MXPA00004491A

MXPA00004491A - Thienopyrimidine and thienopyridine derivatives useful as anticancer agents

Info

Publication number: MXPA00004491A
Application number: MXPA/A/2000/004491A
Authority: MX
Inventors: Michael John Munchhof; Susan Beth Sobolovjaynes
Original assignee: Pfizer Products Inc
Priority date: 1997-11-11
Filing date: 2000-05-09
Publication date: 2001-12-13

Abstract

The invention relates to compounds of formulas (1) and (2) and to pharmaceutically acceptable salts and hydrates thereof, wherein X1, R1, R2 and R11 are as defined herein. The invention also relates to pharmaceutical compositions containing the compounds of formulas (1) and (2) and to methods of treating hyperproliferative disorders in a mammal by administering the compounds of formulas (1) and (2).

Description

DERIVATIVES OF TIENOPIRIMIDINA AND TIENOPIRIDINA USEFUL AS AGENTS ANTICANCERIGENOS BACKGROUND OF THE INVENTION This invention relates to novel bicyclic pyrimidine and pyridine derivatives which are useful in the treatment of hyperproliferative diseases, such as cancers, in mammals. This invention also relates to a method for the use of these compounds in the treatment of hyperproliferative diseases in mammals, especially humans, and to pharmaceutical compositions containing said compounds. Compounds that are useful in the treatment of hyperproliferative diseases are also described in the following pending patent applications together with the present: PCT international patent application number PCT / IB97 / 00675 (filed June 11, 1997), application US Provisional Patent No. 60/0401846 (filed April 9, 1997), US Provisional Patent Application No. 60/0311862 (filed November 27, 1996), US Provisional Patent Application No. 60/028881 (filed on 17 October 1996), PCT international patent application number PCT / IB97 / 00584 (filed May 22, 1997), US patent application number 08 / 653,786 (filed May 28, 1996), patent application publication International PCT number WO 96/40142 (published December 19, 1996), PCT international patent application publication number WO 97/13771 (published on April 17, 1997) and the PCT international patent application publication number WO 95/23141 (published August 31, 1995). Each of the US and international PCT patent applications are incorporated herein by reference. It is known that a cell can become cancerous by virtue of the transformation of a part of its DNA into an oncogene (that is, an oncogene that when activated results in the formation of malignant tumor cells). Many oncogenes code for proteins that are aberrant tyrosine kinases capable of causing cell transformation. Alternatively, overexpression of a normal proto-oncogenic tyrosine kinase can also produce proliferative disorders, sometimes leading to a malignant phenotype. Tyrosine kinase receptors are large enzymes that traverse the cell membrane and possess an extracellular binding domain for growth factors, such as epidermal growth factor, a transmembrane domain and an intracellular portion that functions as a kinase to phosphorylate the specific residue of tyrosine in proteins, and thus, influence cell proliferation. The above tyrosine kinases can be classified as receptors for a growth factor (eg, EGFR, PDGFR, FGFR and erB2) or as non-receptors (eg, c-scr and bcr-abl) kinases. It is known that such kinases are often aberrantly expressed in common human cancers, such as breast cancer, gastrointestinal cancer, such as colon cancer, rectal cancer or stomach cancer, leukemia, ovarian cancer, cancer. bronchial cancer or pancreatic cancer. Aberrant arB2 activity has been implicated in breast, ovarian, non-small cell, pancreatic, gastric and colon cancers. It has also been seen that the epidermal growth factor receptor (EGFR) is mutated or overexpressed in many human cancers, such as brain, lung, squamous cell, bladder, gastric, breast, head and neck, esophageal, gynecological and thyroid. Thus, it is believed that inhibitors of the receptor tyrosine kinase, such as the compounds of the present invention, are useful as selective inhibitors of the growth of mammalian cancer cells. It has also been shown that EGFR inhibitors may be useful in the treatment of pancreatitis and renopathy (such as proliferative glomerulonephritis and diabetes-induced renopathy) and can successfully reduce blastocyst implantation and, therefore, it may be useful as a contraceptive. See PCT International Application Publication No. WO 95/19970 (published July 27, 1995). It is known that polypeptide growth factors, such as vascular endothelial growth factor (VEGF) that have a high affinity for the receptor containing the insert domain of the human kinase (KDR) or the murine fetal hepatic kinase receptor 1 (FLK-1) are associated with the proliferation of endothelial cells and more especially with vasculogenesis and angiogenesis. See PCT international application publication number WO 95/21613 (published August 17, 1995). Agents, such as the compounds of the present invention, which are capable of binding to or modulating the receptor (KDR / FLK-1 can be used to treat disorders related to vasculogenesis and angiogenesis, such as diabetes, diabetic retinopathy, hemangioma, glioma, melanoma, Kaposi's sarcoma and ovarian, breast, lung, pancreatic, prostate, colon and epidermo.de cancer.

