienof2,3-c1pyridine-2-carboxylate Example 93A was processed as in Example 17C except at 0-25 ° C to provide the main compound. MS (DCI / NH3) m / z 274 (M + H) +; 1 H NMR (500 MHz, DMSO-d 6) d 3.95 (s, 3 H), 7.99 (s, 1 H), 8.67 (s, 1 H), 9.31 (s, 1 H). Example 93C 4-bromothienof2,3-clpyridine-2-carboxamide Example 93B was processed as in Example 44 to provide the main compound. MS (DCI / NH3) m / z 157 (M + H) +; • 5 1 H NMR (400 MHz, DMSO-d6) d 7.97 (br s, 1 H), 8.1 1 (s, 1 H), 8.33 (br s, 1 H), 8.43 (s, 1 H), 9.24 ( s, 1 H). Example 94 4-chlorothienof2,3-c1pyridine-2-carboxamide. 3,5-Dichloropyridine was processed as in Example 93 to provide the main compound. MS (DCI / NH3) m / z 213 (M + H) +; F 1 H NMR (300 MHz, DMSO-dβ) d 7.93 (br s, 1 H, NH), 8.28 (s, 1 H), 8.55 (br s, 1 H, NH), 8.58 (s, 1 H), 9.28 (s, 1 H). Example 95 15 4-f4- (trifluoromethyl) phenylthienof2.3-c1pyridine-2-carboxamide Example 95A methyl 4-f4- (trifluoromethyl) phenynthienof2.3-clpyridine-2-carboxylate A solution of Example 93B (272 mg, mmol), 4- (trifluoromethyl) phenyl boronic acid (209 mg, 1.1 mmol) in cesium fluoride 20 (347 mg, 2.1 mmol) in DME (5 mL) was degassed for 15 minutes, treated with titanium ester ( triphenylphosphine) palladium (0) (35 mg, 0.03 mmol), heated at 80 ° C for 6 hours, stirred at room temperature for 12 hours, filtered through Celite®, and concentrated. The residue was purified by flash chromatography on silica gel with 5% acetone / hexane to provide the compound principal. MS (DCI / NH3) m / z 338 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 3.92 (s, 3 H), 7.94 (m, 4 H), 8.06 (s, 1 H), 8.66 (s, 1 H), 9.47 (s, 1 H). Example 95B 4-f4- (trifluoromethyl) phenynthienof2,3-clpyridine-2-carboxamide Example 95A was processed as in Example 44 to provide the main compound. MS (APCI) m / z 323 (M + H) +, 321 (MH) "and 357 (M + Ci) '; 10 1 H NMR (400 MHz, DMSO-d 6) d 7.81 (br s, 1 H), 7.93 (m, 4H), 8.24 (s, 3H), 8.45 (br s, 1 H), 8.59 (br s, 1 H), 9.37 (br s, 1 H) • Example 96 N-methyl-4- f4- (trifluoromethyl) phenyphenyl-2,3-clpyridine-2-carboxamide Example 95A was processed as in Example 44 but substituting methylamine (2.0 M in methanol) for methanolic ammonium to provide the main compound MS (APCI) m / z 337 (M + H) +, 335 (MH) \ and 371 (M + CI) "; 1 H NMR (400 MHz, DMSO-d 6) d 2.82 (d, 3 H), 7.90 (d, 2 H), 7.94 (d, 2 H), 8.17 (s, 1 H), 8.58 (s, 1 H), 8.93 ( br d, 1 H), 9.36 (s, 1 H); 20 13C NMR (100 MHz, DMSO-dβ) d: 26.1 (CH3), 121.6 (Ar-CH), 123.1, 125.3 (C), 125.7 (CH), 125.8 (CH), 128.3, 128.6, 128.8, 129.1 ( CF3), 129.9 (2xAr-CH), 136.6 (C), 140.6 (C), 142.4 (C), 142.5 (CH), 145.0 (2xCH), 146.6 (C), 161.1 (C). Example 97: 4-phenylthienof2,3-clpyridine-2-carboxamide Example 97A Methyl 4-phenylthienof2,3-c1pyridine-2-carboxylate Example 93B and phenylboronic acid were processed as in Example 95 to provide the designated compound. • 5 MS (DCI / NH3) m / z 338 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 3.92 (s, 3 H), 7.94 (m, 4 H), 8.06 (s, 1 H), 8.66 (s, 1 H), 9.47 (s, 1 H). Example 97B 4-phenylthienof2.3-clpyridine-2-carboxamide Example 97A was processed as in Example 44 to provide the main compound. • MS (DCI / NH3) m / z 255 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 7.52-7.69 (m, 5H), 7.78 (br s, 1 H), 8.23 (s, 1 H), 8.44 (br s, 1 H), 8.52 (s, 1 H), 9.30 (s, 1 H); 15 Anal. Cale, for C 14 H 10 N 2 OS: C, 66.12; H, 3.96; N, 1 1 .02. Found: C, 66.02; H, 3.94; N, 1 1 .00. Example 98 4-ff 1.1 '-biphenip-4-ethylthio) thienor 2,3-clpyridine-2-carboxamide Example 73 and phenylboronic acid were processed and purified as in Example 95 then further purified by HPLC (reverse phase C18 , 0-90% acetonitrile gradient in water containing 0.1% TFA) to provide the main compound. MS (DCI / NH3) m / z 363 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 7.36-7.48 (m, 5 H), 7.63-7.68 (m, 4 H), 25 7.91 (br s, 1 H), 8.30 (s, 1 H), 8.54 (s) , 1 H), 8.57 (br s, 1 H), 9.36 (s, 1 HOUR). Example 99 Methyl 4-f3- (2.3.4.5-Tetrahydrofuranyl) oxptienof2.3-clpyridine-2-carboxamide Example 99A Methyl 4-f3- (2,3,4,5-tetrahydrofuranyl) oxptienof2,3-clpyridine-2-carboxylate A Solution of Example 236E (10 mg, 0.53 mmol) in anhydrous tetrahydrofuran (10 mL) at room temperature under nitrogen atmosphere was added 3-hydroxytetrahydrofuran (0.043 mL)0.53 mmol), triphenylphosphene (138 mg, 0.53 mmol) and diethyl azodicarboxylate (0.083 mL, 0.53 mmol). After 22 hr the reaction mixture was diluted with ethyl acetate (100 mL), filtered and the filtrate was concentrated under reduced pressure. The obtained residue was purified by flash chromatography on silica gel (Biotage Flash 40 S) eluting with 10% acetone-hexane to obtain the main compound in 22% product. 1 H NMR (400 MHz, DMSO-d 6) d 2.05-2.18 (m, 1 H), 2.26-2.49 (m, 1 H), 3.61 -3.77 (m, 2 H), 3.93 (s, 2 H), 4.25-4.31 (m, 2H), 5.32-5.39 (m, 1 H), 8.10 (s, 1 H), 8.26 (s, 1 H), 8.99 (s, 1 H); MS (APCI) m / e 280 (M + H) +. Example 99B Methyl 4-f3- (2,3,4,5-Tetrahydrofuranyl) oxptenic acid 2,3-clpyridine-2-carboxylate The main compound (5.7 mg, 19%) was prepared from the Example 99A (30 mg, 0.108 mmol) as described in the Example 171. The product was isolated by reverse phase HPLC C-18 eluting with a gradient of 20% CH3CN-H2O containing 0.1% trifluoroacetic acid. 1 H NMR (400 MHz, DMSO-d 6) d 2.05-22.13 (m, 1 H), 2.30-2.40 (m, 1 H), 2.81 (d, J = 5 Hz, 3 H), 3.78-3.84 (m, 1 H) ), 3.90-4.01 (m, 3H), 5.32-5.37 (m, 1 H), 8.13 (s, 1 H), 8.21 (s, 1 H), 8.90 (s, 1 H), 8.85 (d, J) = 5Hz, 1 H); 13 C NMR (75 MHz, DMSO-d 6) d 26.2 (CH 3), 32.5 (CH 2), 66.4 (CH 2), 72.3 (CH 2), 78.5 (CH), 1 19.6 (CH), 126.7 (CH), 135.6 (C ), 137.3 (C), 137.8 (CH), 144.3 (C), 148.6 (C), 161.1 (CO); MS (APCI) m / e 279 (M + H) +, 313 (M + CI). EXAMPLE 100 Ethyl 4-ff2- (aminocarbonyl) thienor-2,3-clpyridin-4-inox-benzoate A solution of Example 73 (120 mg, 0.33 mmol), palladium (11) acetate (11 mg, 0.05 mmol), 1,3-bis (diphenylphosphino) propane (20.6 mg, 0.05 mmol), and triethylamine (100 mg, 0.99 mmol) in DMF (6 mg). mL) and ethanol (3 mL) was purged with carbon monoxide, heated at 105 ° C under monoxide (balloon) atmosphere for 12 hours, treated with ether, sequentially rinsed with brine and water, dried (Na 2 SO), filtered and concentrated . The residue was purified by flash chromatography (20% ethyl acetate / hexane) to provide the main compound. MS (DCI / NHs) m / z 358 (M + H) + Example 101 4-ff2- (aminocarbonyl) thienof2.3-cTpyridin-4-ipoxpbenzoic acid A solution of Example 100 (50 mg) in DMF (5 mL) and methanol (10 mL) was treated with a solution of NaOH (200 mg) in water (0.5 mL), stirred for 13 hours, treated sequentially with acid acetic acid (500 mg) and water and filtered. The residue was recrystallized from DMF / water to provide the main compound. MS (DCI / NH3) m / z 315 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 7.1 3 (dt, 1.8 Hz, 2 H), 7.86 (br s, 1 H), 7.98 (dt, 2 H), 8.09 (s, 1 H), 8.31 ( s, 1 H), 8.44 (br s, 1 H), 9.22 (s, 1 H); Anal. Cale, for C15H10N2O4S: C, 57.32; H, 3.21; N, 8.91.

Found: C, 57.32; H, 3.30; N, 8.92. Example 102 4- (1-phenylethenyl) thienof2.3-clpyridine-2-carboxamide, Example 102A Styrene-boronic acid A solution of styrene a-bromine (5.5 g, 30 mmol) in diethyl ether (30 mL) a - 78 ° C was treated with a tert-BuLi solution (1.7 mg solution, 21.2 mL, 36 mmol), stirred at -78 ° C for 0.5 hour, treated with triisopropyl borate (8.31 mmol, 36 mmol) for 48 minutes, stirred for 1 hour, heated to room temperature. environment for 18 hours, diluted with diethyl ether (100 mL), treated with 1 M HCl (100 mL), stirred at room temperature for 5 hours, concentrated to remove THF, adjusted pH 14 with 1 N NaOH, rinsed with hexane, adjusted to pH 1 with 1 M HCl, and extracted with ethyl acetate. The extract was dried (Na2SO), filtered and concentrated to provide the main compound. 1 H NMR (300 MHz, DMSO-dβ) d 5.75 (d, 1 H), 5.83 (d, 1 H), 7.2-7.39 (m, 5H, Ar-CH). Example 102B methyl 4- (1-phenylethenyl) t-inof2,3-clpyridine-2-carboxylate Example 93B and styrene-a-boronic acid were processed as in Example 95 to provide the main compound. • 5 MS (APCI) m / z 296 (M + H) +; 1 H NMR (400 MHz, DMSO-dβ) d 3.84 (s, 3 H), 5.56 (s, 1 H), 5.95 (s, 1 H), 7.31 (m, 2 H), 7.36 (m, 3 H), 7.47 (s, 1 H), 8.5 (s, 1 H), 9.40 (s, 1 H); 13 C NMR (100 MHz, DMSO-dβ) d 53.03 (OCH3), 1 18.37 (vinyl CH2), 126.79 (Ar-CH), 127.60 (Ar-CH), 128.38 (Ar-CH), 128.75 (Ar-CH) , 10 132.55 (Ar-CH), 137.20 (C), 138.10 (C), 139.59 (C), 141.88 (C), 142.97 (3-CH), 144.03 (C), 145.39 (CH), 161. 69 (CO). Example 102C 4- (1-Phenylethenyl-trien-2,3-clpyridine-2-carboxamide Example 102B was processed as in Example 44 to provide the main compound MS (DCI) m / z 281 (M + H) +; 1 H NMR (400 MHz, DMSO-d 6) d 5.53 (S, 1 H), 6.04 (S, 1 H), 7.31 (m, 2 H), 7.35 (m, 3 H), 7.72 (br s, 1 H), 7.82 (s, 1 H), 8.33 (s, 1 H), 8.37 (br s, 1 H), 9.29 (s, 1 H); 20 13 C NMR (100 MHz, DMSO-dβ) d 1 18.0 (CH2), 123.10 (CH), 126.73 (Ar-CH), 128.22 (Ar-CH), 128.60 (Ar-CH), 132.41 (C), 136.59 (C), 139.42 (C), 142.73 (3- CH), 143.41 (C), 144.01 (C), 144.66 (5-CH), 146.0 (C), 162.5 (CO) Example 103 25 4-R (4-methylphenyl) thio1-tienof2.3-c1pyridine-2-methanol A suspension of NaBH (28 mg, 0.743 mmol) in 2: 3 THF / ethanol (2 mL) was stirred at 0 ° C for 10 minutes, treated with CaCl2 (41.2 mg, 0.37 mmol), stirred for 15 minutes, treated with a solution of Example 17C (17 mg, 0.37 mmol) in 2: 3 THF / ethanol (3 • 5 mL), stirred at 0 ° C for 4 hours, treated with 20% aqueous acetic acid (5 mL), and concentrated to remove the lower boiling solvents. The resulting mixture was adjusted to pH 7 with NaHCO3 and extracted with ethyl acetate. The extract was dried (MgSO4), filtered and concentrated. The residue was purified by gel column chromatography of silica eluting with 15% acetone / hexane to provide the main compound. • MS (DCI / NH3) m / z 288 (M + H) +; 1 H NMR (500 MHz, DMSO-de) d 2.25 (s, 3 H), 4.80 (s, 2 H), 5.90 (br, 1 H), 7.14 (d, 2 H), 7.18 (d, 2 H), 7.32 ( s, 1 H), 8.36 (s, 1 H), 9.15 (s, 1 H). Example 103A 4- (4-chlorophenoxy) -N-methylthienof2.3-clpyridine-2-carboxamide A solution of Example 61A (100 mg, 0.3135 mmol) and methylamine (2M solution in THF, 0.467 mL, 0.941 mmol) in THF (2 mL) at 0 ° C was treated with NaH (12 mg, 0.47 mmol), stirred at room temperature for 1 hour, treated with water (0.1 mL), and concentrated. The residue was purified by flash chromatography on silica gel with 20% acetone / hexane to provide the main compound. MS (APCI) m / z 319 (M + H) +; 25 1 H NMR (300 MHz, DMSO-dβ) d 2.80 (d, 3H), 7.13 (d, 2H), 7.45 (d, 2H), 8.06 (s, 1 H), 8.19 (s, 1 H), 8.94 (d, 1 H), 9.16 (s, 1 H). EXAMPLE 104 4- (4-Chlorophenoxy) -N, N-dimethylthienof2.3-c1pyridine-2-carboxamide Example 61A and dimethylamine were processed as in Example 1 03A to provide the main compound. MS (APCI) m / z 333 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 3.03 (br s, 3 H), 3.12 (br s, 3 H), 7.17 (d, 2 H), 7.46 (d, 2 H), 7.62 (s, 1 H), 8.18 (s, 1 H), 9.15 (s, 1 H). Example 105 4- (4-chlorophenoxy) -N, N-diethyltienor-2,3-clpyridine-2-carboxamide Example 61A and dimethylamine were processed as in Example 103A to provide the main compound. MS (APCI) m / z 361 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 1.09 (m, 6 H), 3.42 (m, 4 H), 7.15 (d, 2 H), 7.45 (d, 2 H), 7.49 (s, 1 H), 8.74 (s, 1 H), 9.17 (s, 1 H). Example 106 4- (4-Chlorophenoxy) -N-cyclopropyl thienof2,3-clpyridine-2-carboxamide Example 61A and cyclopropylamine were processed as in Example 103A to provide the main compound. MS (APCI) m / z 345 (M + H) +; 1 H NMR (500 MHz, DMSO-d 6) d 2.85 (m, 1 H), 7.12 (d, 2 H), 7.46 (d, 2 H), 8.1 1 (s, 1 H), 8.13 (s, 1 H), 8.93 (d, 1 H), 9.12 (s, 1 H). Example 107 1-ff4- (4-chlorophenoxy) thienor-2,3-clpyridin-2-ipcarboninpinOlidine Example 61A and pyrrolidine were processed as in Example 103A to provide the main compound. MS (APCI) m / z 359 (M + H) +; 1H NMR (400 MHz, DMSO-d6) d 1.83-1.93 (m, 4H), 3.53 (t, 2H), 3.71 (t, 2H), 7.17 (d, 2H), 7.47 (d, 2H ), 7.70 (s, 1 H), 8.16 (s, 1 H), 9.12 (s, 1 H). Example 108 1-ff4- (4-chlorophenoxy) thienof2,3-c1pyridin-2-incarbonipiperidine Example 61 A and piperidine were processed as in Example 103A to provide the main compound. MS (APCI) m / z 373 (M + H) +; 1 H NMR (400 MHz, DMSO-d 6) d 1.52 (m, 3 H), 1.62 (m, 2 H), 3.53 (m, 5 H), 7.14 (d, 2 H), 7.46 (d, 2 H), 7.47 (s, 1 H), 8.20 (s, 1 H), 9.14 (s, 1 H). Example 109 4-fr4- (4-chlorophenoxy) thienoyl-2,3-c1pyridin-2-incarboninmorpholine Example 61 A and morpholine were processed as in Example 103A to provide the main compound. MS (APCI) m / z 375 (M + H) +; 1 H NMR (500 MHz, DMSO-dβ) d 3.6 (m, 8 H), 7.14 (d, 2 H), 7.45 (d, 2 H), 7.55 (s, 1 H), 8.17 (s, 1 H), 9.14 ( s, 1 H). Example 1 10-fr4- (4-chlorophenoxy) thienof2.3-clpyridin-2-incarbonyl-4-methylpiperazine Example 61A and methylpiperazine were processed as in Example 103A to provide the main compound. MS (APCI) m / z 388 (M + H) +; 1 H NMR (400 MHz, DMSO-d 6) d 2.2 (s, 3 H), 2.32 (br s, 4 H), 8.58 (br s, 4 H), 7.15 (dd, 1 H), 7.47 (dd, 1 H), 7.49 (s, 1 H), 8.2 (d, 1 H), 9.15 (s, 1 H). fc Example 1 1 1 5 1-ff4- (4-chlorophenoxy) t-inof2,3-clpyridin-2-incarbonin-4-phenylpiperazine Example 61A and phenylpiperazine were processed as in Example 103A to provide the main compound. MS (APCI) m / z 450 (M + H) +; 1 H NMR (500 MHz, DMSO-dβ) d 3.18 (br s, 4 H), 3.73 (br s, 4 H), 6.81 10 (t, 1 H), 6.95 (d, 2 H), 7.15 (d, 2 H) , 7.24 (d, 2H), 7.46 (d, 2H), 7.57 (s, f 1 H), 8.20 (s, 1 H), 9.17 (s, 1 H). Example 1 12-rf4- (4-chlorophenoxy) thienof2.3-clpyridin-2-pcarbonin-4- (phmethyl) piperazine Example 61A and benzylpiperazine were processed as in Example 103A to provide the main compound. MS (APCI) m / z 464 (M + H) +; 1 H NMR (500 MHz, DMSO-dβ) d 2.38 (br s, 4 H), 3.51 (s, 2 H), 3.58 (br s, 4 H), 7.13 (d, 2 H), 7.32 (m, 5 H), 7.45 ( d, 2H), 7.47 (s, 1 H), 8.91 (s, f 1 H), 9.13 (s, 1 H). Example 1 13 1-ff4- (4-chlorophenoxy) thienof2.3-c1pyridin-2-incarbonin-4- (2-pyridinyl) piperazine Example 61A and 2-pyridylpiperazine were processed as in Example 103A to provide the main compound. MS (APCI) m / z 451 (M + H) +; 25 1 H NMR (500 MHz, CDCl 3 -d) d 3.65 (br s, 4 H), 3.85 (br s, 4 H), 6.70 (m, 2H), 7.07 (d, 2H), 7.34 (d, 2H), 7.50 (s, 1 H), 7.54 (m, 1 H), 8.15 (s, 1 H), 8.29 (m, 1 H) ), 8.96 (s, 1 H). Example 1 14 if 4- (4-chlorophenoxy) -N- (2-hydroxyethyl) lthienof2,3-clpyridine-2-carboxamide Example 61 A and ethanolamine were processed as in Example 103A to provide the main compound. MS (DCI / NH3) m / z 349 (M + H) +; 1 H NMR (400 MHz, DMSO-d 6) d 3.33 (m, 2 H), 3.51 (m, 2 H), 5.76 (t, 1 H), 7.12 (d, 2 H), 7.26 (d, 2 H), 8.17 (s) , 2H), 8.98 (br.t, 1 H), 9.14 (s, 10 1 H); 13 C NMR (100 MHz, DMSO-d 6) d 42.3 (N-CH 2), 59.4 (O-CH 2), 1 19.2 (CH), 1 19.3 (Ar-CH), 127.6 (C), 130.0 (Ar-CH), 1 33.2 (CH), 137.5 (C), 137.9 (C), 141.4 (CH), 146.4 (C), 147.1 (C), 155.6 (C), 160.6 (CO). Example 1 15-4-fr4- (4-chlorophenoxy) thienor-2,3-clpridide-2-carboncarnin-N- (1-methylethyl) -1- piperazineacetamide. trifluoroacetate (salt) Example 61A and N-isopropylpiperazine acetamide were processed as in Example 103A to provide the compound A main. The residue was purified by reverse phase HPLC C-18 with a gradient of 20% CH3CN / water and 100% CH3CN containing 0. 1% trifluoroacetic acid to provide the main compound. MS (APCI) m / z 473 (M + H) +; 1 H NMR (400 MHz, DMSO-dβ) d 1.09 (m, 6H), 3.05 (br s, 4 H), 3.43 (s, 25 2 H), 3.87 (br s, 4 H), 7.16 (d, 2 H) , 7.67 (d, 2H), 7.68 (s, 1 H), 8.20 (s, 1 H), 9.18 (s, 1 H). Example 1 4- (4-chlorophenoxy) -N- [1- (hydroxymethyl) etyptienof2,3-c1pyridine-2-carboxamide i Example 61A and DL-2-amino-1-propanol were processed as in Example 103A to provide the main compound. MS (APCI) m / z 363 (M + H) +, 361 (MH) \ 397 (M + CI) "; 1 H NMR (400 MHz, DMSO-dβ) d 1.14 (d, 3H), 3.36- 3.40 (m, 1 H), 3.43- 3.5 (m, 1 H), 3.97-4.04 (m, 1 H), 4.77 (t, 1 H), 7.15 (d, 2H), 7.48 (d, 2H), 8.14 (s, 1 H), 8.26 (s, 1 H), 8.67 (d, 1 H), 9.14 (s, 1 H); 10 13 C NMR (100 MHz, DMSO-d6) d 16.87 (CH3), 47.74 (CH), 64.06 f (CH2OH), 1 19.16 (3-CH), 1 19.46 (2xAr-CH), 127.72 (C), 130.08 (2xAr-CH), 132.84 (5-CH), 137.51 (C), 1 37.91 (C), 141.20 (7-CH), 146.62 (C), 147.28 (C), 155.53 (C), 160.01 (CO) Example 1 17 15 4- (4-chlorophenoxy) -Np .1 -bis (hydroxymethyl) ethyl 1-tienof 2,3-clpyridine-2-carboxamide Example 61 A and 2-amino-2-methyl-1,3-propanediol were processed as in Example 103A to provide the major compound: • MS (APCI) m / z 393 (M + H) +; 391 (MH) "; 393 (M + CI) "; 20 1 H NMR (400 MHz, DMSO-dβ) d 1.28 (s, 3H), 3.56-3.66 (m, 4H), 4.71 (t, 2H), 7.16 (d, 2H), 7.48 (d, 2H), 7.92 (s, 1 H), 8.1 1 (s, 1 H), 8.31 (s, 1 H), 9.12 (s, 1 H); 13C NMR (100 MHz, DMSO -d6) d 18.45 (CH3), 59.80 (C), 63.08 (CH2), 1 19.46 (CH), 1 19.74 (2xAr-CH), 127. 83 (C), 130.09 (2xAr-CH), 132.53 (CH), 137.43 (C), 1 37.84 (C), 140.99 (CH), 147.38 (C), 147.50 (C), 2o1 - 1 55.40 (C), 160.59 (C). Example 1 18 (D, L) -4- (4-chlorophenoxy) -N- (2-hydroxypropyl) thienof2,3-clpyridine-2-carboxamide Example 61 A and DL-1-amino-2-propanol were processed as in Example 103A to provide the main compound. MS (APCI) m / z 363 (M + H) + and 397 (M + CI) "; 1 H NMR (400 MHz, DMSO-dβ) d 1.08 (d, 3H), 3.21 (m, 2H), 3.75-3.84 (m, 1 H), 4.8 (br s, 1 H), 7.14 (d, 2 H), 7.48 (d, 2 H), 8.17 (s, 1 H), 8.22 (s, 1 H), 8.98 (br s, 1 H), 9.15 (s, 1 H), 13 C NMR (100 MHz, DMSO-dβ) d 21.13 (CH3), 47.24 (CH2), 64.84 (CH), 1 19.30 (2xAr-CH) ), 1 19.42 (2xAr-CH), 127.66 (C), 130.04 (2xAr-CH), 133.05 (CH), 137.48 (C), 137.92 (C), 141.30 (CH), 146.37 (C), 147.16 (C), 155.58 (C), 160.59 (C) Example 1 19 4- (4-Chlorophenoxy) -N-r 2 - (4-morpholinyl) ethynthienof 2,3-clpyridine-2-carboxamide Example 61A and 4- (2-aminoethyl) morpholine were processed as in Example 103A to provide the major compound: MS (APCI) m / z 418 (M + H) +, 452 (M + CI) '; 1 H NMR (400 MHz, DMSO -dß) d 2.41 (t, 4H), 2.48 (m, 2H), 3.40 (m, 2H), 3.56 (t, 4H), 7.15 (d, 2H), 7.47 (d, 2H), 8.13 (s, 1 H), 8.17 (s, 1 H), 8.94 (t, 1 H), 9.04 (s, 1 H), 13 C NMR (100 MHz, DMSO-d 6) d 36.73 (N-CH 2), 53.21 (ring morpholine 2xN-CH2), 57.07 (N-CH2), 66.12 (ring of morpholine 2x-OCH2), 1 19.14 (3-CH), 1 19.50 (2xAr-CH), 127.73 (C), 130.06 (2xAr-CH), 132.96 (pyridyl ring CH), 137.35 (C), 137.91 ( C), 141 .29 (pyridyl (CH) ring, 146.20 (C), 147.20 (C), 155.40 (C), 160.45 (CO) Example 120 4- (4-chlorophenoxy) thienof2.3-clpyridine-2-sulfonamide To a solution of the Example 124A (261 mg, 1 mmol) in Anhydrous THF (5 mL) at -78 ° C was added tert-BuLi (1.7 M solution in hexanes, 0.647 mL, 1.1 mmol) under nitrogen atmosphere. The reaction mixture was stirred at -78 ° C for 15 minutes and SO2 gas was bubbled into the solution for 15 minutes. Then it was stirred at -72 ° C for 2.5 hours, and at 0 ° C for 4 hours. The reaction mixture was diluted with hexane (10 mL) and evaporated, and the residue obtained was suspended in CH2Cl2 (5 mL) and treated with N-chlorosuccinimide (214 mg, 1.6 mmol) at 0 ° C. After 2 hours at room temperature the reaction mixture was diluted with CH2Cl2, rinsed with 10% aqueous NaHSO3 solution (3x25 mL) followed by brine (3x25 mL). The dried organic layer (MgSO) was evaporated to dry under reduced pressure to obtain the crude sulfonyl chloride as an oil. This was dissolved in acetone (5 mL) and treated with cold NH OH solution (5 mL) at 0 ° C. After 2 hr at 0 ° C, the reaction mixture was evaporated from toluene to obtain the crude product as an oil. The main compound (57 g, 16%) was obtained by flash chromatography on silica gel eluting with 20% acetone-hexane followed by 40% acetone-hexane, 1 H NMR (400 MHz, DMSO-dβ) d 7.21 (d , J = 9Hz, 2H), 7.51 (d, J = 9Hz, 2H), 7.79 (s, 1 H), 8.14 (br.s, 2H), 8.30 (s, 1 H), 9.27 (s, 1 H); 3C NMR (100 MHz, DMSO-d6) d 1 19.65 (CH), 120.88 (CH), 127.94 (C), 130.12 (CH), 133.67 (CH), 135.61 (C), 141.65 (CH), 152.1 1 (C), 155.41 (C); MS (APCI) m / z 341 (M + H) +, 339 (M-H) '; 375 (M + CI) \ Example 121 4-f (4-methylphenyl) methyntienor 2,3-clpyridine-2-carboxamide Example 121 A Methyl 4-f (4-methylphenyl) methynthienof 2,3-clpyridine-2-carboxylate Example 121A processed as in J. Org. Chem, 1988, 53, pp. 2392-2394. For example, a suspension of Zn powder (92 mg, 1.4 mM) in THF (2 ml) containing 1.1-dibromoethane (0.05 ml, 0.054 mmol) is heated at 65 ° C for 12 minutes, cooled to 25 ° C , treated with trimethylsilyl chloride (0.009 ml, 0.043 mM), stirred at room temperature for 25 minutes, cooled to 0 ° C, treated slowly with a solution of 4-methylbenzyl bromide (0.248 mL, 1.0 mmol) in THF (5%). mL), warmed to 40 ° C for 3 hours, cooled to -10 ° C, treated with CuCN (106 mg, 1.18 mM) and LiCI (100 mg, 2.35 mM) in THF (10 mL), stirred at 0 °. C for 30 minutes, slowly treated with a solution of Example 93B (272 mg, 1 mmol) in THF (5 mL), stirred at 0 ° C for 3 hours, heated at 25 ° C for 18 hours, treated with ethyl acetate , rinsed sequentially with saturated NH4CI and brine, dried (MgSO), filtered and concentrated. The residue was purified by flash chromatography on silica gel to provide the main compound.

Example 121 B 4-f (4-methylphenyl) methyntienor 2,3-c1pyridine-2-carboxamide Example 121A is processed as in Example 44 to provide the main compound. Example 122 Methyl 4- (4-morpholino) thienor 2,3-c1pyridine-2-carboxamide Example 122 (241 mg, 72%) was prepared as described in Example 308, substituting 1,4-dioxo-8-azapiro [4 , 5] decane (0.256 mL, 2 mmol) per 4-methylaniine. 1 H NMR (400 MHz, DMSO-dβ) d 1.91 (m, 4 H), 2.85 (d, J = 4 Hz, 3 H), 3.25 (m, 4 H), 3.96 (s, 4 H), 8.10 (s, 1 H), 8.12 (s, 1 H), 8.87 (s, 1 H), 8.96 (d, J = 4 Hz, 1 H); 13 C NMR (100 MHz, DMSO-dβ) d 26.1 (CH3), 35.0 (CH2), 49.7 (CH2), 63.8 (CH2), 69.8 (CH2), 106.1 (C), 121.3 (CH), 132.0 ( CH), 136.9 (C), 138.3 (C), 138.7 (CH), 143.6 (C), 143.8 (C), 161.3 (C); MS (APCI) m / z 334 (M + H) +, 368 (M + CI), - Example 123: 4- (4-chlorophenoxy) thienof2,3-clpyridine-2-carboxamide. N-oxide Example 123A methyl (4-c! Orophenoxy) thienof2,3-clpyridine-2-cartyl) xyl, N-oxide A solution of methyl 4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxylate (319 mg, 1 mmol) in dichloromethane (15 mL) at 0 ° C was treated with 3-chloroperoxybenzoic acid (302 mg, 1.75 mmol), stirred 0.5 hours at 0 ° C and 4 hours at room temperature , rinsed sequentially with water, saturated sodium bicarbonate, water and brine, dried (Na2SO), filtered and concentrated to provide the main compound. MS (DCI / NH3) m / z 336 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 3.89 (s, 3 H), 7.30 (m, 2 H), 7.52 (m, 2 H), 7.84 (s, 1 H), 7.88 (s, 1 H), 9.02 ( s, 1 H). Example 123B 4- (4-chlorophenoxy) thienoi 2,3-cjpyridine-2-carboxamide. N-oxide Example 123A was processed as in Example 44 to provide the main compound. H NMR (300 MHz, DMSO-d6) d 7.30 (m, 2H), 7.52 (m, 2H), 7.74 (d, 1 H), 7.81 (br s, 1 H), 8.10 (s, 1 H), 8.34 (br s, 1 H), 8.93 (s, 1 H). Example 124 4- (4-chlorophenoxy) -2- (2-methoxyphenyl) thienof2,3-clpyridine Example 124A 4- (4-Chlorophenoxy) thienof2.3-clpyridine Example 88 (4.5 g, 14.75 mmol) was added to a solution of diphenyl ether (55 ml) at 210 ° C and kept at this temperature for 10 hours. The cooled reaction mixture was purified directly by flash chromatography on silica gel eluting with hexane followed by 10% acetone-hexane to obtain the main compound (3.83 g, 99.5%). mp 87-89 ° C; MS (DCI / NH3) m / e 262 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 7.09 (d, J = 9 Hz, 2 H), 7.35 (d, J = 6 Hz, 1 H), 7.45 (d, J = 9 Hz, 2 H), 8.13 (d, J = 9Hz, 1 h), 8.18 (s, 1 H), 9.15 (s, 1 HOUR); Anal. cale, for C13H8Cl? N, O? S? : C, 59.66; H, 3.08; N, 5.35.

Found: C, 59.52; H, 3.08; N, 5.15. EXAMPLE124B 4- (4-Corophenoxy) thieno.2.3-clpyridine-2-boronic acid A solution of sec-butyllithium (0.92 mmol) in THF (2 mL) at -78 ° C was treated dropwise with Example 124 in THF (1 mL), stirred at -78 ° C for 30 minutes, treated dropwise with tributylborate, stirred for 5 minutes at -78 ° C, stirred at room temperature for 45 minutes, treated with 2 M NaOH (3 mL), stirred for 5 minutes, rinsed with hexanes, and acidified to pH 2 with 6M HCl. The precipitate that formed was collected and dried under vacuum to provide the main compound. MS (APCI) m / z 262, 264 (M + HB (OH) 2) +, 340, and 342 (M + CI-) "; 1 H NMR (300 MHz, CD3OD) d 7.29 (d, 2H), 7.53 (d, 2H), 8.08 (s, 1 H), 8.1 1 (s, 1 H), 9.40 (s, 1 H) Example 124C 4- (4-chlorophenoxy) -2- (methoxyphenyl) t-inof2. 3-Chiridin Example 124B was processed as in Example 95 but substituting 2-iodoanisole for Example 93B and Example 124B for 4- (trifluoromethyl) phenylboronic acid to provide the main compound Example 125 4- (4-Chlorophenoxy) -3 -methylthienyl 2,3-clpyridine-2-carboxamide Example 125A Methyl 4- (4-chlorophenoxy) -3-methylthienor-2,3-clpyridine-2-carboxylate 4-Chlorophenol was dissolved in THF (20 mL) and treated with 1 M potassium t-butoxide (13 mL, 13 mmol) and stirred at room temperature for 1 hour. To this solution was added Example 17A (1.76 g, 10 mmol) in THF (5 mL). The reaction was heated at 70 ° C for 4 hours, and cooled to room temperature. It was poured into water diluted with brine and extracted with ethyl acetate. The ethyl acetate was then rinsed (3x20 mL), dried and evaporated. The residue was dissolved in THF (20 mL) and cooled in a cold bath, to which 3 M of methyl magnesium bromide in ethyl ether (4 mL, 12 mmol) was added. The reaction was stirred at room temperature overnight. The excess Grignard reagent was decomposed with a saturated ammonium chloride solution (25 mL) and then extracted with ethyl acetate (3x25 mL). The ethyl acetate was rinsed with brine (3x25 mL), dried and evaporated to give the desired phenoxy alcohol. This alcohol is then subjected to a Swern oxidation, using the following conditions. To a solution of oxalyl chloride (1.1 mL, 12 mmol) in anhydrous methylene chloride (20 mL) cooled to -78 ° C dimethylsulfoxide (1.85 mL, 24 mmol) was added over 30 minutes. Then a solution of the above phenoxy alcohol in methylene chloride (20 mL) was added for 15 minutes. Triethylamine (7.5 mL) was added and the reaction allowed to enter room temperature for 2 hours. The cold water was then added and the mixture was extracted with ethyl acetate. The ethyl acetate was rinsed with brine (3x20 mL), dried and evaporated. To a solution at 0 ° C of this residue in THF (20 mL) was added methyl thioglycolate (0.88 mL, 10 mmol) and cesium carbonate (3.2 g, 10 mmol). The reaction was then heated at 70 ° C for 1 hour, cooled, poured into water, diluted with brine and extracted with ethyl acetate. The ethyl acetate was then rinsed with 1 N NaOH (2X20 mL), brine (3x20 mL), dried and evaporated to give an oil. This oil was triturated with methanol to give the desired compound. mp 140-141 ° C MS (DCI / NH 3) m / e 334 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.80 (s, 3 H), 3.90 (s, 3 H), 7.22 (d, 2H), 7.45 (d, 2H), 8.12 (s, 1 H), 9.15 (s, 1 H); Anal. cale, for C1 ßH12CIN? 3S-0.5H2O: C, 56.06; H, 3.82; N, 4.09.

Found: C, 56.03; H, 3.43; N, 3.71. Example 125B 4- (4-Chlorophenoxy) -3-methylthienof2.3-clpyridine-2-carboxylic acid A solution of Example 125A (1.1 g, 3.3 mmol) and LiOH H 2 O (0.30 g, 6.9 mmol) in THF (20 mL) and H 2 O (10 mL) was heated at 50 ° C for 1 hour, then cooled, acidified with formic acid, and extracted with ethyl acetate. The ethyl acetate extract was rinsed with brine (3x15 mL), then dried and evaporated to give the desired product as a white solid. mp 315-317 ° C; MS (DCI / NH3) m / e 320 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 2.76 (s, 3 H), 3.30 (m, 1 H), 7.10 (d, 2 H), 7.45 (d, 2 H), 8.12 (s, 1 H), 9.15 ( s, 1 H).

Example 125C 4- (4-Chlorophenoxy) -3-methylthioenof2.3-clpyridine-2-carboxamide Example 125B was processed as in Example 92 to provide the main compound. mp 174-175 ° C; MS (DCI / NH3) m / e 319 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.55 (s, 3 H), 7.05 (d, 2 H), 7.45 (d, 2 H), 7.90 (m, 1 H), 7.95 (m, 1 H), 8.15 (s, 1 H), 9.12 (s, 1 H); Anal. cale, for dsHnCINzOzS: C, 56.52; H, 3.48; N, 8.79. Found: C, 56.36; H, 3.50; N, 8.69. Example 126 4- (4-Chlorophenoxy) -3-hydroxytofen-2,3-clpyridine-2-carboxamide Example 126 A Ethyl 3,5-dichloropyridine-4-carboxylate To a stirred solution of lithium diisopropylamide (45 mL, 1. 5 M in THF, 67.6 mmol) in 150 mL of THF at -78 ° C was treated with 3,5-dichloropyridine (10 g, 67.6 mmol) in 40 mL THF for 1.5 hours, stirred for 1 hour at - 78 ° C, treated with ethyl chloroformate (9.5 mL, 100 mmol), stirred for 2 hours, transferred into saturated sodium bicarobate (200 mL) at 0 ° C, treated with diethyl ether (200 mL) and extracted with ethyl ether (2x100 mL). The extract was rinsed sequentially with saturated sodium bicarbonate solution (2x100 mL), brine (2x100 mL), dried (MgSO4) and concentrated. The residue was purified by flash chromatography on silica gel with hexane / ethyl acetate to provide the compound principal. Example 126B Rnetyl 4- (4-chlorophenoxy) -3-hydroxythienof2.3-clpyridine-2-carboxylate Example 126A is treated as in Example 61A to provide the main compound. Example 126C 4- (4-chlorophenoxy) -3-hydroxythienof2.3-c1pyridine-2-carboxamide Example 126B is treated as in Example 61 B to provide the main compound. Example 127 4- (4-chlorophenoxy) -3- (1-methylethoxy) thienof2.3-clpyridine-2-carboxamide Example 127 is processed as in J. Medicinal. Chem. 1992, 35, p. 958. Example 126C (0.10 g, 0.3 mmol) in 50 ml of THF and cesium carbonate (1.0 g, 0.1 mmol) was treated with 2-bromopropane (0.37 g, 0.3 mmol), heated for 2 hours, poured into ice, Extract with ethyl ether, rinse sequentially with 1 N aqueous sodium hydroxide and brine and concentrate. The residue was purified by flash chromatography on silica gel with hexane-acetone (7: 3) to provide the main compound. Example 128 3-Bromo-4- (4-chlorophenoxy) thienof2.3-clpyridine The method described in (Arkiv For Kemi (1970-74), 32, 9. 249) can be adapted. Example 124A in thionyl chloride is treated with bromine at 90 ° C for 4 hours to provide the main compound.

Example 129 4- (4-chlorophenoxythienyl) 2,3-clpyridine-3-carboxylic acid The method described in (Arkiv For Kemi (1970-74), 32, 9. 249) can be adapted Example 128 cooled to -78 ° C treated with ethillithium followed by reaction with carbon dioxide to provide the main compound Example 130 4- (4-chlorophenoxy) thienof2, 3-Clpyridine-3-carboxamide Example 129 can be treated as in Example 19 to provide the main compound. Example 131 3-amino-4- (4-chlorophenoxy) thienor-2,3-c1pyridine-2-carboxamide Example 131 A 3,5-Dichloropyridine-4-carbonitrile Example 17A (2.0 g, 1 1.4 mmol) in acid Formic (10 mL) was treated with hydroxylamine hydrochloride (1.04 g, 11.4 mmol) and concentrated sulfuric acid (0.05 mL), stirred at reflux for 18 hours and concentrated. The residue was partitioned between 1: 1 ethyl acetate.water, and rinsed sequentially with saturated sodium bicarbonate, water, brine, dried (Na 2 SO 4) and concentrated. The residue was recrystallized from hexanes to provide the main compound, mp 1 17-1 18 ° C; 1 H NMR (300 MHz, CDCl 3) d 8.70 (s); IR (KBr, v crn-1) 1710, 1525, 1400, 1250, 1190, 1100, 920, 820, 800, 750.

Example 131 B Methyl 3-amino-4- (4-chlorophenoxy) thienof2.3-clpyridine-2-carboxylate A solution of 4-chlorophenol (1.12 g, 8.72 mmol) in THF (20 mL) at 0 ° C was added. treated with a solution of potassium t-butoxide (8.72 mL, 8.72 mmol, 1 M in THF), stirred at 0 ° C for 1 hour, treated with Example 131A (1.5 g, 8.72 mmol) in THF (10 mL). mL) at 0 ° C, warmed to room temperature, stirred overnight, concentrated, partitioned between 1: 1 ethyl acetate-water, and extracted. The extract was rinsed with brine, dried (NaSO4) and concentrated. A solution of concentrate in DMF (50 mL) at 0 ° C was treated with potassium carbonate (2.42 g, 17.51 mmol) and methyl thioglycolate (778 μL, 8.72 mmol), warmed to room temperature, stirred overnight and poured in ether (400 mL). The organic layer was rinsed with brine, dried (Na2O4) and concentrated. The residue was purified by flash chromatography on silica gel with 0-5% acetone-hexane to provide the main compound, mp 194-196 ° C; MS (APCI) m / e 335 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 3.81 (s, 3 H), 6.86 (br s, 2 H), 7.22-7.32 (m, 2 H), 7.45-7.56 (m, 2 H), 7.88 (s, 1 H ), 8.89 (s, 1 H); Anal. cale, for C15HnCIN2? 3S: C, 53.81; H, 3.31; N, 8.36. Found: C, 53.80; H, 3.27; N, 8.27. Example 131 C 3-Amino-4- (4-chlorophenoxy) t-inof2.3-clpyridine-2-carboxylic acid The main compound was prepared from Example 131 B using the procedure of Example 1 8. mp 173-176 ° C (dec); 1 H NMR (300 MHz, DMSO-dβ) d 7.29 (m, 2H), 7.52 (m, 2H), 7.88 (s, 1 H), 8.89 (s, 1 H). • 5 MS (ESI) m / e 321 (M + H) +; Anal. cale, for C14H9CIN2O3S 0.25H2O: C, 51.70; H, 2.94; N, 8.61. Found ?? Example 131 D 3-amino-4- (4-chlorophenoxy) thienof2.3-clpyridine-2-carboxamide A solution of Example 131 C (96 mg, 0.3 mmol) in DMF (2 mL) was treated with 1-hydroxybenzyltriazole hydrate (67 mg, 0.44). • mmol), NH4CI (61 mg, 1.14 mmol) and 4-methylmorpholine (100 μL, 0.9 mmol), cooled to 0 ° C, treated with 1 - [3- (dimethylamino) propyl] -3-ethylcarbodiimide hydrochloride (86 mg, 0.45 mmol), warmed to room temperature, stirred overnight, poured into saturated NaHCO3, collected, rinsed with water and dried. The residue was recrystallized from methanol / toluene / hexanes to provide the main compound. mp 202-204 ° C; MS 20 (APCI) m / e 320 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 6.84 (br s, 2H), 7.21 -7.30 (m, 2H), 7. 39 (br s, 2H), 7.47-7.56 (m, 2H), 7.88 (s, 1 H), 8.90 (s, 1 H); Anal. Cale, for C 14 H 10 CIN 3 O 2 S: C, 52.58; H, 3.15; N, 1 3.14. Found: C, 52.63; H, 3.18; N, 13.12. 25 Example 132A ethyl 4-chlorothien? i2,3-bipyridine-5-carboxylate Example 1 32A was processed as in J. Heterocyclic Chem. 1977, 14, pp 807-812 to provide the major compound, mp 71-72 ° C; • 5 MS (DCI / NH3) m / z 259 (M + H) +; 242 (M + NH4) +; 1 H NMR (300 MHz, DMSO-dβ) d 1.37 (t, 3 H), 4.41 (q, 2 H), 7.64 (d, 1 H), 8.17 (d, 1 H), 8.95 (s, 1 H); Anal. cale, for C10H8CINO2S: C, 49.69; H, 3.33; N, 5.79; S, 13.26. Found: C, 49.46; H, 3.13; N, 5.62; S, 13.42. Example 132B Ethyl 4-r (4-methylphenyl) thio1-tienor-2,3-bipyridine-5-carboxylate • Example 132A and thiocresol were processed as in Example 2 to provide the main compound, mp 60-63 ° C; MS (DCI / NH3) m / z 347 (M + NH4) + and 330 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 1.30 (t, 3 H), 2.28 (s, 3 H), 4.26 (q, 2 H), 7.00 (d, 1 H), 7.17 (m, 2 H), 7.24 (m , 2H), 7.91 (d, 1 H), 8.81 (s, 1 H); Anal. Cale, for C17H? 5NO2S2: C, 61.98; H, 4.59; N, 4.25. Found: C, 61.92; H, 4.53; N, 4.21. Example 132C 4-r.4-methylphenyl) thiolien2,3-blpyridine Example 132B was processed as in Example 18 and 42 to provide the main compound, mp 90-92 ° C; MS (DCI / NH3) m / z 275 (M + NH4) + and 258 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 2.39 (s, 3 H), 6.66 (d, 1 H), 7.38 (m, 2 H), 7.46 (d, 1 H), 7.53 (m, 2 H), 7.46 (m, d, 1 H), 7.53 (m, 2H), 7.95 (d, 1 H), 8.12 (d, 1 H); Anal. Cale, for C14Hn NS2: C, 65.33; H, 4.30; N, 5.44. Found: C, 65.40; H, 4.26; N, 5.26. Example 132D 4-f (4-methylphenyl) thiolthienof2, 3-blpyridine-2-carboxamide Diisopropylamine (0.056 g, 0.56 mmol) in THF (10 mL) at -78 ° C was treated with n-butyllithium (0.22 mL, 0.56 mmol, 2.5 M in hexanes), stirred for 15 minutes , treated with Example 132C (0.13 g, 0.51 mmol) in THF (5 mL), stirred for 0.5 hour, warmed at 0 ° C for 1 minute, cooled again to -78 ° C, poured into solid CO2, stirred during 0.5 hours, diluted with saturated NH4Cl and extracted with ethyl acetate. The extract was rinsed with brine, dried (MgSO4) and concentrated to provide the main compound, mp 280-282 ° C.; MS (DCI / NHg) m / z 318 (M + NH 4) + and 301 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 2.41 (s, 3 H), 6.62 (d, 1 H), 7.40 (m, 2 H), 7.57 (m, 2 H), 7.77 (br s, 1 H), 8.26 (s, 1 H), 8.36 (d, 1 H), 8.43 (br s, 1 H); Anal. cale, for C15H12N2OS2: C, 59.97; H, 4.02; N, 9.32. Found: C, 59.83; H, 4.03; N, 9.1 1. Example 133 4-Eloro-N- (4-chlorophenyl) thienof2.3-blpyridine-5-carboxamide Example 132A was processed as in examples 18 and 19 but replacing 4-chloroaniline with concentrated NH4OH in Example 19 to provide the main compound, mp 199-202 ° C; MS (DCI / NH 3) m / z 340 (M + NH 4) +, 342 (M + NH 4) +, 323 (M + H) +, 325 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 7.6 (m, 2 H), 7.62 (d, 2 H), 7.77 (m, 2 H), 8.19 (d, 1 H), 8.79 (s, 1 H); Anal. cale, for C 14 H 8 Cl 2 N 2 OS 2: C, 52.03; H, 2.49; N, 8.67. Found: C, 52.02; H, 2.15; N, 8.50. Example 134 Ethyl 4-f (5-methyl-1,3,4-thiadiazol-2-yl) thio1-tienof2.3-blpyridine-5-carboxylate Example 132A and 5-methyI-1, 3,4-thiadiazole-2-thiol were processed as in Example 17B to provide the main compound. mp 93-94 ° C; MS (DCI / NH3) m / z 355 (M + NH4) + and 238 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 1.32 (t, 3 H), 2.66 (s, 3 H), 4.36 (q, 2 H), 7.34 (d, 1 H), 8.13 (d, 1 H), 9.00 (s, 1 H); Anal. cale, for C, 46.27; H, 3.28; N, 12.45; S, 28.50. Found: C, 46.04; H, 3.20; N, 12.32; S, 28.39. Example 135 7-f (4-methylphenyl) thiolthienof3.2-blpyridine-2-carboxamide Ethyl 7-chlorothieno [3,2-b] pyridine-6-carboxylate was processed as in Example 17B, 18 and 19 to provide the compound principal.

MS (DCI / NHs) m / z 301 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 2.38 (s, 3 H), 6.83 (d, 1 H), 7.37 (br, 1 H), 7.56 (m, 2 H), 7.56 (m, 2 H), 8.25 (s, 1 H), 8.41 (br s, 1 H), 8.53 (d, 1 H); Anal. cale, for C ^ H ^ NzOSs: C, 59.98; H, 4.03; N, 9.33. Found: C, 59.79; H, 4.01; N, 9.16. Example 136 methyl 6-f (4-methylphenyl) thio1-tienor-2,3-blpyridine-2-ca? T) oxylate Example 136A 2.6.Dichloro-3-pyridinecarbonitrile Example 136B methyl 3-amino-6-chlorothienor2.3-blpyridine-2- carboxylate Example 136A and methyl thioglycolate were processed as in Example 1 D to provide the desigand compound. Example 136C Methyl 6-f (4-methyphenyl) thio1-tienof2.3-bipyridine-2-carboxylate Example 136B (32 g, 1.34 mmol) in 75% H2SO4 (7.4 mL) at 0 ° C was treated dropwise with aqueous NaNO2 (0.24 g / 1 .5 mL, 3.5 mmol), stirred for 30 minutes, poured into 50% cold H PO3 (1 1 .8 mL), stirred for 30 minutes, stored at 0 ° C for 60 hours, warmed to room temperature, treated with NaHCO3 and extracted with ether.

The extract was dried (MgSO4), filtered and concentrated. The residue was dissolved in methanol (7 mL), heated to 50 ° C, treated sequentially with NaOCH3 (0.08 g, 1.45 mmol) and p-thiocresol (0.18 g, 1.45 mmol), stirred at room temperature for 18 hours, and concentrated. The residue is treated with 10% citric acid and extracted with dichloromethane. The extract was dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography on silica gel with 25% ethyl acetate / hexanes to provide the main compound. mp 127-130 ° C; MS (DCI / NH3) m / z 316 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.39 (s, 3 H), 3.89 (s, 3 H), 7.02 (d, 7.36 (m, 2 H), 7.57 (m, 2 H), 8.13 (s, 1 H) 8.23 (d, 1 H) Anal Cale, for C1ßH13NO2S2: C, 60.93; H, 4.15; N, 4.44 Found: C, 60.79; H, 4.18; N, 4.35 Example 137 6-f (4- methylphenyl) thioethenium (2,3-blpyridine-2-carboxamide) The main compound can be prepared from Example 136C using the procedure of Example 44. EXAMPLE 138 2-bromo-4-f (4-methylphenyltinthio-3,2-clpyridine Para-thiocresol (500 mg, 4 mmol) in DMF (10 mL) was treated with potassium t-butoxide (451 mg, 4 mmol) at room temperature, after 15 minutes it was cooled to 0 ° C, treated with 2-bromo-4-chlorothieno [3,2-c] pyridine (prepared in 6 stages according to the method of F. Eloy and A. Deryckere (Bull, Soc. Chim, Belg, 1970, 79, 301) (1.0 g, 4.0 mmol), stirred at 0 ° C for 2 hours and at room temperature for 12 hours, poured into water and extracted with diethyl ether.The extract was rinsed with water, dried (Na 2 SO 4) and concentrated in vacuo. The residue was purified by flash chromatography on silica gel with 1: 20 ethyl acetate-hexane to provide the main compound. MS (DCI / NH3) m / z 336, 338 (M + H) +; 1 H NMR (300 MHz, CDCl 3) d 2.36 (s, 3 H), 7.18 (d, 2 H), 7.40 (d, 2 H), • 5 7.48 (br s, 1 H), 7.52 (br d, 1 H), 8.16 (d, 1 H). Example 139 4-R (4-methylphenyl) thiolthienof3.2-c1pyridine-2-carboxamide Example 139A 4-chlorothienof3,2-clpyridine-2-carbonitrile 10 A solution of 4-oxo-4,5-dihydrothieno [3,2- c] pyridiha-2-nitrile (500 mg, 2.84 mmol) prepared as in F. Eloy and A. Deryckere • Bull. Soc. Chim. Belg. 1970, 79, 301) and phosphoryl chloride (5 mL) was heated to reflux for 1 hour. The red solution formed was poured into ice and extracted with methylene chloride (2 x 150 mL). The dichloromethane solution was dried over anhydrous NaSO 4, filtered and concentrated. The residue was purified by flash chromatography with 1: 10 EtOAc / hexanes to provide the main compound. MS (DCI / NHs) m / z 195 (M + H) +; 1 H NMR (300 MHz, CDCl 3) d 7.74 (d, 1 H), 8.10 (s, 1 H), 8.41 (d, 1 H). Example 139B 4-f (4-methylphenyl) thiolthiene (3,2-clpyridine-2-carbonitrile Para-thiocresol (192 mg, 1.54 mmol) in DMF (5 mL) at room temperature was treated with potassium tert-butoxide ( 173 mg, 1. 54 mmoi), stirred for 15 minutes, cooled to 0 ° C, treated with the Example 139A (200 mg, 1.03 mmol), stirred first at 0 ° C and then at room temperature for 48 hours, treated with water, and extracted with dichloromethane. The extract was dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography on silica gel with 1: 7 ethyl acetate-hexane to provide the main compound.