BRIEF DESCRIPTION OF THE INVENTION The present invention relates to the compounds of formulas 1 and 2 1 and pharmaceutically acceptable salts thereof, wherein: X1 is N or CH; R1 is H, C6 alkyl, or -C (O) (C6 alkyl); R2 is C 1 -C 12 aryl or a 5-13 membered heterocycle, wherein said R 2 groups are optionally substituted with 1 to 5 R 5 substituents, each R 3 is independently selected from H, -C (O) OR and C alkyl -? - C6, wherein said alkyl is optionally substituted with 1 to 3 R5 groups; R4 is R3, -OR9 or -NR9R10; each R5 is independently selected from halogen, cyano, nitro, trifluoromethoxy, trifluoromethyl, azido, -C (0) R8, -C (0) OR8, -OC (0) R8, -OC (O) OR8, -NR6C (O ) R7, -C (0) NR6R7, -NR6R7, -OR9, -S02NR6R7, CrC6 alkyl, - (CH2) jO (CH2) qNR6R7, - (CH2) tO (CH2) qOR9, - (CH2) tOR9, -S (O) j (CrC6 alkyl), - (CH2) t (C6-C10 aryl), - (CH2) t (5-10 membered heterocyclic), -C (O) - (CH2) t (C6-C10 aryl) ), - (CH2) tO (CH2) j (aryl C6-C, 0) - (CH2) tO (CH2) q (5-10 membered heterocyclic), -C (O) (CH2) t (CH2) t (5-10 membered heterocyclic), - (CH2) jNR7 (CH2) qNR6R7, - (CH2) tNR7CH2C (0) NR6R7, - (CH2) jNR7 (CH2) qNR9C (O) R8 , (CH2) jNR7 (CH2) tO (CH2) qOR9, - (CH2) jNR7 (CH2) qS (o) j (C6 alkyl), (CH2) jNR7 (CH2) tR6, -S02 (CH2) t- ( C6-C10 aryl) and -S02 (CH2) t (5-10-membered heterocyclyl), where j is an integer ranging from 0 to 2, t is an integer ranging from 0 to 6, q is an integer ranging from 2 to 6, optionally including the radicals - (CH2) q- and - (CH2) t- of the above groups R5 a double or triple carbon-carbon bond, where t is an integer between 2 and 6, and the alkyl, aryl and heterocyclic radicals of the above R5 groups are optionally substituted with 1 to 3 substituents independently selected from halogen, cyano, nitro, trifluoromethyl, azido, - (C (O) R8, -C (O ) OR8, -OC (O) R8, -OC (O) OR8, --NR6C (0) R7, -C (0) NR6R7, - (CH2) tNR6R7, C6 alkyl, - (CH2) t (alkyl) C6-C? 0), - (CH2) t (heterocyclic 5-10 links), - (CH2) tO (CH2) qO R9 and - (CH2) tOR9, wherein t is an integer ranging from 0 to 6 and q is an integer ranging from 2 to 6; each R6 and R7 is independently selected from H, alkyl CrC6, - (CH2) t (aryl C6-C? 0), - (CH2) t (heterocyclic 5-10 links), - (CH2) tO (CH2) qOR9 and - (CH2) tOR9, where t is an integer ranging from 0 to 6 and q is an integer ranging from 2 to 6 and the alkyl, aryl and heterocyclic radicals of the above groups R6 and R7 are optionally substituted with 1 to 3 substituents independently selected from halogen, cyano, nitro, trifluoromethyl, azido, -C (0) R8, -C (O) OR8, -CO (0) R8, -OC (0) OR8, -NR9C (0) R10, -C (0) NR9R10, -NR9R10 , Ci-Cß alkyl, - (CH2) t (C-C-io aryl), - (CH2) t (5-10 membered heterocyclic), - (CH2) tO (CH2) qOR9 and - (CH2) tOR9, in the one that t is an integer that oscillates between 0 and 6 and q is an integer that oscillates between 2 and 6; with the proviso that when R6 and R7 are both attached to the same nitrogen, then R6 and R7 are not attached to the nitrogen directly through an oxygen; each R8 is independently selected from H, Ci alkyl Cío, - (CH2) t (C6-C10 aryl), - (CH2) t (C6-C10 aryl) and - (CH2) t (5-10 heterocyclic link), where t is an integer ranging from 0 and 6; each R 9 and R 10 is independently selected from H and C C β alkyl; R11 is H, C6 alkyl, -C (O) NR6R9, -C (O) (C6-C10 aryl), - (CH2) t (C6-C10 aryl) or - (CH2) t (5-10 heterocyclic link) ), wherein t is an integer ranging from 0 to 6, wherein said R11 groups, other than H, are optionally substituted with 1 to 5 R5 groups; and R12 is H, C6 alkyl, -C (O) (C6-C6 alkoxy), -S (O) j (C-alkyl) C6), -S02 (CH2) t (aryl C6-C? 0), (CH2) t (aryl C6-C10), - (CH2) t (heterocyclic 5-10 links), - (CH2) tO (CH2) qOR9 or - (CH2) tOR9, where j is an integer that ranges from 0 to 2, t is an integer that ranges from 0 to 6, and q is an integer that ranges from 2 to 6. Preferred compounds! include those of formula 1 in which R 1 is - (CH 2) t (C 1 -C 6 aryl) or - (CH 2) t (5-10 heterocyclic link), wherein t is an integer ranging from 0 to 6, wherein said R11 groups are optionally substituted with 1 to 5 R5 groups. Preferred specific groups R11 include phenyl or pyridyl, wherein said phenyl and pyridyl are optionally substituted with 1 to 5 R5 groups. Other preferred compounds include those of formula 1 wherein X1 is CH. Other preferred compounds include those of formula 1 wherein R2 is phenyl optionally substituted with 1 to 5 substituents R5 or R2 is a group of formula wherein X2 is -S- or -N (R6) -, X3 is N or CH , the dotted line in formula 3 represents an optional double bond, and the previous R2 groups of formulas 3 and 5 are optionally substituted by 1 to 5 substituents R5 and the R2 groups of formulas 4 and 6 are optionally substituted by 1 to 3 substituents R5. Specifically preferred are compounds that include those in which R2 is a group of formula 3 above wherein said group is optionally substituted by 1 to 5 substituents R5. Specific embodiments of the present invention include the following compounds; (3-ethynyl-phenyl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-if) -amine; (3-ethynyl-pheny] - [6- (4-methoxy-phenyl) -thieno [3,2-d] pyrimidin-4-yl] -amine; benzo [b] thiophen-5-yl- (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; (1 H-indol-5-yl) - [6- (4-methoxy-phenyl) -thione [3,2-d] pyrimidin-4-yl] -amine; (1 H-indol-5-yl) - (6-phenyl] -thieno [3,2-d] pyrimidin-4-yl) -amine; (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) - (2-pyrrol-1-yl-phenyl) -amine; (5-phenyl-1 H -pyrazol-3-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; (5-phenyl-1 H-pyrrazol-3-yl) -thione [3,2-d] pyrimidin-4-yl-amine; (1 H-indol-5-yl) -thieno [3,2-d] pyrimidin-4-yl-amine; N- (5-phenyl) -1- (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -1 H- [1,4] triazole-3,5-diamine; 3- [3-phenyl-5- (6-phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -pyrazol-1-yl] -propionitrile; (5-furan-2-yl-2H-pyrazol-3-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) - (5-thiophen-2-yl-2H-pyrazol-3-yl) -amine, N- (6-phenyl-thieno) [3,2-d] pyrimidin-4-yl) -benzene-1,4-diamine; N- [4- (6-phenyl-thieno [3,2-d] pyrimidin-4-ylammonyl) -phenyl] -benzamide; N-Methyl-N '- (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -benzene-1,4-diamine; (1 H-indazol-5-yl) - (6-phenyl-thieno [3,2-d] pyrimid-4-yl) -amine; [5- (4-chloro-phenyl) -2H-pyrazol-3-yl] - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; Benzothiazol-6-yl- (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; 4- (6-phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -benzamide; 4-Methyl-N- [4- (6-phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -phenyl] -benzenesulfonamide; N-Phenyl-N '- (6-phenyl-t-ene [3,2-d] pyrimidin-4-yl) -benzene-1,4-diamine; (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) - (2H-pyrazol-3-yl) -amina; (1 H-indazol-6-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; N, N-Dimethyl-N '- (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -benzene-1,4-diamine; (2,3-Dimethyl-1 H-indol-5-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; N-Ethyl-N '- (6-phenyl-t-ene [3,2-d] pyrimidin-4-yl) -benzene-1,4-diamine; [4- (1 H-indol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -phenyl-methanone; (1 H-indol-5-yl) - (6-p-tolyl-thieno [3,2-d] pyrimidin-4-yl) -amine; (5-Furan-2-yl-2H-pyrazol-3-yl) -thieno [3,2-d] pyrimidin-4-yl-amine; Tieno [3,2-d] pyrimidin-4-yl- (5-thiophen-2-yl-2H-pyrazol-3-yl) -amine; [5- (4-chloro-phenyl) -2H-pyrazol-3-yl] -thieno [3,2-d] pyrimidin-4-yl) -amine; (2H-Pyrazol-3-yl) -thieno [3,2-d] pyrimidin-4-yl-amine; Tieno [3,2-d] pyrimidin-4-yl- (5-p-tolyl-2H-pyrazol-3-yl) -amine; 4- [4- (1 H -indol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl) -benzaldehyde; [6- (4-chloro-phenyl) -thieno [3,2-d] pyrimidin-4-yl) - (1 H -indol-5-yl) -amina; [6- (4-fluoro-phenyl) -thieno [3) 2-d] pyrimidin-4-yl) - (1 H -indol-5-yl) -amine; (1 H-indol-5-yl) - (6-thiophen-3-yl-t-ene [3,2-d] pyrimidin-4-yl) -amine; 2- [3- (4-chlorophenyl) -5- (t-ene [3,2-d] pyrimidin-4-ylamino) -pyrazol-1-yl] -ethanol; (1 H-indol-5-yl) - [6- (4-trifluoromethyl-phenyl) -thieno [3,2-d] pyrimidin-4-yl) -amine; (1 H-indol-5-yl) - [6- (4-methylsulfanyl-phenyl) -thieno [3,2-d] pyrimidin-4-yl) -amine; (1 H -indole-5-yl) - [6- (3-nitro-phenyl) -thieno [3,2-d] pyrimidin-4-yl) -amine; [6- (3-chloro-4-fluoro-phenyl) -thieno [3,2-d] pyrimidin-4-yl] - (1 H -indol-5-yl) -amine; [5- (4-methoxy-phenyl) -2H-pyrazol-3-yl] -thieno [3,2-d] pyrimidin-4-yl-amine; 4- [5-Thieno [3,2-d] pyrimidin-4-ylamino) -1 H -pyrazol-3-yl] -benzoic acid methyl ester; (5-methyl-2H-pyrazol-3-yl) -thieno [3,2-d] pyrimidin-4-yl-amine; 5- (6-Phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -1H-indole-2-carboxylic acid ethyl ester; (6-Benzofuran-2-yl) -thione [3,2-d] pyrimidin-4-yl) - (1 H -indol-5-yl) -amine; T-ene [3,2-d] pyrimidin-4-yl- (5-m-tolyl-2 H-pyrrazol-3-yl) -amine; [5- (3-chloro-phenyl) -2H-pyrazol-3-yl] -thieno [3,2-d] pyrimidin-4-ylg-amine; [6- (4-ethyl-phenyl) -thieno [3,2-d] pyrimidin-4-yl) - (1 H -indol-5-yl) -amine; 4- [4- (1 H -indol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzoic acid methyl ester; 4- [5- (Thieno [3,2-d] pyrimidin-4-ylamino) -1 H -pyrazol-3-yl] -benzoic acid; (1 H-indol-5-yl) - (6-thiophen-2-yl-thieno [3,2-d] pyrimidin-4-yl) -amine; [5- (2-chloro-phenyl) -2H-pyrazol-3-yl] -thieno [3,2-d] pyrimidin-4-yl-amine; (1 H-indol-5-y) - (6-pyridin-3-yl-thieno [3,2-d] pyrimidin-4-yl) -amine; (1 H-indol-5-yl) - [6- (3-methoxy-phenyl) -thieno [3,2-d] pyrimidin-4-yl) -amine; . { 4- [4- (1 H -indole-5-ylammon) -thione [3,2-d] pyrimidin-6-yl] -phenyl} -methanol; [6- (3,4-dimethoxy-phenyl) -thieno [3,2-d] pyrimidn-4-yl) - (1 H -indol-5-yl) -amine; [6 - (- 4-dimethylamino-pheny] -thieno [3,2-d] pyrimidin-4-yl) - (1 H -indol-5-yl) -amine; [4- (1 H -indol-5-ylamino) -thione [3,2-d] pyrimidin-6-yl] -phenyl-methanol; 4- (1 H -indoi-5-ylammon) -thieno [3,2-d] pyrimidine-6-carboxylic acid (2-dimethylamino-ethyl) -amide; (1 H-indol-5-yl) - [6- (4-trifluoromethoxy-pheny] -thieno [3,2-d] pyrimidin-4-yl] -amma; (1 H -indole-5-yl) - [6- (2-methoxy-phenyl) -thione [3,2-d] pyrimidin-4-yl) -amine; 4- [4- (1 H -indol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -phenol; [6- (5-diethoxymethyl-thiophen-2-yl) -thieno [3,2-d] pyrimidin-4-yl] - (1 H -indol-5-yl) -amine; 4- (1 H -indol-5-ylamino) -thieno [3,2-d] pyrimidine-6-carboxylic acid (2-methoxy-ethyl) amine; N-. { 4- [4- (1 H -indole-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzyl} - N ', N'-dimethyl-ethane-1,2-diamine; (1 H-indol-5-yl) - (6- { 4 - [(2-methoxy-ethylamino) -methyl] -phenyl} -thieno [3,2-d] pyrimidin-4- il] -amine; (1 H-indol-5-yl) - { 6- [2- (4-methyl-piperazin-1-yl) -phenyl] -thieno [3,2-d] pyrimidine 4-yl.) -amine; 4- (1 H -indole-5-ylamino) -thieno [3,2-d] pyrimidine-6-carboxylic acid proylamide; 4- [4 (1 H-indol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzylamino-ethanol; [6- (2,4-dimethoxy-phenyl) -thieno [3 , 2-d] pyrimidin-4-yl] - (1 H -indol-5-yl) -amine; [6- (4-d.ethylamino-phenyl) -thieno [3,2-d] pyrimidin-4-) il] - (1 H-indol-5-yl) -amine; [6- (4-ethoxy-phenyl) -thieno [3,2-d] pyrimidin-4-yl] - (1 H-indole) 5-yl) -amine; 3- {4- [4- (1 H -indol-5-ylamino) -thione [3,2-d] pyrimidin-6-yl] -benzylamino}. propane-1,2-diol; (1 H-indol-5-yl) - [6- (4-propyllamnomethyl-phenyl) -thieno [3,2-d] pyrimidin-4-yl] -amine; (1 H-indol-5-yl) - (6- { 4 - [(3-methoxy-propylamino) -methyl] -phenyl} - thieno [3,2-d] pyrimidin-4-yl) -amine; [6- (3-fluoro-4-methoxy-pheny] -thieno [3,2-d] pyrimidin-4-yl] - (1 H -indole-5-yl) -amine; (1 H-indol-5-yl) - [6- (3-methylsulfanyl-phenyl) -thieno [3,2-d] pyrimidin-4-yl] -amine; (1 H-indol-5-yl) - [6- (5-methyl-thiophen-2-yl) -thieno [3,2-d] pyrimidin-4-yl] -amine; (1 H-indol-5-yl) - (6- { 4 - [(2-piperazin-1-yl-ethylamino) -methyl] -phenyl} -thienoIS ^^ pyrimidin ^ -ilj-amine; (6-benzo [1,3] dioxol-5-yl-thieno [3,2-d] pyrimidin-4-yl) - (1 H -indol-5-yl) -amine;. {6- [4 - (1-ethoxy-ethoxy) -phenyl] -thieno [3,2-d] pyrimidin-4-yl} - (1 H -indol-5-yl) -amine; ((1 H-indol-5 -yl) - { 6- [4- (2-pyrrolidin-1-yl-ethoxy) -phenyl] -thieno [3,2-d] pyrimidin-4-yl} -amine; (1 H-) indol-5-yl) - { 6- [4- (2-methoxy-ethoxy) -phenyl] -thione [3,2-d] pyrimidin-4-yl} -amine; -indol-5-yl) - (6- { 4 - [(2-morpholin-4-yl-ethylamino) -methyl] -phenyl} -thieno [3,2-d] pyrimidin-4-yl. ] -amine; {. 