^ -P 5 IR (KBr, cm "1) 2200 (w, CN), 1550 (s), 1520 (s) crn" 1; MS (DCI / NH3) m / z 283 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.40 (s, 3 H), 7.25 (d, 2 H), 7.47 (d, 2H), 7.49 (d, 1 H), 8.07 (s, 1 H), 8.33 (d, 1 H); Anal. cale, for C15H10N2S2: C, 63.80; H, 3.57; N, 9.92. Found: 10 C, 63.80; H, 3.52; N, 9.98. Example 139C 4-r (4-methylphenyl) thiolthien.3.2-clpyridine-2-ca? T)? Xarnida 'Example 139B (198 mg, 0.7 mmol) in polyphosphoric acid (5 mL) was heated at 1 10 ° C for 3 hours, cooled, treated with water, and extracted with dichloromethane. The extract was dried (MgSO4), filtered and concentrated. The residue was purified to provide the main compound. IR (KBr) 3300 (m), 3130 (s), 1660 (s), 1600 (s); MS (DCI / NH3) m / z 301 (M + H) +; 20 1 H NMR (300 MHz, DMSO-dβ) d 2.36 (s, 3 H), 7.28 (d, 2 H), 7.47 (d, 2H), 7.78 (br s, 2H), 7.84 (d, 1H), 8.19 (d, 1H), 8.34 (s, 1H), 8.46 (br s, 1H); Anal. Cale, for C15H12N2? S2: C, 59.98; H, 4.03; N, 9.33. Found: C, 59.77; H, 3.88; N, 9.15. Example 140 4- (4-methylphenoxy) thieno (3.2-c1p? Ridine-2-carboxamide Example 140A 4- (4-methylphenoxy) thienof3,2-c1pyridine-9-carbonitrile Example 139A and 4-methylphenol were processed as in Example 139B to provide the main compound: IR (KBr) 2200 (w), 1580 (s), 1540 (s), 1500 (s), 1440 (s) crn "1; MS (DCI / NH3) 267 (M + H) +; 1 H NMR (300 MHz, CDCl 3) d 2.39 (s, 3 H), 7.09 (d t, 2 H), 7.25 (br d, 2 H), 7.43 (dd, 1 H), 8.10 (d, 1 H), 8.21 (s, 1 H); Anal cale, for C15H10N2OS: C, 67.65; H, 3.78; N, 10.52, Found: C, 67.60; H, 3.66; N, 10.48, Example 140B 4- (4-methylphenoxy) thieno (3.2-clpyridine-2-carboxamide Example 140A was processed as in Example 139C to provide the main compound: IR (KBr) 3400 (m), 1680 (m), 1650 (s), 1600 (s), 1500 (s) cm "1; MS (DCI / NH3) m / z 285 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.34 (s, 3H), 7.13 (d, 2H), 7.25 (d, 2H), 7.75 (d 1 H), 7.76 (br s 1 H), 7.95 (d, 1 H), 8.38 (br s, 1 H), 8.41 (s, 1 H); , for C15H12N2? 2S: C, 63.36; H, 4.25; N, 9 .85. Found: C, 63.16; H, 4.18; N, 9.77. Example 141 7- (4-methylphenoxy) oxazolo.5,4-clpyridine-2-carboxamide Example 141A 3-chloropyridine-N-oxide Example 141 A was processed as in Caldwell and Martin (J. Heterocyclic Chem., 1 980, 17, 989). A solution of 3-chloropyridine (15.0 g, 1 32 mmol) in acetic anhydride (75 mL) with cooling to maintain an internal temperature below 30 ° C was treated with hydrogen peroxide (75 mL of 30% aqueous solution) , stirred at room temperature for 3 hours, heated at 60 ° C for 18 hours, diluted with water (200 mL), concentrated and solid sodium bisulfite added in portions until the peroxides were no longer detected (by enzymatic peroxide test ), and the remaining solvent was removed under reduced pressure. The residue was triturated with ethyl acetate. The rinses were filtered and concentrated to provide the designated compound. Example 141 B 4-nitro-3-chloropyridine-N-oxide Example 141 B was processed as in Caldwell and Martin (J. Heterocyclic Chem., 1980, 17, 989). Example 141A (16.8 g, 130 mmol) in sulfuric acid (25 mL, 98%), smoldering sulfuric acid (30% SO 3, 10 mL), and nitric acid (60 mL, 90%) was heated at 120 ° C for 2 hours, cooled to room temperature, poured into cold water (200 mL), solid ammonium carbonate was added to bring the solution to pH = 9 and extracted with methylene chloride (4x100 mL). The extracts were dried (Na2SO4) and concentrated. The residue was recrystallized from ethyl acetate-hexanes to provide a first clean culture of the main compound. The recrystallizations of the second crop provided mixtures of the main compound and by-products. MS (DCI / NH3) m / z 194 (37Cl) / 192 (35Cl), (M + NH 4) +; 177 (37Cl) / 175 (35Cl), (M + H) +; 1 H NMR (CDCl 3, 300 MHz) d 8.01 (d, 1 H), 8.14 (dd, 1 H), 8.32 (d, 1 H). Example 141 C 4-Nitro-3- (4-methylphenoxy) pyridine-N-oxide NaH (834 mg, 34.8 mmol) in DMF (20 mL) at room temperature was treated sequentially with p-Cresol (3.57 g, 33.0 mmol) Example 141 B (5.75 g, 32.9 mmol), stirred for 10 minutes at room temperature and partitioned between ethyl acetate and aqueous 1 N HCl. The aqueous phase was separated and rinsed with ethyl acetate. The organic phases were rinsed with 1 N aqueous HCl, dried (Na2SO) and concentrated. Recrystallization from diethyl ether provided the main compound. MS (DCI / NH3) m / z 264 (M + NH4) +, 247 (M + H) +; 1 H NMR (CDCl 3, 300 MHz) d 2.39 (s, 3 H), 7.02 (d, 2 H), 7.26 (d, 2 H), 7.78 (d, 1 H), 7.89 (dd, 1 H), 7.98 (d, 1 HOUR). Example 141 D 3- (4-methylphenoxy) -4-pyridinamine Example 141 C (3.65 g, 14.8 mmol) was dissolved in methanol (100 mL), treated with raney nickel (1.00 g), rinsed with hydrogen, pressurized to 4 atm , at 37 ° C for 2.5 hours, and filtered. The filtrate was concentrated to provide the main compound. MS (DCI / NH3) m / z 201 (M + H) +; 1 H NMR (CDCl 3, 300 MHz) d 2.32 (s, 3 H), 4.40 (br s, 2 H), 6.68 (br s, 1 H), 6.88 (d, 2 H), 7.12 (d, 2 H), 8.01 (m , 2H). Example 141 E 2,2-Dimethyl-N-l3- (4-methylphenoxy) -4-pyridinylpropanamide Example 141 D (2.80 g, 14.0 mmol) was dissolved in methylene chloride (50 mL), cooled to 0 ° C, treated sequentially with triethylamine (1.78 g, 17.6 mmol) and trimethylacetyl chloride (1.86 g, 15.4 mmol), stirred at room temperature for 15 hours, and poured into water (100 mL) containing a sodium chloride signal . The organic layer was separated, treated with charcoal, filtered through Celite®, rinsed with saturated sodium bicarbonate, dried (Na2SO) and concentrated to provide the main compound. MS (DCI / NH3) m / z 285 (M + H) +; 1 H NMR (CDCl 3, 300 MHz) d 1.24 (s, 9 H), 2.35 (s, 3 H), 6.93 (d, 2 H), 7.18 (d, 2 H), 8.14 (br s, 1 H), 8.15 (s, 1 H), 8.32 (d, 1 H), 8.42 (d, 1 H). Example 141 F 5-Hydroxy-4 - (/ -trimethylacetyl) amino-3- (4-methylphenoxy) pyridine The procedure of Chu-Moyer and Berger (J. Org. Chem. 1995, 60, 5721) was adapted. Example 141 E (5.50 g, 19.3 mmol) was dissolved in diethyl ether and cooled to -78 ° C rt-Butyllithium (24.0 mL of 1. 7 M solution in pentane, 40.8 mmol) was added dropwise and allowed to stir 2 h at -78 ° C. Trimethylborate (5.01 g, 48.3 mmol) was added, and the reaction was slowly warmed to room temperature and stirred for 18 h. Glacial acetic acid (3.9 mL) was added, followed by the addition of 30% aqueous hydrogen peroxide (5.8 mL). The The reaction was stirred at 2 h at room temperature and then poured into water. The resulting mixture was rinsed twice with CH2CI2 and the organic layers were treated with activated charcoal and filtered through celite. The filtrate was rinsed once with water, once with brine, dried (Na2SO) and concentrated under reduced pressure to give a mixture of two compounds, with the highest Rf desired. The mixture was purified by flash silica chromatography using a 40M Biotage cartridge, 1.5% methanol in CH 2 Cl 2 eluent, to give 0.15 mmol (15% product) of the desired product and 0.73 mmol (73%) of the main compound. MS (DCI / NH3) m / e 301 (M + H) +; 1 H NMR (CDCl 3, 300 MHz) d 1 .20 (s, 9 H), 2.27 (s, 3 H), 6.84 (d, 2 H), 7.09 (d, 2 H), 7.65 (br s, 1 H), 8.08 ( s, 1 H), 8.14 (br s, 1 H), 10.26 (br s, 1 H). Example 141 G 5-Hydroxy-4-amino-3- (4-methylphenoxy) pyridine Example 141 F (850 mg, 2.83 mmol) was suspended in aqueous 3N HCl and stirred at 90 ° C for 18 h. The reaction was then cooled to 0 ° C, neutralized with 6N aqueous NaOH, and extracted with CH2Cl2. The organic layers were combined, dried (Na2SO) and concentrated under reduced pressure to give the desired product (612 mg, 100% product). MS (DCI / NH3) m / e 217 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.25 (s, 3 H), 5.16 (s, 2 H), 6.81 (d, 2 H), 7.12 (d, 2), 7.50 (s, 1 H), 7.71 (s) , 1 H), 8.14 (s, 1 H), 9.55 (br s, 1 HOUR). Example 141 H Methyl Oxazolof5.4-cH- (4-methylphenoxy) pyridine-2-carboxylate To Example 141 G (1.00 mmol) in DMF was added pyridine (1.10 mmol) and methyl oxalyl chloride (1. 10 mmol), and the resulting solution is stirred at room temperature overnight. The reaction is then partitioned between methylene chloride and aqueous 1N HCl, and the organic phase is separated, dried (Na2SO) and concentrated under reduced pressure to give the main compound. Example 141 Oxazolof5.4-c1-4- (4-methylphenoxy) pyridine-2-carboxamide Example 141 H can be treated according to the procedure of Example 44 to give the main compound. Example 142 7- (4-Methylphenoxy) f1,3ltiazolof5.4-clpyridine-2-carboxamide Example 142A 5 - (? / ./ \ / - Dimethylthiuran) sulfide-4 - (/. Trimethylacetyl) amino-3- (4 -methylphenoxy) pyridine Example 141 E (284 mg, 1.0 mmol) in diethyl ether (12 mL) at -78 ° C was treated dropwise with ferf-butyllithium (1.3 mL of 1.7 M solution in pentanes, 2.21 mmol, Aldrich), followed by stirring for 3 h at -78 ° C. The tetramethyl thiuram disulfide (529 mg, 2.20 mmol) was added to the resulting dianion, and the rise in temperature and stirring was continued for 18 h. The reaction was quenched with water and extracted with CH2Cl2. The organic phase was dried (NaSO) and concentrated under reduced pressure. The main compound (50 mg, 12% of product) was isolated by flash silica gel column chromatography. MS (DCI / NH3) m / e 404 (M + H) +; 1 H NMR (CDCl 3, 300 MHz) d 2.32 (s, 3 H), 3.55 (s, 3 H), 3.58 (s, 3 H), 6.92 (d, 2 H), 7.12 (d, 2 H), 7.93 (s, 1 H) ), 8.43 (s, 1 H), 8.45 (s, 1 H). Example 142B 5- (α-Dimethylthuran) sulfide-4-amino-3- (4-methylphenoxy) pyridine Example 142A (270 mg, 0.67 mmol) was combined with formic acid (20 mL of 96%, Aldrich) and stirred at 90 ° C for 72 hrs. The reaction is then cooled to room temperature, and the formic acid is removed under reduced pressure. The resulting residue is purified by flash silica gel chromatography (70% EtOAc in hexane) to provide the main compound (96 mg, 45% product). MS (DCI / NH3) m / e 320 (M + H) +; 1 H NMR (CDCl 3, 300 MHz) d 2.33 (s, 3 H), 3.56 (s, 3 H), 3.58 (s, 3 H), 4.93 (br S, 2 H), 6.94 (d, 2 H), 7.15 (d, 2 H) ), 8.04 (s, 1 H), 8.12 (s, 1 H). Example 142C 5- (V-Dimethylthiuran) sulfide 4-methyloxamate-3- (4-methylphenoxy) pyridine Example 142B (90 mg, 0.28 mmol) was combined with CH 2 Cl 2 (7.0 mL). Triethyl amine (0.39 mL, 2.2 mmol) was added, followed by the addition of methyl oxalyl chloride (120 mL, 1.30 mmol, Aldrich). After 6 h, the mixture was combined with saturated aqueous sodium bicarbonate and extracted three times with CH2CI. The organic layers were combined, dried (Na2SO), filtered and concentrated under reduced pressure. MS (DCI / NH3) m / e 406 (M + H) +; 1 H NMR (CDCl 3, 300 MHz) d 2.33 (s, 3 H), 3.54 (s, 3 H), 3.58 (s, 3 H), 3.90 (s, 3 H), 7.00 (d 2 H), 7.15 (d, 2 H), 8.37 (s, 1 H), 8.41 (s, 1 H), 9.20 • 5 (br s, 1 H). Example 142D Methyl 4- (4-Methylphenoxy) thiazolof5.4-clpyridine-2-carboxylate Example 142C (50 mg, 0.12 mmol) was dissolved in formic acid (14 mL, 96%, Aldrich), and heated to reflux. After 4 h, the reaction was cooled, and the volatiles were removed. Column chromatography on flash silica gel (60% EtOAc in hexane) • provided the main compound (15 mg, 39% product) as a white solid. MS (DCI / NH3) m / e 301 (M + H) +, 318 (M + NH3) +; 15 1 H NMR (CDCl 3, 300 MHz) d 2.39 (s, 3 H), 4.10 (s, 3 H), 7.08 (d, J = 8.5 Hz, 2 H), 7.22 (d, J = 8.5 Hz, 2 H), 8.14 ( s, 1 H), 9.00 (s, 1 H). Example 142E 4- (4-Methylphenoxy) thiazolof5.4-c1pyridine-2-carboxamide Example 142D (2.0 mg, 6.7 mmol) was treated according to the procedure of Example 44 to give the main compound (1.5 mg, 75 %) as a white solid. MS (DCI / NH3) m / e 286 (M + H) +, 303 (M + NH3) +; 1 H NMR (CDCl 3, 300 MHz) d 2.39 (s, 3 H), 5.66 (br s, 1 H), 7.06 (d, J = 8.2 Hz, 2 H), 7.22 (d, J = 7.8 Hz, 2 H), 7.32 (br s, 1 H), 8.20 (s, 1 H), 25 9.04 (s, 1 H).

Example 143 7- (4-methylphenoxy) -3H-imidazof4, 5-Clpyridine-2-carboxamide Example 143A N-f3-amino-5- (4-methylphenoxy) -4-pyridinin-2,2-dimethylpropanamide Example 141 F (1.00 mmol) is suspended in ammonium hydroxide (28 %), saturated with sulfur dioxide, heated at 150 ° C in a pressure vessel for 27 hours, and cooled, and extracted with ethyl acetate. The extract was concentrated to provide the main compound. Example 143B 5- (4-methylphenoxy) -3,4-pyridinediamine Example 143A (1.00 mmol) was suspended in HCl (aqueous 3N) and stirred at 90 ° C for 18 hours, cooled to 0 ° C, neutralized with 6N aqueous NaOH, and the water was removed. The resulting residue was triturated with methanol. The rinses are concentrated to provide the main compound. Example 143C Methyl 7- (4-methylphenoxy) -3 H -amidazof 4,5-c1pyridine-2-carboxylate Example 143B (1.00 mmol) in DMF was treated with pyridine (1 .10 mmol) and oxalyl methyl chloride (1.0 mmol), stirred at room temperature overnight, and partitioned between methylene chloride and 1 N aqueous HCl. The organic phase was separated, dried (Na2SO4) and concentrated to provide the main compound. Example 143D 7- (4-methylphenoxy) -3H-imidazof4.5-c1pyridine-2-carboxamide Example 143C can be treated as in Example 44 to give the main compound Example 144 4- (4-chlorophenoxy) thienof2,3-d1-pyridazine-2-carboxamide Example 144A 3-Bromothiophene-2-carboxaldehyde Example 144A can be processed as in Prugh, et. al (J. Med. Chem. 1991, 34, 1805). A solution of dibromothiophene (14 g, 58 mmol) in THF (100 mL) at -78 ° C was treated with n-butyllithium (24 mL, 59 mmol), stirred for 15 minutes, treated with dry DMF (6.8 mL, 87 mmol), stirred at -78 ° C for 10 minutes, warmed slowly to 0 ° C over a period of 15 minutes, poured into 1 N cold aqueous HCl, and extracted with diethyl ether. The extract was rinsed with 1 N aqueous HCl, water, and saturated sodium bicarbonate. The rinses were extracted with diethyl ether. The organic layers were combined, dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel with 5% ethyl acetate / hexanes to provide the main compound. 1 H NMR (CDCl 3, 300 MHz) d 7.16 (d, 1 H), 7.74 (d, 1 H), 10.0 (s, 1 H). Example 144B 3-Bromo-2-.2-dioxolanyl) thiophene Example 144B can be prepared as in Prugh, et al. (J.

Med. Chem. 1991, 34, 1805). A three-necked flask equipped with Dean-Stark tape is charged with Example 144A (5.24 g, 27.4 mmol), ethylene glycol (6.2 mL, 10 mmol), pyridinium thiosylate (276 mg, 1.01 g / mL). mmol), and toluene (30 mL), refluxed for 14 hours, cooled to room temperature, poured into water, and extracted with diethyl ether. The organic layer was rinsed with water and saturated sodium bicarbonate, dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography on silica gel with 5% ethyl acetate / hexanes to provide the main compound. MS (DCI / NH3) m / z 252 (r9Br) / 254 (81 Br), (M + NH4) +; 235 (79Br) / 237 (81Br), (M + H) +; 1 H NMR (CDCl 3, 300 MHz) d 4.1 1 -4.02 (m, 4 H), 6.14 (s, 1 H), 6.97 (d, 1 H), 7.30 (d, 2 H). Example 144C ethyl-2- (2-dioxylanyl) thiophene-3-carboxylate Example 144C can be processed as in Prugh, et al. (J. Med. Chem. 1991, 34, 1805). Example 144B (1.00 g, 4.25 mmol) in THF (12 mL) is treated with n-butyllithium (1.7 mL, 4.25 mmol) while maintaining the temperature between -105 and 95 ° C, treated with diethyl carbonate ( 0.57 mL, 4.68 mmol), and warmed to room temperature. The solution is poured into water and extracted with diethyl ether. The extract was rinsed with brine, dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel with 5% ethyl acetate / hexanes to provide the main compound. Example 144D 2-Formylthiophene-3-carboxylic acid Example 144C (1.0 mmol) and ethanol (1.0 mL) were treated with 1 N aqueous sodium hydroxide solution (100 mmol), stirred for 1 hour, brought to pH = 5 by the addition of glacial acetic acid, stirred for 1 hour, diluted with water, and extracted with ethyl acetate. The extracts were combined, rinsed with water, and extracted with ethyl acetate. The extracts were combined, rinsed with brine, rinsed with saturated sodium bicarbonate, dried (MgSO 4), filtered and concentrated. The designated compound was used are additional purification. Example 144E 4-oxothienof2.3-d1pyridazine Example 144D is processed as in Bull. Soc. Chim. Fr. 1967, 2495. Example 144F 4-chloro-t-enof2.3-dlpyridazine Example 144E is processed as in Bull. Soc. Chim. Fr. 1967, 1495. Example 144G 4- (4-Chlorophenoxy) thienof2,3-dlpyridazine Adapting the method of Roba et al. (Bull. Soc. Chim. Fr. 1967, 4220), Example 144F (100 mg, 0.59 mmol) was combined with 4-chlorophenol (1.0 mL, 10.0 mmol) and sodium metal (21 mg, 0.90 mmol).

The mixture was heated at 100 ° C for 14 h. After cooling to room temperature, the residue was diluted with chloroform and rinsed once with 2N aqueous sodium hydroxide and once with brine. The organic layer was dried (MgSO4), filtered, and concentrated under reduced pressure. Recrystallization from diethyl ether gave the main compound (124 mg, 85%) as a white solid. MS (DCI / NH3) m / e: 363 (M + H) +; 1 H NMR (CDCl 3, 300 MHz) d 7.27 (d, J = 8.9 Hz, 2 H), 7.42 (d, J = 8.9 Hz, • 5 2H), 7.72 (d, J = 5.5 Hz, 1 H), 7.88 (d, J = 5.2 Hz, 1 H), 9.41 (s, 1 H). Example 144H 4- (4-Chlorophenoxy) thienof2.3-d1-pyridazine-2-carboxylic acid Example 144G (1.0 mmol) in THF (1.0 mL) at -78 ° C is treated on 1 -Butyllithium (1.04). mmol), stirred for 15 minutes, saturated with 10 CO 2, warmed slowly to room temperature, divided between 1 N aqueous sodium hydroxide and diethyl ether, separated, and added acid ^ .W glacial acetic acid to the aqueous layer until pH = 5. The acidic solution was extracted three times with methylene chloride. The extracts were combined, washed with dilute sodium bicarbonate, dried (MgSO), filtered, and concentrated to provide the main compound. Example 1441 4- (4-chlorophenoxy) thienof2.3-dlpyridazine-2-carbamide Example 1441 can be processed as in Desai and Stramiello (Tetrahedron Lett, 1993, 34, 7685). Example 144H (1.0 mmol), 1-hydroxybenzotriazole (1.4 mmol), N-methylmorpholine (12 mmol), and DMF (1.0 mL) were combined and cooled to 0 ° C, treated with 1-hydrochloride. (3-Dimethylaminopropyl) -3-ethylcarbodiimid, stirred at 0 ° C for 1 hour, and divided between methylene chloride, bicarbinate saturated sodium and separated. The extract was dried (MgSO4), filtered and concentrated. Recrystallization from hot methanol will provide the main compound. Example 145 7- (4-chlorophenoxy) thienof3.2-c1pyridine-2-carbamide Example 145A 2,5-dibromo-3-thiophenecarboxaldehyde A solution of 3-thiophenecarboxaldehyde is processed as in Bull. Soc. Chim. Fr., 1974, 3040 to provide the main compound. Example 145B Dimethylacetyl- (2,5-dibromo-3-thienyl) carboxyimine ethane Example 145A is processed as in Bull. Soc. Chim. Fr., 1974, 3040 to provide the main compound. Example 145C 6.7-dihydro-7-oxothienof3.2-clpridine Example 145B is processed as in Bull. Soc. Chim. Fr., 1974, 3040 to provide the main compound. Example 145D 7- (4-chlorophenoxy) thienof3.2-clpyridine Example 145D can be processed as in Lindley (Tetrahedron, 1 983, 1433). A solution of Example 145C (1.0 mmol) and DMF (2.0 mL) was treated at 0 ° C with sodium hydride (1.0 mmol), warmed slowly to room temperature, treated with 1-chloro-4-iodobenzene ( 1.0 mmol) and copper iodide (0.1 mmol), warmed to 80 ° C overnight, and cooled. The solution was poured into water and extracted with diethyl ether. The extracts were combined, dried (MgSO), filtered and concentrated. Recrystallization from ethyl acetate / hexanes gives the main compound. EXAMPLE 145E 7- (4-chlorophenoxy) thienoyl-2-clpyridine-2-carboxylic acid The designated compound is processed in the manner described for Example 144H. Example 145F 7- (4-chlorophenoxy) t-inof3.2-clpyridine-2-carboxamide The designated compound is processed in the manner described for Example 1441. EXAMPLE 146 4- (4-Chlorophenoxy) t-inof2,3-clpyridine -2-carbothioamide A solution of Example 61 (50 mg, 0.16 mmol) and Lawesson's reagent (73 mg, 0.18 mmol) in toluene (2 mL) was heated to reflux for 4 hours. The solvent was removed under reduced pressure to obtain the crude product (150 mg) as a yellow residue. The purified main compound (24 mg, 47%) was obtained by flash chromatography on silica gel eluting with 10% methanol in dichloromethane. MS (DCI / NHg) m / e 321 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 7.14 (m, 2 H), 7.47 (m, 2 H), 8.18 (s, 1 H), 8.21 (s, 1 H), 9.14 (s, 1 H), 9.86 (s, 1 H), 10.15 (s, 1 H). Example 147 4- (4-Chlorophenoxy) -N-ethylthienof213-clpyridine-2-carboxamide Example 61A (200 mg, 0.627 mmol) was prepared as in Example 171 but replacing ethylamine (1 mL, 17.65 mmol) for methylamine to give the main compound. MS (DCI / NH3) m / e 333 (M + H) +, 303; 1 H NMR (400 MHz, DMSO-d 6) d 1 .14 (t, J = 8 Hz, 3 H), 3.30 (m, 2 H), 7.14 (d, J = 9 Hz, 2 H), 7.47 (d, J = 9 Hz, 2H), 8.13 (s, 1 H), 8.17 (s, 1 H), 8.91 (t, J = 6 Hz, 1 H), 9.15 (s, 1 H). Example 148 4- (4-Chlorophenoxy) -N- (2,3-dihydroxypropyl) thienor-2,3-c1pyridine-2-carboxamide Example 148 was prepared in a similar manner as in Example 103A, by combining 3-amino-1,2-propanediol (60 mL, 0.782 mmol) with Example 61 A (250 mg, 0.782 mmol) to afford the main compound (133 mg, 45% product) as a solid White. mp 106-1 15 ° C; MS (DCI / NH3) m / e: 379 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 3.16 (m, 2 H), 3.38 (m, 2 H), 3.63 (m, 1 H), 4.56 (t, J = 5.7 Hz, 1 H), 4.81 (d, J = 5.1 Hz, 1 H), 7.13 (d, J = 9.2, 2H), 7.47 (d, J = 9.2 Hz, 2H), 8.18 (s, 1 H), 8.21 (s, 1 H), 8.95 ( t, J = 5.7 Hz, 1 H), 9.16 (s, 1 H); Anal. cale, for C17H? 5CIN2O4S 0.25H2O: C, 53.27; H, 4.08; N 7.31. Found: C, 53.19; H, 4.22; N, 6.22. Example 149 4- (4-Bromophenoxy) -N- (2,3-d-hydroxypropyl) thienor 2,3-clpyridine-2-carboxamide Example 149 was prepared according to the procedure of Example 1 14, with the substitution of methyl 4- (4-bromophenoxy) -thieno [2,3-c] pyridine-2-carboxylate for Example 61A. mp 76-77 ° C; MS (DCI / NH3) m / e: 423, 425 (M + H) +; • 5 1 H NMR (300 MHz, DMSO-d 6) d 3.12 (m, 2 H), 3.41 (m, 3 H), 3.63 (m, 2 H), 7.06 (d, 2 H, J = 8.8 Hz), 7.59 (d, 2H, J = 8.8 Hz), 8.20 (s, 1 H), 8.22 (s, 1 H), 8.99 (t, 1 H, J = 5.5 Hz), 9.18 (s, 1 H). Example 150 N- (2-ClQroethyl) -4- (4-chlorophenoxy) thienof2.3-c1pyridine-2-carboxamide To a solution of Example 14 (0.32 g, 0.92 mmol) in Anhydrous THF (5 mL) was slowly added thionyl chloride (0.34 mL, • 4.60 mmol). The reaction was heated at 50 ° C for 18 h, cooled to room temperature, and neutralized with sat. NaHCO3. The aqueous suspension was extracted with dichloromethane (100 mL) and the organic layer was rinsed with dilute NaHCO3 (2x100 mL), brine (50 mL), partially dried (Na2SO4) and concentrated to a solid. The crude product was purified by flash chromatography on silica gel using EtOAc / hexane as eluent to give the main compound as a solid (0.27 g, 80%). 20 mp 60-62 ° C (dec); MS (DCI / NH3) m / e 367 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 3.60 (m, 2 H), 3.75 (t, J = 6.1 Hz, 2 H), 7.15 (m, 2 H), 7.48 (m, 2 H), 8.18 (s, 1 H) ), 8.18 (s, 1 H), 9.17 (s, 1 H), 9.26 (m, 1 H); 25 Anal. cale, for deC ^ CIzNzOzS: C, 52.33; H, 3.29; N 7.63.

Found: C, 52.22; H, 3.47; N, 7.35. Example 151 4- (4-Bromophenoxy) -N- (2-hydroxyethyl) t-inof2.3-clpridine-2-carboxamide Example 151 was prepared according to the procedure of • Example 1 14, with the substitution of methyl 4- (4-bromophenoxy) -thieno [2,3-c] pyridine-2-carboxylate for Example 61A. mp 158-159 ° C; MS (DCI / NH3) m / e: 393, 395 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 3.32 (m, 2 H), 3.51 (m, 3 H), 4.79 (t, 10 1 H, J = 5.9 Hz), 7.06 (d, 2 H), J = 8.8 Hz ), 7.50 (d, 2H), J = 8.8 Hz), 8.17 (s, 1 H), 8.20 (s, 1 H), 9.02 (t, 1 H, J = 5.5 Hz), 9.17 (s, 1 H) ). Example 152 4- (2-Bromo-4-chlorophenoxy) -N- (2-hydroxyethyl) thienof2,3-clpyridine-2-carboxamide Example 152 was prepared according to the procedure of Example 14, with the substitution of 2. -bromo-4-chlorophenol for 4-chlorophenol. MS (DCI / NH3) m / e: 428 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.86 (q, 2H), J = 5.4 Hz), 3.34 (m, 2H), 3.55 (m, 2H); 7.15 (d, 1 H, J = 8.8 Hz), 7.48 (dd, 1 H, J = 2.4, 8.8 Hz), • 20 7.97 (d, 1 H, J = 2.7 Hz), 8.02 (s, 1 H), 8.25 (s, 1 H), 9.05 (t, 1 H, J = 5.4 Hz), 9.16 (s, 1 H) ). EXAMPLE 153 N- (2-Hydroxyethyl) -4-r4- (trifluoromethyl) phenoxyphenyl-2,3-clpyridine-2-carboxamide A solution of Example 62A (322 mg, 0.912 mmol) in 25 mL of dichloromethane was treated with 226 mg ( 3.65 mmol) of Ethanolamine The solution was heated to reflux for 4 hours. After cooling the crystals are formed. Recrystallization from ethyl acetate gave 170 mg (48.8%) of white crystals, mp 181-182 ° C; • 5 MS (DCI / NH3) m / e: 383 (M + H) +; H NMR (300 MHz, DMSO-d6) d 3.3-3.4 (m, 2H), 3.5-3.6 (m, 2H), 4.80 (t, 2H), 7.21 (d, 2H), 7.79 (d, 2H), 8.15 (s, 1 H), 8.38 (s, 1 H), 9.01 (t, 1 H), 9.25 (s, 1 H); Anal. Cale, for C ^ H ^ FaNzOsS: C, 53.40; H, 3.43; N, 7.33.

Found: C, 53.41; H, 3.62; N, 7.30. Example 154 • N- (2-Aminoethyl) -4- (4-chlorophenoxy) thienof2.3-c1pyridine-2-carboxamide To a suspension of Example 88 (0.50 g, 1.64 mmol) in anhydrous methylene chloride (15 mL ) was added N, N-15 diisopropylethylamine (0.57 mL, 3.28 mmol). The reaction was cooled in an ice bath and pivaloyl chloride (0.24 mL, 1.97 mmol) was added slowly. After 10 minutes, the cold bath was removed and the reaction was stirred at room temperature for 1.5 hr. The contents of the reaction were slowly transferred through cannulas to an anhydrous solution of ethylenediamine (0.33 mL, 4.92 mmol) in methylene chloride (5 mL) at 0 ° C for a period of 5 minutes. The reaction was stirred 15 minutes and the cold bath was removed. The reaction was stirred at 1 hr and then partitioned between CHCl3 / sat. NaHCO3. The organic layer was rinsed with dilute aqueous NaHCO3, brine, dried (Na2SO), and concentrated to produce a yellow foam clear. The crude product was purified by preparative HPLC using a gradient of 25% -65% acetonitrile / water + 0.1% TFA during 40 minutes. The product was neutralized with aqueous, saturated NaHCO3, the precipitate was collected by filtration, and dried in a desiccator to produce the main compound as a white solid (0.45 g, 79%). mp 1 1 1 -1 14 ° C; MS (APCI) m / e 348 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 2.69 (t, J = 6.4 Hz, 2 H), 3.25 (t, J = 6.4 Hz, 2H), 7.14 (m, 2H), 7.47 (m, 2H), 8.16 (s, 1 H), 8.18 (s, 1 H), 9.15 (s, 1 H); Example 155 4- (4-Chlorophenoxy) -N-hydroxythienof2,3-clpyridine-2-carboxamide Example 155 was prepared as in Example 92 by combining Example 88 (161 mg, 0.527 mmol) with hydroxylamine hydrochloride (37.0 mg, 0.527 mmoi) to provide the main compound (40 mg, 24% product) as a white solid. mp 145 ° C (unfolded); MS (DCI / NH3) m / e: 321 (M + H) +; 1 H NMR (300 MHz, CD 3 OD) d 7.1 1 (d, J = 9.2 Hz, 2 H), 7.42 (d, J = 9.2 Hz, 2 H), 7.90 (s, 1 H), 8.05 (s, 1 H), 9.01 (s, 1 H); IR (KBr) 3200-2800 (m), 1660 (s), 1640 (s), 1560 (m), 1485 (s), 1420 (s) cm "1; Anal cale, for C14H9CIN2O3S + 0.25H2O: C, 51.70; H, 2.94; N, 8.61.

Found: C, 51.64; H, 2.71; N, 8.80. Example 156 4- (4-Chlorophenoxy, t-inof2,3-c1pyridine-2-carbohydrazide Example 61 A (0.50 g, 1.56 mmol) was dissolved in dichloromethane (10 mL) and anhydrous hydrazine (1 mL) was added.

After 24 hours, the precipitate was collected by filtration and rinsed with dichloromethane (2x25 mL) and water (2x50 mL). The product was dried in a desiccator to produce the main compound as a white solid (0.35 g, 70%) mp 197-199 ° C; MS (APCI) m / e: 320 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 4.62 (broad s, 2H), 7.12 (m, 2H), 7.46 (m, 2H), 8.03 (s, 1 H), 8.19 (s, 1 H), 9.15 (s, 1 H), 10.24 (br s, 1 H); Anal. calc. _ for C 14 H 10 CIN 3 O 2 S: C, 52.59; H, 3.15; N, 13.14.

Found: C, 52.59; H, 3.12; N, 13.18. Example 157 4- (4-Bromophenoxy) thienof2,3.-clpyridine-2-carbohydrazide Example 73A (0.21 g, 0.58 mmol) was dissolved in dichloromethane (2 mL) and anhydrous hydrazine (1 mL) was added. After 18 hours, the precipitate was collected by filtration and rinsed with dichloromethane (2x25 mL), water (2x5 mL), acetonitrile (2x5 mL) to yield white solid. The rinses were combined, diluted with sat. NaHCO3. (100 mL) and extracted with dichloromethane (4x25 mL).

The organic extracts were combined, partially dried (Na2SO4) and concentrated to yield a white solid which was combined with the collected precipitate and dried in a desiccator (0.21 g, 99%). mp 176-178 ° C; MS (APCI) m / e: 364 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 4.62 (br s, 2 H), 7.06 (m, 2 H), 7.58 (m, 2 H), 8.02 (s, 1 H), 8.21 (s, 1 H), 9.16 (s, 1 H), 10.24 (br s, 1 H); Anal. cale, for C14H10BrN3O2S: C, 46.17; H, 2.77; N, 1 1 .54. Found: C, 46.08; H, 2.90; N, 1 1.41. Example 158 4-f4-p "rifluoromethyl) phenoxythienof2,3-c1pyridine-2-carbohydrazide Example 62A was treated according to the procedure of Example 157 to provide the main compound, mp 146-147 ° C; MS (APCI) m / e: 353.9 (M + H) +; 1 H NMR (300 MHz, DMSO-de) d 3.18 (d, 2 H), 4.1 1 (t, 1 H), 7.19 (d, 2 H), 7.77 (d, 2 H), 7.78 (s, 1 H), 8.36 (s, 1 H), 9.21 (s, 1 H). EXAMPLE 159 2- (4-4- (4-Chlorophenoxy) thienof2.3-c1pyridin-2-carboncarbyl> amino) acetic acid Example 159A 4- (4-Chlorophenoxy) thienoyl-2,3-clpyridine-2-carboxylic acid A suspension of Example 61 A (354 mg, 1.1 mmol) in 3 mL methane and 1 mL of water was treated with lithium hydroxide monohydrate (98 mg, 2.33 mmoi) and the resulting mixture was stirred at room temperature ( under N2) for 20 hours. The reaction was acidified with 0. 13 mL of 90% formic acid, and the white suspension was stirred for 5 minutes, then the solid was isolated by suction filtration. The solid was sequentially rinsed with 15 mL of water and mL of diethyl ether, then dried under vacuum to provide 302 mg (89%) of the main product. MS (DCI-NH3) m / e: 306, 308 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 7.15 (m, 2H), 7.47 (m, 2H), 7.82 (s, 1 H), 8.23 (s, 1 H), 9.21 (s, 1 H), 13-15 (vbr s, 1 H); Anal. Cale, for C17H8CINO3S: C, 55.00; H, 2.64; N, 4.58. Found: C, 54.77; H, 2.60; N, 4.44. Example 159B Methyl 2- ( { F4- (4-Chlorophenoxy) thienor-2,3-clpyridin-2-incarbonyl amino) acetate The main compound was prepared from Example 159A in analogy to Example 92, with the substitution of hydrochloride of methyl ester glycine for ammonium chloride. HPLC: Supelco column C-18, eluent gradient of water: acetonitrile 0: 90-90: 0 for 30 minutes, detection at 254 nm, flow rate of 0.8 mL / min, RT 19.04 minutes; MS (APCI) m / e: 377 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 3.68 (s, 3 H), 4.05 (d J = 6 Hz, 2 H), 7.13 (m, 2 H), 7.49 (m, 2 H), 8.19 (s, 1 H ), 8.21 (s, 1 H), 9.19 (s, 1 H), 9.50 (br t, J = 6 Hz, 1 H); Anal. Cale, for C17H13CIN2O4S: C, 54.19; H, 3.48; N, 7.43. Found: C, 53.92; H, 3.61; N, 7.52. Example 159C 2 - ((r4- (4-Chlorophenoxy) thienof2.3-cjpyridin-2-incarbonyl amino) acetic acid The main compound was prepared from Example 159B using the procedure of Example 18 to provide the main compound MS (APCI) m / e: 363 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 3.95 (d, J = 6 Hz, 2 H), 7.13 (m, 2 H), 7.48 (m, 2 H), 8.19 (s, 1 H), 8.21 (s, 1 H), 9.19 (s, 1 H), 9.41 (br t, J = 6 Hz, 1 H), 12.77 (br s, 1 H); Anal. Cale, for C16H11CIN2O4S «1 H2O C, 50.46; H, 3.44; N, 7.36. Found: C, 50.33; H, 3.38; N, 7.29. Example 160 N- (2-Amino-2-oxoethyl) -4- (4-chlorophenoxy) thienor-2,3-c1pyridine-2-carboxamide The main compound was prepared from Example 159C in analogy to Example 92. mp 222-225 ° C; MS (APCI) m / e: 362 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 3.82 (br s, 2 H), 7.12 (m, 2 H), 7.49 (m, 2 H), 8.19 (s, 1 H), 8.21 (s, 1 H), 9.20 (s, 1 H), 9.29 (br s, 1 H); Anal. cale, for C1 ßH12CIN3O3S «1 .35 H2O: C, 49.77; H, 3.84; N, 10.88. Found: C, 49.86; H, 3.79; N, 10.59. Example 161 N- (2-Amino-2-oxoethyl) -4- (4-bromophenoxy) thienof2.3-cypyridine-2-carboxamide Example 161A Methyl N- (2-amino-2-oxoethyl) -4- ( 4-bromophenoxy) thienof2.3-c1pyridine-2-carboxylate Example 73A was hydrolysed according to the procedure of Example 18. The carboxylic acid derivative was coupled to the methyl ester hydrochloride glycine in analogy to Example 92. MS (DCI / NH3) m / e: 421 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 370 (s, 3 H), 4.11 (br d, 2 H), 7.11 (br d, 2 H), 7.61 (brd, 2 H), 8.22 (brd, 2 H), 9.19 ( s, 1H), 9.51 (brt, 1H); 13 C NMR (100 MHz, DMSO-d 6) d 41.15, 51.84, 104.95, 115.57, 119.74, 119.97, 132.93, 133.32, 137.36, 138.04, 141.45, 145.06, 147.03, 156.10, 161.09, 169.80; Anal. cale, for C17H? 3BrN2O4S: C, 48.47; H, 3.11; N, 6.65. Found: C, 48.16; H, 3.27; N, 6.65. Example 161 B 2- ( { F4- (4-Bromophenoxy) thienof2.3-clpyridin-2-ipcarbonyl > amino) acetic acid The main compound was prepared from Example 161A using the procedure of Example 18 to provide the main compound . MS (DCI / NH3) m / e: 407 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 4.11 (br d, 1 H), 7.10 (br d, 2 H), 7.60 (br d, 2 H), 8.21 (br d, 2 H), 9.19 (s, 1 H), 9.40 (br t, 1H); 13 C NMR (100 MHz, DMSO-dβ) d 41.50, 115.85, 120.00, 120.09, 133.25, 133.25, 133.67, 137.76, 138.34, 141.79, 145.74, 147.29, 156.46, 161.28, 171.05; Anal. cale, for C1ßH11BrN2? 4S »H2O: C, 45.19; H, 3.08; N, 6.59. Found: C, 45.20; H, 3.15; N, 6.45. Example 161C N- (2-Amino-2-oxoethyl) -4- (4-bromophenoxy) thienof2,3-clpyridine-2-carboxamide The main compound was prepared from Example 161B in analogy to Example 92. using the procedure of Example 18 to provide the main compound.