6- [4- (2-D-methylammon-ethoxy) -phenyl] -thieno [3,2-d] pyrimidin-4-yl) - (1 H-indole) 5-yl) amine; (1 H -indole-5-yl) - [6- (4-methylaminomethyl-phenyl) -thieno [3,2-d] pyrimidin-4-yl] -amine; 5- (6-phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -1,3-dihydro-indol-2-one; (1H-benzotriazol-5-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) - [4- (2H-tetrazol-5-yl) -phenyl] -amine; N-. { 4- [4- (1 H -indol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzyl} -N'-methyl-ethane-1,2-diamine; (1-Benzenesulfonyl-1 H-indol-5-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; 3-. { 4- [4- (1 H -indol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzylamino} -propan-1 -ol; (1 H -indole-5-1) -. { 6- [4- (4-Methyl-piperazin-1-ylmethyl) -phenyl] -thieno [3,2-d] pyrimidin-4-yl} -amine; 2-. { 4- [4- (1 H -indole-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzylamino} -propane-1,3-diol; 2 - ((2-hydroxy-ethylH4- [4- (1 H -indole-5-ylamino) -thieno-3,2-d] pyrimidin-6-yl] -benzyl} -amino) -ethanol; {. 5- [4- (1 H -indol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -thiophen-2-yl} - methanol; 2- (2-. {4- [4- (1 H -indol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzylamino} -ethoxy) -ethanol; 2- (2-. { 4- [4- (1 H -indol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzylamino] -ethylamino) -ethanol; [6- (4- { [2- (1 H-imidazol-4-yl) -ethylamino-methyl] -phenyl) -thieno [3,2-d] pyrimidin-4-yl ] - (1 H -indole-5-yl) -amina; (1 H -indole-5-yl) -. { 6- [4- (2-morpholin-4-yl-ethoxy) -phenyl] -thieno [3,2-d] pyrimidin-4-yl} -amine; 2-. { 4- [4- (1 H -indol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -phenoxy} -ethanol; [4- (2-ethyl-oxazol-5-yl) -phenyl- (6-phenyl] -thione [3,2-d] pyrimid-4-yl) -amine; N- (2-methoxy-phenyl) -N '- (6-phenyl] -thieno [3,2-d] pyrimidin-4-yl) -benzene-1,4-diamine; N- (4-methoxy-phenyl) -N '- (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -benzene-1,4-diamine; 5- [4- (1 H-indol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -thiophene-2-carbaldehyde; [5- (6-phenyl] -thieno [3,2-d] pyrimidin-4-ylamino) -1 H -indol-2-yl] -methanol; (2-phenyl-1 H-indol-3-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; (9H-carbazol-3-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; (2-methyl-1 H-indol-5-yl) - (6-phenyl-t-ene [3,2-d] pyrimidin-4-yl) -amine; (1-phenyl-ethyl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; (1 H-indol-5-yl) - [6- (4-. {[[(Thiophen-2-ylmethyl) -amino] -methyl} - phenyl) -thieno [3,2-d] pyrimidine- 4-yl] -amine; Acid methyl ester 3-. { 4- [4- (1 H -indol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzylamino} -propionic; [6- (4-. {[[(Furan-2-ylmethyl) -amino] -methyl] -phenyl) -thieno [3,2-d] pyrimidin-4-yl] - (1 H- indole-5-yl) -amine; 1 - (3- { 4- [4- (1 H -indol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzylamino.} - propyl) -pyrrolidin-2 -one; N-. { 4- [4- (1 H -indol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzyl} - N ', N'-dimethyl-propane-1,3-diamine; (1 H-indol-5-yl) - [6- (4-morpholin-4-methylmethyl) -thieno [3,2-d] pyrimidin-4-yl] -amine; Ethyl (2- {4- [4- (1 H -indol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzylamino} -acetylamino) ethyl ester -1- (4- { 4- [4- (1 H -indol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzyl.}. -piperazin-1-yl ) -etanone; (6- { 4 - [(2,2-diphenyl-ethylamino) -methyl-phenyl] -thieno [3,2-d] pyrimidin-4-yl] - (1 H-indole -5-yl) -amine; (1 H -indol-5-yl) -. {6- [4- (2-methoxymethyl-pyrrolidin-1-ylmethyl) -phenyl] -thieno [3,2-d] pyrimidin-4-yl.}. -amine; N- (2- {4- [4- (1 H -indol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] - benzylamino.).-ethyl) -acetamide; [6- (4-cyclopropylaminomethyl-phenyl) -thieno [3,2-d] pyrimidin-4-yl] - (1 H -indol-5-yl) -amine; - { 4- [4- (1 H -indole-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzyl-amino} -butan-1-ol; ( { 5- [4- (1 H -indol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -thiophen-2-lmethyl} -amino) - ethanol; (1 H-indol-5-yl) - (6- { 4 - [(2-pyrrolidin-1-yl-ethylamino) -methyl] -phenyl} -thieno [3,2-d] pyrimidin-4-yl) -amine; (1 H-indol-5-yl) - (2-thiophen-2-yl-thieno [3,2-d] pyrimidin-7-yl) -amine; . { 6- [4- (benzylamino-methyl) -phenyl] -thieno [3,2-d] pyrimidin-4-yl} - (1 H-indol-5-yl) -amine; Amide of the acid -. { 4- [4- (1 H -indole-5-ylamino) -thione [3,2-d] pyrimidin-6-yl] -benzyl} -piperidine-4-carboxylic acid; (1 H-indol-5-yl) -. { 6- [4- (pyrrolidin-3-ylaminomethyl) -phenyl] -thieno [3,2-d] pyrimidin-4-yl) -amine; 4- [7- (1 H -indol-5-ylammon) -thieno [3,2-b] pyridin-2-yl] -benzaldehyde; (6- { 4 - [(3-Midazol-1-yl-propylamino) -methyl] -phenyl] -thieno [3,2-d] pyrimidin-4-yl) - (1 H-indole -5-il) -amine; N-. { 4- [4- (1 H -indol-5-ylamino) -thieno [3,2-b] pyrimidin-6-yl] -benzyl} -N ', N'-dimethyl-hexane-1,6-diamine; (1-Allyl-1 H-indol-5-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; (1-methyl-1 H -indole-5-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; (1 H-indol-5-yl) -. { 6- [4- (4-phenyl-piperazin-1-ylmethyl) -phenyl] -thieno [3,2-d] pyrimidin-4-yl) -amine; N-. { 5- [4- (1 H -indol-5-ylamino) -thieno [3,2-b] pyrimidin-6-yl] -thiophen-2-ylmethyl} -N ', N'-dimethyl-ethane-1,2-diamine; N-. { 5- [4- (1 H -indole-5-ylamino) -thieno [3,2-b] pyrimidin-6-yl] -thiophen-2-ylmethyl} -N'-methyl-ethane-1,2-diamine; (1 H-indol-5-yl) - (6-. {5 - [(2-methoxy-ethylamino) -methyl-thiophen-2-yl} -thieno [3,2-d] pyrimidin-4 -yl) -amine; 2-amino-3- (3. {4- [4 (1 H -indol-5-ylamino) -thieno [3,2-b] pyrimidin-6-yl] -benzyl] methyl ester. -3H-imidazol-4-yl-propionic acid, 3- {4- [4- (1 H -indol-5-ylamino) -thieno [3,2-b] pyrimidin-6-yl] -benzylamino}. -2,2-dimethyl-propan-1-ol; 4- [7- (1 H -indol-5-ylammon) -thieno [3,2-b] pyrimidin-2-yl] -phenol; -ethyl-9H-carbazol-3-yl) - (6-phenyl-thieno [3,2-b] pyrimidin-4-yl] -amine; 1- (2-diethylamino-ethyl) -1H-indole -5-yl] - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; [1- (3-diethylamino-propyl) -1 H -indol-5-yl] - ( 6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; (2-Bromo-thieno [3,2-b] pyridin-7-yl) - (1 H-indol-5-yl) ) -amine; [6- (4-Aminomethyl-phenyl) -thione [3,2-d] pyrimidin-4-yl] - (1 H -indol-5-yl) -amine; -hydroxy-2- {4- [4- (1 H -indol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzylamino} -propionic acid; il- (4- { 4- [4- (1 H -indole-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzyl.} - piperazin-1- il) -metanone; (1 H-lndol-5-yl) - [2- (4-methylsulfanyl-pheny] -thieno [3,2-b] pyri din-7-yl] -amine; [6- (4-dimethylaminomethy1-phenyl) -thieno [3,2-d] pyrimidin-4-yl] - (1 H -indol-5-yl) -amine; 2- (. {4- [4- (1 H-lndol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzyl] -methyl-amino) -ethanol; (1- { 4- [4- (1 H-lndol-5-ylamino) -thione [3,2-d] pyrimidin-6-yl] -benzyl.} - pyrrolidin-2-yl) -methanol; 2- [2- (4- { 4- [4- (1 H-lndol-5-ylamino) -thieno [3,2-dlpyrimidin-6-yl] -benzyl}. -piperazin-1-yl ) -ethoxy] -ethanol; [2- (4-Fluoro-phenyl) -thione [3,2-b] pyridin-7-yl] - (1 H -indol-5-yl) -amine; 4- [4- (1 H-lndol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzoic acid; (1 H-lndol-5-yl) -thieno [3,2-b] pyrimidin-7-yl-amine; 2-. { 4- [7- (1 H-lndol-5-ylamino) -thieno [3,2-b] pyridin-2-yl-phenoxy} -ethanol; (1 H-lndol-5-yl) - (2-methyl-6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine N- (4-methoxy-phenyl) -N ' - (2-methyl-6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -benzene-1,4-diamine; N- (2-Benzyloxy-ethyl) -N '- (6-phenyl-thieno [3,2-] pyrimidin-4-yl) -benzene-1,4-diamine; 5- (6-Phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -1 H -indole-3-carbaldehyde; [2- (4-Dimethylamino-phenyl) -thieno [3,2-b] pyridin-7-yl] - (1 H -indole-5-yl) -amine; 4- [7- (1 H-lndol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzoic acid methyl ester; (1 H-lndol-5-yl) - (2-thiophen-3-yl-thieno [3,2-b] pyridin-7-yl) -amine; (1 H-lndol-5-yl) - (2- { 4 - [(2-methoxy-ethylamino) -methyl] -phenyl} -thieno [3,2-b] pyridin-7-yl) -amine; Furan-2-l- (4- (4- [7- (1 H -indol-5-ylammon) -thione [3,2-b] pyridin-2-yl] -benzyl .}. -piperazin-1-yl) -methanone; (3-bromo-1 H -indole-5-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; N- (1 H-indol-3-methyl) -N '- (6-phenyl-t-ene [3,2-d] pyrimidin-4-yl) -benzene-1,4-diamine; N- (6-bromo-thieno [3,2-d] pyrimidin-4-yl) -N '- (4-methoxy-phenyl) -benzene-1,4-diamine; N- (4-Methoxy-phenyl) -N, - [6- (2-nitro-phenyl) -thieno [3,2-d] pyrimidin-4-yl] -benzene-1,4-diamine; N- (4-Methoxy-phenyl) -N '- [6- (4-methoxy-pheny] -thieno [3,2-d] pyrimidin-4-yl] -benzene-1,4-diamine; N- (4-Methoxy-phenyl) -N '- [6- (6-methoxy-pyridin-3-yl) -thieno [3,2-d] pyrimidin-4-yl] -benzene-1, 4 -diamine; N ^ -Metoxy-pheni-N'-y? -thiophene ^ -yl-thienop ^ -djpyrimidin ^ -yl) -benzene-1,4-diamine; (1 H-lndol-5-yl) - [6- (4-thiomorpholin-4-ylmethyl-phenyl) -thieno [3,2-d] pyrimidin-4-yl] -amine; 2- (2- { 4- [7- (1 H-lndol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamino} -ethoxy) -ethanol; 2- (2- { 4- [7- (1 H-lndol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamino.} - ethanol; N-. { 4- [7- (1 H-lndol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzyl} -N ', N'-dimethyl-hexane-1,6-diamine; 2- (. {4- [7- (1 H-lndol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzyl} -methyl-amino) -ethanol; (1 H-lndol-5-yl) - (2- { 4 - [(2-piperazin-1-yl-ethylamino) -methyl] -phenyl) -thieno [3,2-b] pyridin-7 il) -amine; (2- {4 - [(3-lmidazol-1-yl-propylamino) -methyl] -phenyl} -thieno [3,2-b] pyridin-7-yl) - (1 H-) indole-5-yl) -amine; 2 - ((2-Hydroxy-ethylH4- [7- (1 H -indol-5-ylamino) -thione [3,2-b] pyridin-2-yl] -benzyl}. amino) ethanol; [2- (4-Dimethylaminomethyl-phenyl) -thieno [3,2-b] pyridin-7-yl] - (1 H -indol-5-yl) -amine; N-. {4- [7- (1 H-lndol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzyl] -N ', N'-dimethyl-ethane-1,2-diamine; (1- {4- [7- (1 H-lndol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzyl} - pyrrolidin-2-yl-methanol; 2- (4- { 4- [7- (1 H-lndol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzyl.}. -piperazin-1-yl ) -etanol (1 H-lndol-5-yl) - { 2- [4- (2-morpholin-4-yl-ethoxy) -phenyl] -thieno [3,2-b] pyrid n-7-yl} -amine; 1- {4- {7- (1 H-lndol-5-ylamino) -thieno [3,2-b] pyridin-2-l acid amide ] -benzyl.}. -piperidine-4-carboxylic acid; {. 4- [7- (1 H-lndol-5-ylammon) -thieno [3,2-b] pyridin-2-yl] -phenyl .}. -methanol; 6- (6-Phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -benzothiazole-2-thiol; 2-. { 4- [7- (1 H-lndol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamino} -butan-1-ol; N-. { 4- [7- (1 H-lndol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzyl} -N'-methyl-ethane-1,2-diamine; (1 H-lndol-5-yl) - [2- (4-morpholin-4-methyl-1-phenyl) -thieno [3,2-b] pyridin-7-yl] -amine; 3-. { 4- [7- (1 H-lndol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamino} -propan-1-ol; 1 - (3- { 4- [7- (1 H-lndol-5-ylammon) -thieno [3,2-b] pyridin-2-yl] -benzylamino.