MS (APCI) m / e: 406 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 3.81 (br d, J = 6 Hz, 2 H), 7.08 (m, 2 H), 7.10 (br s, 1 H), 7.60 (m, 2 H), 8.19 (s) , 1 H), 8.22 (s, 1 H), 9.20 (s, 1 H), 9.28 (br t, J = 6 Hz, 1 H); Anal. Cale, for C1ßH12BrN3? 3S * 0.3H2 ?: C, 46.68; H, 3.09; N, 10.21. Found: C, 46.68; H, 3.30; N, 10.16. Example 162 Nf (1S) -2-Amino-1- (hydroxymethyl) -2-oxoetin-4- (4-chlorophenoxy) thienof213-cjpyridine-2-carboxamide Example 162A (2S) -2- (ff4- (4- Chlorophenoxy) thienof2,3-clpyridin-2-incarbonyl > amino) -3-hydroxypropanoic Example 162A was prepared in analogy to Example 92, with the substitution of ethyl L-ester serine hydrochloride for ammonium chloride. The intermediate ester was then hydrolyzed according to the procedure of Example 18 to provide the main compound. HPLC: Remove it column C-18, eluent gradient water. Acetonitrile 0: 90-90: 0 for 30 minutes, detection at 254 nm flow rate of 0.8 mL / min, RT 15.93 minutes. MS (APCI) m / e: 392 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 3.70 (m, 2 H), 4.43 (br t, 2 H), 5.04 (br s, 1 H), 7.13 (m, 2 H), 7.49 (m, 3 H), 8.18 (s, 1 H), 8.37 (s, 1 H), 8.98 (br s, 1 H), 9.18 (s, 1 H). Example 162B »N-f (1S) -2-Amino-1- (hydroxymethyl) -2-oxoetin-4- (4-chlorophenoxy) thienof2,3-clpyridine-2- carboxamide Example 162B was prepared from Example 162A in analogy to Example 92. HPLC: Remove it from column C-18, eluent gradient from 4É water. acetonitrile 0: 90-90: 0 for 30 minutes, detection at 254 nm flow rate of 0.8 mL / min, RT 15.93 minutes. MS (APCI) m / e: 392 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 3.70 (m, 2 H), 4.43 (br t, 2 H), 5.04 (br s, 1 H), 7.13 (m, 3 H), 7.49 (m, 3 H), 8.18 (s, 1 H), 8.37 (s, 1 H), 8.98 (br s, 1 H), 9.18 (s, 1 H). Example 163 f (2R) -2 - ((f4- (4-Chlorophenoxyptienor-2,3-clpyridin-2-ipcarbonyl) amino) -3-hydroxypropanoic acid Example 163 was prepared in analogy to Example 92, using D-ester hydrochloride of methyl serine in place of ammonium chloride 15. The ester derivative was hydrolyzed according to the procedure of Example 18 to give the main compound HPLC: Exit it column C-18, eluent gradient of water: acetonitrile 0: 90-90: 0 for 30 minutes, detection at 254 nm j < fl flow rate of 0.8 mL / min, RT 16.47 minutes, 20 MS (ESI) m / e: 393 (M + H) +; 1 H NMR (300 MHz, DMSO -dβ) d 3.78 (br d, 2H), 4.49 (m, 1 H), 5.02 (br s, 1 H), 7.13 (m, 2H), 7.48 (m, 2H), 8.18 (s, 1 H) , 8.39 (s, 1 H), 9.14 (d, 1 H), 9.18 (s, 1 H), 12.81 (br s, 1 H) Example 164 25 4- (4-Chlorophenoxy) -Nf (1R) - 1-methyl-2- (methylamino) -2-oxoetillthienof2,3-clpyridine-2- carboxamide Example 164A Acid (2R) -2- ( { [4- (4-Chlorophenoxy) thieno [2,3-c] pyridin-2-yl] carboniI] amino) propane Example 164A was prepared in analogy to Example 92, 5 using methyl D-ester alanine hydrochloride in place of ammonium chloride. The ester derivative was hydrolyzed according to the procedure of Example 18 to give the main compound. HPLC: Remove column C-18, water eluent gradient: acetonitrile 0: 90-90: 0 for 30 minutes, detection at 254 nm 10 flow rate of 0.8 mL / min, RT 18.36 minutes. F MS (DCI / NH3) m / e: 377 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 1 .40 (d, J = 7 Hz, 3 H), 4.41 (q, J = 7 Hz, 1 H), 7.15 (m, 2 H), 7.49 (m, 2 H ), 8.19 (s, 1 H), 8.32 (s, 1 H), 9.17 (s, 1 H), 9.23 (d, J = 7 Hz, 1 H), 12.71 (br s, 1 H). Example 164B 4- (4-Chlorophenoxy) -Nr (1R) -1-methyl-2- (methylamino) -2-oxoetyptienof2,3-c1pyridine-2-carboxamide Example 164 was prepared in analogy to Example 92, using hydrochloride D-methyl ester alanine instead of ammonium chloride. The ester derivative was treated according to the procedure of Example 171 to give the main compound. HPLC: Remove column C-18, gradient eluent of water. 0: 90-90: 0 acetonitrile for 30 minutes, detection at 254 nm flow rate of 0.8 mL / min, RT 17.46 minutes. MS (DCi / NH3) m / e: 390 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 1.32 (d, 3 H), 2.60 (d, 3 H), 4.41 (m, 1 H), 7.13 (m, 2 H), 7.49 (m, 2 H), 7.96 (br d, 1 H), 8.19 (s, 1 H), 8.38 (s, 1 H), 9.13 (br d, 1 H), 9.19 (s, 1 H). Example 165 5 4- (4-Chlorophenoxy) -Nf (1S) -1-methyl-2- (methylamino) -2-oxoetyntienof2.3-clpyridine-2-carboxamide Example 165A (2S) -2- acid ((r4- (4-Chlorophenoxy) thienor-2,3-clpyridin-2-carbonyl) amino) propane Example 165A was prepared in analogy to Example 92, 10 using methyl L-ester alanine hydrochloride in place of ammonium. The ester derivative was hydrolyzed according to the procedure of Example 18 to give the main compound. HPLC: Remove column C-18, eluent gradient of water: acetonitrile 0: 90-90: 0 for 30 minutes, detection at 254 nm 15 flow rate of 0.8 mL / min, RT 18.40 minutes. MS (DCI / NH3) m / e: 377 (M + H) +; 'H NMR (300 MHz, DMSO-d6) d 1.40 (d, J = 7 Hz, 3H), 4.41 (q, J = 7 Hz, 1 H), 7.15 (m, 2H), 7.48 (m, 2H) , 8.18 (s, 1 H), 8.31 (s, 1 H), 9.16 (s, f 1 H), 9.21 (d, J = 7 Hz, 1 H), 12.71 (br s, 1 H); 20 13C NMR (100 MHz, DMSO-d6) d 16.78, 48.46, 1 19.52, 1 19.80, 1 19.97, 127.84, 130.13, 132.97, 137.54, 137.60, 138.09, 141.30, 145.59, 147.38, 155.59, 160.54, 173.68. Example 165B 4- (4-Chlorophenoxy) -N-f (1S) -1-methyl-2- (methylamino) -2-oxoetinntienor 2,3-clpyridine-2-carboxamide Example 165B was prepared from Example 165A in analogy to Example 92, with the substitution of methyl L-ester alanine for ammonium chloride. The ester intermediate compound was converted into the main compound according to the procedure of Example 171, using methanolic methylamine. HPLC: Remove column C-18, gradient eluent of water. 0: 90-90: 0 acetonitrile for 30 minutes, detection at 254 nm flow rate of 0.8 mL / min, RT 17.48 minutes. MS (DCI / NH3) m / e: 390 (M + H) +; 10 1 H NMR (300 MHz, DMSO-d 6) d 1 .32 (d, 3 H), 2.59 (d, 3 H), 4.41 (m, F 1 H), 7.13 (m, 2 H), 7.49 (m, 2 H) , 7.94 (br d, 1 H), 8.18 (s, 1 H), 8.36 (s, 1 H), 9.12 (br d, 1 H), 9.19 (s, 1 H). Example 166 4- (4-Chlorophenoxy) -Nf (1R) -1- (hydroxymethyl) -2- (methylamino) -2-oxoethyntienor 2,3- 15 -pyridine-2-carboxamide The main compound was made in analogy to procedure of Example 164B, using D-methyl ester serine. HPLC: Exit column C-18, eluent gradient of ^ water: acetonitrile 0: 90-90: 0 for 30 minutes, detection at 254 nm flow rate of 0.8 mL / min, RT 16.10 minutes. MS (APCI) m / e: 404 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.59 (d, 2 H), 3.69 (m, 2 H), 4.45 (m, 1 H), 4.96 (t, 1 H), 7.14 (m, 2 H), 7.49 ( m, 2H), 7.97 (m, 1 H), 8.18 (s, 1 H), 8.49 (s, 1 H), 9.01 (br d, 1 H), 9.19 (s, 1 H). 25 Example 167 4- (4-Chlorophenoxy) -Nr (1S) -1- (hydroxymetn-2- (methylamino) -2-oxoethylillienor 2,3-clpyridine-2-carboxamide The main compound was made in analogy to the process of Example 164B, using L-methyl ester serine. - ^ ß 5 HPLC: Remove it column C-18, eluent gradient of water: acetonitrile 0: 90-90: 0 for 30 minutes, detection at 254 nm flow rate of 0.8 mL / min, RT 16.18. MS (APCI) m / e: 404 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.59 (d, 2 H), 3.69 (m, 2 H), 4.45 (m, 10 1 H), 4.96 (t, 1 H), 7.14 (m, 2 H), 7.49 (m, 2H), 7.97 (br d, 2H), 8.18 (s, 1 H), 8.49 (s, 1 H), 9.01 (br d, 1 H), 9.19 (s, 1 H). Example 170 4- (3-pyridinyloxy) thienof2,3-c1pyridine-2-carboxamide Example 17A and 3-Hydroxypyridine were processed as in Example 61 to provide the main compound. MS (DCI / NH3) m / e: 272 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 7.50 (m, 2 H), 7.85 (m, 1 H), 8.20 (s, 2 H), 8.45 (dd, 2 H), 8.55 (d, 1 H), 9.20 ( s, 1 H); Anal. cale, for C13H9N3? 2S «0.25H2O: C, 56.61; H, 3.47; N, 15.24. 20 Found: C, 57.01; H, 3.50; N, 15.16. Example 171 Methyl 4- (4-Bromophenoxy) thienor-2,3-clpyridine-2-carboxamide Example 73A (2 g, 5.5 mmol) was suspended in a solution of methylamine in methanol (2 M solution, 15 mL) and refluxed for 1 hour under nitrogen atmosphere. After the solvent is The residue was purified by flash chromatography on silica gel eluting "with 30% acetone in hexane to obtain the main compound (1.96 g, 98%) mp 78-80 ° C; MS (DCI / NH3) m / e: 363, 365 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.79 (d, 3 H), J = 4.8 Hz), 7.06 (d, 2 H), J = 8.8 Hz), 7.59 (d, 2H, J = 8.8 Hz), 8.06 (s, 1 H), 8.20 (s, 1 H), 8.96 (q, 1 H, J = 4.8 Hz), 9.1 7 (s, 1 H). Example 172 4- (4-Bromophenoxy) -N1N-dimethylthienof2.3-clpyridine-2-carboxamide Example 172 was prepared according to the procedure of Example 104, with the substitution of methyl 4- (4-bromophenoxy) -thieno [2, 3-Cjpyridine-2-carboxylate for Example 61A, mp 93-95 ° C; MS (DCI / NH 3) m / e: 377, 379 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 3.02 (br s, 3 H), 3.13 (br s, 3 H), 7.09 (d, 2 H, J = 8.8 Hz), 7.5 (d, 2 H), J = 8.8 Hz), 7.60 (s, 1 H), 8.19 (s, 1 H), 9.15 (s, 1 H) ppm Example 173 NN-Dimethyl-4-f4- (trifluoromethyl) phenoxy-thienof2,3-c1pyridine-2-carboxamide Example 173 was prepared according to the procedure of Example 104, with the substitution of methyl 4- (4-trifluoromethylphenoxy) -thieno [2,3-c] pyridine-2-carboxylate by Example 61 A. mp 74-76 ° C; MS (DCI / NH3) m / e: 367 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 3.17 (br s, 6 H), 7.1 1 (d, 2 H, J = 8.0 Hz), 7.45 (s, 1 H), 7.63 (d, 2 H, J = 8.0 Hz ), 8.24 (br s, 1 H), 9.01 (br s, 1 H). Example 174 4- (4-Chloro-3-fluorophenoxy) - N -methyl-enof2.3-c1pyridine-2-carboxamide Example 174 was prepared as in Example 103, but substituting 4-chlorophenol for 4-chloro-3-fluorophenol to provide the main compound, mp 62-64 ° C; MS (DCI / NH3) m / e: 337 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 3.05 (d, 3 H, J = 4.7 Hz), 6.24 (br s, 1 H), 6.77 (d, 1 H, J = 9.8 Hz), 6.84 (dd, 1 H, J = 2.4, 9.5 Hz), 7.26 (s, 2H), 7.37 (t, 1 H, J = 8.5 Hz), 7.69 (s, 1 H), 8.21 (s, 1 H), 9.00 (s, 1 HOUR); Anal. Cale, for C15H10N2CIFO2S: C, 53.50; H, 2.99; N, 8.32. Found: C, 53.78; H, 3.26; N, 8.02. EXAMPLE 175 4- (4-Chloro-3-fluorophenoxyethylene) 2,3,3-pyridine-2-carboxamide Example 175 was prepared as in Example 61, but replacing 4-chloro-3-fluorophenol with 4-chlorophenol for provide the main compound, mp 227-228 ° C; MS (DCI / NH3) m / e: 323 (M + H) +; * H NMR (300 MHz, DMSO-d6) d 6.94 (m, 1 H), 7.34 (dd, 1 H, J = 3.0, 10.5 Hz), 7.60 (t, 1 H, J = 8.7 Hz), 7.87 (s, 1 H), 8.1 1 (s, 1 H), 8.26 (s, 1 H), 8.44 (s, 1 H), 9.19 (s, 1 H); Anal. cale, for C? 4H8N2CIFO2S: C, 52.10; H, 2.50; N, 8.68. Found: C, 52.06; H, 2.49; N, 8.52. Example 176 4- (4-Chloro-3-ethylphenoxy) thienof2,3-clpyridine-2-carboxamide Example 17A and 4-Chloro-3-ethylphenol were processed as in Example 61 to provide the main compound, mp 185-187 ° C; MS (DCI / NH3) m / e: 333 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 1 .15 (t, 3 H), 2.70 (q, 2 H), 6.95 (dd, 10 1 H), 7.20 (d, 1 H), 7.45 (d, 1 H ), 7.85 (br s, 1 H), 8.15 (s, 1 H), 8.45 (m, f 1 H), 9.15 (s, 1 H). Example 177 4- (3-Fuorophenoxy) thienor-2,3-clpyridine-2-carboxamide Example 177 was prepared according to the procedure of Example 61, with the substitution of 3-fluorophenol for 4-chlorophenol. mp 215-216 ° C; MS (DCI / NH3) m / e: 289 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 6.90 (m, 1 H), 7.05 (m, 2H), 7.43 (q, f 1 H, J = 8.6 Hz), 7.86 (br s, 1 H), 8.14 (s, 1 H), 8.20 (s, 1 H), 8.45 (br s, 1 H), 9.17 (s, 1 H). Example 178 4- (2,3-Difluorophenoxy) thienor-2,3-c1pyridine-2-carboxamide Example 178 was prepared according to the procedure of Example 61, with the substitution of 2,3-difluorophenol for 4-chlorophenol. 25 mp 207-209 ° C; MS (DCI / NH3) m / e: 307 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 6.97 (t, 1 H, J = 8.5 Hz), 7.22 (q, 1 H, J = 8.5 Hz), 7.32 (q, 1 H, J = 8.5 Hz), 7.87 (br s, 1 H), 8.18 (s, 1 H), 8.21 (s, 1 H), 8.43 (br s, 1 H), 9.1 7 (s, 1 H). Example 179 4- (2,3-Difluorophenoxy) -N-methylthienor-2,3-c1pyridine-2-carboxamide Example 179 was prepared according to the procedure of Example 103, with the substitution of 2,3-difluorophenol for 4-chlorophenol. mp 169-171 ° C; MS (DCI / NH3) m / e: 321 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.88 (d, 3 H, J = 4.4 Hz), 6.94 (t, 1 H, J = 8.5 Hz), 7.21 (q, 1 H, J = 8.5 Hz), 7.31 (q, 1 H, J = 8.5 Hz), 8.14 (s, 1 H), 8.21 (s, 1 H), 8.95 (q, 1 H, J = 4.5 Hz), 9.17 (s, 1 H). Example 180 4- (3-Fluorophenoxy) -N-methylthienor-2,3-c1pyridine-2-carboxamide Example 180 prepared according to the procedure of Example 103 with the substitution of 3-fluorophenol for 4-chlorophenol. mp 194-195 ° C; MS (DCI / NH3) m / e: 303 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.79 (d, 3 H, J = 4.4 Hz), 6.87 (d, 1 H, J = 8.5 Hz), 7.05 (m, 2 H) 7.42 (q, 1 H, J = 8.5 Hz), 8.05 (s, 1 H), 8.23 (s, 1 H), 8.95 (q, 1 H, J = 4.4 Hz), 9.17 (s, 1 H). Example 181 N-methyl-4- (2,3,4-trifluorophenoxy) thienof2,3-c1pyridine-2-carboxamide Example 181 was prepared according to the procedure of Example 103, with the substitution of 2,3,4-trifluorophenol for 4-chlorophenol. mp 170-171 ° C; MS (DCI / NH3) m / e: 339 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.82 (d, 3 H, J = 4.4 Hz), 7.13 (m, 1 H), 7. 35 (q, 1 H, J = 8.5 Hz), 8.16 (s, 1 H), 8.17 (s, 1 H), 8.97 (q, 1 H, J = 4.5 Hz), 9.16 (s, 1 H). EXAMPLE 182 4- (2.3.4-trifluorophenoxy) t-inof2.3-chlorpyridine-2-carboxamide Example 182 was prepared according to the procedure of Example 61, with the substitution of 2,3,4-trifluorophenol for 4-chlorophenol. mp 218-219 ° C; MS (DCI / H3) m / e: 325 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 7.15 (m, 1 H), 7.38 (q, 1 H, J = 8.5 Hz), 7. 89 (br s, 1 H), 8.15 (s, 1 H), 8.23 (s, 1 H), 8.45 (br s, 1 H), 9.15 (s, 1 HOUR). Example 183 N-Methyl-4-f4- (trifluoromethyl) phenoxyptiene-2,3-c1pyridine-2-carboxamide Example 183 was prepared according to the procedure of Example 103, with the substitution of 4-trifluoromethylphenol for 4-chlorophenol. mp 157-158 ° C; MS (DCI / NH3) m / e: 353 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.78 (d, 3H, J = 4.4 Hz), 7.22 (d, 2H, J = 8.5 Hz), 7.76 (d, 2H, J = 8.5 Hz), 8.01 (s, 1 H), 8.34 (s, 1 H), 8.92 (q, 1 H, J = 4.4 Hz), 9.24 (s) , 1 HOUR). Example 184 4-f3-p "rifluoromethyl) phenoxyptienor2i3-c1pyridine-2-carboxamide Example 17A and 3-trifluoromethylphenol were processed as in Example 183 to provide the main compound, mp 175-176 ° C; MS (DCI / NH3) m / e: 353 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 2.80 (d, 3 H), 7.35 (d, 1 H), 7.20 (d, 1 H), 7.60 (m, 3 H) ), 8.10 (s, 1 H), 8.30 (s, 1 H), 9.00 (b, 2H), 9.25 (s, 1 H), Anal cale, for C1ßH11 F3N2O2S-0.25H2 ?: C, 53.86; 3.25; N, 7.85 Found: C, 53.60; H, 3.06; N, 7.78 Example 185 NN-dimethyM- (4-vinylphenoxy) thienof213-c1pyridine-2-carboxamide Example 185 was prepared according to the procedure of Example 107, with the substitution of 4-vinylphenol for 4-chlorophenol mp 80-81 ° C; MS (DCI / NH3) m / e: 325 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 3.02 (br s, 3 H), 3.13 (br s, 3 H), 5.24. (d, 1 H, J = 1 1.4 Hz), 5.78 (d, 1 H, J = 17.3 Hz), 6.74 (dd, 1 H), J = 1 1.4, 17.3 Hz), 7.09 (d, 2H), J = 8.5 Hz), 7.53 (d, 2H, J = 8.5 Hz), 7.61 (s, 1 H), 8.16 (s, 1 H), 9.13 (s, 1 H). Example 186 4- (4-cyanophenoxy) -N-methylthienof2.3-clpyridine-2-carboxamide Example 186 was prepared as in Example 103 but substituting 4-cyanophenol for 4-chlorophenol to provide the main compound. MS (ESI / NH3) m / e: 310 (M + H) +; • 5 1 H NMR (300 MHz, DMSO-dβ) d 2.78 (d, 3 H, J = 4.4 Hz), 7.20 (d, 2 H, J = 8.8 Hz), 7.89 (d, 2 H, J = 8.8 Hz), 7.97 (s, 1 H), 8.37 (s, 1 H), 8.94 (q, 1 H, J = 4.4 Hz), 9.26 (s, 1 H); Anal. cale, for C ^ HuNsOzS O.Od CH2Cl2: C, 61 .46; H, 3.56; N, 13.30. Found: C, 61.29; H, 3.53; N, 13.23. 10 Example 187 • 4- (4-Cyanophenoxy) thienof2.3-c1pyridine-2-carboxamide Example 187 was prepared as in Example 61 but substituting 4-cyanophenol for 4-chlorophenol to provide the main compound. 15 mp 255-257 ° C; MS (ESI / NH3) m / e: 296 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 7.20 (d, 2 H, J = 8.8 Hz), 7.84 (s, 1 H), 7.89 (d, 2 H, J = 8.8 Hz), 8.05 (s, 1 H) , 8.36 (s, 1 H), 8.41 (q, 1 H, J = 4.4 Hz), 9.26 (s, 1 H); 20 Anal. cale, for C15H9N3O2S-1 .5 CH3OH: C, 57.71; H, 3.08; N, 12.24. Found: C, 57.45; H, 3.28; N, 12.43. Example 188 4- (4-aminophenoxy) thienof2,3-c1pyridine-2-carboxamide Example 188A 25 3-Chloro-5- (4- (tert-butyloxycarbonyl) amino) phenoxy-4-pyridinecarboxyaldehyde To a solution of Example 17A (2.0 g, 11.4 mmol) and tert-butyl N- (4-hydroxyphenyl) carbamate (2.38 g, 1 1.4 mmol) which was prepared according to the literature method (A. Vigroux , M. Bergon, C. Zedde, J. Med. Chem. 1995, 38, 3983) in DMF (30 mL) was treated with CsCO3 (3.70 g, 11.1 mmol) at room temperature for 1 hour, and at 70 ° C for 30 minutes. Brine (150 mL) was added, and the mixture was extracted with ether / ethyl acetate (2x200 mL). The organic phases were dried (MgSO4), and concentrated. Flash chromatography of the residue on silica gel with 1: 6 ethyl acetate / hexane gave the designated compound (2.65 g, 67%). MS (ESI / NH3) m / e: 349 (M + H) +; Example 188B Methyl 4 - ((4-tert-butyloxycarbonylamino) phenoxy) thienof2.3-c1 pyridine-2-carboxylate A solution of Example 188A (2.64 g, 7.58 mmol) in THF (30 mL) was treated with methyl thioglycolate (804 mg , 7.58 mmol) at 0 ° C for 0.5 hour, and at room temperature for 1 hour, after which Cs2CO3 (2.47 g, 7.58 mmol) was added. The reaction mixture was stirred at room temperature for 1 hour, and at 70 ° C for 0.5 hour. Brine (150 mL) was added and the mixture was extracted with ethyl acetate (2x150 mL). The combined organic phases were dried (MgSO4) and concentrated. The residue was chromatographed instantaneously on silica gel with 20% ethyl acetate in hexane to provide the designated compound (1.29 g, 43%) MS (ESI / NH3) m / e: 401 (M + H) +; Example 188C 4-r (4- (tert-Butyloxycarbonylamino) phenoxy) thienof2.3-c1 pyridine2-carboxamide Example 188C was prepared as in Example 44 but substituting Example 188B for Example 43 to provide the main compound. MS (ESI / NH3) m / e: 386 (M + H) +; Example 188D 4- (4-Aminophenoxy) thienof2.3-c1pyridine-2-carboxamide Example 188C was dissolved in trifluoroacetic acid (20 mL), and the solution was maintained at room temperature for 1 hour before TFA was removed. The residual oil was treated with a mixture of ethyl acetate and aqueous NaHCO3 solution. The solid formed was collected by filtration, rinsed successively with ethyl acetate, aqueous NaHCO3 solution, water, methanol and ethyl acetate, and dried to provide the main compound (492 mp> 250 ° C; MS (DCI / NH3) m / e: 286 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 5.62 (br s, 2H), 6.65 (d, 2H, J = 8.8 Hz), 6.93 (d, 2H, J = 8.8 Hz), 7.86 (s, 1 H), 8.30 (s, 1 H), 8.44 (s, 1 H), 9.00 (br s, 1 H); Anal cale, for C ^ HuNaOzS O.OS CH3OH : C, 57.59; H, 3.85; N, 13.94 Found: C, 57.69; H, 3.95; N, 13.57 Example 189 4-f4- (Acetylamino) phenoxyptienof2.3-clpyridine-2-carboxamide Example 189 was prepared as in Example 188C but substituting 4- (acetylamino) phenol for t-butyl N- (4-hydroxyphenyl) carbamate to provide the main compound. MS (DCI / NH3) m / e: 328 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.04 (s, 3 H), 7.10 (d, 2 H, J = 8.8 Hz), 7.65 (d, 2 H, J = 8.8 Hz), 7.82 (br s, 1 H) , 7.99 (s, 1 H), 8.20 (s, 1 H), 8.43 (br s, 1 H), 9.06 (s, 1 H), 9.99 (s, 1 H); Anal. cale, for C 16 H 3 N 3 O 3 S-1 .0 CH 3 OH: C, 56.81; H, 3.93; N, 1 1 .69. Found: C, 56.51; H, 3.93; N, 1 1 .57. Example 190 N-methyl-4-r4- (4-morpholinyl) phenoxythienof2.3-c1pyridine-2-carboxamide Example 190A Methyl-4-f4- (4-vodofenoxptienor2.3-c1pyridine-2-carboxylate Example 190A was prepared as in Example 61A but replacing 4-iodophenol with 4-chlorophenol to give the designated compound MS (DCI / NH3) m / e: 412 (M + H) +; Example 190B N-methyl-4-f4- (4- vodofenoxi) ltienor2.3-clpyridine-2-carboxamide A solution of Example 190A (1.4 g, 3.4 mmol) in methylamine / methanol (2.0 M solution, 70 mL) was stirred at 45 ° C for 15 hours, and concentrated The residue was flash chromatographed on silica gel with EtOAc / hexane (1.5 / 1) to give the designated compound (1.3 g, 93%) MS (DCI / NH3) m / e: 411 ( M + H) +, Example 190C N-methyl-4-f4- (4-morpholinyl) phenoxythienor2.3-chlorpyridine-2-carboxamide A two-necked flask was charged with Example 190B (150 mg, 0.37 mmol), NaOBu-t (71 mg, 0.74 mmol), Pd2 (dba) 3 (14 mg, 0.014 mmol), BINAP (27 mg, 0.044 mmol) and 18-crown-6 (196 mg, 0.74 • 5 mmol) and purged with nitrogen. THF anhydrous (10 mL) and morpholine (64 mg, 0.74 mmol) were added successively. The light dark red solution was heated at 60 ° C for 70 hours, and cooled with brine. The mixture was extracted with methylene chloride. The organic layer was dried (MgSO) and concentrated. The crude was flash chromatographed on silica gel (EtOAc / hexane) and further purified on HPLC (C-18, CH3CN / H2O) to provide the • Main compound (26 mg). MS (DCI / NH3) m / e: 370 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.81 (d, 3 H, J = 4.5 Hz), 3.1 (m, 2 H), 15 3.74 (m, 2 H), 6.99 (d, 2 H, J = 8.8 Hz), 7.05 (d, 2H, J = 8.8 Hz), 7.92 (s, 1 H), 8.20 (s, 1 H), 8.98 (q, 1 H, J = 4.8 Hz), 9.04 (s, 1 H). Example 191 4-r4- (Hydroxymethyl) phenoxythienof2.3-clpyridine-2-carboxamide Example 191A 20 Methyl 4- (4-f (trityloxy) metipfenoxythienof2.3-clpyridine-2-carboxylate Example 191 A was prepared as in Example 61 A but substituting 4-trityloxymethylphene which was prepared according to the literature method (Frank, R., Doring, R. Tetrahedron 1988, 44, 6031) by 4-chlorophenol to provide the main compound, 25 MS (DCI / NH3). ) m / e: 558 (M + H) +; Example 191 B 4 4-f (Trityloxy) metillphenoxy} tienor2.3-c1pyridine-2-carboxamide Example 191A was prepared as in Example 61 but replacing 4-trityloxymethylphenol with 4-chlorophenol to provide the • 5 main compound. MS (DCI / NH3) m / e: 543 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 4.10 (s, 2 H), 7.1 1 (d, 2 H, J = 8.5 Hz), 7.26-7.46 (m, 17 H), 7.87 (brs, 1 H), 8.09 ( s, 1 H), 8.21 (s, 1 H), 8.46 (brs, 1 H), 9.12 (s, 1 H) ppm. 10 Anal. cale, for C34H26 2O3S: C, 75.25; H, 4.83; N, 5.16. Found: C, 75.17; H, 4.76; N, 5.15. • Example 191 C Methyl 4-.4-hydroxymethyl) phenoxy} thienoy 2,3-clpyridine-2-carboxylate A solution of Example 191A (5.05 g, 9 mmol) in a mixture of chloroform (20 mL) and methanol (8 mL) was treated with trifluoroacetic acid (10 mL) at 0 ° C. for 6 hours, and then poured into a mixture of ice and saturated NaHCO3. The mixture was extracted with methylene chloride (2x200 mL). The combined organic layers were dried (MgSO), and concentrated. The residue was flash chromatographed on silica gel with 66% EtOAc / hexane to give the designated compound (2.1 1 g, 74%). MS (DCI / NH3) m / e: 316 (M + H) +; Example 191 D 4-f4-Hydroxymethyl) phenoxy) thienof2,3-clpyridine-2-carboxamide Example 191 D was prepared as in Example 61 but substituting Example 191 C for Example 61 A to provide the main compound. MS (DCI / NH3) m / e: 301 (M + H) +; f 1 H NMR (300 MHz, DMSO-dβ) d 4.50 (d, 2H, J = 5.8 Hz), 5.19 (t, 1 H, J = 5.8 Hz), 7.10 (d, 2 H, J = 8.5 Hz), 7.37 (d, 2 H, J = 8.5 Hz), 7.82 (br s, 1 H), 8.03 (s, 1 H), 8.20 ( s, 1 H), 8.43 (br s, 1 H), 9.09 (s, 1 H); Anal. cale, for C15H? 2N2O3S: C, 59.99; H, 4.03; N, 9.33. Found: C, 59.82; H, 3.93; N, 8.82. Example 192 10 4-f4- (Hydroxymethyl) phenoxy-N-methylthienof2.3-c1pyridine-2-carboxamide k Example 192 was prepared as in Example 103 but substituting Example 191 C for Example 61 A to provide the compound principal, mp 195-196 ° C; MS (DCI / NH3) m / e: 315 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.80 (d, 3 H, J = 4.5 Hz), 4.49 (d, 2 H, J = 4.5 Hz), 5.19 (t, 1 H, J = 4.5 Hz), 7.08 ( d, 2H, J = 8.5 Hz), 7.37 (d, 2H, J = 8.5 Hz), 8.07 (s, 1 H), 8.1 1 (s, 1 H), 8.94 (q, 1 H, J = 4.5 Hz ), 9.10 (s, f 1 H); 20 Anal. cale, for C1ßH14N2O3S-0.75 CH3OH: C, 59.45; H, 4.39; N, 8.28. Found: C, 59.31; H, 4.35; N, 8.49. Example 193 4-f4- (Methoxymethyl) phenoxy-N-methylthienor-2,3-clpyridine-2-carboxamide Example 193 was prepared as in Example 188C but substituting 4-methoxymethylphenol for 4-tert-butyloxycarbonylaminophenol and replacing methylamine with ammonium to provide the main compound, mp 163-164 ° C; MS (DCI / NH3) m / e: 329 (M + H) +; ^ 5 1 H NMR (300 MHz, DMSO-dβ) d 2.79 (d, 3 H, J = 4.4 Hz), 3.29 (s, 3 H), 4.40 (s, 2 H), 7.08 (d, 2 H, J = 8.5 Hz) , 7.37 (d, 2H, J = 8.5 Hz), 8.09 (s, 1 H), 8.12 (s, 1 H), 8.94 (q, 1 H, J = 4.4 Hz), 9.12 (s, 1 H); Anal. cale, for C 17 H 16 N 2 O 3 S: C, 62.18; H, 4.91; N, 8.53. Found: C, 61.86; H, 4.79; N, 8.40. Example 194 4- (4-f (2-Methoxyethoxy) metinphenoxy> tienof2.3-clpyridine-2-carboxamide • Example 194 was prepared as in Example 188C but substituting 4- (2-methoxyethoxymethyl) phenol for 4-tert - butyloxycarbonylaminophenol to give the main compound: MS (DCI / NH3) m / e: 359 (M + H) +; 1H NMR (300 MHz, CDCl 3) d 3.40 (s, 3H), 3.60 (m, 2H), 3.65 (m, 2H), 4.56 (s, 2H), 7.02 (d, 2H, J = 8.5 Hz), 7.36 (d, 2H, J = 8.5 Hz), 7.80 (s, 1 H), 8.13 (s, 1 H), 8.94 (s, 1 H); Anal cale, for C18H18N2O4S: C, 60.32; H, 5.06; N, 7.82, Found: 20 C, 60.33; H, 5.03; N, 7.63, Example 195 4- 4-r (2-Methoxyethoxy) methanfenoxi) -N-methylthienof2.3-clpyridine-2-carboxamide Example 195 was prepared as in Example 188C but substituting 4- (2-methoxyethoxymethyl) phenol for 4-tert - butyloxycarbonylaminophenol and substituting methylamine for ammonium to provide the main compound, mp 133-134 ° C; MS (DCI / NH3) m / e: 373 (M + H) +; 1 H NMR (300 MHz, CDCl 3) d 3.01 (d, 3 H, J = 5.1 Hz), 3.40 (s, 3 H), 3.60 (m, 2 H), 3.65 (m, 2 H), 4.54 (s, 2 H), 6.51 (q, 1 H, J = 5.1 Hz), 7.00 (d, 2H, J = 8.5 Hz), 7.34 (d, 2H, J = 8.5 Hz), 7.73 (s, 1 H), 8.14 (s, 1 H) ), 8.94 (s, 1 H); Anal. cale, for C19H2oN2O4S: C, 61.27; H, 5.41; N, 7.52. Found: C, 61.28; H, 5.35; N, 7.46. Example 196 4- (4- (f2- (2-Methoxyethoxy) ethoxymethyl phenoxy) thienof2.3-clpyridine-2-carboxamide Example 196 was prepared as in Example 188C but substituting 4-. { 2- (2-methoxyethoxy) ethoxymethyl} phenol by 4-tert-butyloxycarbonylaminophenol to provide the main compound. MS (DCI / NH3) m / e: 403 (M + H) +; H NMR (300 MHz, CDCl 3) d 3.38 (s, 3 H), 3.57 (m, 2 H), 3.63-3.70 (m, 6 H), 4.55 (s, 2 H), 7.02 (d, 2 H, J = 8.5 Hz) , 7.36 (d, 2H, J = 8.5 Hz), 7.71 (s, 1 H), 8.15 (s, 1 H), 8.95 (s, 1 H). Example 197 4- (4- (f2- (2-Methoxyethoxy) ethoxymethyl} phenoxy) -N-methyltienof2.3-clpyridine-2-carboxamide Example 197 was prepared as in Example 188C but substituting 4 -. {2- (2-methoxyethoxy) ethoxymethyl} phenol by 4-tert-butyloxycarbonylaminophenol to give the main compound MS (DCI / NH3) m / e: 417 (M + H) +; 1 H NMR (300 MHz, CDCl 3) d 3.02 (d, 3 H, J = 4.8 Hz), 3.38 (s, 3 H), 3.57 (m, 2 H), 3.63-3.70 (m, 6 H), 4.54 (s, 2 H) , 6.45 (m, 1 H), 7.00 (d, 2H, J = 8.5 Hz), 7.34 (d, 2H, J = 8.5 Hz), 7.72 (s, 1 H), 8.15 (s, 1 H), 8.94 (s, 1 H). • Example 198 4- (4-f (2,3,4,5-Tetrahydro-2H-pyran-2-yloxy) metiphenoxy> thienof2,3-clpyridine-2-carboxamide Example 198A Methyl 4-l4-ir ( 2.3.4.5-tetrahydro-2H-pyran-2-yl) oxpmethyl) phenoxy) thienor 2,3-clpyridine-2-carboxylate Example 198A was prepared as in Example 188B but • substituting 4 - [(2,3,4,5-tetrahydro-2H-pyran-2-yl) oxy] methylphenol (PA Grieco, et al., J. Org. Chem. 1977, 42, 3772) for 4- tert-butyloxycarbonylaminophenol to provide the designated compound. MS (DCI / NH3) m / e: 400 (M + H) +; Example 198B 4- (4-. {F (2,3,4,5-Tetrahydro-2H-pyran-2-yloxpmethyl) phenoxy) thienof2,3-clpyridine-2-carboxamide Example 198B was prepared as in Example 61 but replacing Example 198A by Example 61 A to provide the designated compound: mp 95-96 ° C; MS (DCI / NH3) m / e: 385 (M + H) +; 1H NMR (300 MHz, DMSO -dß) d 1.49 (m, 4H), 1.69 (m, 2H), 3.49 (m, 25 1 H), 3.80 (m, 1 H), 4.44 (d, 1 HJ = 12.1 Hz), 4.67 (d, 1 H, J = 12.1 Hz), 4. 70 (m, 1 H), 7.10 (d, 2H, J = 8.8 Hz), 7.41 (d, 2H), J = 8.8 Hz), 7.87 (s, 1 H), 8.08 (s, 1 H), 8.20 (s, 1 H), 8.46 (s, 1 H), 9.12 (s, 1 H); Anal. cale, for C2oH2oN2? 4S CH3OH: C, 60.56; H, 5.08; N, 6.73. Found: C, 60.51; H, 5.07; N, 6.59. Example 199 N-Methyl-4- (4-f (tetrahydro-2 H -pyran-2-yloxy) methyphenoxy) thieno (2,3-clpyridine-2-carboxamide Example 199 was prepared as in Example 103 but substituting Example 198A for Example 61 A to provide the designated compound, mp 195-196 ° C; MS (DCI / NH3) m / e: 399 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 1. 49 (m, 4H), 1.69 (m, 2H), 2.79 (d, 3H, J = 4.8 Hz), 3.50 (m, 1 H), 3.80 (m, 1 H), 4.44 (d, 1 H) , J = 12.1 Hz), 4.67 (d, 1 H, J = 12.1 Hz), 4.70 (m, 1 H), 7.09 (d, 2 H, J = 8.8 Hz), 7.40 (d, 2 H, J = 8.8 Hz ), 8.1 1 (s, 1 H), 8.12 (s, 1 H), 8.97 (q, 1 H, J = 4.8 Hz), 9.13 (s, 1 H); Anal cale, for i C21H22N2O4S: C, 63.30; H, 5.56; N, 7.03, Found: C, 63.22; H, 5.58; N, 6.93, Example 200 4-ff2- (Aminocarbonyl) thienor-2,3-clpyridin-4-inoxi) benzyl 2-furoate One solution of Example 191 D (40 mg, 0.133 mmol) in DMF (5 mL) was treated with 2-furoic acid (45 mg, 0.4 mmol), HOBt (54 mg, 0.4 mmol), EDC (77 mg, 0.4 mmol) and 2 drops of triethylamine at room temperature for 48 hours. Brine was added and the The mixture was extracted with EtOAc. The combined organic phases were rinsed with water, dried (MgSO4) and concentrated. The residue was flash chromatographed on silica gel with 65% EtOAc / hexane to provide the designated compound. mp 180-182 ° C; MS (DCI / NH3) m / e: 395 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 5.31 (s, 2 H), 6.70 (dd, 1 H, J = 1.7, 3.4 Hz), 7.14 (d, 2 H, J = 8.5 Hz), 7.36 (d , 1 H, J = 3.4 Hz), 7.50 (d, 2H, J = 8.5 Hz), 7.84 (s, 1 H), 8.00 (dd, 1 H, J = 1 .1, 3.7 Hz), 8.13 (s) , 1 H), 8.17 (s, 1 H), 8.44 (s, 1 H), 9.14 (s, 1 H). EXAMPLE 201 4-f4- (ff (2R.4R.5S.6R) -4.5-Dihydroxy-6- (hydroxymethyl) tetrahydro-2H-pyran-2-fl-oxy) methyl-phenoxy-N-methylthieno-2,3-clpyridine -2-carboxamide Example 201A Methyl 4-f4- (ff (2R.4R.5S.6R) -4.5-Dihydroxy-6- (hydroxymethyl) tetrahydro-2H-pyran-2-yl) methyl) phenoxy-N-methylthienof2. 3-Clpyridine-2-carboxylate A solution of Example 191 C (200 mg, 0.63 mmol) and tri-O-acetyl-D-glical (520 mg, 1.92 mmol) in dry CH 2 Cl 2 (10 mL) was treated with Sc (OTf) 3 (380 mg, 0.75 mmol) at room temperature for 12 hours, and flash chromatographed directly on silica gel with 40% EtOAc / hexane to provide the designated compound. MS (DCI / NH3) m / e: 528 (M-OAc) +. Example 201 B 4-f4- (ff (2R.4R.5S.6R) -4.5-Dihydroxy-6- (hydroxymethyl) tetrahydro-2H-pyran-2- Noxi > methyl) phenoxyN-methyl-2,3-entropyl-2-carboxamide A solution of Example 201 A (167 mg) in a 2M solution of methylamine in methanol (10 mL) was heated to 45 ° C. for 12 hours, and concentrated. The residual oil was chromatographed on a gel silica with 8% MeOH / CH 2 Cl 2 to give the designated compound (120 mg, 91%). MS (ESI / NH3) m / e: 443 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.79 (d, 3 H, J = 4.8 Hz), 3.53 (m, 3 H), 3.67 (m, 1 H), 3.87 (m, 1 H), 4.50 (d, 1 H, J = 1 1 .5 Hz), 4.64 (t, 1 H, J = 5.4 Hz), 476, (d, 1 H, J = 1 1.5 Hz), 5.06 (m, 2H), 5.70 (dt, 1 H, J = 10.2, 2.4 Hz), 5.86 (d, 1 H, J = 10.2 Hz), 7.08 (d, 2H, J = 8.5 Hz), 7.40 (d, 2H, • J = 8.5 Hz), 8.10 (s, 1 H), 8.1 1 (s, 1 H), 8.95 (q, 1 H, J = 4.8 Hz), 9.12 (s, 1 H). Example 202: 4- (4-Acetylphenoxy) -N-methylthienof2.3-clpyridine-2-carboxamide A flask, purged with nitrogen, was charged with Example 190B (500 mg, 1.2 mmol), Pd (OAc) 2 (27 mg, 0.12 mmol), (Tol) 3P (10 mg, 0.36 mmol), dry degassed DMF (20 mL), tributylethoxyvinyltin (810 mL, 2.4 mmol), and trethylamine (835 mL, 6 • 20 mmol). This suspension was stirred at 80 ° C for 14 hours. After diluting with ethyl acetate, the reaction mixture was rinsed with 1% aqueous HCl solution, water, dried (MgSO4) and concentrated. The residue was separated by HPLC (C-18, CH3CN / H2O containing 0.1% TFA) to provide the main compound (476 mg, 89%) 25 MS (DCI / NH3) m / e: 327 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 2.56 (s, 3 H), 2.78 (d, 3 H, J = 4.8 Hz), 7.15 (d, 2 H, J = 8.8 Hz), 8.00 (d, 2 H, J = 8.8 Hz), 8.03 (s, 1 H), 8.36 (s, 1 H), 8.98 (q, 1 H, J = 4.8 Hz), 8.28 (s, 1 H); Anal. cale, for C 17 H 14 N 2 O 3 S -1 1.35 CF 3 CO 2 H: C, 49.25; H, 3.45; N, 5.83. Found: C, 49.31; H, 3.60; N, 5.93. Example 203 4-f4- (4-Morpholinylcarbonyl) phenoxythienof2.3-c1pyridine-2-carboxamide Example 203 A Methyl 4-f4- (4-carboxy) phenoxythienof2.3-c1pyridine-2-carboxylate A suspension of methyl 4- bromophenoxythieno [2,3-c] pyridine-2-carboxylate (1.0 g, 2.74 mmol), PdCI2DPPFCH2CI2 (0.284 g), and triethylamine (0.55 g) in a mixture of THF (15 mL) and H2O (15 mL) it was heated to 130 ° C under CO atmosphere (400 psi) for 19 hours. EtOAc (200 mL) was added, and the mixture was rinsed with brine, dried (MgSO4), and concentrated. The residue was flash chromatographed on silica gel with 5% CH3OH / CH2Cl2 to provide the designated compound (31 1 mg, 34%). MS (DCI / NH3) m / e: 330 (M + H) +. EXAMPLE 203B Methyl 4-γ4- (4-morpholinylcarbonyl) phenoxyphenof2.3-chlorpyridine-2-carboxylate A solution of Example 203A (200 mg, 0.61 mmol) in a mixture DMF (5 mL) and CH2Cl2 (15 mL ) was treated with morpholine (80 mg, 0.91 mmol), PyBOP (474 mg, 0.91 mmol) and DIPEA (296 mg, 2.8 mmol) at room temperature for 2 hours. After diluting with CH2Cl2, the solution was rinsed with brine, dried (MgSO4), and concentrated. The residue was flash chromatographed on silica gel with 90% EtOAc / hexane to give the designated compound (277 mg, 100%). 90% EtOAc / hexane 5 MS (DCI / NH3) m / e: 399 (M + H) +. Example 203C 4-f4- (4-morpholinylcarbonyl) phenoxyptienor 2,3-clpyridine-2-carboxamide Example 203C was prepared as in Example 64 but substituting Example 203B for Example 61A to provide the main compound, mp > 260 ° C; • MS (DCI / NH3) m / e: 401 (M + NH4) +; 1 H NMR (300 MHz, DMSO-dβ) d 3.50 (m, 4 H), 3.60 (m, 4 H), 7.14 (d, 2 H), J = 8.5 Hz), 7.48 (d, 2 H, J = 8.5 Hz), 7.86 (s, 1 H), 8.15 (s, 1 H), 8.22 15 (s, 1 H), 8.45 (s, 1 H), 9.17 (s, 1 H); Anal. cale, for C? 9 H 17 N 3 O 4 S: C, 59.52; H, 4.47; N, 10.96. Found: C, 59.64; H, 4.52; N, 10.90. Example 204 N-methyl-4-f4- (4-morpholinylcarbonyl) phenoxyptienor 2,3-clpyridine-2-carboxamide Example 204 was prepared as in Example 103 but substituting Example 203B for Example 61A to provide the main compound, mp 173-175 ° C; MS (DCI / NH3) m / e: 415 (M + H) +; H NMR (300 MHz, DMSO-d6) d 2.79 (d, 3H, J = 4.4 Hz), 3.50 (m, 4H), 3.60 (m, 4H), 7.12 (d, 2H, J = 8.5 Hz), 7.48 (d, 2H, J = 8.5 Hz), 8.07 (s, 1 H), 8.24 (s, 1 H), 8.96 (q, 1 H, J = 4.4 Hz), 9.18 (s, 1 H); Anal. cale, for C2oH19N3O4S-1 .5 CH3OH: C, 57.96; H, 4.64; N, 9.43. 5 Found: C, 57.99; H, 4.86; N, 9.63. EXAMPLE 206 4-r4- ( { F2- (4-Morpholinyl) ethynamino} carbonyl) phenoxythienof2,3-clpyridine-2-carboxamide Example 206A Methyl 4-r4- ( { R2- ( 4-morpholinyl) ethylamino.} Carbonyl) phenoxyptienor2.3-c1pyridine-2-carboxylate A solution of Example 203A (200 mg, 0.61 mmol) in DMF (11 mL) was treated with 4- (2-aminoethyl) morphsin (158 mg, 1.2. • mmol), EDC (232 mg, 1.21 mmol), HOBt (164 mg, 1.21 mmol) and triethylamine (122 mg, 1.21 mmol) at room temperature for 18 hours. After diluting with EtOAc, the reaction mixture was rinsed with brine, dried (MgSO4), and concentrated. The residue was flash chromatographed on silica gel with 10% MeOH / EtOAc to provide the designated compound (239 mg, 89%). MS (DCI / NH3) m / e: 442 (M + H) +. • Example 206B 4-f4 - ((f2- (4-Morpholinyl) etipamino> carbonyl) phenoxyptofenof2,3-c1pyridine-2-carboxamide Example 206B was prepared as in Example 61 but substituting Example 206A for Example 61A for provide the main compound 25 mp 214-216 ° C; MS (DCI / NH3) m / e: 427 (M + H) +; H NMR (300 MHz, DMSO-d6) d 2.41 (t, 4H, J = 4.8 Hz), 3.37 (q, 2H, J = 6.1 Hz), 3.56 (t, 4H, J = 4.8 Hz), 7.14 (d , 2H, J = 8.8 Hz), 7.84 (s, 1 H), 7.87 (d, 2H, J = 8.8 Hz), 8.1 1 (s, 1 H), 8.22 (s, 1 H), 8.39 (t, 1 H, J = 6.0 5 Hz), 8.43 (s, 1 H), 9.17 (s, 1 H). Example 207 N-Methyl-4-y4- ( { F2- (4-morpholinyl) ethylamino) carbonyl) phenoxy-thienof2,3-clpyridine-2-carboxamide Example 207 was prepared as in Example 103 but 10 substituting Example 206A by Example 61A to provide the main compound, • mp 226-228 ° C; MS (DCI / NH3) m / e: 441 (M + H) +; 1 H NMR (300 MHz, DMSO-de) d 2.42 (m, 4 H), 2.78 (d, 3 H, J = 4.4 Hz), 15 3.36 (q, 2 H, J = 6.1 Hz), 3.56 (t, 4 H, J = 4.8 Hz), 7.12 (d, 2H, J = 8.5 Hz), 7.89 (d, 2H, J = 8.5 Hz), 8.03 (s, 1 H), 8.26 (s, 1 H), 8.41 (t, 1 H, J = 6.0 Hz), 8.95 (q, 1 H, J = 4.4 Hz), 9.20 (s, 1 H). Example 208 4-f4-f (E) -3- (4-Morpholinyl) -3-oxo-1-propeniphenoxy > tienof2.3-c] pyridine-2-carboxamide • 20 Example 208A Methyl 4- (4-f (E) -3- (tert-butyloxy) -3-oxo-1-propenynphenoxy thienof2.3-clpyridine-2-carboxylate A flask, purged with nitrogen, was charged with Example 73 (50 mg, 1.37 mmol), Pd2 (dba3 (63 mg, 0.069 mmol), tri-o-25-tolylphosphine (64 mg, 0.1 mmol), dry degassed DMF (20 mL), acrylate of t-butyl (602 mL, 4.1 1 mmol), and triethylamine (575 mL, 4.1 1 mmol). This suspension was stirred at 100 ° C under nitrogen for 12 hours. After diluting with methyl acetate, the reaction mixture was rinsed with brine, water, dried (MgSO), and concentrated. The residue • 5 was flash chromatographed on silica gel with 20% EtOAc / hexane to provide the main compound (323 mg, 57%). MS (DCI / NH3) m / e: 412 (M + H) +. Example 208B 10 Methyl 4- (4-f (E) -propenoic acid-1-phenoxy.) Thieno-2,3-clpyridine-2-carboxylate A solution of Example 208A (1.76 g, 4.2 mmol) in • chloroform (50 mL) was treated with trifluoroacetic acid (10 mL) at room temperature for 4 hours, and then poured into cold aqueous NaHCO3. The white solid formed was collected by filtration rinsed with water MeOH, CH2CI2, and dried to provide the designated compound (1.38 g, 100%). mp 80-81 ° C; MS (DCI / NH3) m / e: 356 (M + H) +; Example 208C 20 Methyl 4- 4-r (E) -3- (4-morpholinyl) -3-oxo-1-propeninphenoxy thienof2,3-clpyridine-2-carboxylate A solution of Example 208B (260 mg, 0.73 mmol ) in a mixture of DMF (5 mL) and CH2CI2 (10 mL) was treated with morpholine (127 mg, 1.46 mmol), PyBOP (760 mg, 1.46 mmol), and DIPEA (380 mg, 2.92 mmol) at room temperature for 12 hours. After diluting with CH2Cl2, the solution was rinsed with brine, dried (MgSO) and concentrated. The residue was flash chromatographed on silica gel with 90% EtOAc / hexane to give the designated compound. MS (DCI / NH3) m / e: 425 (M + H) +. Example 208D 4- (4-f (E) -3- (4-morpholinyl) -3-oxo-1-propeninphenoxyHienof2,3-clpridine-2-carboxamide Example 208D was prepared as in Example 61 but substituting Example 208C for Example 61A to provide the major compound: MS (DCI / NH3) m / e: 410 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 3.59 (m, 6H), 3.70 ( m, 2H), 7.13 (d, 2H, J = 8.5 Hz), 7.20 (d, 1 H, J = 15.5 Hz), 7.52 (d, 1 H, J = 15.5 Hz), 7.79 (d, 2H, J = 8.5 Hz), 7.86 (s, 1 H), 8.16 (s, 1 H), 8.18 (s, 1 H), 8.45 (s, 1 H), 9.17 (s, 1 H) Example 209 4-f4 - ((E) -3-y2- (4-morpholinyl) ethylamino) -3-oxo-1-propenyl) phenoxy-1-eneof2.3-clpyridine-2-carboxamide Example 209A Methyl 4-f4- ((E) -3- { F2- (4-morpholinyl) ethylamino> -3-oxo-1-propenyl) phenoxyphenof2.3-clpyridine-2-carboxylate Example 209A was prepared as in Example 208C but substituting 4 - (2-aminoethyl) morpholine by morpholine to provide the designated compound. MS (DCI / NH3) m / e: 468 (M + H) +. Example 209B 4-f4 - ((E) -3-ff2- (4-morpholinyl) ethylamino-V-3-oxo-1-propenyl) phenoxyptiene-2,3-clpyridine-2-carboxamide Example 209B was prepared as in Example 61 but substituting Example 209A for Example 61A to provide the main compound. MS (DCI / NH3) m / e: 453 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.44 (m, 4 H), 3.30 (m, 4 H), 3.59 (t, 4 H, J = 4.8 Hz), 6.60 (d, 1 H, J = 15.8 Hz) , 7.13 (d, 2H, J = 8.8 Hz), 7.42 (d, 1 H, J = 15.8 Hz), 7.61 (d, 2H, J = 8.8 Hz), 7.87 (s, 1 H), 8.06 (t, 1 H, 10 J = 4.8 Hz), 8.16 (s, 1 H), 8.21 (s, 1 H), 8.45 (s, 1 H), 9.17 (s, 1 H). Example 210 • N-methyl-4-f4 - ((E) -3 f2- (4-morpholinyl) ethylamino-V-3-oxo-1-propenyl) phenoxyethyl 2,3-clPyridine-2-carboxamide Example 210 was prepared as in Example 103 but 15 substituting Example 209A for Example 61A to provide the main compound. MS (DCI / NH3) m / e: 467 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 2.38 (m, 4 H), 2.79 (d, 3 H, J = 4.4 Hz), 3.59 (m, 8 H), 6.58 (d, 1 H, J = 15.8 Hz), 7.1 1 (d, 2H, J = 8.8 Hz), 7.42 (d, • 20 1 H, J = 15.8 Hz), 7.61 (d, 2H, J = 8.8 Hz), 8.05 (s, 1 H), 8.23 (s, 1 H), 8.95 (q, 1 H, J = 4.4 Hz ), 9.17 (s, 1 H). Example 21 1 4- (4 (E) -3-f (2,3-Dihydroxypropyl) amino-1-oxo-1-propenyl phenoxy) thieno (2,3-c1pyridine-2-carboxamide Example 21 1 A Methyl 4- (4 - ((E) -3 - [(213-Dihydroxypropyl) amino-3-oxo-1-propenyl} phenoxy) tiene (2,3-clpyridine-2-carboxylate A solution of Example 208B ( 250 mg, 0.71 mmol)) in DMF (10 mL) was treated with 3-amino-1,2-propanediol (128 mg, 1.41. • 5 mmoi), EDC (270 mg, 1.41 mmol), HOBt (191 mg, 1.41 mmol) and triethylamine (142 mg, 1.41 mmol) at room temperature for 18 hours. After diluting with EtOAc, the reaction mixture was rinsed with brine, dried (MgSO), and concentrated. The residue was flash chromatographed on silica gel to provide the designated compound (189 mg, 63%) MS (DCI / NH3) m / e: 429 (M + H) +. Example 21 1 B 4- (4-i (E) -3-r (2,3-Dihydroxypropyl) amino-1-oxo-1-propenyl) phenoxy) thieno (2,3-clpyridine-2-carboxamide 15 Example 21 1 B was prepared as in Example 61 but substituting Example 21 1 A for Example 61A to provide the main compound, mp 185-187 ° C; MS (DCI / NH 3) m / e: 414 (M + H) +; 20 1 H NMR (300 MHz, DMSO-dβ) d 3.10 (m, 1 H), 3.30 (m, 2 H), 3.54 (m, 1 H), 4.60 (t, 1 H, J = 5.9 Hz), 4.84 (d, 1 H, J = 4.8 Hz), 6.66 (d, 1 H, J = 15.8 Hz), 7.13 (d, 2H, J = 8.8 Hz), 7.42 (d, 1 H, J = 15.8 Hz), 7.61 (d, 2H, J = 8.8 Hz), 7.86 (s, 1 H), 8.08 (t, 1 H, J = 5.5 Hz), 8.16 (s, 1 H), 8.21 (s, 1 H), 8.45 (s, 1 H), 9.17 (s, 1 H), 25 Anal cale, for C2oH19N3O5S: C, 58.10; H, 4.63; N, 10.16.

Found: C, 57.99; H, 4.54; N, 10.08. Example 212 4- (4-f (E) -3-f (2,3-Dihydroxypropyl) amino-3-oxo-1-propenyl) phenoxy) -N-methylthienof2.3-clyridine-2-carboxamide • Example 212 was prepared as in Example 103 but substituting Example 21 1 A for Example 61 A to provide the main compound, mp 225-226 ° C; MS (DCI / NH3) m / e: 428 (M + H) +; 10 1 H NMR (300 MHz, DMSO-dβ) d 2.79 (d, 3 H, J = 4.8 Hz), 3.10 (m, 1 H), 3.30 (m, 2 H), 3.54 (m, 1 H), 4.60 (t , 1 H, J = 5.5 Hz), 4.84 (d, 1 H, J = 4.8 • Hz), 6.66 (d, 1 H, J = 15.8 Hz), 7.1 1 (d, 2H, J = 8.8 Hz), 7.42 (d, 1 H, J = 15.8 Hz), 7.61 (d, 2H, J = 8.8 Hz), 8.06 (s, 1 H), 8.08 (t, 1 H, J = 5.5 Hz), 8.23 (s, 1 H), 8.97 (q, 1 H, J = 4.8 Hz), 9.18 (s) , 1 HOUR); 15 Anal. cale, for C21H21N3O5S: C, 59.00; H, 4.95; N, 9.83. Found: C, 58.85; H, 4.90; N, 9.58. Example 213 4-f4 - ((E) -3-f | "2- (1H-lmidazol" 4-yl) etipaminoV-3-oxo-1-propenyl) phenoxy-N-methylthienof2,3-clpyridine-2 -carboxamide Example 213 was prepared as in Example 212 but substituting 2- (1 H-imidazol-5-yl) ethylamine for 3-amino-1, 2-propanediol to provide the main compound. MS (DCI / NH3) m / e: 448 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.79 (d, 3 H, J = 4.5 Hz), 2.85 (t, 2 H, 25 J = 6.6 Hz), 3.49 (q, 2 H, J = 6.0 Hz), 6.53 ( d, 1 H, J = 15.8 Hz), 7.1 1 (d, 2H, J = 8.5 Hz), 7.42 (d, 1 H, J = 15.8 Hz), 7.47 (s, 1 H), 7.61 (d, 2H, J = 8.5 Hz), 8.07 (s, 1 H), 8.24 (s, 1 H), 8.27 (t, 1 H, J = 5.5 Hz), 8.97 (q, 1 H, J = 4.8 Hz), 9.01 (s, 1 H), 9.21 (s, 1 H). Example 214 • 5 4- (4-r (E) -3 - ((2 -bis (2-Hydroxyethyl) amino'-1-3-oxo-1-propeninphenoxyVN-methylthienof2.3-clpyridine-2-carboxamide Example 214 was prepared as in Example 212 but substituting 2- [bis (2-hydroxyethyl) amino] ethylamine for 3-amino-1, 2-propanediol to give the main compound 10 MS (DCI / NH3) m / e: 485 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.79. (D, 3H, J = 4.8 Hz), 3.34 (m, 6H), • 3.58 (q, 2H, J = 6.1 Hz), 3.77 (t, 4H, J = 5.1 Hz), 6.55 (d, 1 H, J = 15.6 Hz), 7.13 (d, 2H, J = 8.5 Hz), 7.48 (d, 1 H, J = 15.6 Hz), 7.64 (d, 2H, J = 8.5 Hz), 8.07 (s, 1 H), 8.24 (s, 1 H), 8.43 (t, 1 H, J = 4.8 Hz), 8.97 (q, 15 1 H, J = 4.8 Hz), 9.20 (s, 1 H). Example 215 4- (4-f (E) -3- (. {2-Ibis (2-hydroxyethyl) aminoethyl) amino) -3-oxo-1-propenyphenyl-2,3-clpyridine-2-carboxamide Example 215 prepared as in Example 21 1 but substituting bis (2-hydroxyethyl) aminoethylamine for 3-amino-1, 2-propanediol to provide the major compound: MS (DCI / NH3) m / e: 471 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.56 (m, 4H), 3.21 (m, 2H), 3.41 (m, 4H), 4.37 (t, 2H, J = 5.6 Hz), 6.56 (d, 1 H, J = 15.4 Hz), 7.13 (d, 2H, J = 8.8 Hz), 7.42 (d, 1 H, J = 15.4 Hz), 7.61 (d, 2H, J = 8.8 Hz), 7.86 (s, 1 H), 8.00 (t, 1 H, J = 5.5 Hz), 8.15 (s, 1 H), 8.21 (s, 1 H), 8.45 (s, 1 H), 9. 17 (s, 1 H); Anal. cale, for C 23 H 26 N 4 O 5 S CH 3 OH: C, 56.36; H, 5.41; N, 1 1 .15.

Found: C, 56.40; H, 5.76; N, 1 1 .40. Example 216 4- (4- (3-Hydroxy-3-f4- (f2-f (methylamino) carbonyl-inof2.3-clpyridin-4-yl) oxy) phenylbutanolyl) phenoxy) -N-methylthienoyl2.3-c > pyridine-2-carboxamide A solution of Example 202 (200 mg, 0.45 mmol) in THF (5 mL) was treated with methylmagnesium bromide (3 M solution in ether, 0.18 mL, 0.55 mmol) at -50 ° C for 30 minutes, and slowly warmed to room temperature for 10 minutes.

An aqueous NH 4 Cl solution was added, and the mixture was extracted with ether. The combined organic phases were rinsed with brine, water, dried (MgSO4) and concentrated. The residue was flash chromatographed on silica gel with 5% MeOH / EtOAc to provide the main compound (60 mg, 40%). MS (ESI / NH3) m / e: 653 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 1.58 (s, 3 H), 2.77 (d, 3 H, J = 4.8 Hz), 2. 80 (d, 3H, J = 4.8 Hz), 3.35 (d, 1 H, J = 13.0 Hz), 3.49 (d, 1 H, J = 13.0 Hz), 5.27 (s, 1 H), 7.02 (d, 2H, J = 8.8 Hz), 7.08 (d, 2H, J = 8.8 Hz), 7.53 (d, 2H, J = 8.8 Hz), 7.96 (d 2H, J = 8.8 Hz), 7.99 (s, 2H), 8.13 (s, 1 H), 8. 30 (s, 1 H), 8.94 (m, 2H), 9.08 (s, 1 H), 9.21 (s, 1 H); Anal. cale, for C34H28N4? ßS2-CH3OH: C, 61 .39; H, 4.27; N, 8.18.