} - propyl) -pyrrolidin-2-one; (3-Met l-1 H-indol-5-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; (I H-Indol-d-ylJ ^ -fethoxy-ethoxyHenylj-thienofS ^ -bjpyridin ^ -yl.} -amine; 2- (2- { 4- [7- { 1 H-lndol-5 -ylamino) -thieno [3,2-b] pyridin-2-yl-benzylamino] -ethylamino) -ethanol; S ^ - ^ - ÍI H-Indol-d-ylaminoHienoP ^ -bjpiridin ^ -ilj-benzilamino} -2,2-dimethyl-propan-1 -ol; 3-. { 4- [7- (1 H-lndol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamino} -propane-1,2-diol; [2- (4- { [2- (1 H-lmidazol-4-yl) -ethylamino] -methyl] -phenyl) -thieno- [3,2-b] pyridin-7-yl] - (1 H-indol-5-yl) -amine; N- (2- { 4- [7- (1 H-lndol-5-ylamino) -thione [3,2-b] pyridin-2-yl] -benzylamino] -ethyl) acetamide; 2-. { 4- [7- (1 H-lndol-5-ylamino) -thione [3,2-b] pyridin-2-yl] -benzylamine) -acetamide; 2-. { 4- [7- (1 H-lndol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamino} -propane-1,3-diol; N- (4-Methoxy-phenyl) -N '- [2- (3-nitro-phenyl) -thieno [3,2-b] pyridin-7-yl] -benzene-1,4-diamine; (7-Methoxy-1 H -indole-5-yl) - (2-phenyl-thieno [3,2-b] pyridin-7-yl) -amine; (1 H-lndol-5-yl) - [2- (4-methylaminomethyl-pheny] -thieno [3,2-b] pyridin-7-yl] -amine; N-. { 4- [7- (1 H-lndol-5-ylamino) -thione [3,2-b] pyridin-2-yl] -benzyl} -etane-1, 2-diamine; Acid methyl ester. { 4- [7- (1 H-lndol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamino} -acetic; N-. { 4- [7- (1 H-lndol-5-ylamino) -thione [3,2-b] pyridin-2-yl] -benzyl} -N ', N'-dimethyl-propane-1,3-diamine; N- (4-Methoxy-phenyl) -N'-thieno [3,2-d] pyrimidin-4-yl-benzene-1,4-diamine; (1 H-lndol-5-yl) - (2-pyridin-2-yl-thieno [3,2-b] pyridin-7-yl) -amine; (1 H-lndol-5-yl) - (2- { 4 - [(2-morpholin-4-yl-ethylamino) -methyl] -phenyl.} - -thione [3,2-b] pyridin-7-yl) -amine; (1 H-lndol-5-yl) -. { 2- [4- (pyrrolidin-3-ylaminomethyl) -phenyl] -thieno [3,2-b] pyridin-7-yl} -amine; 1_ (4- { 4- [7- (1 H-lndol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzyl.} - piperazin-1-yl) - ethanone; Amide of acid 1-. { 4- [7- (1 H-lndol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzyl} -pyrrolidine-2-carboxylic acid; N- (4-Methoxy-phenyl) -N '- [2- (6-methoxy-pyridin-3-yl) -thieno [3,2-b] pyridin-7-yl] -benzene-1, 4 -diamine; (1 H-lndol-5-yl) - (2-pyridin-3-yl-thieno [3,2-b] pyridin-7-yl) -amine; N- (2-Methoxy-phenyl) -N '- (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -benzene-1,4-diamine N- (6-phenyl-thieno [3] , 2-d] pyrimidin-4-yl) -N'-o-totyl-benzene-1,4-diamine; N- (6-Phenyl-t-ene [3,2-d] pyrimidin-4-yl) -N'-p-to-1-benzene-1,4-diamine; N- (3,4-Dimethoxy-phenyl) -N '- (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -benzene-1,4-diamine; N - (- Phenyl-t-ene [3,2-d] pyrimidin-4-yl) -N '- (3,4,5-trimethoxy-phenyl) -benzene-1,4-diamine; N- (6-Phenyl-t-ene [3,2-d] pyrimidin-4-yl) -N'-m-tolyl-benzene-1,4-diamine; N- (4-Chloro-phenyl) -N '- (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -benzene-1,4-diamine; 4- [7- (1 H-lndol-5-ylammon) -thieno [3,2-b] pyridin-2-yl] -but-3-yn-1-ol; (1 H-lndol-5-yl) - [6- (6-methoxy-pyridin-3-yl) -thieno [3,2-d] pyrimidin-4-yl] -amine; N- (4-dimethylamino-phenyl) -N '- (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -benzene-1,4-diamine; N- (3-Methoxy-phenyl) -N '- (6-phenyl-t-ene [3,2-d] pyrimidin-4-yl) -benzene-1,4-diamine; (1,3-Dibromo-1 H -indol-5-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; N- (4-Methoxy-phenyl) -N '- (2-thiophen-2-yl-thieno [3,2-b] pyridin-7-yl) -benzene-1,4-diamine; (6-Chloro-1 H -indol-5-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; [5- (6-Phenylt-thieno [3,2-d] pyrimidin-4-ylamino) -1 H -indol-3-yl] -methanol; N- (2-Hydroxy-ethyl) -4- [7- (1 H -indol-5-ylamino) -thieno (3,2-b] pyridin-2-yl] -benzamide; N- (3-lmidazole- 1-yl-propyl) -4- [7- (1 H -indol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] benzamide; 3- [4- (4- { 4- [7- (1 H-lndol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamino} -butyl) -piperazin-1-yl] -propan-1 -ol: (1 H-lndol-5-yl) - [2- (4- { [4- (4-methyl-piperazin-1-yl) -butylamino] -methyl} -phenyl) -thiene [3,2-b] pyridin-7-yl] -amine; 2- [4- (4- { 4- [7- (1 H-lndol-5-ylamino) -thieno [3,2-b] ] pyridin-2-yl] -benzylamino.} - butyl) -piperazin-1-yl] -ethanol; 1-lmidazol-1-yl-3-. { 4- [7- (1 H -indol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamino} -propan-2-ol; 5-. { 4- [7- (1 H-lndol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamino} -pentan-1-ol: 2- [2- (4- { 4- [7- (1 H-lndol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] - benzyl.} - piperazin-1-yl) -ethoxy] -ethanol; (1 H-lndol-5-yl) - (2- {4 - [(2-methylsulfanyl-ethylamino) -methyl] -phenyl} -thieno [3,2-b] pyridin-7-yl) -amine; 2 - [(2-Hydroxy-ethyl) - (3- {4- [7- (1 H -indol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] - benzylamino.}. - propyl) -amino] -ethanol; N- (2-Amino-ethyl) -N'-. { 4- [7- (1 H -indole-5-ylamino) -thione [3,2-b] pyridin-2-yl] -benzyl} -ethane-1, 2-diamine; 2- (3- { 4- [7- (1 H-lndol-5-ylammon) -thione [3,2-b] pyridin-2-yl] -benzylamino.}. -propylamino) -ethanol; N-. { 4- [7- (1 H-Indol-d-ylaminoHienotS ^ -bjpyridin ^ -ilj-benzyl.} - hexano-1,6-diamine; (2-Methyl-1 H-indol-5-yl) - [ 2- (4-morpholin-4-ylmethyl-phenyl) -thieno [3,2-b] pyridin-7-yl-amine; (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) - {.3 - [(3-pyrazol-1-yl-propylamino) -methyl] -1H-indol-5-yl}. -amine; Acid methyl ester { [5- ( 6-Phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -1H-indol-3-ylmethyl] -amino.