Found: C, 61.26; H, 4.29; N, 7.95. Example 217 4-f4- (1 H-lmidazol-1-l) phenoxy-1-phenyl-2,3-clpyridine-2-carboxamide Example 217A Methyl 4- [4- (1 H-imidazol-1-yl) phenoxythienof 2, 3-pyridine- 2-carboxylate Example 17A (0.88 g, 5 mmol) in THF (15 mL) and DMF (5 mL) was treated with 4- (1-imidazolyl) phenol and potassium t-butoxide (1 N in THF, 5.0 mL, 5 mmol) at 70 ° C for 4 hours, then cooled to 0 ° C, added methyl thioglycolate (0.4 mL, 5 mmol) and cesium carbonate (1.62 g, 5 mmol) then refluxed for 1 hour. The reaction was poured into water, diluted with brine and extracted with ethyl acetate. The ethyl acetate was then rinsed with 1 N NaOH (2x20 mL), then brine (3x20 mL), dried (MgSO4) to give the major compound MS (DCI / NH3) m / e: 352 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 3.90 (s, 3 H), 7.10 (s, 1 H), 7.30 (d, 2 H), 7.70 (s, 1 H), 7.25 (d, 2 H), 8.00 ( s, 1 H), 8.25 (d, 2H), 9.25 (s, 1 JH). Example 217B 4-β4- (1 H-lmidazol-1-l.fenoxfltiene-2,3-clpyridine-2-carboxamide Example 217A was dissolved in 2 M methanolic ammonium and heated at 50 ° C in a sealed tube for 24 hours The reaction was then evaporated and crystallized from methanol to give the main compound, mp 310-312 ° C; MS (DCI / NH 3) m / e: 337 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ ) d 7.10 (s, 1 H), 7.28 (m, 2H), 7.68 (t, 1 H), 7.25 (dd, 2H), 7.85 (br s, 1 H), 8.15 (s, 1 H), 8.20 (d, 2 H), 8.45 (br s, 1 H), 9.15 (s, 1 H) ); Anal. cale, for C17H12N4O2S-0.50 H2O: C, 59.12; H, 3.79; N, 16.22. Found: C, 59.40; H, 3.63; N, 16.30. Example 218 N-methyl-4-f4- (1 H-pyrrazol-1-yl) phenoxyptofenof2.3-c1pyridine-2-carboxamide Example 218A Methyl-4-f4- (1H-pyrazol-1-yl) phenoxy-tienolf2,3 -c1pyridine-2-carboxylate Example 17A (0.8 g, 5 mmol) in THF (15 mL) was treated with 4- (1 H-pyrazol-1-yl) phenol and cesium carbonate (1.6 g, 0.5 g). mmol) under reflux for 4 hours, then cooled to 0 ° C, then methyl thioglycolate (0.4 mL, 5 mmol) and cesium carbonate (1.62 g, 5 mmol) were added, then the mixture was refluxed for 1 hour. hour. The mixture was poured into water, diluted with brine and extracted with ethyl acetate. The ethyl acetate was then rinsed with 1 N NaOH (2x20 mL), then brine (3x20 mL), dried (MgSO) to give the main compound. MS (DCI / NH3) m / e: 352 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 3.80 (s, 3 H), 6.55 (m, 1 H), 7.30 (d, 2 H), 7.42 (d, 1 H), 7.75 (d, 1 H), 7.90 (d, 2H), 8.25 (s, 1 H), 8.50 (d, 1 H), 9.22 (s, 1 H). Example 218B N-Methyl-4-.4- (1 H-pyrazo-1-yl-phenoxy-1-tienof2, 3-clpyridine-2-carboxamide Example 218A was dissolved in 2M methanolic methylamine and heated at 50 ° C in a bottom flask round for 4 hours. the reaction was then evaporated and crystallized from methanol to give the main compound, mp 192-194 ° C; MS (DCI / NH3) m / e: 351 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.70 (d, 3 H), 6.55 (m, 1 H), 7.25 (d, 2 H), 7.75 (br s, 1 H), 7.90 (d, 2 H), 8.12 (s, 1 H), 8.20 (s, 1 H), 8.50 (d, 1 H), 9.00 (m, 1 H), 9.18 (s, 1 H); Anal. cale, for C18H14N4O2S 0.25 H2O: C, 60.15; H, 4.21; N, 15.59. Found: C, 60.30; H, 3.93; N, 15.73. Example 219 N-Methyl-4-r4- (1 H-1, 2,4-triazol-1-yl) phenoxythienof2.3-clpyridine-2-carboxamide Example 17A and 4- (1 H-1, 2,4- triazol-1-yl) phenol were processed as in Example 218 to provide the main compound. mp 214-215 ° C; MS (DCI / NH3) m / e: 352 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.70 (d, 3 H), 7.30 (d, 2 H), 7.55 (b, 1 H), 7.90 (d, 2 H), 8.12 (s, 1 H), 8.25 ( d, 1 H), 9.00 (q, 1 H), 9.30 (s, 1 H). Example 220 N-Meti - (4-f5- (trifluoromethyl) -1,2,4-oxadiazol-3-yl-1-phenoxy) thienof2.3-clpyridine-2-carboxamide Example 220A N-Methyl-4-f4- (N-hydroxyamindino) phenoxythienof2 .3-clpyridine-2-carboxamide A solution of Example 189 (500 mg, 1.662 mmol) in a mixture of DMF (10 mL) and EtOH (10 mL) was treated with triethylamine (279 mg, 2.75 mmol) and hydroxylamine hydrochloride (169 mg, 2.43 mmol). ) at room temperature for 18 hours. The white solid formed was collected by filtration, rinsed with EtOH, dried to provide the designated compound (376 mg, 68%). MS (ESl / NHs) m / e: 343 (M + H) +; Example 220B N-Methyl-4-γ4-r5- (trifluoromethyl) -1.2.4-oxadiazole-3-ipphenoxy-thienof2.3-clpyridine-2-carboxamide A suspension of Example 220a (200 mg, 0.58 mmol) in pyridine (8 mL) was treated with trifluoroacetic anhydride (178 mg, 0.85 mmol) at room temperature for 1 hour. The resulting yellow solution was heated at 120 ° C for 18 hours, and concentrated. The residue was separated by HPLC (C-18, CH3CN / H2O containing 0.1% TFA to provide the main compound (169 mg, 69%) mp 174-176 ° C; MS (ESI / NH3) m / e: 421 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.78 (d, 3 H, J = 4.4 Hz), 7.26 (d, 2 H, J = 8.8 Hz), 8.03 (s, 1 H), 8.10 (d, 2H, J = 8.8 Hz), 8.38 (s, 2H), 8.96 (q, 1 H, J = 4.4 Hz), 9.25 (s, 1 H); Anal cale, for C18HnN4O3SF3: C, 51 .43; H, 2.64; N, 13.33, Found: C, 51.56; H, 2.76; N, 13.32, Example 221 4-r4- (4,5-D-Hydro-1H-imidazol-2-yl) phenoxy1-N-methylthienof2,3-c] pyridine-2-carboxamide A solution of Example 186 (800 mg, 2.6 mmol) in a mixture of MeOH (30 mL), Et 2 O (20 mL), and CH 2 Cl 2 (30 mL) was introduced hydrogen chloride gas at 0 ° C for 1.5 hours. , stirred at room temperature for 24 hours, and concentrated. The residue was dissolved in MeOH (30 mL) and ethylenediamine (3 mL), and heated at 70 ° C for 2 hours. After the reaction was cooled, the resulting white solid was collected by filtration, rinsed with methanol, and dried to provide the main compound (804 mg, 88%). mp > 280 ° C; MS (ESI / NH3) m / e: 353 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.78 (d, 3 H, J = 4.4 Hz), 3.32 (br s, 4 H), 6.88 (br s, 1 H), 7.1 1 (d, 2 H, J = 8.8 Hz), 7.85 (d, 2H, J = 8.8 Hz), 8.04 (s, 1 H), 8.22 (s, 2H), 8.93 (q, 1 H, J = 4.4 Hz), 9.17 (s, 1 H); Anal. cale, for C? 8H16N4O2S: C, 59.36; H, 4.46; N, 14.57. Found: _C, 59.60; H, 4.55; N, 14.40. Example 222 N-Methyl-4-f4- (2-thienyl) phenoxyphenyl-2,3-c1pyridine-2-carboxamide A flask, purged with nitrogen, was charged with Example 190B (200 mg, 0.48 mmol), Pd (OAc) 2 (1.1 mg, 0.048 mmol), tri-o-tolifosphine (44 mg, 0.14 mmol), dry degassed DMF (10 mL), 2-trubutylstanyl thiophene (305 mL, 0.96 mmol), and triethylamine (334 mL, 2.4 mmol) . This suspension was stirred at 80 ° C for 15 hours. After diluting with ethyl acetate, the reaction mixture was rinsed with brine, H2O, dried (MgSO4) and concentrated. The residue was separated by HPLC (C-18, CH3CN / H2O containing 0.1% TFA) to provide the main compound (212 mg, 90%). MS (ESl / NHg) m / e: 367 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.80 (d, 3 H, J = 4.4 Hz), 7.13 (m, 1 H), 7.17 (d, 2 H, J = 8.8 Hz), 7.48 (d, 1 H, J = 3.7 Hz), 7.54 (d, 1 H, J = 5.1 Hz), 7.71 (d, 2H, J = 8.8 Hz), 8.15 (s, 1 H), 8.24 (s, 1 H), 9.02 (q , 1 H, J = 4.4 Hz), 9.22 (s, 1 H). Example 223 4- (f 1, 1'-b'fenip-4-yloxy) -N-methylthienof2,3-clpyridine-2-carboxamide Example 223 was prepared as in Example 222 but substituting tributylphenyltin for (trubutylstanyl) thiophene to provide the main compound. MS (ESI / NH3) m / e: 361 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.80 (d, 3 H, J = 4.5 Hz), 7.19 (d, 2 H, J = 8.8 Hz), 7.36 (t, 1 H, J = 7.4 Hz), 7.47 ( t, 2H, J = 7.3 Hz), 7.66 (d, 2H, J = 7.3 Hz), 7.72 (d, 2H, J = 8.8 Hz), 8.15 (s, 1 H), 8.23 (s, 1 H), 9.00 (q, 1 H, J = 4.4 Hz), 9.19 (s, 1 H). Example 224 N-Methyl-4-r4- (1-methyl-1H-imidazol-5-yl) phenoxy1-thienof2.3-clpyridine-2-carboxamide Example 224 was prepared as in Example 222 but substituting 1-methyl - (5-tibutylstannyl) imidazole, which was prepared according to a literature method (K. Gaare, et al., Acta Chem, Scand., 1993, 47, 57) by 2-tributylstannylthiophene to provide the main compound. mp 256-258 ° C; MS (ESI / NH3) m / e: 365 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.80 (d, 3 H, J = 2.1 Hz), 3.67 (s, 3 H), 7.03 (s, 1 H), 7.17 (d, 2 H, J = 8.8 Hz), 7.53 (d, 2H, J = 8.8 Hz), 7.69 (s, 1 H), 8.12 (s, 1 H), 8.22 (s, 1 H), 9.00 (q, 1 H, J = 2.1 Hz), 9.16 (s, 1 H); • 5 Anal. cale, for C1 ßH16N4? 2S: C, 62.62; H, 4.43; N, 15.37. Found: C, 62.38; H, 4.23; N, 15.13. Example 225 4- | 4-p- (Hydroxymethyl) cyclopropinphenoxy > -N-methylthienor 2,3-clpridine-2-carboxamide Example 225A 4- (1-Hydroxymethylcyclopropyl) anisole A solution of 1- (4-methoxyphenyl) -1-cyclopropane-carboxylic acid (5.0 g, 26 mmol) in THF (100 mL) was slowly treated with LiAIH4 (0.95 g, 25 mmol) at -20 ° C for 0.5 hours, and then warmed to room temperature for 2 hours. The excess of L iAIH4 15 was consumed by slowly adding EtOH. After diluting with ether, the reaction mixture was wiped with 2% HCl in brine, water, dried (MgSO 4) and concentrated to provide the designated compound (5.0 g, 100%). MS (DCI / NH3) m / e: 196 (M + NH4) +; Example 225B 4- (1-Hydroxymethylcyclopropyl) phenol To a suspension of NaH (60% in mineral oil, 392 mg, 9.8 mmol) in DMF (10 mL) was slowly added clean ethanethiol (610 mg, 9.8 mmol) at room temperature. The reaction mixture was stirred for 10 minutes to form a clear solution.

Example 225A (500 mg, 2.8 mmol) was then heated, and the mixture was heated at 145 ° C for 4 hours. After diluting with ether, the reaction mixture was rinsed with 2% HCl in brine, dried (MgSO4) and concentrated. The residue was chromatographed instantaneously • 5 silica gel with 50% EtOAc / hexane to provide the designated compound (373 mg, 81%). MS (DCI / NH3) m / e: 182 (M + NH4) +; Example 225C 4- (1-Triphenylmethoxymethylcyclopropyl) phenol A solution of Example 225B (1.0 g, 6 mmol) in pyridine (7 mL) was treated with triphenylmethyl chloride (1.87 g, 6.7 mmol) at • room temperature for 18 hours. After diluting with ether, the reaction mixture was rinsed with 1% aqueous HCl, water and dried (MgSO4). The residue was flash chromatographed on silica gel with 12% EtOAc / hexane to provide the designated compound. MS (DCI / NH3) m / e: 407 (M + H) +; Example 225D Methyl 4-f4- (1-triphenylmethoxymethylcyclopropyl) phenoxy-r2.3-clpyridine-2-carboxylate Example 225D was prepared as in Example 61A but substituting Example 225C for 4-chlorophenol to provide the designated compound. MS (DCI / NH3) m / e: 598 (M + H) +; Example 225E 25 Methyl 4-f4- (1-hydroxymethyl) cyclopropinphenoxy-f2,3-clpyridine-2-carboxylate A solution of Example 225D (230 mg, 0.38 mmol) in a mixture of CH2Cl2 (10 mL) and MeOH (5 mL) was treated with trifluoroacetic acid (1 mL) at 0 ° C for 1 hour, allowed to warm to room temperature and stirred for 1 hour, and poured into solution • 5 aqueous NaHCO3. The mixture was extracted with methylene chloride. The combined organic phases were rinsed with water, and dried (MgSO4). The residue was flash chromatographed on silica gel with 65% EtOAc / hexane to provide the designated compound (78 mg, 58%). MS (DCI / NH3) m / e: 356 (M + H) +; Example 225F • 4-f4-l- (Hydroxymethyl) cyclopropylphenoxy} -N-methylthienof2.3-c] pyridine-2-carboxamide Example 225F was prepared as in Example 103 but substituting Example 225E for Example 61A to provide the designated compound. MS (ESI / NH3) m / e: 335 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 0.72 (m, 2 H), 0.82 (m, 2 H), 2.80 (d, 3 H, J = 4.7 Hz), 3.51 (d, 2 H, J = 5.8 Hz), 4.66 (t, 1 H, J = 5.8 Hz), 7.01 (d, 2H, J = 8.8 Hz), 7.34 (d, 2H, J = 8.8 Hz), 8.06 (s, 1 H), 8.13 (s, 1 H) ), 8.96 • 20 (q, 1 H, J = 4.7 Hz), 9.10 (s, 1 H). Example 226 4-f4- (1-fí2- (2-Ethoxyethoxy) ethoxymethyl) cyclopropyl) phenoxy-N-methylthienof2.3-clpyridine-2-carboxamide Example 226A 25 4- (2- (2-Ethoxyethoxy) ethoxy-1-methylcyclopropyl) anisola A solution of Example 225A (1.0 g, 5.6 mmol) in THF (15 mL) was treated with NaH (60% in mineral oil, 312 mg, 7.8 mmol) and 15-crown-5 (1.33 mL, 6.7 mmol) at room temperature for 15 minutes followed by the addition of 2- (2-ethoxyethoxy) ethyl tosylate (1.93 g, • 5 6.7 mmol) that was prepared according to the method of the literature (C. Almansa et al., Tetrahedron 1991, 47, 5867). The brown mixture was stirred at room temperature for 5 hours and poured into brine. The mixture was extracted with CH2Cl2 and the combined organic phases were dried (MgSO4) and concentrated. The residue was chromatographed Instantaneously on silica gel with 25% EtOAc / hexane to provide the designated compound (1.58 g, 95%). • MS (ESI / NH3) m / e: 312 (M + NH4) +; Example 266B 4- (2- (2-Ethoxyethoxy) ethoxy-1-methylcyclopropyl) phenol A solution of Example 226A (1.5 g, 5.1 mmol) in DMF (15 mL) was treated with sodium thiomethoxide (1.25 g, 17.8 mmol) at 145 ° C for 5 hours. After cooling to room temperature, methylepoyl chloride (100 mL) was added, and the mixture was wiped with 2% HCl in brine. The organic layer was dried (MgSO4), concentrated and the The residue was flash chromatographed on silica gel with 35% EtOAc / hexane to give the designated compound (1.33 g, 93%). MS (ESI / NH3) m / e: 298 (M + NH4) +; Example 226C 25 Methyl 4-f4- (1- {f2- (2-Ethoxyethoxy) ethoxy] methyl-> cyclopropyl) phenoxy-N-methylthienof2.3- Clpyridine-2-carboxylate Example 226C was prepared as in Example 61A but substituting Example 226B for 4-chlorophenol to provide the designated compound. MS 5 (ESI / NH 3) m / e: 472 (M + H) +; Example 226D 4-f4- (1- { R2- (2-Ethoxyethoxy) ethoxymethyl> cyclopropyl) phenoxy-N-methylthieno-2,3-clpyridine-2-carboxamide Example 226D was prepared as in Example 103 but replacing the Example 226C by Example 61A to provide the designated compound. • MS (ESI / NH3) m / e: 471 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 0.84 (m, 2 H), 0.87 (m, 2 H), 1.06 (t, 3 H, J = 6.7 Hz), 2.82 (d, 3 H, J = 4.4 Hz), 3.37 (t, 2H, J = 6.7 Hz), 3.39- 15 3.55 (m, 10H), 7.07 (d, 2H, J = 8.8 Hz), 7.36 (d, 2H, J = 8.8 Hz), 8.13 (s, 1 H), 8.26 (s, 1 H), 9.10 (q, 1 H, J = 4.4 Hz), 9.28 (s, 1 H); Anal. cale, for C25H3oN4O5S: C, 59.22; H, 6.16; N, 5.52. Found: C, 59.50; H, 6.16; N, 5.26. Example 227 • 20 N-Methyl "4-r4- (trifluoromethoxy) phenoxyphenyl-2,3-clpridine-2-carboxamide Example 227 was prepared as in Example 103 but substituting 4-chlorofenol for 4-trifluoromethoxyphenol to give the designated compound, mp 132-133 ° C; 25 MS (ESI / NH 3) m / e: 368 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.80 (d, 3 H, J = 4.4 Hz), 7.20 (d, 2 H, J = 9.2 Hz), 7.41 (d, 2 H, J = 9.2 Hz), 8.08 (s) , 1 H), 8.21 (s, 1 H), 8.95 (q, 1 H, J = 4.4 Hz), 9.18 (s, 1 H); Anal. cale, for dßHuNsOaSFs: C, 52.17; H, 3.01; N, 7.61. • 5 Found: C, 52.21; H, 3.26; N, 7.29. Example 228 5- (4-r4- (1- {f2- (2-Ethoxyethoxy) ethoxylmethyl> cyclopropyl) phenoxyphenof2,3-clPyridin-2-yl) -1.3.4-oxadiazol-2-amine Example 228 prepared as in Example 275 and Example 156 but substituting Example 226C for Example 61 A to provide the designated compound, mp 13-1 14 ° C; MS (ESI / NH3) m / e: 497 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 0.82 (m, 2 H), 0.85 (m, 2 H), 1.05 (t, 15 3 H, J = 7.1 Hz), 3.40 (t, 2 H, J = 7.1 Hz ), 3.42-3.54 (m, 10H), 7.00 (d, 2H, J08.8 Hz), 7.33 (d, 2H, J = 8.8 Hz), 7.55 (s, 1 H), 7.58 (s, 2H), 8.18 (br s, 1 H), 9.15 (br s, 1 H). Example 229 4-f4- (1, 1 -Difluoro-2-hydroxyethyl) phenoxy-N-methylthiene r2,3-clpyridine-2-carboxamide • 20 Example 229A 4-f4- (1,1-Difluoro-2-ethoxy-2-oxoethyl) phenoxy-N-methylthiene f2.3-clpyridine-2-carboxamide A suspension of activated copper (512 mg, 8 mmol) in Dry DMSO (5 mL) was treated with ethyl iododifluoroacetate (1.0 g, 4 mmol) at room temperature for 10 minutes. Added Then phenol (188 mg, 2 mmol) and Example 190B. The mixture of The reaction was stirred at room temperature for 20 hours. After it was diluted with 1: 1 ether / EtOAc, the mixture was rinsed with 1% HCl in brine, water, dried (MgSO 4) and concentrated. The residue was flash chromatographed on silica gel with 65% EtOAc / hexane, and further purified on HPLC (C-18, CH3CN / H2O containing 0.1% TFA) to provide the designated compound (85 mg, 15%). . MS (ESI / NH3) m / e: 407 (M + H) +; Example 229B 4-f4- (1,1-Difluoro-2-hydroxyethyl) phenoxy-N-methylthieno f2,3-cjpyridine-2-carboxamide A solution of Example 229A (40 mg, 0.1 mmol) in MeOH (5 mL) was treated with NaBH 4 (50 mg) at room temperature for 2 hours. The brine was added, and the mixture was extracted with EtOAc. The combined organic phases were dried (Na2SO4) and concentrated. The residue was purified by HPLC (C-18, CH 3 CN / H 2 O containing 0.1% TFA) to give the main compound (44.4 mg, 94%). MS (ESI / NH3) m / e: 365 (M + H) +; 1 H NMR (300 MHz, CD 3 OD) d 2.94 (s, 3 H), 3.93 (t, 2 H, J = 13.5 Hz), 7.278 (d, 2 H, J = 9.2 Hz), 7.65 (d, 2 H, J = 9.2 Hz ), 8.15 (s, 2H), 2.94 (s, 1 HOUR); Anal. cale, for C, 47.70; H, 3.16; N, 5.86.

Found: C, 47.67; H, 3.10; N, 5.76. EXAMPLE 230 4- (4 - (- f2- (2-Ethoxyethoxy) ethoxy-1,1-difluoroethyl) phenoxy) -N-methyl-triene-2,3-c-pyridine-2- carboxamide A solution of Example 229B (40 mg, 0.1 1 mmol) in THF (3 mL) was treated with NaH (60% in mineral oil, 7 mg, 0.16 mmol) and 15-crown-5 (35 mg, 0.16 mmol) at room temperature for 15 minutes. 2- (2-ethoxyethoxy) ethyl tosylate (46 mg, 0.16 mmol) which was prepared according to the literature method (C, Almansa, et al., Tetrahedron 1991, 47, 5867) was then added. The reaction mixture was stirred at room temperature for 15 hours, and then was then directly separated on HPLC (C-18, CH3CN / H2O containing 0.1% TFA) to provide the main compound (46 mg, 81%). MS (ESI / NH3) m / e: 481 (M + H) +; 1 H NMR (300 MHz, CD 3 OD) d 1 .16 (t, 3 H, J = 7.1 Hz), 2.97 (s, 3 H), 3.49 (q, 2 H, J = 7.1 Hz), 3.57 (m, 6 H), 3.70 (m, 2H), 4.01 (t, 2H, J = 12.7 Hz), 7.37 (d, 2H, J = 8.8 Hz), 7.72 (d, 2H, J = 8.8 Hz), 8.22 (s, 1 H), 8.33 (s, 1 H), 9.46 (s, 1 H). EXAMPLE 231 Trifluoroacetate 4- (4-chlorophenoxy) -6- (f (2,2-dimethylpropanoyl) oxpmethyl} -2- [(methylamino) carbonylthienof2.3-c1pyridin-6-io Example 103 (47.4 mg, 0.149 mmol) was dissolved (under N2 atmosphere) in 1.5 mL dry acetonitrile (with heating), and chloromethyl pivalate (25 mg, 0.167 mmol) was added at room temperature, the reaction was stirred for 16 hours, then iodide was added. tetrabutylammonium (1 mg), and then the solution was heated to reflux for 48 hours. it was concentrated under reduced pressure, and the residue was purified by preparative HPLC (column C-18, gradient eluent 20-27% acetonitrile-0.1% aqueous TFA, elution 60 minutes) to provide 24 mg (34%) of the compound Main as a foam. ^ 5 HPLC: Supelco column C-18, eluent gradient of 0.1% aqueous TFA: acetonitrile 0: 90-90: 0 for 30 minutes, detection at 254 nm, flow rate of 0.8 mL / min, RT 20.0 minutes. MS (APCI +) m / e: 433 (M) +; 1 H NMR (300 MHz, DMSO-dβ) d 1.18 (s, 9H), 3.01 (s, 3H), 6.4-6.6 (br s, 2 H), 7.1 -7.3 (br s, approx 2 H), 7.49 (br s, 2 H), 7.74 (br s, 1 H), 8.41 (br s, 1 JH), 8.64 (br s, 1 H), 9.3-9.9 (vbr s, 1 H); • Anal. cale, for C23H22F3CI2OßS: C, 45.43; H, 3.51; N, 4.24. Found: C, 45.93; H, 3.70; N, 4.34. Example 232 15 4- (4-Bromophenoxy) -6-. { f (2,2-dimethylpropaneol) oxylmethyl} -2- r (methylamino) carboniptienof2.3-clpyridin-6-io Example 171 (69.4 mg, 0.191 mmol) was dissolved in 2 mL of acetonitrile, then tetrabutylammonium iodide (1 mg) was added, followed by chromoethyl pivalate ( 22 mg, 0.146 mmol). The solution The reaction mixture was heated to reflux for 24 hours. An additional portion of chloromethyl pivalate (11 mg, 0.073 mmol) was added and the reaction was refluxed for an additional 72 hours. The reaction was concentrated under reduced pressure, and the solid was partitioned between 15 mL of water and 15 mL of EtOAc. The aqueous phase was extracted with 2x15 mL of EtOAc, then the aqueous phase was concentrated under reduced pressure in a yellow solid (93.5 mg). HPLC purification (C-18 column, 20-75% acetonitrile-0.1% aqueous TFA) provided the pure master compound (55.9 mg, 49%). HPLC: Supelco column C-1 8, eluent gradient of 0.1% TFA • 5 aqueous: acetonitrile 0: 90-90: 0 for 30 minutes, detection at 254 nm, flow rate of 0.8 mL / min, RT 20.3 minutes. MS (APCI-) m / e: 475, 477 (MH) "; 1 H NMR (300 MHz, DMSO-d6) d 1.17 (s, 9H), 3.02 (br m, 3H), 6.0-6.07 ( vbr s, 2H), 7.14 (br d, 3H), 7.64 (br d, 2H), 7.78 (s, 1 H) 8.07-8.17 (br s, 1 H), 8.34 (s, 1 H), 9.44 -9.65 (vbr s, 1 H); Anal. cale, for C23H22F3BrN2O6S-1 .5 H2O: C, 40.99; H, 3.58; N, 3.82.

• Found: C, 40.94; H, 3.25; N, 3.76. Example 233 2- (Aminocarbonyl) -4- (4-chlorophenoxy) -6-. { f (isopropoxycarbonyl) oxpmethyl) thienof2.3-15-clpyridin-6-io To a solution of Example 61 (300 mg, 0.94 mmol) in acetonitrile (15mL) under a nitrogen atmosphere was added tetraphenylboron sodium (387 mg, 1.13 mmol), sodium iodide (169 mg, 1.13 mmol) and [(isopropyloxycarbonyl) oxy] methyl chloride (172 mg, 1.13 mmol). mmol). The reaction mixture was refluxed for 4 hours, cooled to room temperature and diluted with acetonitrile (100 mL) before filtering through Celite®. The filtrate was concentrated in a foam which was triturated in methanol to provide the pyridinium tetraphenylborate salt (550 mg) as a yellow solid. The salt of Tetraphenylborate was dissolved in 1: 1 CH3CN: i-PrOH and passed over a ion exchange column using Dowex 1 X2 chloride, 5-100 network. The eluent was concentrated and the resulting residue was triturated with EtO2 to provide Example 233 as a white solid (210 mg, 49%). 5 MS (FAB) m / e: 421 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 1.26 (d, J = 7 Hz, 6H), 4.81 (q, J = 7 Hz, 1 H), 6.44 (s, 2H), 7.41 (m, 2H ), 7.62 (m, 2H), 8.31 (br s, 1 H), 8.59 (s, 1 H), 8.68 (s, 1 H), 8.80 (br s, 1 H), 9.98 (s, 1 H); Anal. cale, for C19H18Cl2N2? 5S: C, 49.90; H, 3.96; N, 6.13. 10 Found: C, 49.74; H, 3.95; N, 6.14. Example 234 4- (Cyclopentyloxy) -N-methylthienof2.3-c1pyridine-2-carboxamide Example 234A 5-chloro-3-cyclopentyloxypyridine The main compound (5.91 g, 77%) was prepared as described in Example 236A except substituting cyclopentanol (4.2 mL, 46.31 mmol) for benzyl alcohol. MS (APCI) m / e: 198 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 1.53-1.76 (m, 6H), 1.86-2.02 (m, 2H), 20 4.92-4.99 (m, 1 H), 7.55 (t, J = 2.25 Hz, 1 H), 8.18 (d, J = 2.25 Hz, 1 H), 8.22 (d, J = 3 Hz, 1 H). Example 234B 5-Chloro 3-cyclopentilloxy pyridine-4-carboxaldehyde The main compound (5.22 g, 77%) was prepared as described in Example 236B except substituting Example 234A (5.9 g, 30 mmol) by Example 236A. MS (APCI) m / e: 226 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 1.55-1.85 (m, 6H), 1.93-2.04 (m, 2H), 5.14-5.22 (m, 1H), 8.36 (s, 1H), 8.63 (s, 1H ), 10.31 (s, 1H). EXAMPLE 234C Methyl 4-f cyclopentyloxyptienof2,3-clpyridine-2-cartyloxylate The main compound (4.31 g, 67%) was prepared as described in Example 236C except substituting 234B (5.2 g, 23.11 mmol) for Example 236B . MS (APCI) m / e: 278 (M + H) +; 1 H NMR (400 MHz, DMSO-dβ) d 1.59-1.69 (m, 2H), 1.74-1.81 (m, 2H), 1.83-1.90 (m, 2H), 1.97-2.07 (m, 2H), 3.93 (s) , 3H), 5.12-5.17 (m, 1H), 8.05 (s, 1H), 8.24 (s, 1H), 8.94 (s, 1H); 13 C NMR (100 MHz, DMSO-dβ) d 23.63 (CH2), 32.30 (CH2), 52.98 (OCH3), 80.33 (CH), 125.52 (CH), 127.09 (CH), 134.72 (C), 136.45 (C) , 137.44 (C), 138.05 (C), 149.27 (C), 161.90 (C = O). Example 234D 4- (Cyclopentyloxy) thienor 2,3-clpyridine-2-N-methylamide Example 234C (1.6 g, 61%) was prepared as described in Example 171 except substituting Example 234C (2.6 g, 9.4 mmol) for the Example 73A. mp 216-217 ° C; MS (APCI) m / e: 277 (M + H) +, 244 (M + CI) "; 1 H NMR (400 MHz, DMSO-dβ) d 1.60-1.69 (m, 2H), 1.73-1.90 (m, 4H), 1.97-2.08 (m, 2H), 2.83 (d, J = 4 Hz, 3H), 5.10-5.17 (m, 1H), 8.11 (s, 1 H), 8.19 (s, 1 H), 8.85 (s, 1 H), 8.93 (d, J = 4 Hz, 1 H); 13C NMR (1 00 MHz, DMSO-d6) d 23.60 (CH2), 26.14 (NCH3), 32.34 (CH2), 80.14 (CH), 1 19.68 (CH), 126.91 (CH), 135.73 (C), 137.17 ( C), 144.2 (C), 149.02 (C), 161 .18 (C). EXAMPLE 235 4- (2-Cyclohexen-1-yloxy) -N-methylthin-2,3-clpyridine-2-carboxamide Example 235A Methyl 4-f2-cyclohexene-3-oxmtienof2,3-clpyridine-2-carboxylate The main compound (158 mg, 57%) was prepared as described in Example 99A except substituting 2-cyclohexenol (0.1 13 mL, 0.1 15 mmol) for 3-hydroxytetrahydrofuran. The pure product was obtained by flash chromatography on silica gel eluting with 10 acetone-hexane. MS (APCI) m / e: 290 (M + H) +, 288 (M-H) \ 324 (M + CI) '; 1 H NMR (400 MHz, DMSO-dβ) d 1.95-1.62 (m, 1 H), 1.66-2.14 (m, 1 H), 3.92 (s, 3 H, OCH 3), 5.22-5.26 (m, 1 H), 5.91 -5.99 (m, 2H), 8.03 (s, 1 H, CH), 8.36 (s, 1 H, CH), 8.95 (s, 1 H, CH). Example 235B 4- (2-Cyclohexen-1-yloxy) -N-methylthienof2.3-c1pyridine-2-carboxamide The main compound of Example 235 (59 mg, 40%) was prepared from Example 235A (150 mg, 0.519 mmol) as described in Example 171. MS (APCI) m / e: 289 (M + H) +, 287 (MH) \ 323 (M + CI) "; 1 H NMR (500 MHz, DMSO-d 6) d 1 .62-1.70 (m, 1 H), 1 .78-1 .91 (m, 2H), 1.96-2.17 (m, 3H), 2.82 (d, J = 5 Hz, 3H), 5.21 (br s, 1 H), 5.93-5.98 (m, 1 H), 6.01 -6.05 (m, 1 H), 8.14 (s, 1 H), 8.30 (s, 1 H), 8.87 (s, 1 H), 8.75 (d, J = 5 Hz, 1 H); 13C NMR (75 MHz, DMSO-d6) d 18.2 (CH2), 24.6 (CH2), 26.2 (CH3), 27.7 (CH2), 71.3 (CH), 1 19.7 (CH), 125.6 (CH), 127.4 (CH), 132.6 • 5 (CH), 136.0 (C), 137.3 (C), 137.4 (CH), 144.1 (C), 149.0 (C), 161.2 (C). Example 236 4- (Benzyloxy) thienof2.3-clpyridine-2-carboxamide Example 236A 10 5-Chloro-3-benzyloxypyridine To a stirred solution of 5-chloro-3-pyridinol (10 g, 77.19 • mmol) in anhydrous tetrahydrofuran (155 mL) at 0 ° C and under a nitrogen atmosphere was added benzyl alcohol (9.6 mL, 92.63 mmol), triphenylphosphine (26.32 g, 100.35 mmol) and diethyl azodicarboxyiate. (15.8 mL, 100.35 mmol). The reaction mixture was stirred at room temperature overnight and the solvent was removed under reduced pressure. The residue (70 g) obtained was treated with diethyl ether (2 × 300 mL) and the solids were removed by filtration. The filtrate obtained was concentrated under reduced pressure and the residue was purified by flash chromatography on silica gel eluting with 5% acetone and hexane to obtain the main compound in 36% (5.8 g) of product. MS (APCI) m / e: 220 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 5.22 (s, 2 H), 7.33-7.49 (m, 5 H), 7.77 (t, J = 5 Hz, 1 H), 8.23 (d, J = 5 Hz, 1 H), 8.34 (d, J = 5 Hz, 1 H).

EXAMPLE 236B 5-Chloro-3-benzyloxypihydrin-4-carboxaldehyde To a stirred solution of diisopropylamine (4.5 mL, 31.78 mmol) in anhydrous tetrahydrofuran (20 mL) under a nitrogen atmosphere at -5 ° C was added drop drop n-BuLi in hexanes (2.5 M solution, 12.8 mL, 31.78 mmol) maintaining internal temperature of the reaction mixture below 0 ° C. The reaction mixture was stirred at -10 ° C for 10 minutes, then at 0 ° C for 30 minutes.

This was cooled to -78 ° C and a solution of Example 236A (5.8 g, 26.5 mmol) in anhydrous tetrahydrofuran (30 mL) was added slowly. Stirring at -78 ° C was continued for 1 hour. The reaction was then cooled with the dropwise addition of methyl formate (5 mL, 79.5 mmol) in anhydrous THF (15 mL) and stirred at -78 ° C for 3.5 hours. The internal temperature of the reaction mixture was maintained at or below -74 ° C throughout the reaction. After 3.5 hours, the reaction mixture was poured into a saturated aqueous solution of cold NaHCO3 (200 mL) and stirred for 15 minutes. The mixture was partitioned with ethyl acetate (250 mL), the organic layer was separated and rinsed with brine (2x60 mL). The dried organic layer (MgSO 4) was concentrated under reduced pressure to obtain the crude product (8.5 g). The main compound was obtained in 75% product (4.2 g) by flash chromatography on silica gel eluting with 6% acetone-hexane. MS (APCI) m / e: 248 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 5.42 (s, 2H), 7.33-7.45 (m, 3H), 7.48- 7. 52 (m, 2H), 8.41 (s, 1 H), 8.72 (s, 1 H), 10.39 (s, 1 H). Example 236C Methyl 4-benzyloxytienor 2,3-clpyridine-2-carboxylate To a cold solution of Example 236B (4.2 g, 17 mmol) in • 5 Anhydrous tetrahydrofuran (42 mL) under nitrogen atmosphere was added methyl thioglycolate (1.83 mL, 20.4 mmol) followed by cesium carbonate powder (6.65 g, 20.4 mmol). Then the reaction mixture was allowed to warm to room temperature with stirring under nitrogen. After 30 minutes, the reaction was refluxed for 15 minutes and cooled to room temperature. The reaction mixture was cooled with ice (50 mL) and partitioned with ethyl acetate (250 mL). • mL). The separated organic layer was rinsed with a cold solution of saturated NaCl (3x60 mL), dried (Na2SO4) and concentrated under reduced pressure to obtain the crude product which was recrystallized from methanol. The stock solution was purified by flash chromatography on silica gel eluting with 7% acetone-hexane. The combined fractions gave the main compound in 55% product (3.07 g). MS (APCI) m / e: 300 (M + H) +; 20 H NMR (300 MHz, DMSO-dβ) d 3.92 (s, 3 H), 5.42 (s, 2 H), 7.35-7.47 (m, 3 H), 7.52-7.57 (m, 2 H, Ar-CH), 8.12 ( s, 1 H), 8.36 (s, 1 H), 8.98 (s, 1 H). Example 236D Methyl 4-hydroxythienof2,3-clpyridine-2-carboxylate To a suspension of 10% by weight of Pd in carbon activated (38 mg, 10% w / w) in absolute ethanol (3 mL) was added a cold solution of Example 236C (380 mg, 1.3 mmol) in ethanol (82 mL) under nitrogen atmosphere. The reaction mixture was then degassed and stirred at room temperature with 10% by weight of additional Pd on activated carbon (190 mg, 50% w / w) and stirred under nitrogen atmosphere. The additional catalyst (100 mg, 26% w / w) was added to the reaction mixture after 48 hours. The reaction mixture was stirred under a hydrogen atmosphere for a further 24 hours and filtered through Celite < § > . The filtrate was evaporated to dryness under reduced pressure to obtain the crude product (320 mg). The main compound of Example 236E was obtained in 75% product (200 mg) by flash chromatography on silica gel eluting with 5% acetone-hexane followed by 40% acetone-hexane. MS (APCI) m / e: 210 (M + H) +; 208 (M-H) "; 244 (M + CI)"; 1 H NMR (300 MHz, DMSO-dβ) d 3.93 (s, 3 H), 8.08 (s, 1 H), 8.21 (s, 1 H), 8.81 (s, 1 H), 10.66-10.90 (br, s, 1 HOUR). Example 236E 4-Benzyloxytene.2,3-clpyridine-2-carboxamide The main compound (50 mg, 67%) was prepared as described in Example 44 using Example 236C (75 mg, 0.25 mmol). MS (APCI) m / e: 285 (M + H) +; 319 (M + CI) '; 1 H NMR (400 MHz, DMSO-dβ) d 5.43 (s, 2 H), 7.49-7.50 (m, 3 H), 7.58-7.63 (m, 2 H), 7.79 (br s, 1 H), 8.30 (s, 1 H), 8.36 (s, 1 H), 8.48 (br s, 1 H), 8.93 (s, 1 H); 13 C NMR (100 MHz, DMSO-dβ) d 70.13 (CH2), 120.56 (CH), 126.21 (CH), 127.5 (CH), 128.14 (CH), 128.51 (CH), 135.30 (C), 136.35 (C) , 137.48 (C), 137.86 (CH), 144.75 (C), 149.82 (C), 162.61 (C). , Example 237 4- (4-Chlorobenzoyl) -N-methylthienor-2,3-c1pyridine-2-carboxamide Example 237A Methyl 4-chlorotinenof2.3-c] pyridine-2-carboxylate Example 17A (15.00 g, 85.22 mmol) was Dissolved in THF (80 mL) and cesium carbonate (27.77 g, 85.22 mmol) was added. The methyl thioglycolate (7.62 mL, 85.22) diluted in THF (20 mL) was added dropwise over a period of 20 minutes. The reaction was stirred for 1.5 hours then it was heated at 40 ° C for 1 hour. The reaction mixture was poured into 850 mL of stirring water. After 10 minutes, the precipitate was collected by filtration and rinsed twice with water. The product was dried in a desiccator to produce the main compound as a solid (15.2 g, 78%). MS (DCI / NH3) m / e: 228 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 3.96 (s, 3 H), 8.15 (s, 1 H), 8.65 (s, 1 H), 9.38 (s, 1 H). EXAMPLE 237B 4-Clorothienof2.3-c1pyridine-2-carboxylic acid Example 237A (15.17 g, 66.63 mmol) was suspended in a solution of 1: 4 MeOH / water (500 mL) and LiOH hydrate (4.34 g, 103. 50 mmol) was added. The reaction was stirred for 1.5 hours then concentrated (100 mL). The aqueous phase was rinsed with Et2O and then acidified to pH 5 with 1 N HCl (aq). The precipitate was isolated by filtration, rinsed once with water, then twice with acetonitrile. The product was dried in a desiccator to produce 4-chlorothieno [2,3-c] pyridine-2-carboxylic acid as a solid (12.10 g, 85%). MS (DCI / NH3) m / e: 214 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 8.05 (s, 1 H), 8.62 (s, 1 H), 9.34 (s, 1 H). Example 237C Dimethylethyl 4-chlorothienoyl 2,3-clpyridine-2-carboxylate To a suspension of Example 237B (12.07 g, 56.50 mmol) in THF (200 mL) at 0 ° C, tert-butyl 2,2,2-trichloroacetamidate was added. (25.00 g, 1 14.41 mmol) followed by the dropwise addition of boron trifluoride-diethyl etherate (2.14 mL, 16.95 mmol). The reaction was allowed to warm to room temperature and stirred for 18 hours. Additional Tert-butyl 2,2,2-trichloroacetamide (12.50 g, 57.21 mmol) was added and the reaction was stirred for 3 hours. The stirred reaction was treated with NaHCO3 (14 g) and then diluted with water (300 mL). The reaction was divided between water (300 mL) and 50% EtOAC / Et2O. The organic layer was rinsed with sat. NaHCO3. rinsed with brine, partially dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography on silica gel neutralized with Et3N using EtOAc / hexane as eluent.

The main compound was isolated as a solid (10.04 g, 66%). MS (DCI / NH3) m / e: 270 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 1.59 (s, 9 H), 8.04 (s, 1 H), 8.64 (s, 1 H), 9.35 (s, 1 H). Example 237D Dimethylethyl 4- (ethoxycarbonyl) thienof2.3-clpyridine-2-carboxylate To a solution of Example 237C (1.00 g, 3.71 mmol), 1,3-bis (diphenylphosphino) propane (0.46 g, 1.1. mmol), triethylamine (1.55 mL, 11.1 mmol) in 2: 3 EtOH / DMF (25 mL), palladium (11) acetate (0.25 g, 1.1 mmol) was added. The reaction was suctioned with a stream of CO (g) for 15 minutes. A balloon of CO (g) was applied and the reaction was heated to 105 ° C for 16 hours then cooled to room temperature. The reaction was poured into water (400 mL). The aqueous was diluted with brine (25 mL) and sat. NaHCO3. (25 mL), then extracted with EtOAc (4x50 mL). The organic extracts were combined, rinsed with 20% sat. NaHCO3. (2x200 mL), brine (2x100 mL), partially dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography on silica gel using EtOAc / hexane as an eluent to give the compound as a solid (0.60 g, 53%). MS (APCI) m / e: 308 (M + H) +; 1 H NMR (300 MHz, CD 2 Cl 2) d 1.44 (t, J = 7.1 Hz, 3 H), 1.59 (s, 9 H), 4.44 (q, J = 7.1 Hz, 2 H), 8.65 (s, 1 H), 9.12 ( s, 1 H), 9.25 (s, 1 H). Example 237E Dimethylethyl 4-formylthienof2.3-clpyridine-2-carboxylate To a stirred solution of NaBH4 (0.18 g, 4.89 mmol) in 50% MeOH / anhydrous THF at 0 ° C was added CaCl2 powder (0.54 g, 4.89 mmol). The suspension was stirred 20 minutes and a solution of Example 237D (0.50 g, 1.63 mmol) in 50% MeOH / anhydrous THF was added slowly over a period of 10 minutes. The reaction was stirred for 1 hour at 0 ° C followed by 16 hours at room temperature. The reaction was cooled in a mixture of dilute AcOH (aq) / ice. After all evolution of gas with occasional agitation ceased, the aqueous was made basic with sat. NaHCO3. The aqueous was extracted with dichloromethane (3x40 mL) and the extracts were combined. The organic phase was dried (NaS? 4), filtered and concentrated. The residue was purified by flash chromatography on silica gel using EtOAc / hexane as eluent to give dimethylethyl 4- (hydroxymethyl) -thieno [2,3-c] pyridine-2-carboxylate compound as a solid (0.14 g, 32% ) MS (APCI) m / e: 266 (M + H) +; 1 H NMR (300 MHz, CD 2 Cl 2) d 1.54 (s, 9 H), 4.94 (s, 2 H), 8.08 (s, 1 H), 8.40 (s, 1 H), 9.02 (s, 1 H). To a stirred solution of oxalyl chloride (0.10 mL, 1.17 mmol) in anhydrous dichloromethane (1 mL) at -78 ° C was added DMSO (0.19 mL, 2.65 mmol). After 20 minutes, a solution of dimethylethyl 4- (hydroxymethyl) -thieno [2,3-c] pyridine-2-carboxylate (0.28 g, 1.06 mmol) in anhydrous dichloromethane (4 mL) was added dropwise. The reaction was stirred 1 hour at -78 ° C then treated with triethylamine (0.74 mL, 5.30 mmol). After 5 minutes, the reaction was left Heat at room temperature for 30 minutes. The reaction was quenched with water (5 mL) and partitioned between dichloromethane (50 mL) and 50% sat. NaHCO3. aq. (50 mL). The organic phase was rinsed with 50% sat. NaHCO3. aq. (1 x 50 mL), dried (Na 2 SO 4), filtered and concentrated and dried in a desiccator to produce the main one as a solid (0.25 g, 90%). MS (APCI) m / e: 264 (M + H) +; 1 H NMR (300 MHz, CD 2 Cl 2) d 1.59 (s, 9 H), 8.74 (s, 1 H), 8.91 (s, 1 H), 9.31 (s, 1 H), 10.24 (s, 1 H). Example 237F Dimethylethyl 4-f (4-chlorophenyl) (hydroxy) methylthienor 2,3-clpyridine-2-carboxylate To a solution of Example 237E (0.25 g, 0.95 mmol) in anhydrous THF (5 mL) at -5 ° C was added slowly add a 1 M solution of p-chlorophenylmagnesium bromide in diethyl ether (2.85 mL, 2.85 mmol). The reaction was cooled after 10 minutes with dropwise addition of water (1 mL) and partitioned between dichloromethane (25 mL) and 50% sat. NaHCOs. (50 mL). The aqueous phase was extracted with dichloromethane (25 mL) and the organic extracts combined, dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography on silica gel using EtOAc / hexane as eluent to provide the main compound as a foam, which was pressed and dried in a desiccator to produce a powder (0.6 g, 100%). MS (APCI) m / e: 376 (M + H) +; 1 H NMR (300 MHz, CD 2 Cl 2) d 1.52 (s, 9 H), 6.18 (d, 1 H), 725-7.34 (series of m, 4H), 7.96 (s, 1 H), 8.47 (s, 1 H), 9.03 (s, 1 H). Example 237G Methyl 4-f (4-chlorophenyl) (hydroxy) methyptienor 2,3-clpyridine-2-carboxylate Example 237F (0.12 g, 0.32 mmol) was dissolved in a • 5 solution of 10% H2SO4 / MeOH (10 mL) and heated at 50 ° C for 18 hours. The reaction was cooled in sat. NaHCO3. (1 x 100 mL), brine (1x100 L), partially dried (Na 2 SO 4), filtered and concentrated. The product was dried in a desiccator to produce the main compound as a solid (0.10 g, 94%). MS 10 (APCI) m / e: 334 (M + H) +; 1 H NMR (300 MHz, CD 2 Cl 2) d 3.85 (s, 3 H), 6.17 (d, 1 H), 7.23-7.33 • (series of m, 4H), 8.05 (s, 1 H), 8.48 (s, 1 H), 9.05 (s, 1 H). Example 237H Methyl 4- (4-chlorobenzoyl) -N-methylthienof2.3-chlorpyridine-2-carboxylate To a stirred solution of oxalyl chloride (0.23 mL, 0. 26 mmol) in anhydrous dichloromethane (1 mL) at -78 ° C was added DMSO (0.045 mL, 0.63 mmol). After 15 minutes, a solution of Example 237G (0.07 g, 0.21 mmol) in 1: 4 DMSO / anhydrous dichloromethane (5 mL) was added dropwise. The reaction was stirred 1 hour at 78 ° C then treated with triethylamine (0.15 mL, 1.05 mmol). After 5 minutes, the reaction was allowed to warm to room temperature for 1 hour. The reaction was quenched with water (2 mL) and partitioned between EtOAc (50 mL) and sat aq NaHCOs. (50 mL). The organic layer was rinsed with 50% sat. NaHCO3. (2x50 mL), brine (1 x 50 mL), dried (Na 2 SO 4), filtered and concentrated. The product was dried in a dissector to produce the main compound as a white solid (0.07 g, 100%). MS (APCI) m / e: 332 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 3.95 (s, 3 H), 7.68 (m, 2 H), 7.87 (m, 2 H), 8.31 (s, 1 H), 8.74 (s, 1 H), 9.66 ( s, 1 H);) +; IR (KBr) 3208, 2959, 1719, 1657, 1585, 1567, 1434, 1308, 1268 cm'1. Example 237I 4- (4-Chlorobenzoyl) -N-methylthienof2,3-clpridine-2-carboxamide Example 237H (70 mg, 0.21 mmol) was suspended in MeOH (5 mL) and chloroform was added until the solid dissolved. An ammonia balloon was applied and the reaction was heated at 50 ° C for 20 hours. The reaction was concentrated and the residue was purified by flash chromatography on silica gel using EtOAc / hexane as eluent. The obtained main compound was dried on drying to produce a white solid (35 mg, 53%). mp 216-218 ° C; MS (APCI) m / e: 317 (M + H) +; 1 H NMR (DMSO-dβ) 7.68 (m, 2 H), 7.86 (br s, 1 H), 7.88 (m, 2 H), 8.38 (s, 1 H), 8.53 (br s, 1 H), 8.67 (s, 1 H), 9.55 (s, 1 H); 13C NMR (DMSO-dβ) d 123.4, 128.0, 129.3, 132.0, 135.9, 137.9, 138.9, 143. 2, 145.1, 148.8, 148.9, 162.7, 193.6. IR (KBr) 3289, 3145, 1681, 1655, 1399, 1270 cm'1. Anal. cale, for C15H9CIN2O2S 0.1 CßH14: C, 57.59; H, 3.22; N, 8.61.

Found: C, 57.58; H, 3.22; N, 8.41. Example 238 N-4- (4-Chlorophenyl) thienoyl 2,3-clpyridine-2,4-dicarboxamide Example 238A 4- (Ethoxycarbonyl) thienof 2,3-clpyridine-2-carboxamide Example 94 was treated according to the procedure of Example 237D to provide the main compound . Example 238B 4- (Carboxy.tienof2.3-clpyridine-2-carboxamide Example 238A was treated according to the procedure of Example 159A to provide the main compound Example 238C N-4- (4-Chlorophenol) thienor 2,3- Clpyridine-2,4-dicarboxamide Example 238b was treated according to the procedure of Example 24 to provide the main compound, mp> 270 ° C; MS (ESI) m / e: 332 (M + H) +; 1H NMR (300 MHz , DMSO-d6) d 7.46 (m, 2H), 7.84 (br s, 1 H), 7.85 (m, 2H), 8.52 (m, 1 H), 8.56 (br s, 1 H), 8.90 (m, 1 H), 9.47 (m, 1 H), 10.79 (br s, 1 H). Example 239 f4- (4-Bromophenoxy) thienor-2,3-clpyridin-2-yl-methanol Example 239 (900 mg, 97%) was prepared as described in Example 90 except substituting Example 73 (1 g, 2.74 mmol) for the Example 61A MS (APCI) m / e: 336; 338 (M + H) +; 370; 372 (M + CI) "; 1 H NMR (300 MHz, DMSO-dβ) d 4.78 (d, J = 6 Hz, 2H), 5.88 (t, J = 6 Hz, 1H), 6.98 (d, J = 9 Hz, 2H), 7.14 (s, 1H), 7.55 (d, J = 9 Hz, 2H), 8.19 (s, 1H), 9.06 (s, 1H). Example 240 4- (4-Bromophenoxy) thienor-2,3-c1pyridine-2-carbaldehyde Example 240 (400 mg, 80%) was prepared as described in Example 91A except substituting Example 239 (500 mg, 1.49 mmol) for Example 90. MS (APCI) m / e: 334; 336 (M + H) +; 333; 335 (M-H) '; 1 H NMR (300 MHz, DMSO-d 6) d 7.62 (d, J = 9 Hz, 2 H), 7.62 (d, J = 9 Hz, 2 H), 8.26 (S, 1 H), 8.40 (s, 1 H), 9.27 (s, 1H), 10.21 (s, 1H). Example 241 4- (4-Chlorophenoxy) thienoyl-2,3-clpyridine-2-carbaldehyde oxime The main compound was prepared from Example 91A in a manner similar to Example 30. HPLC: Supelco column C-18, water: acetonitrile 0: 90- 90: 0, 30 minutes of elution, flow rate of 0.8 mL / min, rt 19.61 min. and 20.28 min; 1 H NMR (300 MHz, DMSO-dβ) d 2.40 (s, 3 H, toluene), 7.15 (m, 4 H), 7.25 (m, 5 H, toluene), 7.48 (m, 4 H), 7.58 (s, 1 H); 7.75 (s, 1H), 8.16 (m, 3H), 8.51 (s, 1H), 9.05 (s, 1H), 9.14 (s, 1H), 11.91 (s, 1H), 12.66 (s, 1H); 13C NMR (100 MHz, DMSO-dβ) d 119.28, 119.33, 120.58, 122.21, 125.25, 127.51, 128.13, 128.82, 129.99, 133.03, 133.84, 135.37, 136.10 ,. 136.60, 139.40, 137.11, 139.40, 139.95, 140.83, 141.28, 143.24, 143.66, 146.31, 146.58, 155.69.

Anal. cale, for C 14 H 9 CIN 2 O 2 S »0.4 toluene: C, 59.07; H, 3.60; N, 8.20. Found: C, 59.15; H, 3.65; N, 8.25. Example 242 4- (4-Chlorophenoxy) thienof2.3-clpyridine-2-carbaldehyde O-methyloxime Example 242 was prepared from Example 91 A in a manner similar to Example 26. The spectral data for E-isomer: HPLC: Supelco column C-18 , water: acetonitrile 0: 90-90: 0, 30 minutes of elution, flow rate of 0.8 mL / min, rt 22.72 min. and 23.60 min; MS (ESI) m / e 319 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 3.94 (s, 3 H), 7.12 (m, 2 H), 7.47 (m, 2 H), 7.65 (s, 1 H), 8.18 (s, 1 H), 8.61 (s, 1 H), 9.08 (s, 1 H); 13C NMR (100 MHz, DMSO-dβ) d 62.29, 1 19.35, 122.26, 124.01, 127.60, 130.01, 133.77, 136.85, 140.91, 141 .38, 144.34, 146.46, 155.58. Example 243A Mike Staeger 1 -f4- (4-Chlorophenoxy) thienof2.3-c1pyridin-2-ip-1-ethanone O-methyloxime Example 159A was treated in a manner similar to the procedure of Example 22. The derivatized amide was treated according to procedure of Example 33, to produce the corresponding methyl acetone. This acetone was treated according to the procedure of Example 26 to provide the main compound as a mixture of E and Z isomers. The isomers were separated by column chromatography using Type H silica gel (Sigma) and with 25% EtOAc : hexanes.

Spectral data for Z isomer: mp 126-128 ° C; MS (APCI) m / e 333 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 2.29 * (s, 3 H), 3.97 (s, 3 H), 7.15 (m, • 5 2H), 7.48 (m, 2H), 7.72 (s, 1 H), 8.09 (s, 1 H), 9.01 (s, 1 H); 3C NMR (100 MHz, DMSO-d6) d 12.18, 62.32, 1 18.85, 1 19.88, 127.77, 130.01, 132.98, 136.94, 136.98, 140.32, 145.60, 146.94, 150.84, 155.40; Anal. cale, for C, 57.74; H, 3.94; N, 8.42. 10 Found: C, 58.03; H, 3.92; N, 8.14. Example 243B • 1-r4- (4-Chlorophenoxy) thienof2.3-c1pyridin-2-yl-1-ethanone O-methyloxime Isomer E isolated from the preparation of Example 243A: MS (APCI) m / e 333 (M + H ) +; 15 1 H NMR (300 MHz, DMSO-d 6) d 2.28 (s, 3 H), 4.04 (s, 3 H), 7.18 (m, 2 H), 7.48 (m, 2 H), 7.82 (s, 1 H), 8.1 1 (s, 1 H), 9.12 (s, 1 H); 13 C NMR (100 MHz, DMSO-d 6) d 19.25, 62.16, 1 19.88, 120.17, 121 .60, 127.95, 130.04, 131.98, 134.49, 136.52, 138.85, 140.68, 146.21, 147.39, 155.22; Example 244A oxime 1 -r4- (4-chlorophenoxy) thieno.2,3-clpyridin-2-ip-1-ethanone Example 244A was prepared in a manner similar to Example 243A, with the substitution of hydroxylamine hydrochloride for methoxylamine hydrochloride. . MS (APCI) m / e 319 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 2.23 (s, 3 H), 7.15 (m, 2 H), 7.48 (m, 2H), 7.62 (s, 1H), 8.10 (s, 1H), 9.02 (s, 1H), 11.89 (s, 1H); 13C NMR (100 MHz, DMSO-dβ) d 11.41, 117.45, 119.73, 124.45, 127. 65, 129.97, 133.14, 136.78, 137.17, 140.28, 146.72, 147.39, 149.85, 155.51; Anal. cale, for dsHuCINzO? S: C, 54.96; H, 3.69; N, 8.55.

Found: C, 55.37; H, 3.47; N, 8.37. Example 244B oxime 1 -f4- (4-chlorophenoxy) thienoyl-2,3-c1pyridin-2-n-1-ethanone Isomer Z isolated from the preparation of Example 244A: MS (APCI) m / e 319 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 2.38 (s, 3 H), 7.15 (d, J = 9 Hz, 2 H), 7. 48 (d, J = 9 Hz, 2H), 7.73 (s, 1H), 8.10 (s, 1H), 9.12 (s, 1H), 12.35 (s, 1 HOUR); 13C NMR (100 MHz, DMSO-d6) d 19.32, 118.36, 119.96, 120.01, 127. 81, 130.02, 132.08, 134.60, 136.99, 138.95, 140.73, 145.08, 147. 18, 155.40; Example 245 1-f4- (4-Chlorophenoxy) thienor-2,3-clpyridin-2-n-1-propanone The main compound was prepared in analogy to Example 33, substituting ethylmagnesium bromide for methylganesium bromide. mp 101-102 ° C; MS (APCI) m / e: 318 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 1.11 (t, J = 8 Hz, 3 H), 3.18 (d, J = 8 Hz, 2H); 7.21 (m, 2H), 7.51 (m, 2H), 8.1 3 (s, 1 H), 8.32 (s, 1 H), 9.19 (s, 1 H). Example 246 oxime 1 - [4- (4-Chlorophenoxy) thieno-2,3-c1pyridin-2-yn-1-propanone • The main compound was prepared from Example 245 in analogy to Example 26, substituting hydroxylamine hydrochloride to provide a mixture of E and Z isomers. mp 195-198 ° C; MS (APCI) m / e: 333 (M + H) +; 10 1 H NMR (300 MHz, DMSO-d 6) d 1 .10 (m, 6 H), 2.77 (m, 4 H), 7.17 (m, 4 H), 7.48 (m, 4 H), 7.61 (s, 1 H), 7.71 (s, 1 H), 8.09 (s, 1 H), 8.1 1 (s, • 1 H), 9.00 (s, 1 H), 9.12 (s, 1 H), 1 1 .88 (s, 1 H), 12.42 (s, 1 H); HPLC: Supelco column C-18, water: acetonitrile 0: 90-90: 0 in 30 minutes, detection at 254 nm, flow rate of 0.8 mL / min, RT = 15 20.21 min. and 21 .10 min (E and Z isomers); Anal. cale, for C, 57.74; H, 3.94; N, 8.42. Found: C, 57.51; H, 4.12; N, 8.22. Example 247 2 4- (4-Chlorophenoxy) thienof2.3-clpyridin-2-in-N-methoxy-N-methyl-2-oxoacetamide Example 88 (0.38 mmol) was prepared as reported in Example 42 and then combined with THF (1.0 mL) and LDA (0.92 mL of a 0.5 M solution freshly prepared in THF, 0.46 mmol) at -78 ° C. The pale yellow, clear solution was stirred at -78 ° C for 1 .25 hours before the solution is transferred through cannulas to a solution of bs (N, 0-dimethylhydroxyl) oxamide (88 mg, 0.50 mmol) in THF (1.0 mL) at -78 ° C. The solution was slowly warmed to room temperature, diluted with 2N aqueous HCl (20 mL), and extracted with CH2Cl2 (3x10 mL). The organic extracts were combined, rinsed with brine (1 x 10 mL), dried (MgSO), and concentrated to a yellow solid. Flash column chromatography on flash silica gel (15% acetone in hexane) gave the main compound (25 mg, 17% product) as a yellow solid. mp 135.0-1 37.8 ° C; MS (DCI / NH3) m / e: 377 (35Cl) / 379 (37Cl); 1 H NMR (300 MHz, DMSO-d 6) d 3.31 (s, 3 H), 3.64 (s, 3 H), 7.27 (d, J = 8.8 Hz, 2 H), 7.52 (d, J = 8.8 Hz, 2 H), 8.15 (s, 1 H), 8.22 (s, 1 H), 9.26 (s, 1 H). Example 248 4- (4-Chlorophenoxy) thienof2.3-c1pyridine-2-carbonitrile A solution of the resultant compound of Example 61 B (500 mg, 1.64 mmol) in pyridine (7 mL) under nitrogen at -78 ° C was added. treated with trifluoroacetic anhydride (1 mL, 6.6 mmol), stirred at -78 ° C for 30 minutes, allowed to slowly warm to room temperature, and stirred two more hours. This mixture was diluted with ethyl acetate, rinsed with saturated NaHCO3, brine, dried (MgSO4) and concentrated. The resulting light purple solid was dissolved in a minimum amount of ethyl acetate, filtered through a silica plug, rinsed all with 50/50 hexane / ethyl acetate and concentrated to give 395 mg of the Main compound as a white solid (84%). mp 140-142 ° C; MS (APCI-NHs) m / e: 287 (M + H) +; 1 H NMR (300 MHz, CDCl 3) d 7.04 (d, 2 H), 7.40 (d, 2 H), 8.00 (s, 1 H), 8.14 (s, 1 H), 8.96 (s, 1 H); Anal. cale, for C l 4H7CIN2OS: C, 58.64; H, 2.46; N, 9.77. Found: C, 58.45; H, 2.62; N, 9.52. Example 249 4- (4-Chlorophenoxy) -N'-hydroxytylene 2,3-clpyridine-2-carboximidamide A solution of the compound resulting from Example 248 (100 mg, 0.35 mmol) in ethanol (2 mL) under nitrogen at room temperature was treated with triethylamine (90 mL, 0.6 mmol), hydroxylamine hydrochloride (40 mg, 0.53 mmol) and stirred for 18 hours. The resulting heterogeneous, white mixture was diluted with ethyl acetate, rinsed with saturated NaHCO3, brine, dried (MgSO4) and concentrated to give 120 mg of a whitish foam. This foam was dissolved in ethyl acetate, filtered through a silica plug and concentrated to give the main compound as a white solid (10 mg, 98%). mp 140-142 ° C; MS (APCI-NH3) m / e: 320 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 10.23 (s, 1 H), 9.02 (s, 1 H), 8.13 (s, 1 H), 7.87 (s, 1 H), 7.46 (d, 2 H), 7.1 1 (d, 2H), 6.26 (br s, 2H); Anal. cale, for C 14 H 10 CIN 3 O 2 S: C, 52.59; H, 3.15; N, 13.14. Found: C, 52.72; H, 3.05; N, 12.82. Example 250 4- (4-Chlorophenoxy) -N'-cyanothienof2,3-clpyridine-2-carboximidamide A solution of the resultant compound of Example 248 (100 mg, 0.35 mmol) in THF (2 mL) under nitrogen at room temperature was treated with cyanamide (74 mg, 1.75 mmol), 1,8-diazabicyclo [5.4.0] undec-7-ene (52 mL, 0.35 mmol) and stirred for 24 hours. The resulting yellow homogeneous solution was diluted with ethyl acetate, rinsed with saturated NaHCO3, brine, dried (MgSO4), concentrated to give a light yellow solid, triturated with CH2CI to give 123 mg of a white powder, dissolved in ethyl acetate, ethyl and THF, rinsed with distilled water, brine, dried (MgSO 4), concentrated to give 99 mg of a white powder (MgSO 4) which was triturated with CH 2 Cl 2 and then placed in a vacuum oven overnight at 60 ° C to give the main compound as a white powder (78 mg, 69%). mp 265-268 ° C; MS (APCI-NH3) m / e: 329 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 9.58 (br s, 1 H), 9.17 (s, 1 H), 9.05 (br s, 1 H), 8.41 (s, 1 H), 8.19 (s, 1 H), 7.48 (d, 2H), 7.15 (d, 2H); Anal. cale, for C15H10CIN4OS: C, 54.80; H, 2.76; N, 17.04. Found: C, 54.50; H, 3.01; N, 17.16. Example 251 (2-Aminophenyl) f4- (4-chlorophenoxy) thienof2,3-clpyridin-2-inmetanone Example 251A r4- (4-Chlorophenoxytienof2,3-clpyridin-2-yl-2-nitrophenyl) methane To a stirred solution of the Example 124A (1.00 g, 3.82 mmol) in THF (40 mL) at -78 ° C, a 1.3 M suspension of sec-butyllithium. in cyclohexane (3.52 mL, 4.58 mmol) was added dropwise over a period of 10 minutes. After 40 minutes, the reaction was transferred through cannulas to a stirred solution of 2-nitrobenzaldehyde (1.43 g, 9.55 mmol) in THF (10 mL) at -48 ° C. After 20 minutes, the reaction was cooled by slow addition of MeOH (6 mL). The reaction was diluted with EtOAc (125 mL) and the organic was rinsed with 1: 1 sat. NaHCO3. water (1 x 75 mL), brine (1 x 75 mL), partially dried (Na 2 SO 4) and concentrated. The residue was purified by flash chromatography on silica gel using EtOAc / hexane as eluent to afford the main compound as a solid (1.49 g, 95%). mp 85-90 ° C; MS (APCI) m / e: 413 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 6.54 (s, 1 H), 6.95 (s, 1 H), 7.03 (m, 1 H), 7.06 (m, 2 H), 7.42 (m, 2 H), 7.60 (m, 1 H), 7.78 (m, 1 H), 7.85 (m, 1 H), 7.98 (m, 1 H), 8.12 (s, 1 H), 9.02 (s, 1 H); Anal. cale, for C2oH13CIN2O4S 0.3 H2O: C, 57.43; H, 3.28; N, 6.70. Found: C, 52.42; H, 3.45; N, 6.42. Example 251 B (2-Aminophenol) r4- (4-chlorophenoxy) thienor-2,3-clpyridin-2-methanol Example 251 A (0.1 g, 0.24 mmol) was dissolved in EtOH (1.7 mL) and a solution of Tin dihydrate (II) chloride (0.43 g, 1.92 mmol) in concentrated HCl (0.70 mL) was added slowly. The reaction was stirred 18 hours, then partitioned between CHCl3 (50 mL) and sat. NaHCO3. (75 mL). The aqueous layer was extracted with EtOAc (1 x 50 mL) and all organic extracts were combined, partially dried (Na2SO) and concentrated. The residue was purified by flash chromatography on silica gel using EtOAc / hexane as eluent to give the main compound as a lightly colored solid (0.08 g, 87%). mp 85-90 ° C; MS (APCI) m / e: 383 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 5.08 (br s, 2 H), 6.10 (d, J = 4.3 Hz, 1 H), 6.54 (d, J = 4.3 Hz, 1 H), 6.55 (m, 1 H), 6.61 (m, 1 H), 6.98 (m, 1 H), 7.05 (m, 2H), 7.13 (m, 1 H), 7.19 (m, 1 H), 7.42 (m, 2H), 8.09 (s, 1 H), 8.98 (s, 1 H); Anal. cale, for C2oH15CIN2O2S: C, 62.74; H, 3.95; N, 7.32. Found: C, 63.09; H, 4.05; N, 7.06. Example 251 C (2-Aminophenyl) F4-.4-chlorophenoxy) thienof2,3-clpridine-2-ipmetanone To an anhydrous stirred suspension of silica gel (0.13 g) and celite (0.13 g) in dichloromethane (6 mL) ) pyridinium chloromate (0.13 g, 0.59 mmol) was added. A solution of Example 251 B (0.15 g, 0.39 mmol) in anhydrous dichloromethane (9 mL) was slowly added dropwise. After 1 hour, sat. NaHCO3 was added. (5 mL), and the reaction was stirred for 1 hour. The reaction was filtered and the black solid was pressed and rinsed with 5% MeOH / dichloromethane (3x20 mL). The organic filtrate and rinses were combined and rinsed with sat. NaHCO3. (2x100 mL), brine (1x75 mL), partially dried (Na SO4) and concentrated. The residue was purified by flash chromatography on silica gel using EtOAc / hexane as eluent to give the main compound as a lightly colored solid (45 mg, 39%). mp 152-154 ° C; • 5 MS (APCI) m / e: 381 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 6.54 (m, 1 H), 6.87 (m, 1 H), 7.05 (broad s, 2 H), 7.18 (m, 2 H), 7.33 (m, 1 H), 7.47 (m, 2H), 7.57 (s, 1 H), 7.58 (m, 1 H), 8.24 (s, 1 H), 9.21 (s, 1 H); 13 C NMR (300 MHz, DMSO-d 6) d 1 14.5, 1 15.9, 1 17.1, 120.1, 123.8, 10 128.0, 130.0, 132.5, 133.0, 134.9, 136.0, 138.2, 141 .2, 147.8, 148.5, 151 .8 , 155.3, 188.5; IR (KBr) 3440, 341 1, 3293, 3190, 1616, 1587, 1552, 1483, 1409, 1267, 1245, 1219, 1 155 cm'1; Anal. cale, for C2oH13CIN2O2S: C, 63.08; H, 3.44; N, 7.36. 15 Found: C, 62.94; H, 3.51; N, 7.25. Example 252 (3-Aminophenyl) -4- (4-chlorophenoxy) thienof2,3-clpyridin-2-inmetanone Example 252A, 4fe r4- (4-Chlorophenoxy) thienof2.3-c1pyridin-2-yn (3-nitrophenol) ) methanol The procedure of Example 251A was used, substituting 3-nitrobenzaldehyde for 2-nitrobenzaldehyde. mp 79-83 ° C; MS (APCI) m / e: 413 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 6.33 (d, J = 4.4 Hz, 1 H), 6.99 (d, J = 4.4 25 Hz, 1 H), 7.07 (m, 2 H), 7.27 (m, 1 H), 7.43 (m, 2H), 7.66 (m, 1 H), 7.92 (m, 1 H), 8.13 (s, 1 H), 8.15 (m, 1 H), 8.34 (m, 1 H), 9.01 (s, 1 H); Anal. cale, for C2oH13CIN2O4S: C, 58.19; H, 3.17; N, 6.79. Found: C, 57.97; H, 3.23; N, 6.70. Example 252B • 5 (3-Aminophenyl) r4- (4-chlorophenoxy) thienof2.3-c1pyridin-2-methanol Example 252A was treated according to the procedure of Example 251 B to provide the main compound, mp 73-78 ° C; MS (APCI) m / e: 383 (M + H) +; 10 1 H NMR (300 MHz, DMSO-d 6) d 5.03 (s, 2 H), 5.88 (s, 1 H), 6.45 (m series, 2 H), 6.57 (m, 1 H), 6.64 (m, 1 H ), 6.96 (m, 1 H), 7.06 (m, 2H), • 7.1 1 (m, 1 H), 7.42 (m, 2H), 8.08 (s, 1 H), 8.97 (s, 1 H); Anal. cale, for C2oH15CIN2? 2S: C, 62.74; H, 3.95; N, 7.32. Found: C, 63.06; H, 4.22; N, 6.92. Example 252C (3-Aminophenyl) f4- (4-chlorophenoxy) thienof2.3-c1pyridin-2-p-methanone Example 252B was treated according to the procedure of Example 251 C to provide the main compound, mp 174-178 ° C; MS (APCi) m / e: 481 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 5.47 (br s, 2 H), 6.86-8.96 (series of m, 2 H), 7.06 (m, 1 H); 7.16-7.23 (series of m, 3H), 7.48 (m, 2H), 7.77 (s, 1 H), 8.20 (s, 1 H), 9.22 (s, 1 H). Example 253 25 4- (4-Bromophenoxy) -2-vinyl-triene-2,3-clpyridine To a stirred suspension of methyl triphenylphosphonium bromide (13 mg, 0.314 mmol) in anhydrous tetrahydrofuran (2 mL) at -78 ° C was added dropwise a solution of n-BuLi (2.5 M solution in hexanes, 0.125). mL), 0.314 mmol) under nitrogen atmosphere. Then the reaction mixture was stirred at 0 ° C for 40 minutes and cooled below -78 ° C. To this was added a solution of Example 240 (100 mg, 0.3 mmol) in anhydrous tetrahydrofuran (2 mL), while maintaining the internal temperature below -72 ° C. Once the addition was complete the reaction mixture was stirred at 0 ° C for 15 minutes and at room temperature for 1 hour. Then the reaction mixture was partitioned between ethyl acetate (60 mL) and brine (20 mL). The organic layer was rinsed with brine (2x20 mL), dried (MgSO), and evaporated to dryness under reduced pressure to obtain the crude product (145 mg). The main compound was obtained in 26% product (26 mg) by flash chromatography on silica gel eluting with 25% acetone-hexane. MS (APCI) m / e: 332; 334 (M + H) +; 1 H NMR (400 MHz, DMSO-d6) d 5.53 (d, J = 10 Hz, 1 H), 5.86 (d, J = 16 Hz, 1 H), 7.02 (d, J = 9 Hz, 2H), 7.06-7.14 (m, 1 H), 7.37 (s, 1 H), 7.57 (d, J = 9 Hz, 1 H), 8.17 (s, 1 H), 9.04 (s, 1 H). Example 254 1-f4- (4-Chlorophenoxy) thienof2.3-c1pyridin-2-yn-1,2-ethanediol Example 254A 4- (4-Chlorophenoxy) -2-ethenylthienof2.3-clpyridine Example 254A (70 mg, 10%) was prepared as in Example 253 except substituting Example 91 A (700 mg, 2.42 mmol) for Example 240. 1 H NMR (300 MHz, DMSO-dβ) d 5.53 (d, J = 10.5 Hz, 1 H), 5.86 (d, J = 18 Hz, 1 H), 7.04-7.14 (m, 1 H), 7.10 (d, J = 9 Hz, 2 H), 7.38 (s, 1 H); 7.45 (d, J = 9 Hz, 2H), 8.16 (s, 1 H), 9.04 (s, 1 H). Example 254B 1-r4- (4-Chlorophenoxy) thienof2,3-clpyridin-2-n-1,2-ethanediol Example 254A (22 mg, 28%) was prepared as in Example 255 except substituting Example 254A (70 mg , 0.26 mmol) by Example 253. MS (APCI) m / e: 322 (M + H) +, 356 (M + CI) '; 1 H NMR (400 MHz, DMSO-dβ) d 3.50-3.64 (m, 2H), 4.86-4.91 (m, 1 H), 5.0 (t, J = 6 Hz, 1 H), 6.04 (d, J = 4 Hz, 1 H), 7.07 (d, J = 9 Hz, 2 H), 7.21 (s, 1 H), 7.43 (d, J = 9 Hz, 2 H), 8.14 (s, 1 H), 9.04 (s, 1 HOUR); 13C NMR (100 MHz, DMSO-dβ) d: 66.52 (CH2), 70.24 (CH), 1 14.60 (CH), 1 19.06 (CH), 127.22 (C), 129.91 (CH), 133.36 (CH), 137.16 (C), 137.42 (C), 140.79 (CH), 145.79 (C), 155.91 (C), 156.59 (C). Example 255 1-f4- (4-Bromophenoxy) thienof2.3-clpyridin-2-in-1,2-ethanediol To a solution of Example 253 (90 mg, 0.271 mmol) in tetrahydrofuran (2 mL) was added 4- Methylmorpholine N-oxide (63.5 mg, 0. 542 mmol) and osmium tetroxide (14 mg, 0.054 mmol) in water (0.5 mL) at room temperature. The reaction mixture was stirred for 48 hours and the solvents were removed. The obtained residue was purified directly by flash chromatography on silica gel eluting with 20% acetone-hexane to obtain the main compound (52 mg, 53%). MS (APCI) m / e: 366; 368 (M + H) +, 402 (M + CI) ', 1 H NMR (400 MHz, DMSO-dβ) d 3.50-3.64 (m, 2H), 4.89 (m, 1 H), 5.1 (t, J = 6 Hz, 1 H), 6.05 (d, J = 4 Hz, 1 H), 7.01 (d, J = 9 Hz, 2 H), 7.21 (s, 1 H), 7.55 (d, J = 9 Hz, 2H), 8.15 (s, 1 H), 9.04 (s, 1 H); 13C NMR (1 00 MHz, DMSO-d6) d: 66.52 (CH2), 70.25 (CH), 1 14.60 (CH), 1 15.08 (C), 1 1 9.24 (CH), 132.84 (CH), 133.49 (CH) ), 137.18 (C), 137.48 (C), 140.87 (CH), 145.67 (C), 156.46 (C), 156.65 (C). Example 256 r4- (4-chlorophenoxy) thienof2.3-clpyridin-2-ipmethanamine Diethylazodicarboxylate (180 mL, 1.13 mmol) was added to Example 90 (220 mg, 0.750 mmol), THF (7.5 mL), phosphine of triphenyl (297 mg, 1.13 mmol), and eftalamide (166 mg, 1.13 mmol). After 16 hours, the orange solution was concentrated under vacuum in an orange solid. Flash silica gel column chromatography (20% acetone in hexane) provided a compound (100% product) as the main product, which was combined with hydrazine hydrate (230 mL, 7.50 mmol) and ethanol (75 mL) ) and heated to reflux. After four hours, the solution was cooled to room temperature, concentrated, diluted with 5 N HCl (30 mL) and filtered through a glassy porous funnel. The filtrate was combined with 3 N NaOH until pH > 12 and extracted with EtOAc (3x30 mL). The organic extracts were combined, rinsed once with brine (30 mL), dried (MgSO4), filtered and concentrated in vacuo to provide the main compound (1 90 mg, 87% product) as a white solid. mp 78.6-79.8 ° C; MS (DCI / NH3) m / e: 321 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.24 (br s, 2 H), 4.02 (s, 2 H), 7.03 (d, J = 9.1 Hz, 2 H), 7.15 (s, 1 H), 7.42 (d, J = 9.1 Hz, 2H), 8.14 (s, 1 H), 9.01 (s, 1 H); Anal. cale, for d4HnC. 2OS-O.25 H2O: C, 56.95; H, 3.93; N, 9.49. Found: C, 56.86; H, 3.81; N, 9.62. Example 257 f4- (4-chlorophenoxy) thienof2.3-c1pyridin-2-immethyl carbamate Example 90 (50 mg, 0.17 mmol) was combined with CH2Cl2 (0.5 mL), sodium cyanate (22 mg, 0.34 mmol), and acid trifluoroacetic (40 mL, 0.34 mmol); Gas evolution was observed. After 24 hours, the mixture was partitioned between distilled water (15 mL) and CH2CI2 (50 mL). The layers were separated, and the organic layer was dried (MgSO), filtered and concentrated. Column chromatography on silica gel (30% acetone in hexane) provided the main compound (21 mg, 37% product) as a white solid, mp 13-1 15 ° C; MS (DCI / NH3) m / e: 335 (35Cl) / 337 (37Cl); H NMR (300 MHz, DMSO-dβ) d 5.30 (s, 2H), 6.80 (br s, 2H), 7.06 (d, J = 9.2 Hz, 2H), 7.37 (s, 1 H), 7.45 (d, J = 8.8 Hz, 2H), 8.18 (s, 1 H), 9.10 (s, 1 H).

Example 258 N- (f4- (4-chlorophenoxy) thienof2,3-c1pyridin-2-illmethylurea Potassium cyanate (41 mg, 0.50 mmol) was added to a mixture of Example 256 (130 mg, 0.45 mmol), water distilled (2.0 mL) and concentrated HCl (40 mL, 0.45 mmol), and the solution was heated to 50 [deg.] C. After 3 hours, the solution was slowly cooled to 0 [deg.] C., and the resulting precipitate was isolated by filtration. Flash silica gel column chromatography (20% acetone in hexane, changing to 10% MeOH in EtOAc) provided the main compound (63 mg, 42% product) as a white solid, mp 202-204 ° C MS (DCI / NH3) m / e: 334 (35CI) +/336 (37CI) +; 1H NMR (300 MHz, DMSO-d6) d 4.47 (d, J = 6.1 Hz, 2H), 5.68 (s, 2H), 6.68 (t, J = 6.1 Hz, 1 H), 7.05 (d, J = 8.8 Hz, 2H), 7.14 (s, 1 H), 7.43 (d, J = 8.8 HZ, 2H), 8.14 ( s, 1 H), 9.02 (s, 1 H), cale anal, for dsH ^ CINsOzS: C, 53.97; H, 3.62; N, 12.59, Found: C, 53.80; H, 3.67; N, 12.37. 259 (E) -3-f4- (4-Bromophenoxy) tienof2.3-c1pir idin-2-ippropenamide Example 259A Methyl 3- (4-.4-Brornophenoxy) thienof2,3-clpyridine-2-iflpropeonate Example 259A (590 mg, 57%) was prepared as in Example 91 B except substituting Example 240 (890 mg, 2.67 mmol) by Example 91A.

MS (APCl) m / e: 390; 392 (M + H) +, 389; 391 (MH) ', 1 H NMR (300 MHz, DMSO-d 6) d 3.75 (s, 3 H), 6.58 (d, J = 16 Hz, 1 H), 7. 07 (d, J = 9 Hz, 2 H), 7.59 (d, J = 9 Hz, 2 H), 7.89 (s, 1 H); 8.02 (d, J = 16 Hz, 1 H), 8.17 (s, 1 H), 9.12 (s, 1 H). Example 259B 3- (4- (4-Bromophenoxy) thienof2,3-clpyridine-2-yl) propenoic acid Example 259A and the procedure of Example 88 was used to provide the main compound (270 mg, 93%). MS (APCl) m / e: 376; 378 (M + H) +; * H NMR (300 MHz, DMSO-dβ) d: 6.45 (d, J = 16 Hz, 1 H), 7.07 (d, J = 9 Hz, 2H), 7.58 (d, J = 9 Hz, 2H), 7.81 (s, 1 H), 7.90 (d, J = 16 Hz, 1 H), 8. 16 (s, 1 H), 9.10 (s, 1 H). Example 259C 3- (4- (4-Bromophenoxy.tienof2,3-c1pyridin-2-yl) propenamide Example 259B (222 mg, 81%) and the procedure in Example 92, except substituting Example 259B for Example 91 C, was used to provide the main compound. mp 195-196 ° C; MS (APCl) m / e: 375.377 (M + H) +, 409; 41 1 (M + CI) '; 1 H NMR (400 MHz, DMSO-d 6) d 6.62 (d, 16 Hz, 1 H), 7.04 (d, J = 9 Hz, 2H), 7.26 (s, 1 H), 7.56 (d, J = 9 Hz, 2H), 7.64 (s, 1 H), 7.68 (s, 1 H), 7. 72 (d, J = 16 Hz, 1 H), 8.13 (s, 1 H), 9.05 (s, 1 H); 13C NMR (100 MHz, DMSO-d6) d 1 15.55 (C), 1 19.98 (CH), 122.1 1 (CH), 126.68 (CH), 131.80 (CH), 132.91 (CH), 133.71 (CH), 136.69 (C), 137.48 (C), 140.84 (CH), 145.79 (C), 146.43 (C) , 156.07 (C), 165. 37 (C). Example 260 Methyl (E) -3-r4- (4-Bromophenoxy) thienor-2,3-clpyridin-2-n-propenamide Example 260 (25 mg, 50%) was prepared from Example 259A • (50 mg, 0.13 mmol), as described in Example 1 71. MS (APCl) m / e: 389 (M + H) +; 1 H NMR (400 MHz, DMSO-dβ) d 2.71 (d, J = 4.5 Hz, 3 H), 6.62 (d, J = 16 Hz, 1 H), 7.06 (d, J = 9 Hz, 2 H), 7.58 ( d, J = 9 Hz, 2H), 7.69 (s, 1 H), 7.74 (d, J = 16 Hz, 1 H), 8.15 (s, 1 H), 8.27 (d, J = 4.5 Hz, 1 H ), 9.08 (s, 1 H); 10 13C NMR (100 MHz, DMSO-dβ) d 25.7 (CH 3), 1 15.6 (C), 120.0 (CH), F 122.1 (CH), 126.4 (CH), 131.1 (CH), 132.9 (CH), 133.7 (CH), 136.7 (C), 137.5 (C), 140.9 (CH), 145.9 (C), 146.4 ( C), 156.1 (C), 164.3 (C). Example 261 Methyl 3-f4- (4-Bromophenoxy) thienor-2,3-clpyridin-2-ip-2,3-d-hydropropanamide Example 260 (52 mg, 53%) was prepared as described in Example 255, except substituting Example 260 (90 mg, 0.232 mmol), to provide the main compound. MS (APCl) m / e: 423; 425 (M + H) +, 456 (M + CI) '; 1 H NMR (300 MHz, DMSO-d 6) d 2.61 (d, J = 4.5 Hz, 3 H), 4.09 (br d, J = 3 Hz, 1 H), 5.27 (br d, J = 3 Hz, 1 H), 5.68 (d, J = 6 Hz, 1 H), 6.09 (d, J = 6 Hz, 1 H), 7.00 (d , J = 9 Hz, 2H), 7.23 (s, 1 H), 7.56 (d, J = 9 Hz, 2H), 7.77 (d, J = 4.5 Hz, 1 H), 8.14 (s, 1 H), 9.04 (s, 1 H); 13 C NMR (75 MHz, DMSO-d 6) d 25.5 (CH 3), 70.3 (CH), 75.1 (CH), 1 15.0 (CH), 1 15.1 (C), 1 19.5 (CH), 132.9 (CH), 133.5 (CH), 137.5 (C), 137.5 (C), 140.9 (CH), 145.8 (C), 156.3 (C), 156.5 (C), 171.7 (C).

Example 262 3-r4- (4-Bromophenoxy) thienor 2,3-clpyridin-2-n-2,3-dihydropropanamide The procedure of Example 261 and the product of Example 259C can be used to prepare the main compound. Example 263 4- (4-Chlorophenoxy) thieno.2,3-c1pyridin-2-ylamine A mixture of Example 159A (0.500 g, 1.64 mmol) and 1,8-bis (dimethylamino) naphthalene, N, N, N \ N-tetramethi-1, 8-naphthalenediamine (0.350 g, 1.64 mmol) in 90 mL of anhydrous THF was heated until all solids entered the solution. The solution was stirred for 15 m, while diphenylphosphoryl acid (0.450 g, 1.64 mmol) was added. The solution was heated to reflux for 18 hours. The resulting deep red solution was evaporated to dryness under reduced pressure. The product was passed through 5 g of silica gel, eluting with 20% ethyl acetate / hexanes to provide 422 mg of the intermediate isocyanate as a bright orange solid. The resulting product was dissolved in 100 mL of toluene and the solution was heated to reflux for 6 hours. The product was evaporated to dryness. The resulting dark orange solid was dissolved in 20 mL of 2.0 M hydrogen chloride in dioxane. The solution was evaporated, leaving 313 mg (84.9%) of the main compound. MS (APCl) m / e: 277 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 6.91 (s, 1 H), 7.18 (d, 2 H), 7.47 (d, 2 H), 8.34 (s, 1 H), 9.21 (s, 1 H); Example 264 4- (4-Chlorophenoxy) thienof2,3-clpyridin-2-lformamide A mixture of 5 mL of acetic anhydride and 1.8 mL of 96% formic acid was heated at 70 ° C for 3 hours. The solution • 5 was allowed to cool while the amine obtained from Example 263 (32 mg, 0.12 mmol) was added. The mixture was stirred for 4 days and then poured into 50 mL of diluted HCl. The mixture was extracted with ethyl acetate, the combined extracts were rinsed with saturated sodium carbonate and then water, dried (MgSO4) and evaporated. Purification of the resulting product by preparative HPLC using a gradient of 30% -70% acetonitrile / water + 0.1% TFA • for 40 minutes provided 18 mg (49%) of the main compound. MS (APCl) m / e: 305 (M + H) +; 1 H NMR (300 MHz, CD 3 OD) d 7.16 (s, 1 H), 7.24 (d, 2 H), 7.46 (d, 2 H), 15 8.08 (s, 1 H), 8.61 (s, 1 H), 9.13 ( s, 1 H); EXAMPLE 265 N-r4- (4-Chlorophenoxy) thienof2,3-c1pyridin-2-urea A mixture of the isocyanate obtained from Example 263 (1 mg, 0.364 mmol) in 10 mL of ammonium hydroxide was stirred vigorously for 20 minutes. hours. The resulting red solid was collected and dried under vacuum to provide 60.7 g (52.2%) of the main compound. MS (APCl) m / e: 320 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 7.20 (d, 2 H), 7.34 (s, 1 H), 7.50 (d, 25 2 H), 7.65-7.79 (m, 4 H), 8.06-8.16 (m, 2 H) ), 9.18 (s, 1 H); Example 266 N-f4- (4-Chlorophenoxy) thienof2.3-clpyridin-2-in-N'-methylthiourea A solution of the amine obtained from Example 263 (150 mg, 0.542 mmol) in 5 mL of pyridine was treated with isothiocyanate of methyl (198 mg, 2.71 mmol). The solution was heated to 100 ° C under a nitrogen atmosphere for 5 days. All volatiles were removed under reduced pressure. The resulting product was purified by flash column chromatography on silica gel eluting with chloroform / NH OH, yielding 10 mg (58.1%) of the major compound, MS (APCl) m / e: 350 (M + H) +; 1 H NMR (300 MHz, CD 3 OD) d 3.31 (s, 3 H), 6.61 (bs, 1 H), 6.96 (d, 2 H), 7.34 (d, 2 H), 7.88 (s, 1 H), 7.96 (s, 1 H), 8.67 (s, 1 H); Example 267 Methyl 4- (4-chlorophenoxy) thienof2,3-clpyridine-2-sulfonamide To a solution of Example 124A (261 mg, 1 mmol) in anhydrous THF (2 mL) at -78 ° C was added n-BuLi ( 2.5 M solution in hexanes, 0.60 mL, 1.5 mmol) under nitrogen atmosphere. This was stirred at -78 ° C for 2 hours and a rapid stream of SO2 was introduced to the surface of the reaction mixture. After 15 minutes the reaction mixture was allowed to warm to 0 ° C with continuous introduction of SO2. The gas stream of SO2 was discontinued after 10 minutes at 0 ° C and the reaction mixture was allowed to warm to 10 ° C. then the solvent and excess SO2 gas were removed under reduced pressure to obtain the lithium salt of sulfinic acid such as solid colored cream. This material was dissolved in saturated aqueous NaHCO3 solution (1 mL) and treated with N-chlorosuccinimide (200 mg, 1.5 mmol) at 0 ° C. The reaction mixture was stirred at 0 ° C for 1 hour and at room temperature for 2 hours. The formed product • 5 was extracted into CH2Cl2 (2x50 mL) and rinsed with water (2x20 mL). The dried organic layer (Na2SO) was evaporated to dry under reduced pressure to obtain the sulfonyl chloride derivative. A portion of this material (143 mg, 0.398 mmol) was dissolved in CH2CI2 (1 mL) at -5 ° C and treated with diisopropylethylamine (0.083 mL, 0.478 mmol) and 2 M solution of methylamine in methanol (0.239 mL, 1.2 mmol) under nitrogen atmosphere. The reaction mixture was stirred • room temperature for 1 hour. This was purified directly by flash chromatography on silica gel eluting with 10% acetone-hexane followed by 25% acetone-hexane for Obtain the main compound (19 mg, 13.5%) MS (APCl) m / e: 335 (M + H) +, 353 (M-H) '; 1 H NMR (300 MHz, DMSO-d 6) d 2.57 (s, 3 H), 7.19 (d, J = 9 Hz, 2 H), 7.49 (d J = 9 Hz, 2 H), 7.76 (s, 1 H), 8.16 (br d, J = 3 Hz, 1 H), 8.24 (s, 1 H), 9.24 (s, 1 H). Example 268 2.3-Dihydroxypropyl 4- (4-chlorophenoxy) thienor-2,3-clpyridine-2-sulfonamide Example 268 (8.6 mg, 7.5%) was prepared as described in Example 267 except substituting 3-amino-1, 2-propanediol (0.086 mL, 1.12 mmol) by methylamine. MS (APCl) m / e: 415 (M + H) +, 413 (M-H) '; 1 H NMR (300 MHz, DMSO-d 6) d 2.76 (d, J = 7.5 Hz, 1 H), 2.81 (d, J = 7.5 Hz, 1 H), 3.02 (d, J = 4.5 Hz, 1 H), 3.08 (d, J = 4.5 Hz, 1 H), 3.44-3.55 (m, 1 H), 4.47-4.64 (m, 1 H), 4.80 (d, J = 6 Hz, 1 H), 7.17 (d, J = 9 Hz, 2H), 7.48 (d, J = 9 Hz, 2H), 7.77 (s, 1 H), 8.23 (s, 1 H), 9.22 (s, 1 H). Example 269 2.3-Hydroxyethyl 4- (4-chlorophenoxy) thienor-2,3-clpyridine-2-sulfonamide Example 269 (25 mg, 16%) was prepared as described in Example 267 except substituting 2-hydroxyethylamine (0.072 mL, 1. 2 mmol) by methylamine. MS (APCl) m / e: 385 (M + H) +, 383 (M-H) '; 1 H NMR (300 MHz, DMSO-d 6) d 2.97 (t, J = 6 Hz, 2 H), 3.38-3.45 (m, 2 H), 4.69-4.78 (m, 1 H), 7.18 (d, J = 9 Hz , 2H), 7.48 (d, J = 9 Hz, 2H), 7.78 (s, 1 H), 8.23 (s, 1 H), 9.21 (s, 1 H); 13 C NMR (75 MHz, DMSO-d 6) d 45.4 (CH 2), 59.7 (CH 2), 1 19.9 (CH), 122.2 (CH), 128.0 (C), 130.1 (CH), 133.3 (CH), 135.5 (C ), 138.2 (C), 141.4 (CH), 147.5 (C), 148.4 (C), 155.2 (C). Example 270 4-f4- (4-Chlorophenoxy) thienof2.3-clpyridin-2-pfenol Example 270A 4-R4- (4-Chlorophenoxy) thienof2.3-c1pyridin-2-boronic acid A suspension of 1.3 M sec-butyllithium in cyclohexane (3.52 mL, 4.58 mmol) was added to THF (10 mL) at -78 ° C. A solution of Example 124A (1.00 g, 3.82 mmol) in THF (5 mL) was added dropwise. The reaction was stirred at 30 minutes and tributyl borate (1.55 mL, 5.73 mmol) was slowly added. The cold bath is it was removed and the reaction was stirred for 45 minutes while heating to room temperature. A solution of 2N NaOH (15 mL) was added. After 10 minutes, the reaction was diluted with hexane (15 mL) and the aqueous layer was collected. The organic layer was extracted with 2 N NaOH • 5 (2x5 mL) and all the aqueous extracts were combined, acidified to pH 2 with 6 N HCl and extracted with 10% MeOH / CH2CI2 (4x25 mL). The organic extracts were combined and concentrated. The resulting solid was rinsed with acetonitrile (1 x 25 mL) and dried in a desiccator to produce the main compound as a solid. tanning (0.83 g, 71%). MS (APCl) m / e: 262 (M + H-B (OH) 2) +, m / e: 340 (M + CI) '; • 1H NMR (300 MHz, DMSO-d6) d 7.15 (m, 2H), 7.48 (m, 2H), 8.03 (s, 1 H), 8.24 (s, 1 H), 9.29 (s, 1 H). Example 270B 15 4-r4- (4-Chlorophenoxy) thienof2.3-clpyridin-2-ipanisol A mixture of Example 270A (0.25 g, 0.82 mmol), 4-iodoanisole (0.1 9 g, 0.82 mmol), complex [ 1, 1 '- bis (diphenylphosphino) ferrocene] dichloropalladium (II) dichloromethane (1: 1) (0.10 g, 0.12 mmol), cesium fluroride (0.37 g, 2.46 mmol), Triethylamine (0.1 mL, 0.82 mmol), in DME (7 mL) was sucked 10 minutes with anhydrous nitrogen. The reaction was heated to 75 ° C for 18 hours and then partitioned between EtOAc (100 mL), and sat. NaHCO3. (100 mL), brine (75 mL), partially dried (Na2SO4) and concentrated to a concentrated wet solid. The residue was purified by flash chromatography on silica gel using EtOAc / hexane as the eluent to produce a colored solid. The main product was crystallized from hot acetonitrile (0.1 1 g, 37%). mp 121-123 ° C; MS (APCl) m / e: 368 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 3.82 (s, 3H), 7.05 (m, 2H), 7.13 (m, 2H), 7.45 (m, 2H), 7.67 (s, 1 H), 7.81 (m, 2H), 8.13 (s, 1 H), 9.05 (s, 1 HOUR); Anal. cale, for C20H? 4CINO2S: C, 65.30; H, 3.84; N, 3.81.

Found: C, 65.06; H, 3.69; N, 4.05. Example 270C 4-r4- (4-Chlorophenoxy) thienof2.3-clpyridin-2-pfenol To a solution of Example 270B (0.09 g, 0.24 mmol) in Anhydrous CH 2 Cl 2 (4 mL) was added a solution of 1 M boron tribromide in CH 2 Cl 2 (0.96 mL, 0.96 mmol). After 2 hours, the reaction was cooled by slow addition of MeOH (2 mL) and then concentrated. The residue was diluted with CH2Cl2 (50 mL) and the organic was rinsed with 1: 1 NaHCO3 sat./salmuera (50 mL), partially dried (Na2SO), then concentrated. The residue was purified by flash chromatography on silica gel using EtOAc / hexane as eluent to afford the main compound as a solid (0.08, 96%). mp 213-215 ° C; MS (ESI) m / e: 354 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 6.86 (m, 2 H), 7.1 1 (m, 2 H), 7.45 (m, 2 H), 7.56 (s, 1 H), 7.68 (m, 2 H), 8.13 ( s, 1 H), 9.03 (s, 1 H), 9.99 (s, 1 HOUR). Anal. cale, for C19H12CINO2S 0.5 H2O: C, 62.90; H, 3.61; N, 3.86. Found: C, 62.96; H, 3.61; N, 3.52. Example 271 5 3-f4- (4-Chlorophenoxy) thienor-2,3-clpyridin-2-inaniline Example 272 4-r4- (4-Chlorophenoxy) thienof2,3-clpyridin-2-yl) aniline Example 272A 4-f4- (4-Chlorophenoxy) thienof2.3-c1pyridin-2-nitrobenzene A mixture of Example 170A (0.25 g, 0.82 mmol), 1-iodo-4-nitrobenzene (0.20 g, 0.82 mmol), complex of [1.1] - ^ 'bis (diphenylphosphino) ferrocene] dichloropalladium (ll) dichloromethane (1: 1) (0.10 g, 0.12 mml), cesium fluoride (0.37 g, 2.46 mmol), triethylamine (0.1 1 mL, 0.82 mmol ), in DME (8 mL) was sucked 10 minutes with 15 anhydrous nitrogen. The reaction was heated at 70 ° C for 18 hours and then partitioned between EtOAc (100 mL) and sat. NaHCOs. (100 mL). The organic layer was rinsed with sat. NaHCO3. (100 mL), brine (75 mL), partially dried (Na2SO) and concentrated in a colored oil. The residue was purified by flash chromatography on silica gel using EtOAc / hexane as eluent to give the main compound as a colored solid (0.15 g, 48%). mp 193-195 ° C; MS (ESI) m / e: 383 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 7.17 (m, 2 H), 7.48 (m, 2 H), 8.15 (m, 25 H), 8.17 (s, 1 H), 8.19 (m, 2 H), 8.32 (m, 2H), 9.17 (s, 1 H); Anal. cale, for C? 9HnCIN2? 3S: C, 59.61; H, 2.90; N, 7.32. Found: C, 59.35; H, 2.94; N, 7.22. Example 272B 4-r4- (4-Chlorophenoxy) thienof2,3-c1pyridin-2-nananiline To a suspension of Example 272A (0.13 g, 0.34 mmol) in EtOH (3.5 mL), a solution of tin chloride dihydrate (ll) (0.31 g, 1.36 mmol) in conc. HCl. (0.68 mL) was added slowly. The reaction was stirred for 22 hours and partitioned between dichloromethane (75 mL), and 1 N NaOH (75 mL). The organic layer was rinsed with 1 N NaOH 10 (1 x 50 mL), brine (1x50 mL), partially dried (Na 2 SO 4) and concentrated to a colored solid (0.13 g). The desired product is • crystallized from acetonitrile to produce colored crystals (0.08 g, 68%). mp 178-182 ° C; MS (APCl) m / e: 353 (M + H) +; 1H NMR (300 MHz, DMSO-d6) d 5.68 (br s, 2H), 6.62 (m, 2H \, 7.09 (m, 2H), 7.39 (s, 1 H), 7.44 (m, 2H), 7.51 ( m, 2H), 8.1 1 (s, 1 H), 8.97 (s, 1 H), Anal cale, for dgH.sCINzOS: C, 64.68; H, 3.71; N, 7.94. • 20 Found: C, 64.65; H, 3.73; N, 8.13. Example 273 6-f4- (4-Chlorophenoxy) thienor-2,3-clpyridin-2-p-3-pyridinem Example 273A 6-f4- (4-Chlorophenoxy) thienof2.3-cjpyridin-2-ip-3- Nitropyridine Example 273A (120 mg, 32%) was prepared as in Example 272A substituting 2-bromo-5-nitropyridine for 1-iodo-4-nitrobenzene. mp 221-223 ° C; MS (APCl) m / e: 384 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 7.20 (m, 2 H), 7.49 (m, 2 H), 8.16 (s, 1 H), 8.50 (s, 1 H), 8.61 (d, J = 8.8 Hz, 1 H), 8.70 (dd, J = 8.8, 2.4 Hz, 1 H), 9.17 (s, 1 H), 9.44 (d, J = 2.4 Hz, 1 H). Example 273B 6-f4- (4-Chlorophenoxy) thienor-2,3-c1pyridin-2-p-3-pyridinamine Example 273B (0.07 g, 59%) was prepared as in Example 272B. mp 225-227 ° C; MS (APCl) m / e: 354 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 5.82 (broad s, 2H), 6.92 (dd, J = 8.5, 2.6 Hz, 1 H), 7.05 (m, 2H), 7.39 (m, 2H), 7.60 ( m, 1 H), 7.79 (d, J = 8.5 Hz, 1 H), 7.91 (d, J = 2.6 Hz, 1 H), 8.04 (s, 1 H), 8.93 (s, 1 H); Anal. cale, for C18H12CIN3OS: C, 61.10; H, 3.42; N, 1 1 .88. Found: C, 60.97; H, 3.39; N, 12.08. Example 274 5-f4- (4-Chlorophenoxy) thienor-2,3-clpyridin-2-in-2-pyridinamine A mixture of Example 270A (0.20 g, 0.65 mmol), 2-amino-5-bromopyridine (0.1 1 g, 0.65 mmol), [1,1-bis (diphenylphosphino) ferrocene] dichloropalladium complex (ll) dichloromethane (1: 1) (0.1 1 g, 0.13 mml), cesium fluoride (0.30 g, 1.95 mmol), triethylamine (0.09 mL, 0.65 mmol), in DME (6 mL) was aspirated 20 minutes with anhydrous nitrogen. The reaction was heated to reflux for 4 hours then concentrated. The residue was dissolved in 10% of PrOH / CHCl3 (100 mL), filtered and the organic was rinsed with sat. NaHCO3. (2x100 mL), partially dried (Na2SO4), then concentrated to yield a crude colored solid (0.25 g). The crude material was purified by preparative HPLC using a gradient of 25% -65% acetonitrile / water + 0.1% TFA for 40 minutes. The product was neutralized with sat. NaHCO3, the precipitate was collected by filtration and dried in a desiccator to produce the main compound as a lightly colored solid (54mg, 23%). mp 208-210 ° C; MS (APCl) m / e: 254 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 6.50 (br s, 2 H), 6.53 (dd, J = 8.9, 0.9 Hz, 1 H), 7.1 1 (m, 2 H), 7.44 (m, 2 H), 7.55 (s, 1 H), 7.85 (dd, J = 8.9, 2.6 Hz, 1 H), 8.1 1 (s, 1 H), 8.41 (dd, J = 2.6, 0.9 Hz, 1 H), 9.00 (s, 1 HOUR); Anal. cale, for C18H12CIN3OS: C, 61.10; H, 3.42; N, 1 1.88. Found: C, 60.92; H, 3.45; N, 1 1 .90. Example 275 5-r4- (4-Chlorophenoxy) thienor-2,3-c1pyridin-2-n-1,3,4-oxadiazol-2-amine Example 156 (0.1 5 g, 0.47 mmol) was suspended in 1,4-dioxane ( 3 mL) and a 5M solution of cyanogen bromide in acetonitrile (0.10 mL, 0.50 mmol) was added. The reaction was allowed to stir 10 minutes and a solution of NaHCO3 (0.04 g, 0.50 mmol) in water (1.4 mL) was added dropwise. The colored reaction was stirred 2 hours, then poured into sat. NaHCO3. (75 mL). The organic phase s it was extracted with 10% of iopropanol / CHCl3 (4x25 mL). The organic extracts were combined, dried (Na2SO4), and concentrated to yield a solid (0.13 g). A portion of the crude was purified by HPLC using a gradient of 30% -70% acetonitrile / water + 0.1% TFA for 40 minutes to produce the main compound as a tan solid, mp 262-263 ° C; MS (APCl) m / e: 345 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 7.15 (m, 2 H), 7.47 (m, 2 H), 7.52 (s, 1 H), 7.60 (broad s, 2 H), 8.24 (s, 1 H), 9.17 (s, 1 H); 3C NMR (DMSO-dβ) d 164.3, 155.6, 153.1, 146.6, 141.2, 137.0, 136.9, 134.0, 131 .4. 130.1 (2C), 127.7, 1 19.5 (2C), 1 17.5; IR (KBr) 3325, 3234, 3080, 1665, 1578, 1547, 1486, 141 1, 1287, 1257, 1229, 1203 cm'1. Anal. cale, for C? 5H9CIN4O2S: C, 52.26; H, 2.63; N, 16.25. Found: C, 52.40; H, 2.68; N, 16.23. Example 276 5-f4-? 4-Bromophenoxy) thienor-2,3-clpyridin-2-ill-1, 3,4-oxadiazol-2-ylamine Example 157 (0.15 g, 0.41 mmol) was suspended in 1,4-dioxane ( 4 mL) and a 5M solution of cyanogen bromide in acetonitrile (0.10 mL, 0.50 mmol) was added. The reaction was allowed to stir 10 minutes and a solution of NaHCO3 (0.04 g, 0.50 mmol) in water (1.4 mL) was added dropwise. The colored reaction was stirred 3 hours, then poured into sat. NaHCO. (75 mL). The aqueous was extracted with 10% IPA / CHCl3 (4x25 mL). The organic extracts are they combined, partially dried (Na2SO), and concentrated to produce a solid. A portion of the crude was purified by HPLC using a gradient of 30% -70% acetonitrile / water + 0.1% TFA for 40 minutes to produce the main compound as a • 5 solid tanning material, mp 270-273 ° C; MS (APCl) m / e: 389 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 7.08 (m, 2 H), 7.52 (s, 1 H), 7.56 (br s, 2 H), 7.59 (m, 2 H), 8.27 (s, 1 H), 9.1 9 (s, 1 H); 10 Anal. cale, for C15H9BrN4O2S: C, 46.29; H, 2.33; N, 14.39. Found: C, 46.08; H, 2.59; N, 14.12. ^ Example 277 5-r4- (4-Chlorophenoxy) thienof2.3-clpyridin-2-yn-4H-1,2,4-triazole-3-amine To a dry flask containing 61 A (0.33 g, 1.03 mmol) and aminoguanidine hydrochloride (3.45 g, 31.20 mmol) was slowly added to a 25% by weight solution of NaOMe / MeOH (7.13 mL, 34.32 mmol). The reaction was stirred at room temperature for 1 hour then it was heated at 50 ° C for 20 hours, then 70 ° C for 24 hours. The reaction was poured into water (200 mL) and neutralized aqueous with 3N HCl (10 mL). The precipitate was collected by filtration, rinsed with water (2x20 mL) and dried in a desiccator. The crude material was purified by preparative HPLC using a gradient of 25% -65% acetonitrile / water + 0.1% TFA for 40 minutes. The product was neutralized with sat. NaHCO3, and the The precipitate was collected by filtration then dried in a dissector to produce the main compound as a white solid (0.16 g, 45%). mp > 270 ° C; MS (APCl) m / e: 344 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 6.46 (br s, 2 H), 7.27 (m, 2 H), 7.58 (m, 2 H), 7.67 (s, 1 H), 8.31 (s, 1 H), 9.21 (s, 1 H); Anal. cale, for C15H? 0CIN5OS: C, 52.41; H, 2.93; N, 20.37. Found: C, 52.21; H, 3.02; N, 20.45. Example 278 5-f4- (4-Chlorophenoxy) thienof2.3-clpyridin-2-n-1,3,4-thiadiazol-2-amine Example 88 (0.36 g, 1.18 mmol) was suspended in thionyl chloride (4). mL) and the suspension was heated at 45 ° C for 2 hours. The reaction was concentrated and the residue was diluted with CH2Cl2 (2x5 mL) and concentrated to yield a colored solid. The crude solid was dissolved in DMF (5 mL) and thiosemicarbacid (2.69 g, 29.50 mmol) was added and the reaction was stirred 24 hours. The reaction was poured into water (250 mL) and the aqueous suspension was treated with sat. NaHCO3. (10 mL) until pH > 7. The precipitate was collected, rinsed with water (2x20 mL) and dried in a desiccator to yield the corresponding acyl semicarbazate as a solid (0.30 g) [MS (APCI) m / e: 377 (M + H) + j . The crude material (0.20 g) was suspended in toluene (2 mL) and methanesulfonic acid (0.10 mL, 1.60 mmol) was added. The reaction was refluxed for 4 hours, then allowed to cool to room temperature. The heterogeneous mixture was diluted with hexane (5 mL) and the solvent was decanted away from the colored residue. The waste was crushed with hexane (2x10 mL) and dried under vacuum. The solid was suspended in water (15 mL) and treated with NH4OH until pH 9 was achieved. The precipitate was collected and rinsed with water (2x5 mL). The crude material was partially purified on silica gel by chromatography • 5 instantaneous using acetone as eluent. This product was further purified by preparative HPLC using a gradient of 25% -65% acetonitrile / water + 0.1% TFA for 40 minutes. The product was neutralized with sat. NaHCO3. ac. and the precipitate was collected by filtration, then dried in a desiccator for produce the main compound as a tanning solid (0.04 mg, 14% total), ^ mp > 270 ° C; MS (APCl) m / e: 361 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 7.15 (m, 2H), 7.46 (m, 2H), 7.68 (s, 1 H), 7.75 (br s, 2 H), 8.1 1 (s, 1 H), 9.06 (s, 1 H); Anal. cale, for C15H19CIN4OS2: C, 49.93; H, 2.51; N, 15.53. Found: C, 49.82; H, 2.64; N, 15.58. Example 279 F 4- (4-Chlorophenoxy) -2- (5-methyl-1,2,4-oxadiazol-3-yl) thieno F 2,3-clpyridine A solution of the compound resulting from Example 249 (160 mg, 0.5 mmol) in pyridine (20 mL) under nitrogen at room temperature was treated with acetyl chloride (50 mL, 0.55 mmol) and heated at reflux for 15 hours. The resulting dark yellowish homogeneous solution was diluted with ethyl acetate, rinsed with NaHCO3 Saturated, brine, dried (MgSO4), filtered through a plugged silica and concentrated to give 169 mg of a whitish powder. This solid was flash chromatographed on silica gel with 30-50% ethyl acetate / hexane to provide the main compound (150 mg, 87%) mp 120-121 ° C; MS (APCI-NH3) m / e: 344 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 9.24 (s, 1 H), 8.27 (s, 1 H), 7.89 (s, 1 H), 7.48 (d, 2 H), 7.16 (d, 2 H), 2.69 (s, 3H); Anal. cale, for C16H10CIN3O2S: C, 55.90; H, 2.93; N, 12.22. Found: C, 56.10; H, 3.16; N, 12.01. Example 280 5- (4-4 4-p "rifluoromethyl) phenoxyphenyl-2,3-c1pyridin-2-yl) -1.3.4-oxadiazol-2-amine Example 1 58 was treated according to the procedure of Example 275 to provide the main compound MS (APCl) m / e: 358.9 (M + H) +; 1H NMR (300 MHz, DMSO-d6) d 7.22 (d, 2H), 7.51 (s, 1 H), 7.60 (s, 2H), 7.79 (d, 2H), 8.40 (s, 1 H), 9.25 (s, 1 H) Example 281 4- (4-Chlorophenoxy) -2-f5- (methylsulfanyl) -1.3.4-oxadiazole-2-intienor2 .3-Clpyridine Example 281A 5-f4- (4-chlorophenoxy) thieno [2,3-c1pyridin-2-p-1.3.4-oxadiazole-2-thiol The compound of Example 156 (100 mg, 0.31 mmol) was suspended in Ethanol (2 ml) and cooled to 0 ° C. Carbon disulfide (0.04 ml, 0.71 mmol) was added followed by potassium hydroxide (20 mg, 0.31 mmol) / The reaction was stirred 1 hr and the cold bath was removed.

After 1 h at room temperature, the reaction was refluxed for 3 hours then concentrated in a solid. The crude solid was triturated with chloroform (1 x 5 ml) and concentrated. The residue was dissolved in water (15 ml) and acidified with formic acid. The resulting precipitate was isolated by filtration, rinsed with water (2x15 mL) and dried in a desiccator to produce the main compound (106 mg, 94%). mp 236-240 ° C; MS (ESI) m / e: 362 (M + H) +; 1 H NMR (300 MHz, CD 2 Cl 2) d 7.15 (m, 2 H), 7.46 (m, 2 H), 7.65 (m, 1 H), 8.24 (s, 1 H), 9.18 (s, 1 H); Anal. cale, for dsHßCINaOzSa: C, 47.89; H, 2.57; N, 1 1 .17. Found: C, 47.89; H, 2.49; N, 10.97. Example 281 B 4- (4-Chlorophenoxy) -2-f5- (methylsulfanyl) -1.3.4-oxadiazol-2-ithienof2,3-clpyridine To a stirred suspension of 281A (100 mg, 0.28 mmol) in THF (1 ml ) at 0 ° C a solution of 1 M aqueous sodium hydroxide (0.28 ml, 0.28 mmol) was added. After 30 minutes all the solid was dissolved and iodomethane (0.02 ml, 0.31 mmol) was added dropwise. The reaction was stirred 30 minutes and water (8 ml) was added. The solid was collected by filtration, rinsed with water (2x15 ml) and dried in a desiccator to yield 80 mg of a pale yellow solid. The crude product was purified by flash chromatography on silica gel using acetone / hexane as the eluent to produce the main compound as a solid. (41 mg, 39%). mp 158-160 ° C; MS (ESI) m / e: 376 (M + H) +; 1 H NMR (300 MHz, CD2Cl2) d 2.75 (s, 3H), 7.01 (m, 2H), 7.33 (m, 2H), • 5 7.91 (s, 1 H), 8.12 (s, 1 H), 8.93 (s, 1 H); Anal. cale, for C 16 H 10 CIN 3 O 2 S 2: C, 51 .13; H, 2.68; N, 1 1 .18. Found: C, 51.25; H, 3.02; N, 10.89. Example 282 4- (4-Chlorophenoxy) -2- (2-methyl-2H-1.2.3.4-tetrazol-5-yl) thienor 2,3-clpyridine Example 282A 4- (4-Chlorophenoxy) -2- (1, 2.3.4-tetrazol-5-yl) thienof2.3-clpyridine • A solution of the resultant compound of Example 248 (90 mg, 0.314 mmol) in toluene (1.5 mL) under nitrogen at room temperature was treated with dibutyltin oxide (8 mg, 0.031 mmol), Trimethylolide (125 mL, 0.942 mmol) and refluxed for 24 hours, then stirred an additional 2.5 days at room temperature. The resulting yellow heterogeneous mixture was concentrated and then flash chromatographed with 20% methanol / dichloromethane to give 105 mg of a light yellow powder.

This powder was dissolved in ethyl acetate, extracted with 10% NaHCO3 (2x), the aqueous extracts were combined, acidified to pH 2 with 6 N HCl, extracted with ethyl acetate, dried (Na2SO) and concentrated to give the Main compound as a white powder (63 mg, 61%). 25 mp 250-254 ° C; MS (APCI-NH3) m / e: 330 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 9.26 (s, 1 H), 8.27 (s, 1 H), 8.01 (s, 1 H), 7.48 (d, 2 H), 7.19 (d, 2 H); Anal. cale, for C14H8CIN5OS 0.25 H2O: C, 50.13; H, 2.56; N, 20.95. Found: C, 50.27; H, 2.69; N, 20.78. Example 282B 4- (4-Chlorophenoxy) -2- (2-methyl-2H-1.2.3.4-tetrazol-5-yl) thienor 2,3-clpyridine A solution of the resultant compound of Example 282A (100 mg, 0.3 mmol) in methanol (4 mL) under nitrogen at room temperature was treated with diazomethane in diethyl ether (generated from N-methyl-N'-nitro-N-nitrosoguanidine with diazomethane in diethyl ether and 40% KOH) until a color yellow persisted for more than 5 minutes, stirred an additional 15 minutes and then cooled by the dropwise, slow addition of glacial acetic acid until the yellow color disappeared (evolution of vigorous gas) and then concentrated. The resulting light yellow solid was filtered through a silica gel plug with 5% methanol / dichloromethane and then flash chromatographed on reverse phase silica gel (Dynamaz 21 .4 mm column C-18) with 25-65 % CH3CN with 0.1% TFA / H2O with 0.1% TFA to provide the main compound as a white powder (40 mg, 39%). mp 131-133 ° C; MS (APCI-NH3) m / e: 344 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 9.25 (s, 1 H), 8.28 (s, 1 H), 7.89 (s, 1 H), 7.48 (d, 2 H), 7.18 (d, 2 H), 4.47 (s, 3H); Anal. cale, for Ci5H10CIN5OS 0.25 H2O: C, 51.73; H, 3.04; N, 20.1 1. Found: C, 51.74; H, 2.93; N, 1 9.93. Example 283 5 4- (4-Ciorophenoxy) thienor-2,3-clpyridin-2-yn-4-methyl-4H-1,2,4-triazol-3-amine Sodium hydride (60 &in oil, 0.02 g, 0.42 mmol) was suspended in DMF (1 mL) at 0 ° C. A solution of Example 277 (0.1 1 g, 0.32 mmol) in DMF (1 mL) was added dropwise and the reaction was stirred 20 minutes. Iodomethane (0.06 mL, 0.96 mmol) was added and after 30 minutes the reaction was poured into water (75 mL). The resulting precipitate was collected by filtration, rinsed with water (1 x 20 mL), and 50% EtOAc / hexane (2x25 mL). The crude solid was dried to yield a colored solid (0.1 1 g). The main compound was isolated by preparative HPLC using a gradient of 25% -65% acetonitrile / water + 0.1% TFA for 40 minutes. The product was neutralized with sat. NaHCO3. ac. and the precipitates were collected by filtration, then dried in a desiccator to provide (31 mg, 27%). mp 233-235 ° C; MS (APCl) m / e: 358 (M + H) +; 'H NMR (300 MHz, DMF-d7) d 3.75 (s, 3 H), 6.58 (br s, 2 H), 7.23 (m, 2 H), 7.54 (m, 2 H), 7.61 (s, 1 H), 8.27 (s, 1 H), 9.18 (s, 1 H); Anal. cale, for C1 ßH12CIN5? S: C, 53.71; H, 3.38; N, 19.57. Found: C, 54.00; H, 3.56; N, 19.68. Example 284 4- (4-Chlorophenoxy) -2-r5- (trifluoromethyl) -1, 2,4-oxadiazole-3-intienof2,3-clpyridine A solution of the resultant compound of Example 249 (100 mg, 0.31 mmol) in pyridine (1 .5 mL) under nitrogen at room temperature was treated with trifluoroacetic anhydride (50 mL, 0.31 mmol), • 5 stirred for 20.5 hours, then heated to reflux for three hours. The brown solution was diluted with ethyl acetate, rinsed with saturated NaHCO3, brine, dried (MgSO4), concentrated, then filtered through a plug of silica gel with 50/50 hexane / ethyl acetate and concentrated to give 120 mg of a yellow residue. This waste was chromatographed instantaneously on silica gel twice using 20-33% ethyl acetate / hexane and then 0-1% • methanol / CH2Cl2 to give the main compound as a white solid (67 mg, 54%). mp 52-54 ° C; MS (APCI-NH3) m / e: 398 (M + H) +, 416 (M + NH4) +; 1 H NMR (300 MHz, DMSO-dβ) d 9.30 (s, 1 H), 8.29 (s, 1 H), 8.10 (s, 1 H), 7.48 (d, 2 H), 7.20 (d, 2 H); Anal. cale, for C1 ßH7CIFN3? 2S 0.25 H2O: C, 47.77; H, 1.88; N, 10.45. Found: C, 48.1 5; H, 2.09; N, 10.14. Example 285 5-r4- (4-Chlorophenoxy) thienof2.3-c1pyridin-2-ill-1, 2,4-oxadiazol-3-amine A solution of the resultant compound of Example 250 (100 mg, 0.3 mmol) in methanol (1.5 mL) under nitrogen at room temperature was treated with hydroxylamine hydrochloride (40 mg, 0.45 mL). mmol), triethylamine (70 mL, 0.5 mmol) and stirred for 18 hours, 4 mL THF was added and stirred for two days, the solvent was changed to 50/50 dichloromethane / methane, hydroxylamine hydrochloride (100 mg, 1.4 mmol) and additional triethylamine (200 mL, 2.7 mmol) were added, stirred at room temperature. environment for 24 hours and • 5 then refluxed for 8 hours. The reaction mixture was diluted with ethyl acetate, rinsed with dilute NaHCO3, brine, dried (MgSO4) and concentrated to give 105 mg of a white solid. The resulting solid was flash chromatographed twice on reverse phase silica gel (Dynamax 21 .4 mm column C-18) with 25-65% of CH3CN with 0.1% TFA / H2O with 0.1% TFA, followed by 20-80% of CH3CN with 0.1% TFA / H2O with 0.1% TFA to provide the • Main compound as a white powder (26 mg, 25%) mp 217-219 ° C; MS (APCI-NH3) m / e: 345 (M + H) +; 15 1 H NMR (300 MHz, DMSO-dβ) d 9.26 (s, 1 H), 8.25 (s, 1 H), 8.02 (s, 1 H), 7.49 (d, 2 H), 7.14 (d, 2 H), 6.62 (br s, 2H); Anal. cale, for C15H9CIN4O2S: C, 52.25; H, 2.63; N, 16.25. Found: C, 51.94; H, 2.88; N, 15.98. Example 286 5-f4- (4-Chlorophenoxy) thienor-2,3-c1pyridin-2-ip-N-methyl-1,3,4-thiazol-2-amine The main compound (4% of the total product) was prepared as in Example 278, substituting 4-methylthiosemicarbacid for thiosemicarbacid. 25 mp 226-229 ° C; MS (APCl) m / e: 375 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 2.95 (d, J = 1.7 Hz, 3 H), 7.14 (m, 2 H), 7.45 (m, 2 H), 7.69 (s, 1 H), 8.17 (s) , 1 H), 8.19 (br m, 1 H), 9.07 (s, 1 H); Anal. cale, for dßHuCINgtOSz: C, 51 .27; H, 2.96; N, 14.95. • 5 Found: C, 51.24; H, 3.03; N, 14.85. Example 287 4- (4-Chlorophenoxy) -2- (1, 2,4-oxadiazol-3-yl) thienor-2,3-clpyridine Example 287A 4- (4-Chlorophenoxy) -N '- (diethoxymethoxy) thienof2.3-clpyridine- 2-carboxaimidamide A solution of the compound resulting from Example 249 (100 mg, 0.31 mmol) in triethylorthoformate (1.3 mL) under nitrogen was • heated at 140 ° C for 5 hours, 160 ° C for 2 hours and stirred at room temperature for 14 hours. The resulting light yellow oil (10 mg) was flash chromatographed on silica gel 20-70% ethyl acetate / hexane to give the title compound as a white solid (50 mg, 38%). MS (APCI-NH3) m / e: 422 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 9.05 (s, 1 H), 8.15 (s, 1 H), 7.97 (s, 1 H), 7.46 (d, 2 H), 7.10 (d, 2 H), 6.65 (br s, 2H), 5.66 (s, 1 H); 3.62-3.71 • 20 (m, 4H), 1.15 (t, 6H); Example 287B 4- (4-Chlorophenoxy) -2- (1.2.4-oxadiazol-3-yl) thienof2.3-clpyridine A solution of the resultant compound of Example 287A (50 mg, 0.119 mmol) in toluene (6 mL) under nitrogen it was heated to reflux for 20 hours then it was allowed to cool and concentrated. He The yellow residue (46 mg) was chromatographed instantaneously on silica gel 25-50% ethyl acetate / hexane to give the main compound as a white solid (39 mg, 100%). Analytical HPLC: 4.6x250 mm column C-1 d, 0.8 mL / min, 254 nm, • 5 CH3CH: H2O with 0.1% TFA, 0: 100 (0-3 min), ramp at 90: 10 (3-30 min), 90:10 (30-35 min), ramp at 0: 100 (35- 40 min), Rt = 22.47 min (100% peak area) mp 151-152 ° C; MS (APCI-NH3) m / e: 330 (M + H) +; 10 1 H NMR (300 MHz, DMSO-dβ) d 9.86 (s, 1 H), 9.26 (s, 1 H), 8.27 (s, 1 H), 7.98 (s, 1 H), 7.48 (d, 2 H) , 7.19 (d, 2H); Example 288 2- (1.3.4-Oxadiazol-2-yl) -4-f4- (trifluoromethyl) phenoxyptienor 2,3-clpyridine A solution of Example 183 (100 mg, 0.283 mmol) in Triethyl orthoformate (15 mL) was heated to reflux under a nitrogen atmosphere for 28 hours. All volatiles were removed under reduced pressure. The resulting oil was purified by flash column chromatography eluting with hexane / ethyl acetate (2: 1), affording 65 mg (63%) of the main compound • 20 as a colorless oil that solidifies permanently. MS (ESI) m / e: 364 (M + H) +; 1 H NMR (300 MHz, CDCl 3) d 7.14 (d, 2 H), 7.66 (d, 2 H), 8.05 (s, 1 H), 8.24 (s, 1 H), 8.50 (s, 1 H), 9.07 (s) , 1 HOUR); Anal. cale, for C1 ßH8N3F3? 2S: C, 52.89; H, 2.22; N, 1 1 .57.

Found: C, 53.03; H, 2.25; N, 1 1 .48.

Example 289 3-f4- (4-Chlorophenoxy) thienof2.3-clpyridin-2-yn-1.2.4-oxadiazol-5-amine Example 289A 3-f4- (4-Chlorophenoxy) thienof2,3-clpyridin-2- ill-5- (trichloromethyl) -1,2,4-oxadiazole A solution of the compound resulting from Example 249 (50 mg, 0.156 mmol) pyridine (2 mL) under nitrogen at room temperature was treated with trichloroacetyl chloride (20 mL, 0.17 mmol) and heated to reflux for 1.5 hours, allowed to cool to room temperature, stirred overnight, treated with additional trichloroacetyl chloride (1000 mL, 0.86 mmol) and stirred 4 hours. The reaction mixture was then diluted with ethyl acetate, rinsed with saturated NaHCO3, brine, dried (MgSO) and concentrated. The resulting brown residue was flash chromatographed on silica gel with 25-50% ethyl acetate / hexane to give the main compound as a clear solid (37 mg, 53%). MS (APCI-NHs) m / e: 448 (M + H) +; H NMR (300 MHz, DMSO-d6) d 9.25 (s, 1 H), 8.24 (s, 1 H), 8.09 (s, 1 H), 7.46 (d, 2 H), 7.18 (d, 2 H). Example 289B 3-f4- (4-Chlorophenoxy) thienor-2,3-c1pyridin-2-ill-1.2.4-oxadiazol-5-amine A solution of the compound resulting from Example 289A (30 mg, 0.067 mmol) in 2.0 M ammonium in methanol (6 mL) in a pressure tube was heated at 60 ° C for 15 hours then allowed to cool to room temperature, rinsed from the flask with methanol and distilled water. The volume of methanol was removed under vacuum and the mixture White nebula was filtered and rinsed with distilled water. The resulting yellow-brown solid was flash chromatographed twice on reverse phase silica gel (Dyanamax C-18, 21.4 mm column) with 25-65%, and then 20-80% CH3CN with 0.1% TFA / H2O with 0.1% TFA to give the main compound as a white solid (4 mg, 17%). Analytical HPLC: 4.6x250 mm C-18 column, 0.8 mL / min, 254 nm, CH3CH: H2O with 0.1% TFA, 0: 100 (0-3 min), ramp at 90: 10 (3-30 min), 90: 10 (30-35 min), ramp at 0: 100 (35-40 min), Rt = 19.44 min (100% peak area) mp 268-270 ° C; MS (APCI-NH3) m / e: 345 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 9.21 (s, 1 H), 8.27 (s, 1 H), 8.22 (br s, 2H), 7.67 (s, 1 H), 7.47 (d, 2H), 7.15 (d, 2H). Example 290 2- (5-Methyl-1,3,4-oxadiazol-2-yl) -4-f4- (trifluoromethyl) phenoxylyl-ene-2,3-clpyridine The main compound was prepared as described in Example 288 using triethyl orthoacetate as the solvent. The reflux was maintained for 5 days with the product being 29%. MS (APCl) m / e: 377 (M + H) +; 1 H NMR (300 MHz, CDCl 3) d 2.65 (s, 3 H), 7.13 (d, 2 H), 7.65 (d, 2 H), 7. 94 (s, 1 H), 8.27 (s, 1 H), 9.06 (s, 1 H). Example 291 4- (4-Chlorophenoxy) -2- (2-furyl) thieno.2,3-clpyridine A mixture of Example 270A (0.30 g, 0.98 mmol), 2,5-dibromofuran (0.66 g, 2.94 mmol), cesium fluoride (0.45 g, 2.94 mmol), triethylamine (0.14 mL, 0.98 mmol) in DME (9 mL ) was aspirated 25 minutes with anhydrous nitrogen and complex of [1, 1'-5 bis (diphenylphosphino) ferrocene] dichloropaiad (II) dichloromethane (1: 1) (0.16 g, 0.20 mmol) was added. The reaction was heated to reflux for 4 hr and then stirred at room temperature overnight. The reaction was diluted with EtOAc (100 mL) and filtered. The organic layer was rinsed with sat. NaHCO3. (3x50 mL), brine (75 mL), dried Partially (Na2SO) and concentrated in a colored oil. The residue was purified by flash chromatography on silica gel using • EtOAc / hexane as eluent to produce a colored oil (0.12 g, 0.30 mmol) [MS (APCl) m / e 406 (M + H) *]. This material was dissolved in EtOH (10 mL) and 5% Pd / C (3 mg, 0.02 mmol) was added. balloon of hydrogen gas was applied and the reaction was stirred 3 days at room temperature. The reaction was filtered through celite and washed with celite with MeOH (10 mL) and dichloromethane (10 mL). The filtrate and rinses were combined and concentrated in a colored wet foam. The crude material was purified by HPLC • 20 preparative using a gradient of 30% -70% acetonitrile / water + 0.1% TFA for 40 minutes. The product was neutralized with sat. NaHCO3, the precipitate was collected by filtration, and dried in a desiccator to produce the main compound as a lightly colored solid (15 mg, 5% total product). mp 75-77 ° C; MS (APCl) m / e: 328 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 6.70 (dd, J = 3.4, 1.7 Hz, 1 H), 7.12 (m, 2 H), 7.24 (d, J = 3.4 Hz, 1 H), 7.46 ( m, 2H), 7.59 (s, 1 H), 7.88 (d, J = 1.7, 5 Hz, 1 H), 8.16 (s, 1 H), 9.08 (s, 1 H). Example 292 4- (4-Chlorophenoxy) -2- (2-thienyl.tienof2,3-clpi? Idine Example 292 (50mg, 22%) was prepared as in Example 272a, substituting 2-iodothiophene for 1-iodo-4 -nitrobenzene 10 mp 101 -103 ° C; MS (APCl) m / e: 344 (M + H) +; • 1 H NMR (300 MHz, DMSO-d6) d 7.14 (m 2 H), 7.19 (dd, J = 5.0, 3.4 Hz, 1 H), 7.46 (m, 2H), 7.54 (d, J = 0.9 Hz, 1 H), 7.67 (dd, J = 3.4, 1 .3 Hz, 1 H), 7.73 ( dd, J = 5.0, 1 .3 Hz, 1 H), 8.14 (s, 1 H), 9.05 (s, 1 H); 15 Anal cale, for C17H10CINOS2 0.2 H2O: C, 58.77; H, 3.02; N , 4.03, Found: C, 58.74; H, 2.84; N, 3.72, Example 293 2-r4- (4-Chlorophenoxy) thienof2,3-c1pyridin-2-in-1,3-thiazole-4-carboxamide Example 293A • 20 Ethyl 2-f4- (4-Chloro-phenoxy) thienor-2,3-c1pyridin-2-in-1,3-thiazole-4-carboxylate Ethyl bromopyruvate (390 mL, 2.30 mmol) was combined with Example 146 (672 mg, 2.09 mmol) and absolute ethanol (100 mL) and the orange homogeneous solution was heated to 60 [deg.] C. After 48 hours, the mixture was cooled to room temperature and concentrated to the empty. The purification was achieved by means of gel chromatography of Instantaneous silica (1-5% acetone in hexane) and the main compound (297 mg, 34% product) was obtained as a white solid. MS (DCI / NHs) m / e: 417 (35CI) / 419 (37CI); 1 H NMR (300 MHz, CDCl 3) d 8.94 (s, 1 H), 8.24 (s, 1 H), 8.12 (s, 1 H), • 5 7.88 (s, 1 H), 7.36 (d, J = 8.8 Hz, 2H), 7.04 (d, J = 8.8 Hz, 2H), 4.45 (q, J = 7.0 Hz, 2H), 1 .45 ( t, J = 7 Hz, 3H). Example 293B 2 4- (4-Chlorophenoxy) thienoyl-2,3-clpyridin-2-yn-1,3-thiazole-4-carboxamide Example 293A (32 mg, 77 mmol) was changed with ammonium in methanol (4 mL of a 2.0 M solution) and the solution was heated in a sealed tube at 40 ° C. After 16 hours, the homogeneous solution • cooled to room temperature and concentrated in a brown solid that was dry-loaded onto flash silica gel and eluted with 20% acetone in hexane, followed by 40% acetone in hexane to recover the main compound (8). mg, 27% product), mp 21 5-218 ° C MS (DCI / NH 3) m / e: 388 (M + H) / 405 (M + NH 3), 407 (37Cl + NH 3); 1 H NMR (300 MHz, CDCl 3) d 5.67 (br s, 2 H), 7.06 (d, J = 8.5 Hz, 2 H), 7.38 (d, J = 8.8 Hz, 2 H), 8.09 (s, 1 H), 8.25 (s, 1 H), 8.94 (s, 1 H). • Example 294 tert-Butyl 2-r4- (4-chlorophenoxy) thienor-2,3-clpyridin-2-n-1,3-thiazole-4-ylcarbamate Example 293 was converted to the corresponding carboxylic acid in a similar manner as described in Example 25. Phosphoryl-diphenyl acid (25 μL, 0.10 mmol) was added to a mixture of carboxylic acid (40 mg, 0.10 mmol), tert-butane (10 mL) and triethylamine (20 μL, 0.1 mmol) and the solution was heated to 80 ° C. After 18 hours, the solution was cooled and concentrated. The yellow residue was dissolved in CH2Cl2 (30 mL), rinsed sequentially with 0.5 N aqueous HCl (40 mL) and saturated aqueous NaHCO3 (25 mL), and brine (25 mL). The combined aqueous rinses were extracted again with CH2Cl2 (2x25 mL). The organic layers were combined, dried (MgSO), filtered and concentrated to a yellow residue. Flash column chromatography of flash silica gel (15% acetone in hexane) provided the main compound (13 mg, 28% product) as a bright yellow solid. MS (APCl) m / e: 460 (35Cl) / 462 (37C); 1 H NMR (300 MHz, CDCl 3) d 8.91 (s, 1 H), 8.1 1 (s, 1 H), 7.71 (s, 1 H), 7.35 (d, J = 8.9 Hz, 2 H), 7.03 (d, J = 8.9 Hz, 2H), 3.97 (d, J = 1 1 .4 Hz, 2H), 1.54 (s, 9H). Example 295 2-r4- (4-Chlorophenoxy) thienoyl-2,3-c1pyridin-2-yn-1,3-thiazole-4-amine Trifluoroacetic acid (0.5 mL) was added to Example 294 (9.0 mg, 20 pmol) in CH2Cl2 (1.5 mL) at 0 ° C. After 1 h, the volatiles were removed, and the orange residue was dissolved in 0.5 N aqueous HCl HCl (35 mL). The aqueous phase was rinsed once with Et2O (10 mL); the ether rinse was extracted with 1 N HCl (2x20 mL). The acidic layers were combined, and saturated aqueous potassium carbonate was added until the solution was basic (pH > 12). The alkaline phase was extracted with EtOAc (3x40 mL); the organic extracts are Combine, dry (MgSO4), filter and concentrate to a dark brown solid (9 mg). Purification by flash silica gel column chromatography (20% acetone in hexane) provided the main compound as a bright yellow solid (6.8 mg, 97% product), mp 168-170 ° C (split) MS (APCl) ) m / e: 360 (35CI) / 362 (37CI); 1 H NMR (300 MHz, CDCl 3) d 8.90 (s, 1 H), 8.1 1 (s, 1 H), 7.68 (s, 1 H), 7.35 (d, J = 9.2 Hz, 2 H), 7.02 (d, J = 8.9 Hz, 2H), 6.07 (s, 1 H), 3.89 (br s 2H). Example 296 4- (4-Chlorophenoxy) -2- (4,5-dihydro-1,3-oxazol-2-yl) thienof2,3-clpyridine To a solution of Example 150 (0.14 g, 0.38 mmol) in anhydrous dichloromethane (4%). mL) was added 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU) (0.09 mL, 0.57 mmol). The reaction was stirred 24 hours and an excess of morpholine (0.2 mL) was added to react with any remaining starting material. The reaction was stirred 4 hours then was partitioned between EtOAc (100 mL) and H2O (100 mL). The organic layer was rinsed with dilute NaH2PO4 (100 mL), sat. NaHCO3. (100 mL), brine (100 mL), partially dried (Na2SO4) and concentrated to a solid. The crude product was purified by flash chromatography on silica gel using EtOAc / Hexane as eluent to afford the main compound as a solid (0.07 g, 55%). mp 158-160 ° C (dec); MS (APCl) m / e: 331 (M + H) +; 1 H NMR (300 MHz, DMSO-d6) d 4.01 (t, J = 9.6 Hz, 2H), 4.48 (t, J = 9.6 Hz, 2H), 7.14 (m, 2H), 7.47 (m, 2H), 7.62 (s, 1 H), 8.24 (s, 1 H), 9.19 (s, 1 H); Anal. cale, for dßHuCINzOsS: C, 58.09; H, 3.35; N, 8.47. • 5 Found: C, 58.16; H, 3.31; N, 8.27. Example 297 4- (4-Chlorophenoxy) -2- (1,3-oxazol-2-yl.tieno.2,3-clpyridine The main compound can be produced from Example 296 according to the procedure of Ishibashi, Y., et al. Tetrahedron Lett 10 1996, 37 (17), 2997-3000) Example 298 W 4- (4-Chlorophenoxy) -2- (4,5-dihydro-1H-imidazol-2-yl) thienof2.3-clpyridine A suspension of the Example 154 (0.15 g, 0.43 mmol) and calcium oxide (0.12 g, 2.15 mmol) in phenyl ether (10 mL) were heated to 220-250 ° C. The reaction was stirred for 45 minutes during which the volume of the reaction was reduced due to the evaporation of the solvent. The reaction was cooled to room temperature and diluted with 10% MeOH / dichloromethane (25 mL) then filtered. The filtrate was concentrated and the residue was purified by HPLC preparative using a gradient of 30-90% acetonitrile / water + 0. 1% TFA for 40 minutes. The product containing fractions was combined and neutralized with sat. NaHCO3. The product was crystallized after the 3-day stay and was collected by filtration, and dried in a desiccator to produce the main compound as tanning needles (23 mg, 16%) mp 1 54-155 ° C (dec); MS (APCl) m / e: 330 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 3.46 (td, J = 9.9, 1.7 Hz, 2 H), 3.83 (t, J = 9.9 Hz, H), 7.12 (m, 2 H), 7.34 (br s) , 1 H), 7.46 (m, 2H), 7.81 (s, 1 H), * 5 8.17 (s, 1 H), 9.1 1 (s, 1 H); Anal. cale, for dßH12CIN3OS: C, 58.27; H, 3.67; N, 12.74. Found: C, 58.15; H, 3.50; N, 12.73. Example 299 4- (4-Chlorophenoxy) -2- (1H-imidazol-2-yl) thienof2.3-clpyridine The main compound can be produced from Example 298 according to the procedure of Zimmerman, S.C., et al. (J. Org, Chem, 1989, 54 (6), 1256-1264). Example 300 4-Chloro-3-methylthieno [2,3-clpyridine-2-carboxamide Example 300 was prepared as in Example 125 of the corresponding 4-chloro methyl ester which was isolated by a by-product of example 125A. MS (DCI / NHs) m / e: 227 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 2.55 (s, 3 H), 6.95 (d, 2 H), 7.57 (d, • 20 2H), 7.90 (b, 1 H), 8.00 (b, 1 H), 8.27 (s, 1 H), 9.15 (s, 1 H). Example 301 3-amino-4-chlorothienof2.3-clpyridine-2-carboxamide Methyl 3-amino-4-chlorothieno [2,3-c] pyridine-2-carboxylate was isolated from the crude product mixture of Example 131 B. The mixture was hydrolyzed as described in Example 18, and the resulting acid was coupled with the ammonium chloride using the procedure of Example 92. The product was isolated by filtration and rinsed with water after precipitating the reaction mixture by pouring it into 5% sodium bicarbonate solution. • 5 MS (DCI / NHs) m / e: 228 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 7.01 (br s, 2 H), 7.49 (br s, 2 H), 8.42 (s, 1 H), 9.1 1 (s, 1 H). Example 302 9- (4-Chlorophenoxy) pyridin 4 ', 3': 4151-tienor-3-d-pyrimidine-2. 4 (1 H. 3H) -dione tO To a suspension of Example 131 D (70 mg, 0.22 mmol) in anhydrous tetrahydrofuran (5 mL) under a nitrogen atmosphere was added 1,1-carbonyldiimidazole (71 mg 0.44 mmol) and triethylamine. (60 μL, 0.44 mmol). The reaction mixture was stirred at reflux for 48 hours and then at room temperature for an additional 24 hours.

The reaction mixture was poured into 1: 1 water solution: saturated NH 4 Cl and the resulting solid was collected by filtration. This material was purified by flash chromatography on silica gel eluting with 20% acetone-hexane. The desired fractions were combined, evaporated and stirred in hot EtOAc • 20 to obtain the main compound (39 mg) in 51% of the product. MS (APCl) m / e: (M-H) '344; 1 H NMR (300 MHz, DMSO-dβ) d 7.32 (m, 2 H), 7.55 (m, 2 H), 7.92 (s, 1 H), 9.09 (s, 1 H), 1 1 .22 (br s, 1 H), 1 1.72 (br s, 1 H); HPLC: Supelco column C-18, water: acetonitrile 0: 90-90: 0, elution 30 minutes, flow rate of 0.8 mL / min, rt 20.33 minutes; Example 303 4- (4-Chlorophenoxy) -N-3-dimethylthieno-2,3-clpyridine-2-carboxamide Example 125A was prepared as in Example 18 to provide the main compound. MS (DCI / NH3) m / e: 333 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 2.55 (s, 3 H), 2.80 (d, 3 H), 7.05 (d, 2 H); 7.45 (d, 2H), 8.20 (s, 1 H); 8.55 (b, 1 H), 9.18 (s, 1 H); Example 304 4- (4-Bromophenoxy) -3-methylthienof2.3-clpyridine-2-carboxamide Example 17A and 4-bromophenol were processed as in Example 125 to provide the main compound, mp 177-178 ° C MS (DCI / NH 3) m / e: 364 (M + H) +; 1 H NMR (300 MHz, DMSO-de) d 2.55 (s, 3 H), 6.95 (d, 2 H), 7.57 (d, 2 H), 7.90 (m, 1 H), 8.00 (m, 1 H), 8.27 ( s, 1 H), 9.15 (s, 1 H); Anal. cale, for C15H11BrN2O2S: C, 49.60; H, 3.05; N, 7.71. Found: C, 49.36; H, 3.24; N, 7.61. EXAMPLE 305 7-Chloro-4- (4-chlorophenoxy) -3-methylthienof2.3-c1pyridine-2-carboxamide Example 305A Methyl 4- (4-chlorophenoxy) -3-methylthiophen-2,3-c1pyridine-2-carboxylate. N-oxide Example 125A was prepared according to the procedure of Example 123A to provide the main compound. MS (DCI / NH3) m / e: 350 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.78 (s, 3 H), 3.88 (s, 3 H), 7.28 (m, 2H), 7.51 (m, 2H), 7.68 (br s, 1 H), 8.92 (br s, 1 H). Example 305B Methyl 7-Chloro-4- (4-chlorophenoxy) -3-methylthieno [2,3-clpyridine-2-carboxamide Example 305A was prepared according to the procedure of Example 1 C to provide the main compound. HPLC: Supelco column C-18, gradient elution 0.1% aqueous TFA: acetonitrile 0: 90-90: 0, for 30 minutes, detection at 254 nm, flow rate 0.8 mL / min, RT 31.64 minutes; MS (DCI / NH3) m / e: 368 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 2.78 (s, 3 H), 3.92 (s, 3 H), 7.18 (m, 2 H), 7.48 (m, 2 H), 8.01 (s, 1 H). Example 305C 7-Chloro-4-.4-chlorophenoxy) -3-methylthienof2.3-clpyridine-2-carboxylic acid Example 305B was prepared according to the procedure of Example 18 by replacing tetrahydrofuran with isopropanol to provide the main compound . HPLC: Supelco column C-18, gradient elution 0.1% aqueous TFA: acetonitrile 0: 90-90: 0, for 30 minutes, detection at 254 nm, flow rate 0.8 mL / min, RT 27.25 minutes; MS (APCl) m / e: 354 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.72 (s, 3 H), 7.16 (m, 2 H), 7.49 (m, 2 H), 8.01 (s, 1 H). Example 305D 7-Chloro-4- (4-chlorophenoxy) -3-methylthienof2.3-clpyridine-2-carboxamide Example 305C was prepared according to Example 92 for provide the main compound. HPLC: Supelco column C-18, gradient elution 0.1% aqueous TFA: acetonitrile 0: 90-90: 0, for 30 minutes, detection at 254 nm, flow rate 0.8 mL / min, RT 24.75 minutes; MS (DCI / NHs) m / e: 353 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 2.58 (s, 3 H), 7.10 (m, 2 H), 7.47 (m, 2 H), 8.0 (br s, 1 H). 8.02 (s, 1 H), 8.03 (br s, 1 H). Example 306 tert-Butyl 2- (aminocarbonyl) -4- (4-chlorophenoxy) thienof2,3-clpyridine-3-carboxylate Example 17A was followed except by replacing the methyl formate with t-Butyl chlorooxalate to provide the main compound . MS (DCI / NHs) m / e: 241 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 1.5 (s, 9H), 8.85 (s, 2H). Example 306B tert-Butyl 2- (methoxycarbonyl) -4- (4-chlorophenoxy) thienof2,3-clpridine-3-carboxylate Example 306A and 4-chlorophenol were processed as in Example 61 to provide the main compound. MS (DCI / NH3) m / e: 420 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 1.42 (s, 9 H), 3.95 (s, 3 H), 7.18 (d, 2 H), 7.50 (d, 2 H), 8.05 (s, 1 H), 9.20 (s) , 1 HOUR). Example 306C tert-Butyl 2- (Aminocarbonyl) -4- (4-chlorophenoxy) thienof2,3-clpyridine-3- carboxylate Example 306B was prepared as in Example 217 to provide the main compound. MS (DCI / NH3) m / e: 405 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 1.35 (s, 9 H), 7.10 (d, 2 H), 7.45 (d, 2 H), 7.95 (m, 1 H), 8.08 (s, 1 H), 8.14 (m, 1 H), 9.18 (s, 1 H). Example 306D 2- (Aminocarbonyl-4- (4-chlorophenoxy) thienof2,3-clpyridine-3-carboxylic acid Example 306C (0.08 g, 0.2 mmol) was placed in cold solution of trifluoroacetic acid (0.5 mL) and methylene chloride ( 0.5 mL) and stirred for 1 hour, the solution was evaporated and slowly treated with a cold solution of sodium bicarbonate (20 mL) and then the mixture was extracted with ethyl acetate (3x20 mL). dried and evaporated to give the main compound MS (DCI / NH3) m / e: 349 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 7.05 (d, 2 H), 7.45 (d, 2 H), 7.95 (b, 1 H), 8.05 (m, 1 H), 8.15 (s, 1 H), 9.20 (s, 1 H). Example 307 Methyl 4- (4-toluidino) thienor-2,3-clpyridine-2-carboxamide A mixture of Example 93 C (271 mg, 1 mmol), 4-methyl aniline (150 mg, 1.4 mmol), t sodium-butoxide (134.5 mg, 1.4 mmol), 18-crown-6 (370 mg, 1.4 mmol), Pd2 (dba3) (46 mg, 5 mol%) and BINAP (31 (mg, 5%) mol) were combined in a three-necked round bottom flask equipped with a condenser, temperature probe internal and one N2 input. This was evacuated under nitrogen and anhydrous tetrahydrofuran (5 mL) was added. The reaction mixture was heated at 45 ° C for 3 days, the solid materials were filtered through celite and rinsed with a mixture of ethyl acetate and • 5 acetone. The filtrate was diluted with ethyl acetate (100 mL), rinsed with brine (2x50 mL), dried (MgSO4) and evaporated to dryness under reduced pressure. The main compound was obtained in 29% product (86 mg), by flash chromatography on silica gel eluting with 30% acetone-hexane. MS (DCI / NH3) m / e: 298 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.25 (s, 3 H), 2.80 (d, J = 6 Hz, 3 H), • 7.02 (d, J = 9 Hz, 2H), 7.10 (d, J = 9 Hz, 2H), 8.1 3 (s, 1 H), 8.26 (s, 1 H), 8.36 (m, 1 H), 8.76 (br s, 1 H); 13 C NMR (75 MHz, DMSO-dβ) d 20.4 (CH 3), 26.4 (CH 2), 1 18.2 (CH), 1 18.2 (CH), 122.1 (CH), 130.0 (C), 130.6 (CH), 1 30.7 (C), 135.9 (C), 136.5 (CH), 137.1 (C), 140.3 (C), 142.3 ( C), 161.6 (CO). Example 308 4- (4-chloroanilino) -N-methylthienof2.3-clpyridine-2-carboxamide The main compound (500 mg, 84%) was prepared as in Example 307 except substituting 4-chloroaniline (510 mg, 4 mmol) for 4-methylaniline and the reaction was heated at 60 ° C for 20 hours. MS (APCl) m / e: 318 (M + H) +, 352 (M + CI) '; 1 H NMR (400 MHz, DMSO-dβ) d: 2.83 (d, J = 4 Hz, 3 H), 7.07 (d, J = 9 Hz, 2 H), 7.32 (d, J = 9 Hz, 2 H), 8.1 1 (s, 1 H), 8.38 (s, 1 H), 8.67 (s, 1 H), 8.85 (d, J = 4 Hz, 1 H), 8.91 (s, 1 H); 13C NMR (100 MHz, DMSO-dβ) d 26.3 (CH3), 1 18.1 (2xCH), 121.7 (CH), 123.6 (C), 122.1 (2xCH), 133.0 (CH), 134.4 (C), 137.1 (C), 137.2 (C), 138.2 (CH), 142.6 (C), 143.2 (C), 161.4 (C). Example 309 Methyl-4- (4-morpholinyl) thienof2,3-clpyridine-2-carboxamide The main compound (105 mg, 38%) was prepared as in Example 308 except substituting morpholine (0.175 mL, 2 mmol) for 4- chloroaniline MS (APCl) m / e: 278 (M + H) +, 312 (M + CI) '; 1 H NMR (400 MHz, DMSO-d 6) d: 2.91 (d, J = 4 Hz, 3 H), 3.23 (m, 4 H), 3.91 (m, 4 H), 8.14 (s, 1 H), 8.18 (s) , 1 H), 8.96 (s, 1 H), 8.99 (d, J = 4 Hz, 1 H); 13 C NMR (100 MHz, DMSO-dβ) d 26.1 (CH3), 51.6 (2xCH), 66.3 (CH2), 121.2 (CH), 131.6 (CH), 137.1 (C), 137.9 (C ), 139.0 (C), 143.3 (C), 161 .3 (CO). Example 31 1 7-Chloro-4- (4-chlorophenoxy) thienof2.3-clpyridine-2-carboxamide Example 31 1 A Methyl 7-chloro-4- (4-chlorophenoxy) thieno [2,3-c1pyridine-2-carboxylate Example 61 A was prepared as in Example 1 C to provide the main compound. HPLC: Supelco column C-18, gradient elution of 0.1% aqueous TFA: acetonitrile 0: 90-90: 0, for 30 minutes, detection at 254 nm, flow rate of 0.8 mL / min, RT 30.35 minutes; MS (DCI / NH3) m / e: 354 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 3.91 (s, 3 H), 7.14 (m, 2 H), 7.45 (m, 2 H), 7.91 (s, 1 H), 8.24 (s, 1 H), 9.21 ( s, 1 H). Example 31 1 B 7-Chloro-4- (4-chlorophenoxy) thienof2.3-clpyridine-2-carboxamide Example 31 1 A was prepared according to the procedure of Example 44 to provide the main compound. MS (DCI / NHa) m / e: 339 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 7.20 (m, 2 H), 7.48 (m, 2 H), 7.94 (br s, 1 H), 8.04 (s, 1 H), 8.22 (s, 1 H) 8.49 (br s, 1 H); Anal. Cal, for C 14 H 8 Cl 2 N 2? 2 S: C, 56.42; H, 3.28; N, 10.12. Found: C, 56.31; H, 3.22; N, 10.01. Example 312 7-Chloro-4- (4-chlorophenoxy) -N-methylthienof2,3-cjpyridine-2-carboxamide Example 31 1 A was prepared according to the procedure of Example 44 to provide the main compound. MS (DCI / NH3) m / e: 353 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.80 (d, 3 H), 7.16 (m, 2 H), 7.49 (m 2 H), 8.05 (s, 1 H), 8.17 (s, 1 H); 9.04 (br s, 2H). Example 313 7-Chloro-4- (4-chlorophenoxy) -N- (2-hydroxyethyl) thienor-2,3-c1pyridine-2-carboxamide Example 311 A was prepared according to the procedure of Example 1 14 to provide the main compound HPLC: Supelco column C-18, gradient elution 0.1% aqueous TFA: acetonitrile 0: 90-90: 0, for 30 minutes, detection at 254 nm, flow rate 0.8 mL / min, RT 23.49 minutes; mp 129-1 32 ° C; MS (DCI / NH3) m / e: 382 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 3.33 (m, 2 H), 3.51 (m, 2 H), 4.82 (t, 1 H), 7.1 9 (m, 2 H), 7.48 (m,, 2 H), 8.08 (s, 1 H), 8.27 (s, 1 H), 9.12 (br t, 1 H), 9.18 (s, 1 H), 12.81 (br s, 1 H). Example 314 7-Bromo-4- (4-chlorophenoxy) thienof2.3-clpyridine-2-carboxamide Example 314A Methyl 7-Bromo-4- (4-chlorophenoxy) thienof2,3-c1pyridine-2-carboxylate Example 123A was prepared as in Example 1 C replacing phosphorus oxybromide with phosphorus oxychloride to provide the main compound. MS (ESI) m / e: 400 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 3.91 (s, 3 H), 7.22 (m, 2 H), 7.48 (m, 2 H), 8.19 (s, 1 H), 8.20 (s, 1 H). Example 314B 7-Bromo-4- (4-chlorophenoxy) thienor-2,3-c1pyridine-2-carboxamide Example 314A was prepared according to Example 44 to provide the main compound. HPLC: Supelco column C-18, gradient elution 0.1% aqueous TFA: acetonitrile 0: 90-90: 0, for 30 minutes, detection at 254 nm, flow rate of 0.8 mL / min, RT 24.95 minutes; MS (DCI / NH3) m / e: 385 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 7.22 (m, 2 H), 7.44 (m, 2 H), 7.95 (s, 1 H), 8.02 (s, 1 H), 8.29 (s, 1 H), 8.51 (br s, 1 H).

Example 31 5-Bromo-4- (4-chlorophenoxy) -N-methylthienof2,3-clpyridine-2-carboxamide Example 314A was prepared according to the procedure Example 171 to provide the main compound. HPLC: Supelco column C-18, gradient elution 0.1% aqueous TFA: acetonitrile 0: 90-90: 0, for 30 minutes, detection at 254 nm, flow rate of 0.8 mL / min, RT 25.40 minutes; MS (DCI / NH3) m / e: 397 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 2.81 (d, 3 H), 3.97 (s, 3 H), 7.19 (m, 2 H), 7.48 (m, 2 H), 8.04 (s, 1 H), 8.21 (s) , 1 HOUR); 9.05 (br s, 1 H). Example 316 4- (4-Bromophenoxy) -7-chlorothienof2.3-clpyridine-2-carboxamide Example 316 was prepared as in Example 31 1 but substituting 4-chlorophenol for 4-bromophenol to provide the main compound. MS (DCI / NH3) m / e: 383, 385 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 7.14 (d, 2 H, J = 8.9 Hz), 7.61 (d, 2 H, J = 8.8 Hz), 7.98 (br s, 1 H), 8.05 (s, 1 H), 8.22 (s, 1 H), 8.52 (br s, 1 H); Anal. cale, for C? 4H8N2? 2SBrCI.0.5 H2O: C, 42.82; H, 2.31; N, 7.10. Found: C, 42.62; H, 2.26; N, 6.82. Example 317 4- (4-bromophenoxy) -7-chloro-N-methylthienof2.3-clpyridine-2-carboxamide Example 317 was prepared as in Example 312 but substituting 4-chlorophenol for 4-bromophenol to provide the main compound.

MS (DCI / NH3) m / e: 397, 399 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.80 (d, 3 H, J = 4.7 Hz), 7.13 (d, 2 H, J = 9.2 Hz), 7.60 (d, 2 H, J = 9.2 Hz), 8.07 (s) , 1 H), 8.13 (s, 1 H), 9.03 (q, 1 H, J = 4.7 Hz); Anal. cale, for C15H10N2? 2SBrCI: C, 45.30; H, 2.53; N, 7.04. Found: C, 45.25; H, 2.31; N, 6.86. Example 318 7-Chloro-4-f4- (trifluoromethyl) phenoxyptienor2.3-c1pyridine-2-carboxamide Example 17A and 4-trifluoromethylphenol were processed as in Example 31 1 to provide the main compound, mp 175-176 ° C; MS (DCI / NH3) m / e: 373 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 7.30 (d, 2H), 7.80 (d, 2H); 8.00 (s, 1 H); 8.20 (s, 1 H), 8.25 (s, 1 H), 8.55 (s, 1 H); Anal. cale, for C, 48.33; H, 2.16; N, 7.52. Found: C, 48.26; H, 2.25; N, 7.40. Example 319 7-Chloro-N-methyl-4-f4- (trifluoromethyl-phenoxfltienof2,3-clpyridine-2-carboxamide Example 17A and 4-trifluoromethylphenol were processed as in Example 312 to provide the main compound, mp 178-179 ° C; MS (DCI / NH3) m / e: 387 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.80 (s, 3H), 7.30 (d, 2H), 7.80 (d, 2H ), 8.00 (s, 1 H), 8.25 (s, 1 H), 8.55 (m, 1 H); Anal. cale, for C 16 H 10 ClF 3 N 2 O 2 S: C, 49.68; H, 2.61; N, 7.24. Found: C, 49.58; H, 2.54; N, 6.94. EXAMPLE 320 7-Chloro-N- (2-hydroxyethyl) -4-f4- (trifluoromethyl) phenoxy-thienof2.3-c1pyridine-2-carboxamide Example 320 was prepared according to the procedure of Example 319, with the substitution of aminoethanol by methylamine. mp 96-97 ° C; MS (ESI / NH3) m / e: 415 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 1 H NMR (300 MHz, DMSO-d 6) d 3.66 (t, 2 H, J = 4.8 Hz), 3.87 (t, 2H, J = 4.8 Hz), 6.63 (m, 1 H), 7.1 1 (d, 2H, J = 8.5 Hz), 7.64 (d, 2H, J = 8.5 Hz), 7.72 (s, 1 H), 8.02 (s, 1 H). EXAMPLE 321 4- (4-Chlorophenoxy) -N 7 -d -methylthienof 2,3-c 1pyridine-2-carboxamide Example 321 A Methyl 4- (4-chlorophenoxy) -N 7 -dimethylthienof 2,3-c 1pyridine-2-carboxylate Example 31 1A was prepared as in Example 95A but substituting methyl boronic acid for 4- (trifluoromethyl) phenol boronic acid and substituting dichlorobis (tricyclohexylphosphine) palladium for titanium (triphenophosphine) palladium ester and substituting NMP for DME to provide the main compound . MS (DCI / NH3) m / e: 334 (M + H) +; H NMR (300 MHz, DMSO-dβ) d 2.74 (d, 3 H), 3.91 (s, 3 H), 7.14 (m, 2 H), 7.44 (m, 2 H), 7.91 (s, 1 H), 8.22 (s) , 1 HOUR).

EXAMPLE 321 B 4- (4-Chlorophenoxy) -N, 7-dimethyltienof2.3-clpyridine-2-carboxamide Example 321A was prepared according to the procedure of Example 171 to provide the main compound. HPLC: Supelco column C-18, gradient elution 0.1% aqueous TFA: acetonitrile 0: 90-90: 0, for 30 minutes, detection at 254 nm, flow rate 0.8 mL / min, RT 20.70 minutes; MS (DCI / NHs) m / e: 334 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 2.82 (d, 3 H), 7.04 (m, 2 H), 7.41 (m, 2 H), 8.04 (s, 1 H), 8.1 1 (s, 1 H), 8.92 (br s, 1 H). Example 322 4- (4-Chlorophenoxy) -7-methoxytin [2,3-c1pyridine-2-carboxamide Example 322A 4- (4-Chlorophenoxy) -7-methoxythienof2,3-c1pyridine-2-carboxylic acid Example 31 1 A (100 mg, 0.28 mmol) was dissolved in 25% sodium methoxide in methanol (10 mL) and heated at 60 ° C in a pressure tube for 3 days. The solvent was removed under reduced pressure and the residue redissolved in methylene chloride and acidified with formic acid. The organic layer was dissolved with H2O and brine, dried (Na SO4) and the solvent was removed under reduced pressure to provide the main compound (50 mg, 54%) as an off-white solid. MS (DCI / NH3) m / e: 336 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 4.18 (s, 3 H), 6.92 (m, 2 H), 7.31 (m, 2 H), 7.54 (s, 1 H), 7.69 (s, 1 H).

Example 322B 4- (4-Chlorophenoxy) -7-methoxy-nitro-2,3-clpyridine-2-carboxamide Example 322A (40 mg, 0.12 mmol) was treated according to the procedure of Example 92 to provide the compound • Main (23 mg, 0.58 mmol) as a white solid, mp > 250 ° C MS (DCI / NH 3) m / e: 335 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 4.08 (s, 3 H), 7.01 (m, 2 H), 7.38 (m, 2 H), 7.82 (br s, 1 H), 7.90 (s, 1 H), 8.04 (s, 1 H), 8.43 (s, 1 H). Example 323 4- (4-Chlorophenoxy) -7-oxo-6.7-dihydrothienof2.3-c1pyridine-2-carboxamide • Example 323A Methyl 4- (4-chlorophenoxy) -7-oxo-6.7-d, hydrotienof2.3- 1-pyridine-2-carboxylate A solution of Example 31 1 A (200 mg, 0.597 mmol) in Acetic anhydride (20 mL) was heated to reflux for 18 hours. The reaction was cooled and poured on ice. The mixture was allowed to stir for 1 hour before CH2CI (100 mL) was added. The organic extracts were rinsed with 1 N NaOH (100 mL), H 2 O (50 mL), brine (50 mL), dried (Na 2 SO 4), filtered and rotoevaporated to provide a crude brown residue. This residue was dissolved directly in DMF (20 mL) and H2O (3 mL), treated with K2CO3 and heated at 60 ° C for 2 hours. The reaction was allowed to cool to room temperature and then rotoevaporated. The crude residue was purified by column chromatography on silica gel. with 10% ethyl acetate / hexane with a gradient for 50% of ethyl acetate / hexane to provide the main compound. MS (DCI / NH3) m / e: 336 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 3.82 (s, 3 H), 7.09 (m, 2 H), 7.38 (s, 2 H), 7.42 (s, 1 H), 7.52 (s, 1 H), 1 1 .84 (br s, 1 H). Example 323B 4- (4-Chlorophenoxy) -7-oxo-6,7-dihydrothienof2,3-cypyridine-2-carboxamide Example 323A was prepared according to Example 44 to provide the main compound. HPLC: Supelco column C-18, water eluent gradient: acetonitrile 10 0: 90-90: 0, for 30 minutes, detection at 254 nm, flow rate 0.8 mL / min, RT 18.61 minutes; • mp > 250 ° C; MS (APCl) m / e: 321 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 7.04 (m, 2 H), 7.38 (m, 2 H), 7.40 (s, 15 1 H), 7.75 (s, 1 H), 8.32 (br s, 1 H) . Example 324 4- (4-Chlorophenoxy) -N-methyl-7- (methylamino) thienof2,3-c1pyridine-2-carboxamide Example 31 1 A (27 mg, 76 mmol) was treated according to the procedure of Barraclough, et al. ., (J. Med. Chem. 1990, 33, 2231) • 20 to provide the main compound (12 mg, 45% product). MS (DCI / NHs) m / e: 348 (35Cl) / 350 (37Cl); 1 H NMR (CDCl 3, 300 MHz) d 2.98 (d, 3 H), 3.16 (d, 3 H), 4.65 (d, 1 H), 6.56 (d, 1 H), 6.83 (d, 2 H), 7.27 (d, 2H); 7.47 (s, 1 H), 7.86 (s, 1 H). Example 325 25 N-Methyl-7- (4-methylphenoxy) f1.3] thiazolof5.4-clpyridine-2-carboxamide Example 142D (10 mg, 33 mmol) was treated according to the procedure of Example 96 to give the main compound (1.5 mg, 75%) as a white solid. MS (DCI / NH3) m / e: 300 (M + H) + / 317 (M + NH3) +; 1 H NMR (CDCl 3, 300 MHz) d 2.39 (s, 3 H), 3.07 (d, J = 5.1 Hz, 3 H), 7.06 (d, J = 8.8 Hz, 2 H), 7.23 (d, J = 8.5 Hz, 2H), 7.52 (d, J = 5.5 Hz, 1 H), 8.18 (s, 1 H); 9.02 (s, 1 H). Example 327 4- (4-Chlorophenoxy) furof2.3-c1pyridine-2-carboxamide Example 327A Ethyl 4- (4-chlorophenoxy) furof2.3-clpyridine-2-carboxylate To a solution of 4-chlorophenol (1.08 g, 8.7 mmol ) in anhydrous tetrahydrofuran (25 mL) under a nitrogen atmosphere at 0 ° C was added dropwise a solution of potassium tert-butoxide (1.0 M solution in THF, 8.7 mL, 8.7 mmol). The reaction mixture was then stirred and heated at 65 ° C for 2 hours, cooled to 0 ° C, then treated with Example 17A (1.0 g, 5.7 mmol) in anhydrous tetrahydrofuran. (10 mL) and heated at 65 ° C for 2 hours. The reaction cooled to 0 ° C, ethyl glycolate (1.07 mL, 11.4 mmol) and cesium carbonate (3.0 g, 9.2 mmol) were added, and the mixture was heated at 65 ° C for 3 hours. The reaction was cooled and concentrated, and the residue was then diluted with ethyl acetate (50 mL) and rinsed with brine (3x50 mL), then dried (MgSO4). The ethyl acetate was then evaporated to give an oil. Purification by flash chromatography on silica gel eluting with 10% ethyl acetate- Hexane produced 0.1-10 g (6.1%) of the main compound as a crystalline residue. MS (DCI / NHs) m / e: 318 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 1.35 (t, 2 H, CH 2), 4.4 (q, 3 H, CH 3), 7.2 5 (d, J = 9 Hz, 2 H), 7.5 (d, J = 9 Hz, 2H), 8.09 (s, 1 H), 8.23 (s, 1 H); 9.25 (s, 1 H). Example 327B 4- (4-Chlorophenoxy) furof2,3-c1pyridine-2-carboxylic acid To a solution of lithium hydroxide monohydrate 10 (0.01 13 g, 0.5 mmol) in tetrahydrofuran (5 mL) and water (1 mL) was added. added Example 327A (0.1 g, 0.3 mmol), and the mixture was heated to ^ 50 ° C for 2 hours. The mixture was cooled, and then the formic acid was added until it was acidic (pH?). The mixture was then extracted with ethyl acetate (50 mL) and the extract was rinsed with brine (2x20 mL), dried (MgSO4), and evaporated. Purification by silica gel flask chromatography eluting with 20% acetone-hexane afforded 0.710 g (81.6%) of the main compound as a crystalline residue. MS (DCI / NH3) m / e: 290 (M + H) +; 20 1 H NMR (300 MHz, DMSO-dβ) d 3.4 (br s, 1 H), 7.2 (d, J = 9 Hz, 2 H), 7.5 (d, J = 9 Hz, 2 H), 8.09 (s, 1 H), 8.23 (s, 1 H), 9.25 (s, 1 H). Example 327C 4- (4-Chlorophenoxy) furof2,3-clpyridine-2-carboxamide A solution of Example 327B (0.15 g, 0.5 mmol) in DMF 25 (10 mL) was treated with 1-hydroxybenzotriazole hydrate (0.104 g, 0.66 g). mmol), NH 4 Cl (0.0948 g, 0.017 mmol) and 4-methylmorpholine (0.141 g, 0.14 mmol). The solution was cooled to 0 ° C and treated with 1 [3- (dimethylamino) propyl] -3-ethylcarbodiimide hydrochloride (0.1 15 g, 0.6 mmol), warmed to room temperature, stirred overnight, poured into NaHCO 3 Saturated, filtered, rinsed with brine (3x20 mL), dried (MgSO) and evaporated. Purification by silica gel flask chromatography eluting with 20% acetone-hexane afforded 0.030 g (21%) of the main compound as a crystalline residue. MS (DCI / NH3) m / e: 289 (M + H) +; 10 1 H NMR (300 MHz, DMSO-d 6) d 7.18 (d, 2 H), 7.29 (s, 1 H), 7.5 (d, 2 H), 7.82 (br s, 1 H), 8.25 (s, 1 H) , 8.34 (br s, 1 H), 8.95 (s, 1 H); Example 328 4- (4-Chlorophenoxy) furof2.3-clpyridine-2-carbothioamide -A a solution of Example 327 (0.06 g, 0.2 mmol) in toluene (5 L) was added Lawesson's reagent (0.1 g, 0.2 mmol). The reaction was refluxed for 1 hour, then cooled, evaporated and dissolved in ethyl acetate. The ethyl acetate solution was rinsed with brine (3x15 mL), dried (MgSO4) and evaporated. Purification by silica gel flask chromatography reading with -20% acetone-hexane afforded 0.22 g (37%) of the main compound as a light yellow solid. MS (DCI / NH3) m / e: 305 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 7.20 (d, 2 H), 7.29 (s, 1 H), 7.5 (d, 2 H), 8.25 (s, 1 H), 8.82 (s, 1 H), 9.95 (b, 2H). 25 Example 329 4- (2-Phenyletenynthienof2,3-clpyridine-2-carboxamide Example 329A Tert-Butyl E and Z-4- (2-phenylenedi nieno [2,3-clpyridine-2-carboxylate To a stirred solution of diethyl benzylphosphonate (0.08 mL , 0.38 mmol) in dichloromethane (2 mL) at -78 ° C, a solution of 0.5 M potassium bis (trimethylsilyl) amide in toluene (0.84 mL, 0.42 mmol) was added dropwise. After 45 min, a solution of Example 237E (0.10 g, 0.38 mmol) in dichloromethane (3 mL) was added slowly and the reaction was stirred 1 hour. The bath was removed and the reaction was stirred 20 minutes. The reaction was cooled in a dilute aqueous solution of NaHCO3. The aqueous was extracted with dichloromethane (2x25 mL), ethyl acetate (2x25 mL). All organic phases were combined, dried (Na2SO) and concentrated to produce a coloredo oil. The residue was purified by flash chromatography on silica gel using EtOAc / hexane as eluent. The mixture of stereoisomers was dried in a desiccator to produce a solid (0.07 g, 55%): MS (APCl) m / e: 338 (M + H) +. EXAMPLE 329B E ~ 4- (2-Phenylenediyennetene-2,3-c1pyridine-2-carboxamide Example 329A (0.07 g, 0.21 mmol) was dissolved in a 10% solution of H2SO4 / MeOH (10 mL) .The solution was heated to reflux for 6 hours thereafter was stirred at room temperature for 16 hours.The reaction was concentrated under reduced pressure, then basified with sat'd NaHCO3 (50 mL), the aqueous phase was extracted with dichloromethane (2x50 mL) and the organic extracts were extracted.

They combined. The organic layer was rinsed with a diluted brine solution (100 mL), dried (Na2SO4), filtered and concentrated under reduced pressure in a colored residue. The residue was dissolved in methanol (8 mL) and chloroform (1 mL). A balloon of ammonium gas was applied and the reaction was heated at 35 ° C for 24 hours. The reaction was concentrated and the residue was purified by HPLC using a gradient of 25% -65% acetonitrile / water + 0.1% TFA for 40 minutes. Preferably, they were neutralized with sat. NaHCO3. to produce the main compound (27 mg, 46%) and additionally the corresponding Z-isomer (14 mg, 24%). mp 257-258 ° C; MS (DCI / NH3) m / e: 281 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 7.34 (dd, J = 7.6, 7.2 Hz, 1 H), 7.46 (dd, J = 7.6, 7.2 Hz, 2H), 7.55 (d, J = 16.5 Hz, 1 H), 7.64 (d, J = 16.5 Hz, 1 H), 7.73 (d, J = 7.2 Hz, 2 H), 7.88 (br s, 1 H), 8.37 (br s, 1 H), 8.62 (s) , 1 H), 8.85 (br s, 1 H), 9.18 (s, 1 H); Anal. cale, for (C1 ßH2N2? S 0.2 H2O): C, 67.68; H, 4.40; N, 9.87. Found: C, 67.47; H, 4.18; N, 9.84. Example 330 4- (4-Chlorophenyl) thienor 2,3-clpyridine-2-carboxamide Example 330A 4- (4-Chlorophenyl) thienof 2,3-clpridine-2-carboxalate The main compound (160 mg, 53%) was prepared as in Example 95A but substituting 4-chlorophenyl boronic acid for 4- (trifluoromethyl) phenyl boronic acid.

MS (APCl) m / e: 304 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 3.92 (s, 3 H), 7.69 (m, 4 H); 8.30 (s, 1 H), 8.60 (s, 1 H), 9.42 (s, 1 H). Example 330B • 5 4- (4-Chlorophenyl) thienof2.3-c1pyridine-2-carboxamide Example 330A was prepared as in Example 44 to provide the main compound (60 mg, 60%). MS (APCl) m / e: 289 (M + H) +; 1 H NMR (400 MHz, DMSO-d 6) d 7.63 (d, J = 8 Hz, 2 H), 7.69 (d, J = 8 Hz, 10 2 H), 7.77 (s, 1 H), 8.19 (s, 1 H ), 8.41 (s, 1 H), 8.51 (s, 1 H), 9.30 (s, 1 H). Example 331 • 4-f3- (Trifluoromethyl) phenynthienof2.3-clpyridine-2-carboxamide Example 331A 4-f3- (trifluoromethyl) phenynthienof2.3-clpyridine-2-carboxylate The main compound (100 mg, 30%) was prepared as in Example 95A but substituting 4- (trifluoromethyl) phenyl! boronic acid 4- (trifluoromethyl) phenyl boronic acid. MS (APCl) m / e: 338 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 3.92 (s, 3 H), 7.81 -7.93 (m, 4 H), 8.01 20 (s, 1 H); 8.67 (s, 1 H), 9.46 (s, 1 H). Example 331 B 4-f3- (trifluoromethyl) phenynthienof2.3-clpyridine-2-carboxamide Example 331A was prepared as in Example 44 to provide the main compound (90 mg, 94%). MS (APCl) m / e: 323 (M + H) +; 1 H NMR (400 MHz, DMSO-d 6) d 7.85 (s, 1 H), 7.90-7.97 (m, 4 H), 8.25 (s, 1 H), 8.46 (s, 1 H), 8.69 (s, 1 H) ), 9.38 (s, 1 H). EXAMPLE 332 4- (3-Chlorophenyl) t-inof2.3-clpridine-2-carboxamide Example 332A 4- (3-Chlorophenyl) thienor-2,3-clpyridine-2-carboxalate The main compound (130 mg, 43%) was prepared as in Example 95A but replacing 3-chlorophenyl boronic acid with 4-chlorophenyl boronic acid. MS (APCl) m / e: 304 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 3.92 (s, 3 H), 7.59-7.68 (m, 3 H), 7.75 (s, 1 H), 8.02 (s, 1 H), 8.62 (s, 1 H) , 9.43 (s, 1 H). Example 332B 4- (3-Chlorophenyl) thienor-2,3-clpyridine-2-carboxamide Example 332A was prepared as in Example 44 to provide the main compound (82 mg, 86%). MS (APCl) m / e: 288 (M + H) +; 1 H NMR (400 MHz, DMSO-d 6) d 7.58-7.62 (m, 3 H), 7.62 (s, 1 H), 7.69 (s, 1 H), 8.19 (s, 1 H), 8.49 (s, 1 H) ), 8.51 (s, 1 H), 9.31 (s, 1 H). Example 333 4- (4-Bromophenyl) thienof2,3-c1pyridine-2-carboxamide Example 333A 4- (4-Bromophenyl) thienor 2,3-c 1pyridine-2-carboxylate The main compound (148 mg, 42%) was prepared as in Example 95A but substituting 4-bromophenyl boronic acid for 4- (trifluoromethyl) phenyl boronic acid. MS (APCl) m / e: 305 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 3.91 (s, 3 H), 7.61 (d, J = 5.7 Hz, 2 H), 7.77 (d, J = 7.5 Hz, 2 H), 8.02 (s, 1 H) , 8.57 (s, 1 H), 9.40 (s, 1 H). Example 333B 4- (4-Bromophenyl) t-inof2,3-c1pyridine-2-carboxamide Example 333A was prepared as in Example 44 to provide the main compound (18 mg, 88%). MS (APCl) m / e: 333.335 (1: 1) (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 7.63 (d, J = 7.5 Hz, 2 H), 7.79 (d, J = 7.5 Hz, 2 H), 7.84 (s, 1 H), 8.22 (s, 1 H) , 8.46 (s, 1 H), 9.33 (s, 1 H). Example 334 4- (3-Aminophenyl) thienof2.3-c1pyridine-2-carboxamide Example 334A 4- (3-Amylphenyl) thienof2.3-clpyridine-2-carboxalate The main compound (90 mg, 32%) was prepared as in Example 95A but substituting 3-aminophenyl boronic acid for 4- (trifluoromethyl) phenyl boronic acid. MS (APCl) m / e: 285 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 3.92 (s, 3 H), 5.34 (s, 2 H), 6.67-6.76 (m, 2 H), 6.81 (m, 1 H), 7.22 (t, J = 7.5 Hz , 1 H), 8.07 (s, 1 H), 8.53 (s, 1 H), 9.36 (s, 1 H). Example 334B 4- (3-Aminophenyl) thienof2,3-c | pyridine-2-carboxamide Example 334A was prepared as in Example 44 for provide the main compound (83 mg, 98%). MS (APCl) m / e: 270 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 5.30 (s, 2 H), 6.67-6.82 (m, 3 H), 7.22 (t, J = 7.5 Hz, 2 H), 7.79 (s, 1 H), 8.23 (s) , 1 H), 8.43 (s, 1 H), 8.51 (s, 1 H), • 5 9.25 (s, 1 H). Example 335 4- (3,5-Dichlorophenyl) thienof2,3-clpyridine-2-carboxamide Example 335A 4- (3,5-Dichlorophenol) t'enof2.3-clpyridine-2-carboxylate The main compound (90 mg, 27%) was prepared as in Example 95A but substituting 3,5-dichlorophenyl boronic acid for 4- (trifluoromethyl) phenyl boronic acid. MS (APCl) m / e: 338 (M + H) +; Example 335B 15 4- (3,5-Dichlorophenyl) thienof2,3-clpyridine-2-carboxamide Example 335A was prepared as in Example 44 to provide the main compound (21 mg, 24%). MS (APCl) m / e: 323 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 7.73 (d, J = 2.25 Hz, 2 H), 7.80 (m, 1 H), • 20 7.88 (s, 1 H), 8.20 (s, 1 H), 8.53 (s, 1 H), 8.56 (s, 1 H), 9.36 (s, 1 H). EXAMPLE 336 4- (2,4-Dichlorophenyl) thienof2.3-clpyridine-2-carboxamide Example 336A 4- (2,4-Dichlorophenyl) t-inof2,3-c] pyridine-2-carboxalate 25 The main compound (100 mg, 30%) was prepared as in Example 95A but substituting 2,4-dichlorophenyl boronic acid for 4- (trifluoromethyl) phenyl boronic acid. MS (APCl) m / e: 338 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 3.38 (s, 3 H), 7.59 (s, 1 H), 7.61 (d, J = 2.25 Hz, 1 H), 7.70 (s, 1 H), 7.86 (d , J = 2.25 Hz, 1 H), 8.49 (s, 1 H), 9.45 (s, 1 H). Example 336B 4- (2,4-Dichlorophenyl) thienof2,3-c1pyridine-2-carboxamide Example 336A was prepared as in Example 44 to provide the main compound. 1 H NMR (300 MHz, DMSO-d 6) d 7.60 (s, 1 H), 7.64 (m, 1 H), 7.81 (br s, 1 H), 7.87 (s, 1 H), 7.91 (m, 1 H ), 8.37 (br s, 1 H), 8.45 (s, 1 H), 9.37 (s, 1 H). Example 337 4- (3,4-Dichlorophenyl) thienof2,3-clpyridine-2-carboxamide Example 337A 4- (3,4-Dichlorophenyl) thienof2.3-clpyridine-2-carboxalate The main compound (130 mg, 39%) was prepared as in Example 95A but substituting 3,4-dichlorophenyl boronic acid for 4- (trifluoromethyl) phenyl boronic acid. MS (APCl) m / e: 338 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 3.94 (s, 3 H), 7.67-7.76 (m, 1 H), 7.85 (m, 1 H), 7.79 (d, J = 2.25 Hz, 1 H), 8.06 (s, 1 H), 8.63 (s, 1 H), 9.44 (s, 1 H). Example 337B 4- (3,4-Dichlorophenyl) thienof2,3-c1pyridine-2-carboxamide Example 337A was prepared as in Example 44 to provide the main compound (44 mg, 46%). MS (APCl) m / e: 323 (M + H) +; • 5 1 H NMR (300 MHz, DMSO-dβ) d 7.65-7.68 (m, 1 H), 7.84-7.87 (m, 2H), 8.96 (d, J = 2.25 Hz, 1 H), 8.21 (s, 1 H), 8.47 (s, 1 H), 8.56 (s, 1 H), 9.35 (s, 1 H). Example 338 4-f2,4-Difluorophenyl) thienor 2,3-clpyridine-2-carboxamide Example 338A 4-f 2,4-Difluorophenyl) thienof 2,3-c 1pyridine-2-carboxalate • The main compound (130 mg, 42 %) was prepared as in Example 95A but substituting 2,4-dichlorophenyl boronic acid for 4- (trifluoromethyl) phenyl boronic acid. 15 MS (APCl) m / e: 306 (M + Hf; 1 H NMR (300 MHz, DMSO-dβ) d 3.90 (s, 3 H), 7.26 (m, 1 H), 7.45 (m, 1 H), 7.63 (m, 1 H), 7.81 (d, J = 3 Hz , 1 H), 8.55 (s, 1 H), 9.44 (s, 1 H). Example 338B 4-f2.4-Difluorophenyl) thienof2.3-clpyridine-2-carboxamide • Example 338A was prepared as in Example 44 to provide the main compound. MS (APCl) m / e: 291 (M + H) +; 1 H NMR (300 MHz, DMSO-dβ) d 7.30 (m, 1 H), 7.49 (m, 1 H), 7.66 (m, 1 H), 7.77 (s, 1 H), 7.99 (s, 1 H) , 8.39 (s, 1 H), 8.47 (s, 1 H), 9.34 (s, 1 H). 25 Example 339 4-.4-Fluorophenyl) thienor-2,3-c1pyridine-2-carboxamide Example 339A 4- (4-Fluorophenyl) thienof2,3-clpyridine-2-carboxalate The main compound (100 mg, 35%) was prepared as in ^ Example 95A but substituting 4-fluorophenyl boronic acid for 4- (trifluoromethyl) phenyl boronic acid. MS (APCl) m / e: 288 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 3.89 (s, 3 H), 7.38-7.48 (m, 2 H), 7.55- 7.64 (m, 1 H), 7.78 (d, J = 3 Hz, 1 H), 8.57 (s, 1 H), 9.44 (s, 1 H). Example 339B 4- (4-Fluorophenyl) thienor-2,3-c] pyridine-2-carboxamide • Example 339A was prepared as in Example 44 to provide the main compound. MS (APCl) m / e: 273 (M + H) +; 15 1 H NMR (300 MHz, DMSO-d 6) d 70.40-7.50 (m, 2H), 7.57-7.65 (m, 2H) 7.81 (s, 1 H), 8.01 (s, 1 H), 8.47 (s, 1 H), 8.51 (s, 1 H), 9.36 (s, 1 H). Example 340 5-Chloro-4- (4-chlorophenoxy) thienof2,3-clpridino-2-carboxamide Example 340A 2.3.5-Trichloro-4-formylpyridine A solution of diisopropylamide (7.3 mL, 1.5 M in cyclohexane, 11 mmol) in 10 mL of dry THF under nitrogen at -78 ° C was treated with 2.3 , 5-trichloropyridine (2 g, 11 mmol) in 20 mL of THF for a period of 30 minutes, stirred for an additional 20 minutes, then methyl formate (1.4 mL, 1.3 g, 22 mmol) in 14 mL of THF was slowly added to the brown solution for 1 5 minutes, allowed to slowly warm to room temperature and stirred overnight. The resulting dark brown solution was poured into ice and • 5 saturated NaHCO3, extracted with ethyl acetate, rinsed with brine, dried (Na2SO4) and concentrated. The brown oil was flash chromatographed on silica gel with 20-33% ethyl acetate / hexane to provide the main compound (1.7g, 74%). MS (APCl) m / e: 21 1 (M + H) +, 229 (M + NH 4) +; 10 1 H NMR (300 MHz, DMSO-d 6) d 10.26 (s, 1 H), 8.70 (s, 1 H). Example 340B • 2-Chloro-3,5-bis (4-bromophenoxy) -4-pyridinecarboxaldehyde A solution of 4-bromophenol (1.04 g, 6 mmol) in 4 mL of THF at 0 ° C was treated with t-butoxide of potassium (4 mL, 1 M in THF, 4 mmol) was passed through a syringe, allowed to warm to room temperature and stirred one hour, cooled to 0 ° C, Example 340A (390 mg, 2 mmol) in 2 mL of THF was added, the reaction was heated to 60 ° C. for two hours, and then allowed to cool to room temperature. The reaction mixture was diluted with ethyl acetate, rinsed with 1 N NaOH, brine, dried (Na 2 SO 4) and concentrated. The brown residue was flash chromatographed on silica gel twice with 1-2% methanol / dichloromethane and then 5-20% ethyl acetate / hexane to provide the main compound (235 mg, 24%) MS (APCl) m / e: 483 (MH) \ 517 (M + CI) '; 25 1 H NMR (300 MHz, DMSO-dβ) d 10.20 (s, 1 H), 8.24 (s, 1 H), 7.63 (m, 2H), 7.53 (m, 2H), 7.24 (m, 2H), 6.99 (m, 2H). EXAMPLE 340C Methyl 5-Chloro-4- (4-chlorophenoxy) t-inof2,3-clpyridine-2-carboxylate A solution of 340B (227 mg, 0.47 mmol) in 2 mL of • 5 THF was treated with methyl thioglycolate (50 μL, 0.52 mmol) followed by Cs2CO3 powder (179 mg, 0.55 mmol), stirred at room temperature for 21 hours, heated at 60 ° C for 15 minutes, then allowed to cool to room temperature. The reaction was diluted with ethyl acetate and distilled water, rinsed with 1 M K2CO3, brine, dried (MgSO) and concentrated. The residue was flash chromatographed on silica gel with 5-20% ethyl acetate / hexane followed by • Purification of HPLC (C-18), eluent gradient of 30-90% of CH3CN / H2O with 1% TFA to provide the main compound (6 mg, 3%) 15 MS (APCl) m / e: 400 (M + H) +; 1 H NMR (300 MHz, DMSO-d 6) d 9.20 (s, 1 H), 7.78 (s, 1 H), 7.51 (d, 2 H), 6.93 (d, 2 H), 3.90 (s, 3 H). Example 340D 5-Chloro-4- (4-chlorophenoxy) thienor-2,3-clpyridine-2-carboxamide • 20 A solution of 340C (5 mg, 0.013 mmol) in 1 mL of methanol and 1 mL of dichloromethane was treated with 2M of Ammonium in methanol (3 mL, 6 mmol) in a pressure tube and heated at 60 ° C for 4 hours, allowed to cool to room temperature, and concentrated. The residue was filtered through a silica plug with 95/5 dichloromethane / methanol, concentrated, then purified by Reverse phase HPLC (C-18) 20-75% CH3CN / H2O with 0.1% TFA to provide the main compound (4.2 mg, 84%). HPLC (C-18, 4.6 X 250 nm), 0.8 mL / min,? = 254 nm CH3CN: H2O with 0. 1% TFA 0-90%, RT 23.3 min (98.52% area); MS (APCI-NH3) m / e: 385 (M + H) +; 1 H NMR (300 MHz, MeOH-d 4) d 8.98 (s, 1 H), 7.9 (s, 1 H), 7.49 (d, 2 H), 6. 83 (d, 2H). The foregoing is merely illustrative and is not intended to limit the invention to the disclosed compounds. Variations and changes that are obvious to a person skilled in the art are to be within the scope and nature of the invention as defined in the appended claims.

Claims (10)

CLAIMS A compound that has the formula I
1. I. or a pharmaceutically acceptable salt or premedication thereof, wherein the symbol - represents a single bond or a 10 double link, • provided that when a link is a double link, the adjacent link is a single link; E, F, and G are independently selected from (1) carbon, 15 (2) nitrogen, and (3) N + -O ", provided that at least one of E, F or G is nitrogen or N + -O", and also provided that at least one of E, F or G is carbon; Y and Z are selected independently of (1) carbon, (2) nitrogen, (3) oxygen, and (4) S (O) t, where t is an integer 0-2, provided that at least one of Y or z is other than carbon; 25 LA is selected from (1) a covalent bond, (2) -O-, (3) -S (O) t-, (4) -NR6- wherein R6 is selected from (a) hydrogen, (b) alkyl from one to ten carbons optionally substituted with 1 or 2 substituents independently selected from (j) aryl and (ii) cycloalkyl of three to ten carbons, (c) alkanoyl wherein the alkyl part is from one to ten carbons, and (d) cycloalkyl of three to ten carbons, (5) -C (W) - wherein W is selected from (a) O and (b) S and (6) alkenylene; is selected from (1) halo, (2) alkyl of one to ten carbons optionally substituted with 1, 2 or 3 substituents independently selected from (a) oxo. (b) cycloalkyl of three to ten carbons, (c) -CO2R, wherein R7 is selected from (i) hydrogen and (ii) alkyl of one to ten carbons optionally substituted with 1, or 2 substituents independently selected from aryl and cycloalkyl of three to ten carbons, (d) -NR8Rg wherein R8 and R9 are independently selected from (i) hydrogen, (ii) alkyl of one to six carbons optionally substituted with 1 or 2 substituents independently selected from -OH aryl, heterocycle, cycloalkyl of three to ten carbons, and -NRARB wherein RA and RB are independently selected from hydrogen and alkyl of one to six carbons optionally substituted with 1 or 2 substituents selected from -OH, (iii) alkanoyl wherein the alkyl part is from one to ten carbons, (iv) cycloalkyl of three to ten carbons, (v) alkoxy, (vi) heterocycle, and (vii) aryl, wherein (vi) and (vii) are substituted with 1 or 2 substituents independently selected from alkyl of one to six carbons and ^. halo, (e) -C (W) R10 wherein W is previously defined and R10 is selected from (i) hydrogen, (ii) alkyl of one to ten carbons optionally 10 substituted with 1 or 2 substituents independently selected from aryl and cycloalkyl of three to ten carbons, (iii) -NR8R9, and 15 (iv) -OR7, (f) -OH, (g) aryl, and (h) heterocycle , where (g) and (h) can be optionally substituted with 1, 20 2, 3, 4 or 5 substituents independently selected from (i) alkyl of one to twenty carbons, (ii) -NR8R9, (iii) alkoxy of one to ten carbons, 25 (iv) thioalkoxy of one to ten carbons, (v) halo (vi) perfluoroalkyl of one to three carbons, (vii) alkenyl of two to ten carbons, (viii) alkyl of one to ten carbons optionally • 5 substituted with 1 or 2 substituents independently selected from alkoxy of one to ten carbons and -OH, (ix) -CO2R7, 10 (x) aryl, and (xi) -CHO, • (3) cycloalkyl of three to ten carbons , (4) aryl, (5) heterocycle 15 wherein (4) and (5) can be optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from '(a) alkyl of one to twenty carbons, (b) ) alkyl of one to ten carbons substituted with 1, 2 or 3 substituents independently selected from • 20 (i) -ORn wherein Rn is selected from hydrogen -C (W) R12 wherein R12 is selected from alkyl of one to ten carbons , cycloalkyl of three to ten carbons, 25 aryl, and heterocycle, and heterocycle optionally substituted with 1, 2, 3 or 4 substituents independently selected from -OH and • alkyl of one to six carbons optionally substituted with 1 or 2 substituents selected from -OH, (? i) alkoxy of one to ten carbons optionally substituted with 1 or 2 substituents independently Selected from alkoxy and alkoxyalkoxy, (iii) spiroalkyl of three to ten carbons, and (iv) halo, 15 (c) alkoxy of one to ten carbons optionally substituted with 1 or 2 substituents independently selected from (i) alkoxy, and ( i) alkoxycoxy, 20 (d) thioalkoxy of one to ten carbons, (e) halo, (f) perfluoroalkyl of one to three carbons, (g) alkenyl of two to ten carbons optionally substituted with 1 or 2 substituents independently 25 selected from (i) -C (W) R10 and (ii) -C (W) R12 (h) -CO2R7 (i) -NR8R9, • 5 (j) aryl (k) -C (W) R12, (I) - CHO, (m) -C (O) NR8R9, (n) -CN, 10 (o) heterocycle optionally substituted with 1 or 2 substituents independently selected from • (i) alkyl of one to ten carbons and (i) perfluoroalkyl of one to three carbons, (p) -C (W) R10, 15 (q) ethylenedioxy, and (r) -OCFs, (6) -OR7 , (7) hydrogen, and (8) -NR8R9; • 20 LB is selected from (1) a covalent bond (2) -O-, (3) -S (O) t-, (4) -NRß- 25 (5) -C (W) -, and (6) -C (= NR13) - wherein R13 is selected from (a) hydrogen, (b) -NO2, (c) -CN, and (d) -OR14 wherein R14 is selected from (i) hydrogen ( ii) aryl, and (ii) alkyl of one to ten carbons optionally substituted with 1 or 2 substituents independently selected from aryl and -C (O) R 15 wherein Ris is selected from hydrogen, -OH, alkoxy, and NRARB; is selected from (1) hydrogen (2) alkyl of one to ten carbons optionally substituted with 1, 2 or 3 substituents independently selected from (a) -CO2R7, (b) -NR8R9, (c) -C (W) NR8R9, (d) heterocycle, (e) aryl optionally substituted with 1 or 2 substituents independently selected from (f) alkyl of one to ten carbons, (ii) -NO2, and (iii) -NRARB, 5 (f) -OR? e wherein R is selected from (i) hydrogen and (i) - C (W) NRARB, and (g) -NRAC (W) NR8R9, (3) two to six carbon alkenyl optionally substituted with 10 1 or 2 substituents independently selected from (a) -C (W) NRARB, • (b) ) -CO2R7, and (c) heterocycle, (4) -NR17R18 wherein R7 and R18 are independently selected from (a) hydrogen, (b) alkyl of one to ten carbons optionally substituted with 1, 2 or 3 substituents independently selected from (i) -OH, • 20 (ii) -C (W) R10, (ii) -NRAC (= NR? 3) NRBRi9 wherein RA, RB and R13 are previously defined and R19 is selected from hydrogen, alkyl of one to ten carbons, and 25 -NO2, (iii) heterocycle, (iv) aryl, (v) halo, and (vi) -NRARB, 5 (c) alkoxy (d) aryl optionally substituted with 1, 2 or 3 substituents independently selected from (i) halo, (ii) ) alkyl of one to ten carbons, 10 (iii) akoxy of one to ten carbons, and (iv) perfluoroalkyl of one to three carbons, • (e) heterocycle, (9) -C (O) R20 wherein R20 is selected from 15 (i) hydrogen, (ii) alkyl of one to ten carbons, (iii) -OR12, and (h) cycloalkyl of three to ten carbons, and • 20 (i) -OH, (5) alkoxy, (6) -OH, (7) -NRAC (= NR13) NRBR? 9, (8) -C (W ) NR8R9, 25 (9) aryl (10) heterocycle, wherein (9) and (10) may be optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from (a) halo, • 5 (b) alkyl of one to ten carbons optionally substituted with 1, 2 or 3 substituents independently selected from (i) halo, (ii) alkoxy of one to ten carbons, (? v) -OH, • (v) -CO2R7, (vi) -C (W) NRARB, and (vii) aryl, 15 (c) -N RARB, (d) alkoxy of one to ten carbons, (e) ) thioalkoxy of one to ten carbons, (f) perfluoroalkyl of one to three carbons, (9) -OH, 20 (h) -C (W) NR8R9, (i) -CO2R7, (j) -NRAC (W) OR2 ? where RA is previously defined and R2? is selected from (i) alkyl of one to ten carbons optionally substituted with 1 or 2 substituents selected from aryl and cycloalkyl of three to ten carbons, (ii) aryl, and (iii) cycloalkyl of three to ten carbons 5 (k) alkenyl or two to ten carbons, (I) heterocycle, (m) aryl, (n) -NO2 , (11) -CN, 10 (12) -CHO, (13) halo, and • provided that when R ^ R2, R3, R and R5 are hydrogen or absent, -LA- is a covalent bond, and -LB- is a covalent bond, then one of XA and XB is different from hydrogen; and Ri, R2, R3, R and R5 are absent or independently selected from (1) hydrogen, (2) alkyl of one to six carbons optionally substituted with 1 • 20 or 2 substituents independently selected from (a) -OC (O) R22, wherein R22 is selected from (i) alkyl, (ii) alkoxy, and (viii) N RARB, 25 (b) alkoxy, (c) -OH, (e) heterocycle, and (f) aryl, • 5 (3) -CO2R7, (4) -C (O) N RARB, (5) -SR23 wherein R23 is selected from (a) hydrogen, (b) alkyl from one to six carbons, 10 (c) aryl optionally substituted with 1 or 2 substituents selected from (i) alkyl of one to six carbons and (ii) halo, 15 (7) halo, (8) alkoxy, (9) perfluoroalkyl of one to three carbons, (10) -OH, and (1 1) heterocycle, • 20 provided that when E, F, and Y are carbon, G is nitrogen, Z is sulfur, -LA- is a covalent bond and XA is halo, Ri is different from -CO 2 R 7.
2. 2. A compound according to claim 1, characterized in that F and Y are carbon, E and G are Independently nitrogen or N + -O ", and Z is S (O) t.
3. 3. A compound according to claim 2, selected from the group consists of methyl 2 - [(6-ethylthieno [2,3-d] pyrimidin-4-yl) thio] acetate, 6-ethyl-4 - [(4-methylphenyl) thio ] thieno [2,3-d] pyrimidine, • 5 6-etiI-4- (2-pyridinylthio) thieno [2,3-d] pyrimidine, 6-ethyl-4 - [(2-methylethyl) thio] thieno [ 2,3-d] pyrimidine, 6-etiI-4 - [(phenylmethyl) thio] thieno [2,3-d] pyrimidine, 6-ethyl-4 - [(5-methyl-1,3,4-tiad) azol-2-yl) thio] thieno [2,3-d] pyrimidine, ethyl 6-ethyl-4 - [(4-methylphenyl) thio] thieno [2,3-d] pyrimidine-6-carboxylate, 6- ethyl-N- (phenylmethyl) thieno [2,3-d] pyrimidin-4-amine, 6-ethyl-N- (5-methyl-1, 3,4-thiadiazol-2-yl) thieno [2,3- d] pyrimidine-4-amine, • 4 - [(5-amino-1,3,4-thiadiazol-2-yl) thiol-6-ethyl-2- (phenylmethyl) thieno [2,3-d] pyrimidine, 4-Chloro-6-ethyl-2- (phenylmethyl) thieno [2,3-d] pyrimidine, and 4 - [(5-amino-1, 3,4-thiadiazol-2-yl) thio] -6-ethyl -2- (phenylmethyl) thieno [2,3-d] pyrimidine.
4. 4. A compound according to claim 1, characterized in that F and Y are carbon, E and G are independently nitrogen or N + -O ", and Y is S (O) t
5. 5. A compound according to claim 4, selected from group consisting of • 20 7-methyl-4 - [(4-methylphenyl) thio] thieno [3,2-d] pyrimidine, 7-methyl-4 - [(5-methyl-1,3,4-thiadiazole- 2-yl) thio] thieno [3,2-d] pyrimidine, 7-methyl-4 - [[5- (methylthio) -1,3,4-thiadiazoI-2-yl) thio] thieno [3,2- d] pyrimidine, 4 - [(5-amino-1,3,4-thiadiazol-2-yl) thio] -7-methyltiene [3,2-d] pyrimidine, 7-methyl-N - [(4 - (methytthio) phenyl] thieno [3,2-d] pyrimidin-7-amine, 7-methyl-4 - [(4-methylphenyl) thio] thieno [3,2-d] pyrimidine-6-carboxamide.
6. 6. A compound according to claim 1, characterized in that F and Y are carbon, F is nitrogen or N + -O ", and Z is S (O) t
7. 7. A compound according to claim 6, • selected from the group consisting of methyl 4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridine-2-carboxylate, 4 - [(4-methylphenyl) thio] thieno acid [2,3-] c] pyridine-2-carboxylic acid, 4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridine-2-carboxamide, 4- (2-pyridinylthio) thieno [2,3-c] pyridine-2 -carboxamide, 10 4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridine-2-carboxamide, N-methoxy-N-methyl-4 - [(4-methylphenyl) thio3-thieno [2,3- c] pyridine-2-carboxamide, N-methoxy-4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridine-2-carboxamide, N- (4-chlorophenyl) -4 - [(4- methylphenyl) thio] thieno [2,3-c] pyridine-2-carboxamide, 4 - [(4-methylphenyl) thio] thieno (2,3-c] pyridine-2-carboxaldehyde, 4 - [(4-methylphenyl) thio] ] thieno [2,3-c] pyridine-2-carboxaldehyde, O-methyloxime, 4 - [(4-methylphenyl) thio] t-ene [2,3-c] pyridine-2-carboxaldehyde, O- (phenylmethyl) oxime, 2 - [[[4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridin-2-ylmethylene] amino] oxy] acetic acid, 4 - [(4-methylphenyl) thio] thieno ( 2,3-c] pyridine-2-carboxaldehyde, O-phenyloxime, 4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridine-2-ca rboxaldehyde, oxime, • 20 2 - [[[4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridine-2-ylmethyl] -amino] oxy] acetamide, (E) -3 - [( 4-methylphenyl) thio] thieno [2,3-c] pyridin-2-yl] -2-propenamide, 1- [4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridin-2- il] ethanone, 2-benzoyl-4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridine, 2-ethyl-4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridine, 1- [4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridin-2-yl] ethanone, oxime, N- (2,3-dihydroxypropyl) -4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridine-2-carboxamide, 4 - [(4-Methylphenyl) thio] thieno [2,3-c] pyridine-2-carboxylic acid, hydrazide, N2-4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridine -2-yl] carbonyl] -N6 - [(nitroamino) iminomethyl] -L-lysine, methyl ester, N- (aminoiminomethyl) -4 - [(4-methylphenyl) thio] thieno [2,3 -c] pyridine-2-carboxamide, 4 - [(4-rnethylphenyl) thio] t-ene [2,3-c] pyridine-2-carbothioamide, 4 - [(4-methylphenyl) thio] thieno [2,3 -c] pyridine, methyl 4 - [(2-methoxy-2-oxoethyl) thio] thieno [2,3-c] pyridine-2-carboxylate, 4 - [(2-amino-2-oxoethyl) thio] thieno [ 2,3-c] pyridine-2-carboxamide, 4 - [(4-bromophenyl) th] thieno [2,3-c] pyridine-2-carboxamide, 4- (phenylthio) thieno [2,3 -c] pyridine-2-carboxamide, 4 - [[4- (trifluoromethyl) phenyl] thio] thieno [2,3-c] pyridine-2-carboxamide, 4 - [(2-methylphenyl) thio] thieno [ 2,3-c] pyridine-2-carboxamide, 4 - [(3-methylphenyl) thio] thieno [2,3-c] pyridine-2-carboxamide, 4 - [(3,4-dimethylphenyl) thio] thieno ( 2,3-c] pyridine-2-carboxamide, 4 - [(3,5-dimethylphenyl) thio] thieno [2,3-c] pyridine-2-carboxamide, 4 - [(2,4-dimethylphenyl) thio] thieno [2,3-c] pyridine-2-carboxamide, 4 - [(2-met il-3-furanyl) thio] thieno [2,3-c] pyridine-2-carboxamide, 4 - [[(4-chlorophenyl) methyl] thio] thieno [2,3-c] pyridine-2-carboxamide, - [(3,4-dichlorophenyl) thio] thieno [2,3-c] pyridine-2-carboxamide, 4 - [(4-methoxyphenyl) thio] thieno [2,3-c] pyridine-2-carboxamide, - (cyclohexythio) thieno [2,3-c] pyridine-2-carboxamide, 4 - [(4-methylphenyl) thio] -N- [3- (4-morpholinyl) propyl] thieno [2,3-c] pyridine -2-carboxamide, trifluoromethylacetate salt, 4 - [(4-methylphenyl) sulfinyl] thieno [2,3-c] pyridine-2-carboxamide, methyl 4 - [(4-methylphenyl) sulfonylthieno (2,3-c] pyridine-2-carboxylate, 4- (4-methylphenoxy) thieno [2,3-c] pyridine-2-carboxamide, methyl 4 - (4-methylphenoxy) thieno [2,3-c] pyridine-2-carboxylate, 4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, • 5-methyl-4- (4-chlorophenoxy) ) thieno [2,3-c] pyridine-2-carboxylate, 4- [4- (trifluoromethyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 4- (4-octylphenoxy) thieno [2I3- c] pyridine-2-carboxamide, 4-. {4- (1-methylethyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 4- (2-bromo-4-chlorophenoxy) thieno [2 , 3-c] pyridine-2-carboxamide, 4- (4-ethylphenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-ethenyl-phenoxy) thieno (2,3-c) pyridine- 2-carboxamide, 4 ^ 4- (1,2-dihydroxyethyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 4- [2- (2-propenyl) phenoxy] thieno [2,3 -c] pyridine-2-carboxamide, 4- [2- (2,3-dihydroxypropyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 4- [4- (trifluoromethyl) phenoxy] thieno [ 2,3-c] pyridine-2-carboxamide, 1-oxide, 4- [3- (pentadecyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 4- (4-bromophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (3-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-t-butylphenoxy) ) thieno [2,3-c] pyridine-2-carboxamide, • 4- (4-chloro-3-methylphenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-chloro-2) -methylphenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-methoxyphenoxy) thieno [2,3-c] pyridine-2-carboxamide, ethyl 3 - [[2- (aminocarbonyl) t] eno [2,3-c] pyridin-4-yl] oxy] benzoate, 4-phenoxythieno [2,3-c] pyridine-2-carboxamide, 4- (3-Bromophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-Fluorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (3,5-dimethylphenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (3-chloro) -4-methylphenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-iodophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4- (methoxymethyl) phenoxy) thieno [2,3-c] pyridine-2-carboxamide, 2- (aminocarbonyl) -4- (4-chlorophenoxy) thieno [2,3-c] pyridinium, iodide, 4- (4-chlorophenoxy) thieno [2] , 3-c] pyridine-2-carboxylic acid, N- (4- (4-Chlorophenoxy) thieno [2,3-c] pyridin-2-yl) -O- (3-tetrahydrofuranyl) carbamate, 4- (4- Chlorophenoxy) thieno [2,3-c] pyridine-2-methanol, (E) -3- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -2-propenoic acid, 4- (4-Chlorophenoxy) thieno [2,3-c] pyridine-2-carboxaldehyde, (E) -3- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] - 2-propenamide, 4-bromothieno [2,3-c] pyridine-2-.carboxamide, methyl 4-bromothieno [2,3-c] pyridine-2-carboxylate, 4-chlorothieno [2,3-c] pyridine-2-carboxamide, 4- [4- (trifluoromethyl) phenyl] thieno [2,3-c] pyridine-2-carboxamide, methyl 4- [4- (trifluoromethyl) phenyl] thieno [2, 3-c] pyridine-2-carboxylate, N-methyl-4- [4- (trifluoromethyl) phenyl] thieno [2,3-c] pyridine-2-carboxamide, 4-phenylthieno [2,3-c] pyridine -2-carboxamide, methyl 4-phenylthieno [2,3-c] pyridine-2-carboxylate, 4 - ([1,1'-biphenyl] -4-ylthio) thieno [2,3-c] pyridine-2- carboxamide, 4- (5-formyl-2-furanyl) thieno [2,3-c] pyridine-2-carboxamide, ethyl 4-p2- (aminocarbonyl) thieno [2,3-c] pyridin-4-yl] oxy ] benzoate, 4 - [[2- (aminocarbonyl) thieno [2,3-c] pyridin-4-yl] oxy] benzoic acid, 4- (1-phenylethenyl) thieno [2,3-c] pyridine-2- carboxamide, methyl 4- (1-phenylethenyl) thieno [2,3-c] pyridine-2-carboxylate, 4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridine-2-methanol, 4- (4-Chlorophenoxy) -N-methylthieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) -N, N-dimethylthieno [2,3-c] pyridine-2-carboxamide, 5 - (4-chlorophenoxy) -N, N-diethylthieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) -N-cyclopropyl-thieno [2,3-c] pyridine-2-carboxamide, - [[4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] carbonyl] pyrrolidine, 1 - [[4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2] -yl] carbonyl] piperidine, 4 - [[4- (4-chlorophenoxy) thien [2,3-c] pyridin-2-yl] carbonyl] morpholine, 10 1 - [[4- (4- chlorophenoxy) thieno [2,3-c] pyridin-2-yl] carbonyl] -4-methylpiperazine, 1 - [[4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] carbonyl] -4-phenyl] piperazine, • 1 - [[4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] carbonyl] -4- (phenylmethyl) -piperazine, 1- [[4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] carbonyl] -4- (2-pyridinyl) -piperazine, 4- (4-chlorophenoxy) -N- (2-hydroxyethyl) ) lt-ene [2,3-c] pyridine-2-carboxamide, 15 4 - [[4 - (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] carbonyl] -N- (1-methylethyl) -1-piperazineacetamide, trifluoroacetate salt, 4- (4-chlorophenoxy) -N- [ 1- (hydroxymethyl) ethyl] thieno [2,3-c] pyridine-2-carboxamide, 4- (4-cyranophenoxy) -N- [1,1-bis (hydroxymethyl) ethyl] thieno [2,3- c] pyridine-2-carboxamide, (D, L) -4- (4-chlorophenoxy) -N- (2-hydroxypropyl) thieno [2,3-c] pyridine-2-carboxamide, • 20 4- (4-chlorophenoxy) -N- [2- (4-morpholinyl) ethyl] thieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) thieno [2,3-c] ] pyridine-2-sulfonamide, 4- (4-morpholinyl) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, N -oxide, methyl (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxylic acid, N-oxide, 4- (4-chlorophenoxy) -2- (2-methoxyphenyl) thieno [2,3-] c] pyridine, 4- (4-chlorophenoxy) thieno [2,3-c] pyridine, 4- (4-chlorophenoxy) -3-methylthieno [2,3-c] pyridine-2-carboxamide, methyl 4- (4-chlorophenoxy) ) -3-methylthieno [2,3-c] pyridine-2-carboxylate, 3-amino-4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 5-methyl-3-amino-4 - (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxylate, 3-amino-4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxylic acid, 4- (4 -chlorophenoxy) thieno [2,3-c] pyridine-2-carbothioamide, 4- (4-chlorophenoxy) -N-ethyIthieno [2,3-c] pyridine-2-cartidoxamide, 4- (4-chlorophenoxy) -N- (2,3-dihydroxypropyl) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-bromophenoxy) -N- (2,3-dihydroxypropyl) thieno [2,3-c] pyridine-2-carboxamide, N- (2-chloroethyl) -4- (4-chlorophenoxy) t-ene [2,3-c] pyridine-2-carboxamide, ** ^ ß- 4- (4-bromophenoxy) - N- (2-hydroxyethyl) thieno [2,3-c] pyridine-2-carboxamide, 4- (2-bromo-4-cyranophenoxy) -N- (2-hydroxyethyl) thieno [2,3-c] pyridine- 2-carboxamide, N- (2-hydroxyethyl) -4- [4- (trifluoromethyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, N- (2-aminoethyl) -4- (4- chlorophenoxy) t ieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) -N-hydroxythieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) thieno [2,3 -c] pyridine-2-carbohydrate, 4- (4-bromophenoxy) thieno [2,3-c] pyridine-2-carbohydrate, 4- [4- (trifluoromethyl) phenoxy] thieno [2,3-c] pyridine -2-carbohydrate, • 4- (4-chlorophenoxy) -N-hydrox'-thieno [2,3-c] pyridine-2-carboxamide, 2- (. { [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] carbonyl} amino) acetic, N- (2-amino-2-oxoethyl) -4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, N- (2-amino-2-oxoethyl) -4 - (4-bromophenoxy) thieno [2,3-c] pyridine-2-carboxamide, (2S) -2- ( { [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2) -yl] carbonyl.}. amino) -3- 25 hydroxypropanoic, N - [(1S) -2-amino-1- (hydroxymethyl) -2-oxoethyl] -4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, Acid (2R) -2- ( { [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] carbonyl) amino) -3-hydroxypropanoic, • 5 Acid (2R) -2- ( { [4 - (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] carbonyl] amino) propane, 4- (4-chlorophenoxy) -N - [(1R) -1-methyl-2- (methylamino) -2-oxoethyl] thieno [2,3-c] pyridine-2-carboxamide, (2S) -2- ( { [4- (4-chlorophenoxy) thieno [2,3-c3pyridin-2-yl]] carbonyl.) amino) propanic, 4- (4-chlorophenoxy) -N - [(1S) -1-methyl-2- (methylamino) -2-oxoethyl] thieno [2,3-c] pyridine-2- 10 carboxamide, 4- (4-chlorophenoxy) -N - [(1R) -1- (hydroxymethyl) -2- (methylamino) -2-oxoethyl] thieno [2, 3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) -N - [(1S) -1- (hydroxymethyl) -2- (methylamino) -2-oxoethyl] thieno [2,3-c] pyridine-2-carboxamide, 4- (3-pyridinyloxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-bromophenoxy) -N-methylthieno [2,3-c] pyridine-2- carboxamide, 4- (4-bromophenoxy) -N, N-dimethylthieno [2,3-c] pyridine-2-carboxamide, N, N-dimethyl-4- [4- (trifluoromethyl) phenoxy] thieno [2,3- c] pyridine-2-carboxamide, 4- (4-chloro-3-fluorophenoxy) -N-methylthieno [2,3-c] pyridine-2-carboxamide, • 4- (4-chloro-3-fluorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-chloro-3-ethylphenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (3-fluorophenoxy) thieno [2] 3 -c] pyridine-2-carboxamide, 4- (2,3-difluorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (2,3-difluorophenoxy) -N-methylthieno [2,3- c] pyridine-2-carido D-xamide, 4- (3-fluorophenoxy) -N-methylthieno [2,3-c] pyridine-2-carboxamide, N-methyl-4- (2,3,4-trifluorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (2,3,4-trifluorophenoxy) thieno [2,3-c] pyridine- 2-carboxamide, N-methyl-4- [4- (trifluoromethyl) phenoxy] thieno [2,3-cjpyridine-2-carboxamide, 4-. { 3- (trifluoromethyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 5 N, N-dimethyl-4- (4-vinylphenoxy) thieno [2,3-c] pyridine-2-carboxamide, - (4-cyanophenoxy) -N-methylthieno [2,3-c] pyridine-2-carboxamide, 4- (4-cyanophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-aminophenoxy) ) thieno [2,3-c] pyridine-2-carboxamide, 4- [4- (acetylamino) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 10 N-methi-4- [4 - (4-morpholinyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 4- [4- (hydroxymethyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, • 4- [ 4- (hydroxymethyl) phenoxy] -N-methylthieno [2,3-c] pyridine-2-carboxamide, 4- [4- (methoxymethyl) phenoxy] -N-methylthieno [2,3-c] pyridine-2-carboxamide , 4-. { 4 - [(2-methoxyethoxy) methyl] phenoxy} thieno [2,3-c] pyridine-2-carboxamide, 4-. { 4 - [(2-methoxyethoxy) methyl] phenoxy} -N-methytieno [2,3-c] pyridine-2-carboxamide, 4- (4- { [2- (2-methoxy-ethoxy) ethoxy] methyl} phenoxy) thieno [2,3-c] ] pyridine-2-carboxamide, 4- (4-. {[2- (2-methoxyethoxy) ethoxy] methyl} phenoxy) -N-methylthieno [2,3-c] pyridine-2-carboxamide, 4-. { 4 - [(Tetrahydro-2H-pyran-2-yloxy) methyl] phenoxy} thieno [2,3-c] pyridine-2-carboxamide, • 20 N-methyl-4-. { 4-I (tetrahydro-2H-pyran-2-yloxy) methyl] phenoxy} thieno (2,3-c) pyridine-2-carboxamide, 4-. {I2- (aminocarbonyl) thieno [2,3-c] pyridin-4-yl] oxy} benzyl 2-furoate, 4- [ 4- ( { [(2R, 4R, 5S, 6RH, 5-Dihydroxy-6- (hydroxymethyl) tetrahydro-2H-pyran-2-yl] oxy} methyl) phenoxy] -N-methylthieno [ 2,3-c] pyridine-2-carboxamide, 4- (4-acetylphenoxy) -N-methylthieno [2,3-c] pyridine-2-carboxamide, 4- [4- (4-morpholinylcarbonyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, N-methyl-4- [4- (4-morpholinylcarbonyl) phenoxy] thieno [ 2,3-c] pyridine-2-carboxamide, 4- [4- ( { [2- (4-morpholinyl) ethyl] amino} carbonyl) phenoxy] thieno [2,3-c] pyridine-2 -carboxamide, • 5 N-methyl-4- [4- ( { [2- (4-morpholinyl) ethyl] amino} carbonyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 4-. { 4 - [(E) -3- (4-morpholinyl) -3-oxo-1-propenyl] phenoxy} thieno [2,3-c] pyridine-2-carboxamide, 4- [4 - ((E) -3- { [2- (4-morpholinyl) ethyl] amino.} - 3-oxo-1-propenyl) phenoxy] thieno [2,3-c] pyridine- 2-carboxamide, 10 N-metii-4- [4 - ((E) -3- { [2- (4-morpholinyl) ethyl] amino.} - 3-oxo-1 -propenyl) phenoxy] thieno [2,3- c] pyridine-2-carboxamide, 4- (4- { (E) -3 - [(2,3-dihydroxypropyl) amino] -3-oxo-1-propenyl.) Phenoxy ) thieno (2,3-c) pyridine-2-carboxamide, 4- (4- { (E) -3 - [(2,3-dihydroxypropyl) amino] -3-oxo-1-propenyl}. phenoxy) -N-methyltiene [2,3- 15 c] pyridine-2-carboxamide, 4- [4 - ((E) -3- { [2- (1 H-imidazol-4-yl) ethyl] amino.}. 3-oxo-1-propenyl) phenoxy] -N-methylthieno [2,3-c] pyridine-2-carboxamide, 4- { 4 - [(E) -3- ( {2- [bis (2-hydroxyethyl) amino) -1-3-oxo-1-propenyl] phenoxy} - N-methylthieno [2,3-c] pyridine-2-carboxamide, • 4- {4 - [(E) -3- (. {2- [bis (2-hydroxyethyl) amino] ethyl} amino) -3-oxo-1-propenyl] thieno [2,3-c] pyridine -2-carboxamide, 4- [4- (1H-imidazol-1-yl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, N-methyl-4- [4- (1H-pyrazole-1 -yl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, N-methyl l-4- [4- (1 H-1, 2,4-triazoM-yl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, N-methyl-4- [4- [5- (trifluoromethyl) -1,2,4-oxadiazol-3-yl] phenoxy} thieno [2,3-c] pyridine-2-carboxamide, 4- [4- (4,5-dihydro-1H-imidazol-2-yl) phenoxy] -N-methylthieno [2,3-c] pyridine-2 -carboxamide, N-methyl-4- [4- (2-thienyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 4 - ([1,1 '-biphenyl] -ilox-N-methylthienoP.S- Cypyridine ^ -carboxamide, N-methyl-4- [4- (1-methyl-1H-imidazoi-5-yl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 4-. {4- [1- (hydroxymethyl) cyclopropyl] phenoxy] -N-methylthieno [2,3-c] pyridine-2-carboxamide, 4- [4- (1- { [2- (2-ethoxyethoxy) ethoxy] methyl.}. Cyclopropyl) phenoxy] -N-methylthienot2,3-c] pyridine-2-carboxamide, N-methyl- 4- [4- (trifluoromethoxy) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 5-. { 4- [4- (1- { [2- (2-ethoxyethoxy) ethoxylmethi.} Cyclopropyl) phenoxy] thieno [2,3-c] pyridin-2-yl} -1,4,4-oxadiazol-2-amine, 4- [4- (1,1-difluoro-2-hydroxyethyl) phenoxy] N-methylthieno [2,3-c] pyridine-2-carboxamide, 4- ( 4- { - [2- (2-ethoxyethoxy) ethoxy] -1, 1-difluoroethyl.} Phenoxy) -N-methytieno [2, 3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) -6 - [(2,2-dimethylpropanoyl) oxy] methyl) -2-. { (methylamino) carbonyl] thieno [2,3-c] pyridin-6-io, 4- (4-bromophenoxy) -6-. { [(2,2-dimethylpropanoyl) oxylmethyl} -2 - [(methylamino) carbonyl] -thieno [2,3-c] pyridin-6-io, 2- (aminocarbonyl) -4- (4-chlorophenoxy) -6-. { [(isopropoxycarbonyl) oxy] methyl} thieno [2,3-c] pyridin-6-io, 4- (benzyloxy) thieno [2,3-c] pyridine-2-carboxamide, 4-I (4-chlorophenyl) (hydroxy) methyl] thieno [ 2,3-c] pyridine-2-carboxamide, 4- (4-chlorobenzoyl) -N-methylthieno [2,3-c] pyridine-2-carboxamide, N - (4-chlorophenyl) thieno [2,3-c] pyridine-2,4-dicarboxamide, [4- (4-bromophenoxy) thieno [2,3-c] pyridin-2-yl] methanol, 4- ( 4-bromophenoxy) thieno [2,3-c] pyridine-2-carbaldehyde, oxime 4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carbaldehyde, 4- (4-chlorophenoxy) thieno [2 , 3-c] pyridine-2-carbaldehyde O-methyloxime, 1 - [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -1-ethanone O-methyloxime, 1 - [4 - (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -1-ethanone O-methyloxime, oxime 1 - [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2 -yl] -1-ethanone, oxime 1- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -1-ethanone, 1 - [4- (4-chlorophenoxy) thieno [ 2,3-c] pyridin-2-yl] -1-propanone, oxime 1- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -1-propanone, 2- [ 4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -N-methoxy-N-methyl-2-oxoacetamide, 4- (4-chlorophenoxy) thieno [2,3-c] pyridine -2-carbonitrile, 4- (4-chlorophenoxy) -N, -hydroxythieno [2,3-cjpyridine-2-carboximidamide, 4- (4-chlorophenoxy) -N, -cyanothieno [2,3-c] pyridine-2 -carboximidamide, [4- (4-chlorophenoxy) t-ene [2,3-c] pyridin-2-i l] (2-nitrophenyl) methanol, [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] (2-nitrophenyl) methanone, (2-aminophenyl) [4- (4-chlorophenoxy ) thieno [2,3-c] pyridin-2-yl] methanone, (2-aminophenyl) [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] methanol, [4- ( 4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] (3-nitrophenyl) methanol, (3-aminophenyl) [4- (4-chlorophenoxy) thieno [2,3-c] pyridine) n-2-yl] methanone, (3-aminophenyl) [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] methanol, 4- (4-bromophenoxy) -2-vinyl thieno [2,3-c] pyridine, 1- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -1,2-ethanediol, 1- [4- (4-bromophenoxy) thieno [2,3-c] pyridin-2-yl] -1,2-ethanediol, [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2 -yl] methanamine, [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] methyl carbamate, N-YJ4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2 -il] methyl} urea, • 5 (E) -3- [4- (4-bromophenoxy) thieno [2,3-c] pyridin-2-yl] -2-propenamide, (E) -3- [4- (4-bromophenoxy ) thieno [2,3-c] pyridin-2-yl] -N-methyl-2-propenamide, 3- [4- (4-bromophenoxy) thieno [2,3-c] pyridin-2-yl] -2 , 3-dihydroxy-N-methylpropanamide, 4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-ylamine, 4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-ylformamide , 10 N- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] urea, N- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2 -yl] -N'-methylthiourea, • 4- (4-chlorophenoxy) -N-methylthieno [2,3-c] pyridine-2-sulfonamide, 4- (4-chlorophenoxy) -N- (2,3-dihydroxypropyl) ) thieno [2,3-c] pyridine-2-sulfonamide, 4- (4-chlorophenoxy) -N- (2-hydroxyethyl) thieno [2,3-c] pyridine-2-sulfonamide, 4- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] phenol, 3- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] aniline, 4- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] aniline, 4- (4-chlorophenoxy) -2- (5-nitro-2-pyridinyl) thieno [2,3-c] ] pyridine, 6- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -3-pyridinamine, 5-I4- (4-chlorophenoxy) thieno [2,3- c] pyridin-2-yl] -2-pyridinamine, 5- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -1, 3,4-oxadiazole-2- amine, 5- [4- (4-bromophenoxy) thieno [2,3-c] pyridin-2-yl] -1,4,4-oxadiazol-2-ylamine, S - ^^ - chiorofen? xiJtienop.S- Cjpyridin-1-yl ^ Hl ^^ - triazol-S-amine, 5- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -1) 3,4-thiazole- 2-amine, 4- (4-chlorophenoxy) -2- (5-methyl-1, 2,4-oxadiazol-3-yl) thieno [2,3-c] pyridine, 5-. { 4- [4- (trifluoromethyl) phenoxy] t-ene [2,3-c] pi? Idin-2-yl} -1,3,4-oxadiazol-2-amine, 4- (4-chlorophenoxy) -2- [5- (methylsulfanyl) -1,4,4-oxadiazol-2-yl] thieno [2,3-c] pyridine, 4- (4-chlorophenoxy) -2- (2-methyl-2H-1,2,3,4-tetrazol-5-yl) thieno [2,3-c] pyridine, 5- [4- (4 -chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -4-methyl-4H-1,2,4-riazol-3-yl-amine, 4- (4-chlorophenoxy) -2- [5- (trifluoromethyl) -1,4,4-oxadiazol-3-yl] thieno [2,3-c] pyridine, 5- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2- il] -1,2,4-oxadiazol-3-amine, 5- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -N-methyl-1,3,4- thiadiazol-2-amine, 4- (4-chlorophenoxy) -2- (1, 2,4-oxadiazol-3-yl) thieno [2,3-c] pyridine, 2- (1-J3,4-oxadiazole-2 -yl) -4- [4- (trifluoromethyl) phenoxy] thieno [2,3-c] pyridine, • 3- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -1,2,4-oxadiazol-5-amine, 2- (5-methyl-1,3,4 -oxadiazol-2-yl) -4- [4- (trifluoromethyl) phenoxy] thieno [2, 3- cypyridine, 15 methyl 2- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -1,3-thiazole-4-carboxylate, 2- [4- (4- chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -1,3-thiazole-4-carboxamide, tert-butyl 2- [4- (4-chlorophenoxy) thieno [2,3-c] pyridine- 2-yl] -1,3-thiazole-4-iicarbamate, 2- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -1,3-thiazoI-4-amine, • 20 4-chloro-3-methylthieno [2,3-c] pyridine-2-carboxamide, 3-amino-4-ciorothieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) - N, 3-dimethylthieno [2,3-c] pyridine-2-carboxamide, 4- (4-bromophenoxy) -3-methylthieno [2,3-c] pyridine-2-carboxamide, 7-cloiO-4- (4 -chlorophenoxy) -3-methylthieno [2,3-c] pyridine-2-carboxamide, tert-butyl 2- (aminocarbonyl) -4- (4-cyranophenoxy) thieno [2,3-c] pyridine-3- carboxylate, N-methyl-4- (4-toluidino) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-chloroanilin) -N-methylthieno [2,3-c] pyridine-2 -carboxamide, N-methyl-4- (4-morfoinyl) thieno [2,3-c] pyridine-2-carboxamide, • 5-7-chloro-4- (4-chlorophenoxy) thieno [2,3-c] pyridine -2-carboxamide, 7-chloro-4- (4-chlorophenoxy) -N-methylthieno [2,3-c] pyridine-2-carboxamide, 7-chloro-4- (4-chlorophenoxy) -N- (2- hydroxyethyl) thieno [2,3-c] pyridine-2-carboxamide, 7-bromo-4- (4-chlorophenoxy) thieno [2,3-c3pyridine-2-carboxamide, 7-bromo-4- (4-chlorophenoxy) -N-methylthieno [2,3-c] pyridine-2-carboxamide, 4- (4-bromophenoxy) -7-chlorothieno [2,3-c] pyridine-2-carboxamide, 4- (4-bromophenoxy) - 7-Chloro-N-methylthieno [2,3-c] pyridine-2-carboxamide, • 7-chloro-4- [4- (trifluoromethyl) phenoxy] thieno [2,3-c3pyridine-2-carboxamide, 7-chloro -N-methyl-4- [4- (trifluoromethyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 7-chloro-N- (2-hydroxyethyl) -4- [4- ( trifluoromethyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) -N, 7-dimethylthieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) -7-methoxy-thieno [2,3-c] pyridine-2-carboxamide 4- (4-chlorophenoxy) -N-methyl-7- (methylamine) thieno [2,3-c] pyridine-2-carboxamide, 4 - [(E) -2-phenylethenyl] thieno [2,3-c] ] pyridine-2-carboxamide, • 4- (4-chlorophenyl) thieno [2,3-c] pyridine-2-carboxamide, 4- [3- (trifluoromethyl) phenyl] thieno [2,3-c] pyridine- 2-carboxamide, 4- (3-chlorophenyl) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-bromophenyl) thieno [2,3-c] pyridine-2-carboxamide, 4- (3 -aminophenyl) thieno [2,3-c] pyridine-2-carboxamide, 4- (3,5-dichlorophenyl) thieno [2,3-c] pyridine-2-carboxamide, 4- (2,4-dichlorophenyl) thieno [2,3-c] pyridine-2-carboxamide, 4- (3,4-dichlorophenyl) thieno [2,3-c] pyridine-2-carboxamide, 4- (2,4-difluorophenyl) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-fluorophenyl) thieno [2,3-c] pyridine-2-carboxamide, and 4- (4-bromophenoxy) -5-chlorothieno [2,3-c] pyridine-2-carboxamide. A compound according to claim 1, characterized in that E, F, and Y are carbon, G is nitrogen or N + -O-, and Z is S (O) t. 9. A compound according to claim 8, selected from the group consisting of 4 - [(4-methylphenyl) thio] thieno [2,3-b] pyridine, 44 (4-methylphenyl) thio] thieno [2,3-b] ] pyridine-2-carboxamide, 4-chloro-N- (4-chlorophenyl) thieno [2,3-b] pyridine-5-carboxamide, ethyl 4 - [(5-methyl-1,3,4-thiadiazole-2 -yl) thio] thieno [2,3-b] pyridine-5-carboxylate, methyl 6 - [(4-methylphenyl) thio] thieno [2,3-b] pyridine-2-carboxylate, methyl 3-amino-6 -chlorotiene [2,3-b] pyridine-2-carboxylate. 10. A compound according to claim 1, characterized in that E, F, and Z are carbon, G is nitrogen or N + -O ", and And it is S (O) t. 1 1. A compound according to claim 10, which is 7 - [(4-methylphenyl) th] thieno [3,2-b] pyridine-2-carboxamide. 12. A compound according to claim 1, characterized in that F, G and Y are carbon, E is nitrogen or N + -O ", and And it is S (O) t. 13. A compound according to claim 12, selected from the group consisting of 2-bromo-4 - [(4-methylphenyl) thio] thieno [3,2-c] pyridine, 4 - [(4-methylphenyl) thio] thieno [3,2-c] pyridine- 2-carboxamide, 4 - [(4-methylphenyl) thio] thieno (3,2-c] pyridine-2-carbonitrile, • 4- (4-Methylphenoxy) thieno (3,2-c) pyridine-2-carboxamide , and 4- (4-Methylphenoxy) thieno [3,2-c] pyridine-9-carbonitrile, 14. A compound according to claim 1, characterized in that E and G are carbon, F and Y are independently nitrogen or N + -O ", and Z is S (O) t 10 1 5. A compound according to claim 14 selected from the group consisting of methyl 7- (4-methylphenoxy) [1, 3] thiazoI [5,4-c] pyridine- 2-carboxylate, 7- (4-methylphenoxy) [1, 3] thiazolo [5,4-c] pyridine-2-carboxamide, and.}. N -methyl-7- (4-methylphenoxy) [1, 3] thiazolo [5,4-c] pyridine-2-carboxamide 16. A compound according to claim 1, characterized in that E and G are carbon, F is nitrogen or N + -O ", Y and Z are nitrogen. compound according to claim 1, characterized in that G and Y are carbon, E and F are • independently nitrogen or N + -O ", and Z is S (O) t 1
8. 8. A compound according to claim 1, characterized in that E, G and Z are carbon, F is nitrogen or N + -O", and Y is SW),. 1
9. 9. A compound according to claim 1, characterized in that E and G are carbon, F is nitrogen or N + -O ", Y is nitrogen and Z is oxygen. 20. A compound according to claim 1, characterized in that E, G and Y are carbon, F is nitrogen or N + -O ", Y is nitrogen and Z is O. 21 21. A compound according to claim 20 selected from the group consisting of of 4- (4-chlorophenoxy) furo [2,3-c] pyridine-2-carboxamide, and 4- (4-chlorophenoxy) furo [2,3-c] pyridine-2-carbothioamide, 22. A compound selected from group consisting of 10 methyl 2 - [(6-ethylthieno [2,3-d] pyrimidin-4-yl) thio] acetate, • 6-ethyl-4 - [(4-methylphenyl) thio] thieno [2,3 -d] pyrimidine, 6-etl-4- (2-pyridinylthio) thieno [2,3-d] pyrimidine, 6-ethyl-4 - [(2-methyl-ethyl) thio] thieno [2,3- d] pyrimidine, 15 6-ethyl-4 - [(phenylmethyl) thio] thieno [2,3-d] pyrimidine, 6-ethyl-4 - [(5-methyl-1, 3,4-thiadiazol-2-yl ) thio] thieno [2,3-d] pyrimidine, ethyl 6-ethyl-4 - [(4-methylphenyl) thio] thieno [2,3-d] pyrimidine-6-carboxylate, 6-ethyl-N- (phenylmethyl) ) thieno [2,3-d] pyrimidin-4-amine, 6-ethyl-N- (5-methyl-1,3,4-thiadiazol-2-yl) thieno [2,3-d] pyrimidine- 4-amino, # 20 4 - [(5-amino-1,3,4-thiadiazol-2-yl) thiol-6-ethyl-2- (fe nylmethyl) thieno [2,3-d] pyrimidine, 4-chloro-6-ethyl-2- (phenylmethyl) thieno [2,3-d] pyrimidine, 4 - [(5-amino-1, 3,4-thiadiazole -2-yl) thio] -6-ethyl-2- (phenylmethyl) thieno [2,3-d] pyrimidine, 7-methyl-4 - [(4-methylphenyl) thio] thieno [3,2-d] ] pyrimidine, 7-methyl-4 - [(5-methyl-1,3,4-thiadiazol-2-yl) thio] thieno [3,2-d] pyrimidine, 7-methyl- - [[5- ( metiitio) -1,3,4-thiadiazol-2-yl) thio] thieno [3,2-d] pyrimidine, 4 - [(5-amino-1,3,4-thiadiazol-2-yl) thio] -7-methylthieno [3,2-d] pyrimidine, 7-methyl-N - [(4- (methylthio) phenyl] thieno [3,2-d] pyrimidin-7-amine, 7-methyl-4 - [(4-methylphenyl) thio] thieno [3,2-d] pyrimidine-6-carboxamide, methyl 4 - [(4-methylphenyl)] ) thio] thieno [2,3-c] pyridine-2-carboxylate, • 5 4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridine-2-carboxylic acid, 4 - [( 4-methylphenyl) thio] thieno [2,3-c] pyridine-2-carboxamide, 4- (2-pyridinylthio) thieno [2,3-c] pyridine-2-carboxamide, 4 ^ (4-chlorophenyl) thio] thieno [2,3-c] pyridine-2-carboxamide, N-methoxy-N-methyl-4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridine-2-carboxamide, 10 N-methoxy -4 - [(4-methylphenyl) thiojthieno [2,3-c] pyridine-2-carboxamide, N- (4-chlorophenyl) -4 - [(4-methylphenyl) th] thieno [2,3-c] ] pyridine-2-carboxamide, ^ m 4 - [(4-methylphenyl) thio] thieno (2,3-c] pyridine-2carboboxaldehyde, 4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridine-2-carboxaldehyde, O- Methyloxime, 4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridine-2-carboxyIdehyde, O- (phenylmethyl) oxime, 15 2- [. { [4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridin-2-ylmethylene] amino] oxy] acetic acid, 4 - [(4-methylphenyl) thio] thieno (2,3-c) pyridine -2-carboxaldehyde, O-phenyloxime, 4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridine-2-carboxaldehyde, oxime, 2 - [[[4 - [(4-methyphenyl) thio]] thieno [2,3-c] pyridin-2-ylmethylene] -amino] oxy] acetamide, (E) -3 - [(4-methylphenyl) thio] thieno [2,3-c] pyridin-2-yl] - 2-propenamide, F 20 1 - [4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridin-2-yl] ethanone, 2-benzoyl-4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridine, 2-ethyl-4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridine, 1 -. {4 - [(4-methylphenyl) th]] thieno [2,3-c] pyridin-2-yl] ethanone, oxime, N- (2,3-dihydroxypropyl) -4 - [(4-rnethylphenyl) thio] t-ene [2,3-c] pyridine- 2-carboxamide, 25 4 - [(4-Methylphenyl) thio] thieno [2,3-c] pyridine-2-carboxylic acid, hydrazide, N -4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridin-2-yl] carbonyl] -N6 - [(n -troamino) imnomethyl] -L-lysine, methyl ester, N- (aminoiminomethyl) -4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridine-2-carboxamide, 4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridine-2-carbothioamide, 4 - [(4-methyphenyl) thio] thieno [2,3-c] pyridine, methyl 4 - [(2-methoxy-2-oxoethyl) thio] thieno [2,3 -c] pyridine-2-carboxylate, 4 - [(2-amino-2-oxoethyl) thio] t-ene [2,3-c] pyridine-2-carboxamide, 4 - [(4-bromophenyl) thio] thieno [2,3-c] pyridine-2-carboxamide, 4- (phenylthio) thieno [2,3-c] pyridine-2-carboxamide, 4 - [[4- (trifluoromethyl) phenyl] thio] thieno [2,3 -c] pyridine-2-carboxamide, 4 - [(2-methylphenyl) thio] thieno [2,3-c] pyridine-2-carboxamide, 4 - [(3-methylphenyl) thio] thieno [2,3 -c] pyridine-2-carboxamide, 4 - [(3,4-dimethylphenyl) th] thieno (2,3-c] pyridine-2-carboxamide, 4 - [(3,5-dimethylphenyl) thio] ] thieno [2,3-c] pyridine-2-carboxamide, 4 - [(2,4-dimethylphenyl) thio] thieno [2,3-c] pyridine-2-carboxamide, 4 - [(2-methyl-3-furanyl) thio] thieno [2,3-c] pyridine-2-carboxamide, 4 - [[(4-chlorophenyl) methyl] thio] thieno [2,3-c] pyridine-2-carboxamide, 4 - [(3,4-dichlorophenyl) thio] thieno [2,3-c] pyridine-2-carboxamide, 4 - [(4-methoxyphenyl) thio] thieno [2,3-c] pyridine-2-carboxamide, 4- (cyclohexylthio) thieno [2,3-c] pyridine-2-carboxamide, 4 - [(4-methylphenyl) thioj-N- [3- (4-morpholinyl) propyl] thieno [2,3-c] pyridine-2-carboxamide, trifluoromethyl acetate salt, 4 - [(4-methylphenyl) sulfinyl] thieno [2,3-c] pyridine-2-carboxamide, methyl 4 - [( 4-methylphenyl) sulfinyl] thieno (2,3-c] pyridine-2-carboxylate, 4- (4-methylphenoxy) thieno [2,3-c] pyridine-2-carboxamide, methyl 4- (4-methylphenoxy) thieno [2,3-c] pyridine-2-carboxylate, 4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, methyl 4- (4-chlorophenoxy) ) thieno [2,3-c] pyridine-2-carboxylate, 4- [4- (trifluoromethyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, • 5- 4- (4-octylphenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- [4- (1-methylethyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, - (2-bromo-4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-ethylphenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4- etenylphenoxy) thieno (2,3-c) pyridine-2-carboxamide, 4- [4- (1, 2-dihydroxyethyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 4- [2- (2-propenyl) phenoxy] thieno [2I3-c] pyridine-2-carboxamide, # 4- [2- (2) 3-dihydroxypropyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 4- [4- (trifluoromethyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 1-oxide, 4- [3- (pentadecyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 15 4- (4-bromophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (3-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-t) -butylphenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-chloro-3-methylphenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-chloro-2 -methylphenoxy) thieno [2,3-c] pyridine-2-carboxamide, • 4- (4-methox "? phenoxy) thieno [2,3-c] pyridine-2-carboxamide, ethyl 3 - [[2- ( aminocarbonyl) thieno [2,3-c] pyridin-4-yl] oxy] benzoate, 4-phenoxythieno [2,3-c] pyridine-2-carboxamide, 4- (3-bromophenoxy) thieno. { 2,3-c] pyridine-2-carboxamide, 4- (4-fluorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (3,5-dimethylphenoxy) thieno [2,3-c] ] pyridine-2-carboxamide, 4- (3-chloro-4-methylphenoxy) thieno [2,3-c] pyridine-2: arboxamide, 4- (4-iodophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4 - (methoxymethyl) phenoxy) thieno [2,3-c] pyridine-2-carboxamide, 2- (aminocarbonyl) -4- (4-chlorophenoxy) thieno [2,3-c] pyridinium, iodide, 4-acid ( 4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxylic acid, N- (4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl) -O- (3-tetrahydrofuranyl) carbamate, 4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-methanol, (E) -3-I4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] - acid 2-propenoic, 4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxaldehyde, 10 (E) -3- [4- (4-chlorophenoxy) thieno [2,3-c] pyridine- 2-yl] -2-propenamide, 4-bromothieno [2,3-c] pyridine-2-.carboxamide, F-methyl 4-bromothieno [2,3-c] pyridine-2-carboxylate, 4-chlorothieno [2, 3-c] pyridine-2-carboxamide, 4- [4- (trifluoromethyl) phenyl] thieno [2,3-c] pyridine-2-carboxamide, 15-methyl-4- [4- (trifluoromethyl) phenyl-3-thieno [2, 3-c] pyridine-2-carboxylate, N-methyl-4- [4- (trifluoromethyl) phenyl] thieno [2,3-c] pyridine-2-carboxamide, 4-phenyltiene [2,3-c] pyridine-2-carboxamide, methyl 4-phenylthieno [2) 3-c] pyridine-2-carboxylate, 4 - ([1,1'-biphenyl] -4-thio) thieno [2,3-c] pyridine -2-carboxamide, F 20 4- (5-formyl-2-furanyl) thieno [2,3-c] pyridine-2-carboxamide, ethyl 4 - [[2- (aminocarbonyl) thieno [2,3-c] pyridin-4-yl] oxy] benzoate, 4 - [[2- (aminocarbonyl) thieno [2,3-c] pyridin-4-yl] oxy] benzoic acid, 4- (1-phenylethenyl) thieno [2,3 -c] pyridine-2 -carboxamide, methyl 4- (1-phenylethenyl) thieno [2,3-c] pyridine-2-carboxylate, 4 - [(4-methylphenyl) thio] thieno [2,3-c] pyridine-2-methanol, 4- (4-Chlorophenoxy) -N-methylthieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) -N, N-dimethylthieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) -N, N-diethylthieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) -N-cyclopropyl-thieno [2,3-c] pyridine-2-carboxamide, 1 - [[4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] carbonyl] pyrrolidine, 1 - [[4- (4-chlorophenoxy) thieno [2,3-c] pyridine- 2-yl] carbonyl] piperidine, 4 - [[4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] carbonyl] morpholine, 1 - [[4- (4-chlorophenoxy)] thieno [2,3-c] pyridin-2-yl] carbonyl] -4-methylpiperazine, 1 - [[4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] carbonyl] -4 phenyl] piperazine, 1 - [[4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] carbonyl] -4- (phenylmethyl) -piperazine, 1 - [[4- (4- chlorophenoxy) thien [2,3-c] pyridin-2-yl] carbonyl] -4- (2-pyridinyl) -piperazine, 4- (4-chlorophenoxy) -N- (2-hydroxyethyl) lthieno [2, 3-c] pyridine-2-carboxamide, 4 - [[4- (4-chlorophenoxy) t-ene [2,3-c] pyridin-2-yl] carbonyl] -N- (1-methylethyl) -1- piperazineacetamide, trifluoroacetate salt, 4- (4-chlorophenoxy) -N- [1 - (hyd roxymethyl) ethyl] t-ene [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) -N- [1,1-bis (hydroxymethyl) ethyl] thieno [2,3-c] pyridine-2-carboxamidef (D, L) -4- (4-chlorophenoxy) -N- (2-hydroxypropyl) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) -N- [2- (4-morpholinyl) ethyl] thieno [2,3-c] pyridine -2-carboxamide, 4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-sulfonamide, 4- (4-morpholinyl) thieno [2,3-c] pyridine-2-carboxamide, 4- ( 4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, N-oxide, methyl (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxylic acid, N-oxide, 4- ( 4-chlorophenoxy) -2- (2-methoxyphenyl) thieno [2,3-c] pyridine, 4- (4-chlorophenoxy) thieno [2,3-c] pyridine, 4- (4-chlorophenoxy) -3 -methylthieno [2,3-c] pyridine-2-carboxamide, Methyl 4- (4-chlorophenoxy) -3-methylthieno [2,3-c] pyridine-2-carboxylate, 3-amino-4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, methyl 3-amino- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxylate, 3-amino-4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxylic acid , 5 4 - [(4-methylphenyl) thio] thieno [2,3-b] pyridine, 4 - [(4-methylphenyl) thio] thieno [2,3-b] pyridine-2-carboxamide, 4- chloro-N- (4-chlorophenyl) thieno [2,3-b] pyridine-5-carboxamide, ethyl 4 - [(5-methyl-1,3,4-thiadiazol-2-yl) thio] thieno [ 2,3-b] pyridine-5-carboxylate, 7 - [(4-methylphenyl) thio] thieno [3,2-b] pyridine-2-carboxamide, 10 methyl 6 - [(4-methylphenyl) thio] thieno [ 2,3-b] pyridine-2-carboxylate, methyl 3-amino-6-chlorothieno [2,3-b] pyridine-2-carboxylate, F 2 -bromo- -. { (4-methylphenyl) thio] t-ene [3,2-c] pyridine, 4 - [(4-methylphenyl) thio] thieno [3,2-c] pyridine-2-carboxamide, 4- [ (4-methylphenyl) thio] thieno (3,2-c] pyridine-2-carbonitrile, 4- (4-Methylphenoxy) thieno (3,2-c] pyridine-2-carboxamide, 4- (4- Methylphenoxy) thieno [3,2-c] pyridine-9-carbonitrile, 7- (4-methylphenoxy) oxazolo [5,4-c] pyridine-2-carboxamide, methyl 7- (4-methylphenoxy) oxazole [5 , 4-c] pyridine-2-carboxylate, 4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carbothioamide, F 20 4- (4-chlorophenoxy) -N-ethylthieno [2,3- c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) -N- (2,3-dihydroxypropyl) thieno [2,3-c] pyridine-2-carboxamide, 4- (4- bromophenoxy) -N- (2,3-dihydroxypropyl) thieno [2,3-c] pyridine-2-carboxamide, N- (2-chloroethyl) -4- (4-chlorophenoxy) thieno [2,3-c] pyridine -2-carboxamide, 4- (4-bromophenoxy) -N- (2-hydroxyethyl) thieno [2,3-c] pyridine-2-carboxamide, 4- (2-bromo-4-cyranophenoxy) -N- ( 2-hydroxyethyl) thieno [2,3-c] pyridine-2-carboxamide, N- (2-Hydroxyethyl) -4- [4- (trifluoromethyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, N- (2-aminoethyl) -4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) -N-hydroxy-thieno [2,3-c] pyridine-2 -carboxamide, 4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carbohydrate, 4- (4-bromophenoxy) thieno [2,3-c] pyridine-2-carbohydrate, 4- [4 - (trifluoromethyl) phenoxythieno [2,3-c] pyridine-2-carbohydrate, 4- (4-chlorophenoxy) -N-hydroxythieno [2,3-c] pyridine-2-carboxamide, 2- ( { [ 4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] carbonyl}. Amino) acetic acid, N- (2-amino-2-oxoethyl) -4- (4-chlorophenoxy) thieno [ 2,3-c] pyridine-2-carboxamide, N- (2-amino-2-oxoethyl) -4- (4-bromophenoxy) thieno [2,3-c] pyridine-2-carboxamide, (2S) - 2- ( { [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] carbonyl}. Amino) -3-hydroxypropanoic, N - [(1S) -2-amino- 1- (hydroxymethyl) -2-oxoethylJ-4- (4-chlorophenoxy) thien [2,3-c] pyridine-2-carboxamide, (2R) -2- ( { [4- (4 -chlorophenoxy) thieno [2,3-c] pyridin-2-ylcarbonyl) amino) -3-hydroxypropanoic acid, (2R) -2- ( { [4- (4-chlorophenoxy) thieno [2,3-c] ] pyridin-2-yl] carbonyl] amino) propanic, 4- (4-chlorophenoxy) -N - [(1R) -1-methyl-2- (methylamino) -2-oxoethyl] thieno [2,3-c] pyridine-2-carboxamide, (2S) -2- acid ( { [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] carbonyl}. Amino) propanic, 4- (4-chlorophenoxy) -N - [(1S) -1-methyl-2- (methylamino) -2-oxoethyl] thieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) -N ^ (1R) -1- (hydroxymethyl) -2- (methylamino) -2-oxoethyl] thienoi-2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) -N - [(1 S) -1 - (hydroxymethyl) -2- (methylamino) -2-oxoethyl] thieno [2,3-c] pyridine- 2-carboxamide, 4- (3-pyridiniumoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-bromophenoxy) -N-methylthieno [2,3-c] pyridine-2-carboxamide, - (4-bromophenoxy) -N, N-dimethylthieno [2,3-c] pyridine-2-carboxamide, • 5 N, N-dimethyl-4- [4- (trifluoromethyl) phenoxy] thieno [2, 3-c] pyridine-2-carboxamide, 4- (4-chloro-3-fluorophenoxy) -N-methylthieno [2,3-c] pyridine-2-carboxamide, 4- (4-cioro-3-fluorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-chloro-3-etiiphenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (3-fluorophenoxy) thieno [2, 3-c] pyridine-2-carboxamide, 4- (2) 3-difluorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (2,3-difluorophenoxy) -N-methylthieno [2, 3-c] pyridine-2-carboxamide, 4- (3-fluorophenoxy) -N-methylthieno [2,3-c] pyridine-2-carboxamide, N-methyl-4- (2,3,4-trifluorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (2,3,4-trifluorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 15 N? T? Ethyl-4- [4- (trifluoromethyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 4- [3- (trifluoromethyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, N, N-dimethyl-4 - (4-vinylphenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-cyanophenoxy) -N-methylthieno [2,3-c] pyridine-2-carboxamide, 4- (4-cyanophenoxy) ) t-ene [2,3-c] pyridine-2-carboxamide, • 4- (4-aminophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 4- [4- (acet. ilamino) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, N-methyl-4- [4- (4-morpholinyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 4- [4- (hydroxymethyl) phenoxy] thienoI2,3-c] pyridine-2-carboxamide, 4-I4- (hydroxymethyl) phenoxy] -N-methylthieno [2,3-c] pyridine-2-carboxamide, - [4- (methoxymethyl) phenoxy] -N-methylthieno [2,3-c] pyridine-2-carboxamide, 4-. { 4 - [(2-methoxyethoxy) methyl] phenoxy} thieno [2,3-c] pyridine-2-carboxamide, 4-. { 4 - [(2-methoxyethoxy) methyl] phenoxy} -N-methylthieno [2,3-c] pyridine-2-carboxamide, 4- (4- (J2- (2-methoxyethoxy) ethoxy] methyl.}. Phenoxy) thieno [2,3-c] pyridine-2- carboxamide, • 5 4- (4-. {[2- (2-methoxyethoxy) ethoxy] methyl.}. Phenoxy) -N-methylthieno [2,3-c] pyridine-2-carboxamide, 4-. { 4 - [(Tetrahydro-2H-pyran-2-yloxy) methyl] phenoxy} thieno [2,3-c] pyridine-2-carboxamide, N-methyl-4-. { 4 - [(Tetrahydro-2H-pyran-2-yloxy) methyl] phenoxy} t-ene (2,3-c) pyridine-2-carboxamide, 4-. {[2- (aminocarbonyl) thieno [2,3-c] pyridin-4-yl] oxy} benzyl-2-furoate, 10 4- [4- ( { [(2R, 4R, 5S, 6R) -4,5-Dihydroxy-6- (hydroxymethyl) tetrahydro-2H-pyran-2-yl] oxy} methyl) phenoxy] -N-methylthieno [2,3-c] pyridine-2-carboxamide, 4- (4-acetylphenoxy) -N-methylthieno [2,3-c] pyridine-2-carboxamide, 4- [4- (4 -morpholinylcarbonyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, N-methyl-4- [4- (4-morpholinylcarbonyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 4- [4- ( { L2- (4-morpholinyl) ethyl] amino} carbonyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, N-methyl-4- [4- ( { [2- (4-morpholonyl) ethyl] amino} carbonyl) phenoxy] thieno [2,3-c] pyridine -2- carboxamide, 4-. { 4 - [(E) -3- (4-morpholinyl) -3-oxo-1-propenyl] phenoxy} thieno [2,3-c] pyridine-2-carboxamide, F 20 4-. { 4 - ((E) -3- { [2- (4-morpholinyl) ethyl] amino.} - 3-oxo-1-prOpenyl) phenoxy] thieno [2,3-c] pyridine 2-carboxamide, N-methyl-4- [4 - ((E) -3- { [2- (4-morpholinyl) ethyl] amino.} - 3-oxo-1-propenyl) phenoxy] thieno [2,3- c] pyridine-2-carboxamide, 4- (4- { (E) -3 - [(2,3-dihydroxypropyl) amino] -3-oxo-1-propenyl} phenoxy) thieno (2,3-c) pyridine-2-carboxamide, 4- (4- { (E) -3 - [(2,3-dihydroxypropyl) amino] -3-oxo-1-propenyl} phenoxy) -N-methylthieno [2,3-c] pyridine- 2-carboxamide, 4- [4 - ((E) -3- { I2- (1H-imidazol-4-yl) ethyl] amino.} - 3-oxo-1-propenyl) phenoxy] -N- methylthieno [2,3-c] pyridine-2-carboxamide, 4-. { 4- |; (E) -3- (. {2- [bis (2-hydroxyethyl) amino) -1 -3-0X0-1 -propenyl] phenoxy} -N-methylthione [2,3-c] pyridine-2-carboxamide, 4-. { 4 - [(E) -3- (. {2- [bis (2-hydroxyethyl) amino] ethyl} amino) -3-oxo-1-propenyl] thieno [2,3-c] pyridine -2-carboxamide, 4- [4- (1H-imidazol-1-yl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, N-methyl-4- [4- (1 H -pyrazole- 1-yl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, N-methyl-4- [4- (1 H-1, 2,4-triazol-1-yl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, N-methyl-4-. { 4- [5- (trifluoromethyl) -1,4, 2,4-oxadiazol-3-yl] phenoxy} thieno [2,3-c] pyridine-2-carboxamide, 4- [4- (4,5-dihydro-1 H-imidazol-2-yl) phenoxy] -N-methyltiene [2,3- c] pyridine-2-carboxamide, N-methyl-4- [4- (2-thienyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 4 - ([1,1 '-biphenyl] -4-yloxy) -N-methylthiene [2,3-c] pyridine-2-carboxamide, N-methyl-4- [4- (1-methyl-1H-imidazol-5-yl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide , 4-. { 4- [1 - (hydroxymethyl) dclopropyl] phenoxy} -N-methylthieno [2,3-c] pyridine-2-carboxamide, 4- [4- (1- { [2- (2-ethoxyethoxy) ethoxy] methyl.} Cyclopropyl) phenoxy] -N-methylthieno [2,3-c] pyridine-2-carboxamide, N-methyl-4- [4- (trifluoromethoxy) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 5-. { 4- [4- (1- { I2- (2-ethoxyethoxy) ethoxylmethyl}. Cyclopropyl) phenoxy] thieno [2,3-c] pyridin-2-yl} -1, 3,4-oxadiazol-2-amine, 4- [4- (1,1-difluoro-2-hydroxyethyl) phenoxy] N-methylthieno [2,3-c] pyridine-2-carboxamide, 4- (4-. {- - [2- (2-ethoxyethoxy ) ethoxy] -1, 1-difluoroethyl.} phenoxy) -N-methylthieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) -6-. { [(2,2-dimethylpropanoyl) oxy] methyl) -2 - [(methylamino) carbonyl] thieno [2,3- 5 c] pyridin-6-io, 4- (4-bromophenoxy) -6-fl (2, 2-dimethylpropanoyl) oxylmethyl} -2- [(methylamino) carbonyl] thieno [2,3-c] pyridin-6-io, 2- (aminocarbonyl) -4- (4-chlorophenoxy) -6-. { [(isopropoxycarbonyl) oxy] methyl} thieno [2,3-c] pyridin-6-io, 4- (benzyloxy) thieno [2,3-c] pyridine-2-carboxamide, 4 - [(4-chlorophenyl) (hydroxy) methyl] thieno [2 , 3-c] pyridine-2-carboxamide, 4- (4-chlorobenzoyl) -N-methylthieno [2,3-c] pyridine-2-carboxamide, N 4 - (4-chlorophenyl) thieno [2,3-c] ] pyridine-2,4-dicarboxamide, [4- (4-bromophenoxy) thieno [2,3-c] pyridin-2-yl] methanol, 4- (4-bromophenoxy) thieno [2,3-c] pyridine -2-carbaldehyde, oxy 4- (4-chlorophenoxy) t-ene [2,3-c] pyridine-2-carba-aldehyde, 4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carbaldehyde O -methyl oxime, 1 - [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -1-ethanone O-methyloxime, 1 - [4- (4-chlorophenoxy) thieno [2,3 -c] pyridin-2-yl] -1-ethanone O-methyloxime, • 20 oxime 1- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -1-ethanone, oxime 1 - [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -1-ethanone, 1 - [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2 -yl] -1-propanone, oxime 1 - [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -1-propanone, 2- [4- (4-chlorophenoxy) thieno [ 2,3-c] pyridin-2-yl] -N-methoxy-N-methyl-2- 25 oxoacetamide, 4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carbonitrile, 4- (4-chlorophenoxy) -N'-hydroxy-thieno [2,3-c] pyridine-2-carboximidamide, 4- (4-chlorophenoxy) -N, -cyanotiene [2,3-c] pyridine-2-carboximidamide, [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] (2-nitrophenyl) ) anol, 5 [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] (2-nitrophenyl) anone, (2-aminophenyl) [4- (4-chlorophenoxy) thieno] 2,3-c] pyridin-2-yl] anone, (2-aminophenyl) [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] anol, [4- (4-chlorophenoxy ) thieno [2,3-c] pyridin-2-yl] (3-nitrophenyl) anol, (3-aminophenyl) [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] anone , 10 (3-aminophenyl) [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] anol, 4- (4-bromophenoxy) -2-vinyl thieno [2,3-c] pyridine , • 1 - [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -1,2-ethanediol, 1 - [4- (4-bromophenoxy) thieno [2,3-c] ] pyridin-2-yl] -1,2-ethanediol, [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] anamine, [4- (4-chlorophenoxy) thieno [2] , 3-c] pi? Idin-2-yl] yl carbamate, N-fl4- (4-chlorophenoxy) thieno [ 2) 3-c] pyridin-2-yl] yl} urea, (E) -3- [4- (4-bromophenoxy) thieno [2,3-c] pyridin-2-yl] -2-propenamide, (E) -3- [4- (4-bromophenoxy) thieno [2,3-c] pyridin-2-yl] -N-yl-2-propenamide, 3-. { 4- (4-bromophenoxy) thieno [2,3-c] pyridin-2-yl] -2,3-dihydroxy-N-ylpropanamide, • 20 4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-ylamine, 4- (4-cyranophenoxy) thieno [2,3-c] pyridin-2-ylformamide, N- [4 - (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] urea, N-. { 4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -N'-ylthiourea, 4- (4-chlorophenoxy) -N-ylthieno [2,3-c] pyridine-2-sulfonamide , 4- (4-chlorophenoxy) -N- (2,3-dihydroxypropyl) thieno [2,3-c] pyridine-2-sulfonamide, 4- (4-chlorophenoxy) -N- (2-hydroxyethyl) thieno [2,3-c] pyridine-2-sulfonamide, 4- [4- (4-chlorophenoxy) thieno [2,3-c] pyridine -2-yl] phenol, 3- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] aniline, 4- [4- (4-chlorophenoxy) thieno [2,3-c] ] pyridin-2-yl] aniin, ^ / ß 5 4- (4-chlorophenoxy) -2- (5-nitro-2-pyridinyl) thieno [2,3-c] pyridine, 6- [4- (4- chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -3-pyridinamine, 5- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -2-pyridinamine, 5- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -1,3,4-oxadiazole-2-amino, 5- [4- (4-bromophenoxy) thieno [2,3-c] pyridin-2-yl] -1,4,4-oxadiazol-2-ylamine, 5- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] ] -4H-1, 2,4-triazol-3-amine, 5- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -1,3,4-thiadiazol-2 -amine, 4- (4-chlorophenoxy) -2- (5-yl-1,2,4-oxadiazol-3-yl) thieno [2,3-c] pyridine, 5-. { 4- [4- (trifluoroyl) phenoxy] thieno [2,3-c] pyridin-2-yl} -1,3,4-oxadiazol-2-amine, 4- (4-chlorophenoxy) -2- [5- (ylsulfanyl) -1,4,4-oxadiazoI-2-yl] thieno [2,3-c] pyridine, 15 4- (4-chlorophenoxy) -2- (2-yl-2H-112,3,4-tetrazol-5-yl) thienot2,3-c] pyridine, 5- [4- (4-chlorophenoxy) thieno [ 2,3-c] pyridin-2-yl] -4-yl-4H-1,2,4-triazol-3-amine, 4- (4-chlorophenoxy) -2- [5- (trifluoroyl) -1, 2,4-OxadiazoI-3-yl] thieno [2,3-c] pyridine, 5- [4- (4-chlorophenoxy) thieno [2) 3-c] pyridin-2-yl] -1,2,4 -oxadiazol-3-amine, F 20 5- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -N-yl-1, 3,4-thiadiazol-2-amine, 4- (4-chlorophenoxy) -2- (1,2,4-oxadiazol-3-yl) thieno [2,3-c] pyridine, 2- (1,3,4-oxadiazol-2-yl) -4 -. { 4- (trifluoroyl) phenoxy] thieno [2I3-c] pyridine, 3- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -1,2,4-oxadiazole-5- amine, 2- (5-yl-1,3,4-oxadiazol-2-yl) -4- [4- (trifluoroyl) phenoxy] thieno [2,3-] Cypyridine, yl 2- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -1,3-thiazole-4-carboxylate, 2- [4- (4-chlorophenoxy) thieno] 2,3-c] pyridin-2-yl] -1,3-thiazole-4-carboxamide, tert-butyl 2- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -1,3-thiazole-4- ^ (5-ylcarbamate, 2- [4- (4-chlorophenoxy) thieno [2,3-c] pyridin-2-yl] -1,3-thiazol-4-amine, 4 -chloro-3-ylthieno [2,3-c] pyridine-2-carboxamide, 3-amino-4-chlorothieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) -N, 3 -diylthieno [2,3-c] pyridine-2-carboxamide, 4- (4-bromophenoxy) -3-ylthieno [2,3-c] pyridine-2-carboxamide, 7-cioro-4- (4 -chlorophenoxy) -3-ylthieno [2,3-c] pyridine-2-carboxamide, tert-butyl 2- (aminocarbonyl) -4- (4-chlorophenoxy) thieno [2,3-c] pyridine- 3- carboxylate, N-yl-4- (4-toluidino) thieno [2,3-c] pyridine-2-carboxamide, 4- (4-chloroanilino) -N-ytieno [2,3-c] pyridine- 2-carboxamide, N-yl-4- (4-morpholinyl) thieno [2,3-c] pyridine-2-carboxamide, 7-chloro-4- (4-chlorophenoxy) thieno [2,3-c] pyridine- 2-carboxamide, 7-chloro-4- (4-chlorophenoxy) -N-yl ltieno [2,3-c] pyridine-2-carboxamide, 7-chloro-4- (4-chlorophenoxy) -N- (2-hydroxyethyl) thieno [2,3-c] pyridine-2-carboxamide, # 20 7-bromo-4- (4-chlorophenoxy) thieno [2,3-c] pyridine-2-carboxamide, 7-bromo-4- (4-chlorophenoxy) -N-methylthieno [2,3-c] pyridine -2-carboxamide, 4- (4-bromophenoxy) -7-chlorothieno [2) 3-c] pyridine-2-carboxamide, 4- (4-bromophenoxy) -7-chloro-N-methylthieno [2,3-c] ] pyridine-2-carboxamide, 7-chloro-4- [4- (trifluoromethyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 7-chloro-N-methyl-4- [4- ( trifluoromethyl) phenoxy] thieno [2,3-c] pyridine-2- carboxamide, 7-chloro-N- (2-hydroxyethyl) -4- [4- (trifluoromethyl) phenoxy] thieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) -N, 7-dimethylthieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) -7-methoxy-tieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) -7-oxo-6,7-dihydrothieno [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) -N-methyl-7- (methylamino) thieno [2 , 3-c] pyridine-2-carboxamide, 7- (4-methylphenoxy) [1,3] thiazolo [5,4-c] pyridine-2-carboxamide, N-methyl-7- (4-methylphenoxy) [1 , 3] thiazolo [5,4-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) furo [2,3-c] pyridine-2-carboxamide, 4- (4-chlorophenoxy) furo [2,3 -c] pyridine-2-carbothioamide, 4 - [(E) -2-phenylethenyl] thieno [2,3-c] pyridine-2-carboxamide, 4- (4-cyclophenyl) thieno [2,3-c] pyridine -2-carboxamide, 4- [3- (trifluoromethyl) phenyl] thieno [2,3-c] pyridine-2-carboxamide, 4- (3-chlorophenyl) thieno [2,3-c] pyridine-2- carboxamide, 4- (4-bromophenyl) thieno [2,3-c] pyridine-2-carboxamide, 4- (3-aminophenyl) thieno [2,3-c] pyridine-2-carboxamide, 4- (3.5 -dichlorophenyl) thieno [2,3-c] pyridine-2-carboxamide, 4- (2,4-dichlorophenyl) thieno [2,3-c] pyridine-2-carboxamide, 4- (3,4-dichlorophenyl) thieno [2,3-c] pyridi na-2-carboxamide, 4- (2,4-d? fluorophenyl) thienoI2,3-c] pyridine-2-carboxamide, 4- (4-fluorophenyl) thieno [2,3-c] pyridine-2-carboxamide, and 4- (4-bromophenoxy) -5-chlorothieno [2,3-c] pyridine-2-carboxamide. 23. A method for treating inflammatory diseases and reperfusion injuries comprising administering an effective amount of a compound of claim 1. r. ? "** SUMMARY Compounds having Formula (I) are useful for treating inflammation, pharmaceutical compositions comprising compounds of Formula (I), and methods for inhibiting / treating inflammatory diseases in a mammal are also described.