} -acetic; 2-. { [5- (6-Phenylt-thieno [3,2-d] pyrimidin-4-ylamino) -1 H -indol-3-ylmethyl] -amino} -ethanol; 2-. { 4- [7- (2-Methyl-1 H -indol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamino-ethanol; (1 H-lndol-5-yl) - [2- (6-methoxy-pyridin-3-yl) -thieno [3,2-b] pyridin-7-yl] -amine; . { 5- [7- (1 H-lndol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -pyridin-2-yl} -methanol; N, N-Dimethyl-N'-. { 4- [7- (2-methyl-1 H -indol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzyl} propane-1, 3-diamine; 5- (6-Phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -1H-indole-3-carbaldehyde oxime; (3-Metliminomethyl-1 H-indol-5-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; [3- (2-Nitro-vinyl) -1 H -indole-5-A- (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; 4- [4- (6-Phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -phenylamino] -phenol; 5-Methyl-1- [4- (6-phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -phenyl] -1,2-dihydro-pyrazol-3-one, (2-Methyl-benzothiazole) -6-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine, 2 - [(2-Hydroxy-ethyl) - (3- {4- [7- (2-methyl-1 H-indol-5-ylamino) -thieno [3,2-b] pyridine -2-illbenzylamino.}. -propyl) -amino] -ethanol; 2-. { 4- [7- (2-Met l-1 H -indol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamino} -propane-1,3-diol; 3-. { 4- [7- (2-Methyl-1 H -indol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamino} -propane-1, 2-diol; 1 - (3- { 4- [7- (2-Methyl-1 H -indol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamino} - propyl-pyrrolidin-2-one; N- (2-Amino-ethyl) -N'- { 4- [7- (2-methyl-1 H -indol-5-ylamino) -thieno [3,2- b] pyridin-2-yl] benzyl.} - ethane-1,2-diamine; 2- (2-. {4- [7- (2-Methyl-1 H -indol-5-ylamino) -thiene [3,2-b] pyridin-2-yl] -benzylamino.} Ethylamino) -ethanol; 3- {4- [7- (2-Methyl-1 H -indol-5-ylamino) -t} eno [3-, 2-b] pyridin-2-yl] -benzylamino.}. -propan-1-ol; 1-. {4- [7- (2-methyl-1 H -indol- 5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzyl.} - -piperidine-4-carboxylic acid 2- (2-. {4- [7- (2-methyl-1 H-indol-d-ylaminoHienop ^ -bjpyridin ^ -yl] -benzylamino.}.-Ethoxy) -ethanol; 2- (methyl-. {4- [7- (2-methyl-1 H-indole-5- Lamino) -thieno [3,2-b] pyridin-2-yl] -benzyl]. -amino) ethanol; N-methyl-N, - (4- [7- (2-methyl-1 H-indole -5-ylamino) -thieno [3 > 2-b] pyridin-2-yl] -benzyl.} - ethane-1,2-diamine; (1 H-indol-5-yl) - [2- ( 3-Nitro-pheny!) -thieno [3,2-b] pyridin-7-yl] -amine; N- { 4- [7- (2-methyl-1 H-indole-5- ilamino) -thien or [3,2-b] pyridin-2-yl] -benzyl} -ethane-1, 2-diamine; (2-methyl-1 H-indol-d-yl) - (2- {4 - [(2-piperazin-1-yl-ethylamino) -methyl-phenyl} -thione [3,2 -b] pyridin-7-yl) -amine; N, N-dimethyl-N '- (4- [7- (2-methyl-1 H -indol-d-ylamino) -thieno [3,2- b] pyridin-2-yl] -benzyl}. -ethane-1, 2-d-amines; d 2- (4- [7- (2-methyl-1 H -indol-d-ylamino) -thieno [3,2-b] pyridin-2-yl] - benzylamino) -butan-1-ol; (2-methyl-1 H-indol-d-yl) - (2. {4 - [(2-morpholin-4-yl-ethylamino) -methyl] -phenyl} -thien [3,2-b] pyridin-7-yl) -amine; (2-methyl-1 H-indol-d-yl) - { 2- [4- (pyrrolidin-3-ylaminomethyl) l) -phenyl-0-thieno [3,2-b] pyridin-7-yl}. -amine;. {6- [7- (1 H -indol-d-ylamino) -thieno [3,2-] b] pyridin-2-yl] -pyridin-3-yl.} - methanol; {. 6- [7- (2-methyl-1 H -indol-d-ylamino) -thieno [3,2- b] pyridin-2-yl] -pyridin-3-yl.} - methanol; d (3-methylaminomethyl-1 H -indole-d-1) - (6-phenyl-t-ene [3,2 -b] pyrimidin-4-yl) -amine; 3. [4- (4- { 4- [7- (2-methyl-1 H-indol-d-ylamino) -thieno [3,2 -b] pyridin-2-yl] -benzylamino.} - butyl) -piperazin-1-yl] -propan-1-ol; 2- [4- (4-. {4- [7- (2- methyl-1 H -indole-d-ylamino) -thione [3,2-b] pyridin-2-yl] -0-benzylamino] -butyl) -piperazin-1-yl] -ethanol; - { 4 - [(3-imidazol-1-yl-propylamino) - methyl] -phenyl} -thieno [3,2-b] pyridin-7-yl) - (2-methyl-1 H -indol-d-yl) -amine; 1 - . 1-imidazol-1 -yl-3-. { 4- [7- (2-methyl-1 H-indol-d-ylamino) -thieno [3,2- b] pyridn-2-yl] -benzylamino} -propan-2-ol; 2 - [(2-hydroxy-ethyl) - (4- { 4- [7- (2-methyl-1 H -indol-d-ylamino) -thieno [3,2- b] pyridine-2-pyridine; l] -benzylamino.} - butyl) -amino] -ethanol; d N, N-dethyl-N'-. { 4- [7 - (- methyl-1 H-indol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] benzyl} -propane-1, 3-diamine; [2- (3-amino-phenyl) -thieno [3,2-b] pyridin-7-yl] - (1 H -indole-5-yl) -amine; (2-methyl-1 H-indol-d-yl) - (2- {4 - [(3-morpholin-4-yl-propylamino) -methyl] -phenyl} -thieno [3,2- b] pyridin-7-yl) -amine; 0 [2- (4-dimethylaminomethyl-pheny] -thieno [3,2-b] pyridin-7-yl] - (2-methyl-1 H -indol-d-yl) -amine; 1- [d- (2-pyridin-2-yl-thieno [3,2-b] pyridin-7-ylamino) -2,3-dihydro-indol-1-yl] -ethanone; (2,3-dihydro-1 H-indol-d-yl) - (2-pyridin-2-yl-thieno [3,2-b] pyridin-7-yl) -d amine; (1 H-benzotriazol-d-yl) - (2-pyridin-2-yl-thieno [3,2-b] pyridin-7-yl) -amine; 5- (2-phenyl-thieno [3,2-b] pyridin-7-ylamino) -1 H -indole-3-carbaldehyde; (1 H-indazol-5-yl) - (2-pyridin-2-yl-thieno [3,2-b] pyridin-7-yl) -amine; (2-methyl-1 H-indol-d-1) - (2-pyridin-2-yl-thieno [3,2-b] pyridin-7-yl) -amine; 0 (1 H-benzoimidazol-d-yl) - (2-phenyl-thieno [3,2-b] pyridin-7-yl) -amine; d- (2-pyridin-2-yl-thieno [3,2-b] pyridin-7-ylamino) -1H-indole-2-carboxylic acid diethylamide; . { d- [7- (2-methyl-1 H -indol-d-ylamino) -thieno [3,2-b] pyridin-2-yl] -pyridn-2-yl} -methanol; N- (3-imidazol-1-yl-propyl) -6- [7- (1 H -indol-d-ylamino) -thieno [3,2- b] pyridin-2-yl] nicotinamide; d N- (3-hydroxy-propyl) -6- [7- (2-methyl-1 H -indol-d-ylamino) -thieno [3,2- b] pyridin-2-yl] nicotinamide; [2- (d-amino-pyridin-2-yl) -thieno [3,2-b] pyridin-7-yl] - (2-methyl-1 H -indole-d-yl) -amine; N- [2- (2-hydroxy-ethoxy) -ethyl] -6- [7- (2-methyl-1 H -indol-d-ylamino) -0-thieno [3,2-b] pyridin-2 -yl] -nicotinamide; (4-methoxy-2-methyl-phenyl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; [4- (4-chloro-phenoxy) -phenyl] - (6-phenyl-t-ene [3,2-d] pyrimidin-4-yl) -amine; 6- (6-phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -1 H- benzo [d] [1,3] oxazine-2,4-dione; d 2-diethylaminomethyl-4- (6-phenyl-t-ene [3,2-d] pyrimidin-4-ylamino) -phenol; d-methyl-1 - [4- (6-phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -phenyl] -1,2-dihydro-pyrazol-3-one; [4- (4, d-dichloro-imidazol-1-yl) -phenyl] - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; 0 (6-phenylthieno [3,2-d] pyrimidin-4-yl) - [4- (3-trifluoromethyl-pyrazol-1-yl) -phenyl-amine; [4- (4-methyl-piperazin-1-yl) -phenyl] - (6-phenyl-t-ene [3,2-d] pyrimidin-4-yl) -amine; [4- (4-methyl-piperidin-1-yl) -phenyl] - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; 1 - [4- (6-phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -phenyl} -1 H-tetrazole-d-thiol; d 3- (6-phenylthieno [3,2-d] pyrimidin-4-ylamino) -benzenesulfonamide; (2-methyl-benzothiazol-6-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; [4- (morpholin-4-sulfonyl) -phenyl] - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; [3, d-dimethyl-4- (thiophen-3-ylmethoxy) -phenyl] - (6-phenyl-thieno [3,2-0 d] pyrimidin-4-yl) -amine; [4, d-dimethoxy-2- (1 H -tetrazol-d-yl) -phenyl] - (6-phenylthieno [3,2- d] pyrimidin-4-yl) amine; d- [4- (6-phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -phenyl] -oxazolidine-2,4-dione; d 1 -ethyl-d- (6-phenyl-t-ene [3,2-d] pyrimidin-4-ylammon) -1,3-dihydro-indol-2-one; 6- (6-Phenyltieno [3,2-d] pyrimidin-4-ylamino) -3H-benzooxazol-2-one; dibenzothiophen-4-yl- (6-phenyl-t-ene [3,2-d] pyrimidin-4-yl) -amine; N- (6-phenyl-t-ene [3,2-d] pyrimidin-4-yl) -N'-p-tolyl-benzene-1,2-diamine; (2-furan-2-yl-1-methyl-1 H-benzoimidazol-d-yl) - (6-phenyl-thieno [3,2- d] pyrimidin-4-yl) -amine; d- (6-phenylthieno [3,2-d] pyrimidin-4-ylamino) -benzo [b] -thiophene-2-carbonitrile; (6-phenyl-t-ene [3,2-d] pyrimidin-4-yl) - (2-pyridin-4-yl-1 H-benzoimidazol-d-yl) -amine; d [4- (1-methyl-1 H-imidazol-2-ylsulfanyl) -phenyl] - (6-phenyl-thieno [3,2- d] pyrimidin-4-yl) -amine; (6-phenylthieno [3,2-d] pyrimidin-4-yl) - [4- (pyridin-2-yloxy) -phenyl] -amine; [4- (d-methyl-tetrazol-1-yl) -phenyl] - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; 0 1- [3- (6-phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -phenyl] -1 H -tetrazol-d-thiol; 4- [4- (6-phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -phenylamino] -phenol; [3- (3-methyl-4, d-dihydro-pyrazol-1-yl) -phenyl] - (6-phenyl-thieno [3,2- d] pyrimidin-4-yl) -amine; d benzo [1,2,3] thiadiazol-6-yl- (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; 4- [7- (2-methyl-1 H-indol-d-ylamino-thieno [3,2-d] pyrimidin-2-A-benzaldehyde; [6- (4-fluoro-phenyl) -thieno [3, 2-d] pyrimidin-4-yl] - (1 H -indol-d-yl) -amine; [6- (4-fluoro-pheny] -thione [3,2-d] pyrimidin-4 -yl] - (1 H-indol-5-yl) -amide; and pharmaceutically acceptable salts and hydrates of the above compounds. The present invention also relates to the intermediate compounds of formulas 25 and 26 and pharmaceutically acceptable salts thereof, wherein. X1 is N or CH; Z1 is halogen and Z2 is -NR1R2, or Z1 is R11 and Z2 is halogen, or Z1 and Z2 are independently halogen or R1 is H, C6 alkyl or -C (O) (C6 alkyl); R2 is aryl CT-CIO heterocyclic of d-13 elements, wherein said R2 groups are optionally substituted with 1 to d substituents R5, Each R3 is independently selected from H, -C (O) OR9 and Ci-Cß alkyl, wherein said alkyl group is optionally substituted with 1 to 3 R5 groups; Each R5 is independently selected from halogen, cyano, nitro, trifluoromethoxy, trifluoromethyl, azido, C (O) R8, -C (0) OR8, -OC (O) OR8, -NR6C (0) R7, -C (O) NR6R7, -NR6R7, -OR9, -SO2NR6R7, C6 alkyl, - (CH2) jO (CH2 qNR6R7, - (CH2 tO (CH2) qOR9, - (CH2) tOR9, -S (O) j (C-pCß alkyl ), (CH2) t (C6-C? 0 aryl), - (CH2) t (d-10-membered heterocyclic), -C (O) - (CH2) t (C6-C10 aryl), (CH2) tO (CH2) ¡(C6-C? 0 aryl), - (CH2) tO (CH2) q (d-10-membered heterocyclic), C (O) (C6-C? 0 aryl), (CH2) t (CH2) ) t 3d (heterocyclic of d-10 links), (CH2) tNR7 (CH2) qNR6R7, - (CH2) tNR7CH2C (O) NR6R7, - (CH2) tNR7 (CH2) qNR9C (0) R8, - (CH2) tNR7 (CH2) tO (CH2) qOR9, - (CH2) jNR7 (CH2) jNR7 (CH2) qS (O) j (CH2) t (C6 alkyl), - (CH2) jNR7 (CH2) t0R6, -SO2 (CH2) ) t (CH2) t (aryl C6-C? 0) and -SO2 (CH2) t (heterocyclic of d-10 d links), where j is an integer ranging from 0 to 2, t is a number integer that oscillates between 0 and 6, q is an integer that ranges between 2 and 6, including or optionally the radicals - (CH2) q - and - (CH2) t- of the above groups R5 a double or triple carbon-carbon bond, in which t is an integer between 2 and 6, and the alkyl, aryl radicals and heterocyclics of the above R5 groups are optionally substituted with 1 to 3 substituents independently selected from halogen, cyano, nitro, trifluoromethyl, azido, C (0) R8, -C (0) OR8, -OC (0) OR8, - OC (0) OR8, NR6C (O) R7, -C (O) NR6R7, -NR6R7, - (CH2) tNR6R7, alkyl d-C6. - (CH2) t (aryl C6-C? O), (CH2 t (heterocyclic of d-10 links), - (CH2) tO (CH2) q OR9 and -d (CH2) tOR9, where t is a integer that ranges from 0 to 6 and q is a number that ranges from 2 to 6, each R6 and R7 is independently selected from H, C-Cß alkyl, - (CH2) t (CH2) t (aryl Ce-Cio), - (CH2) t (heterocyclic of d-10 links), (CH2) tO (CH2) q OR9 and - (CH2) tOR9, where t is an integer ranging from 0 to 6 and q which is a whole number 0 which ranges from 2 to 6 and the alkyl, aryl and heterocyclic radicals of the above groups R6 and R7 are optionally substituted with 1 to 3 substituents independently selected from halogen, cyano, nitro, trifluoromethyl, azido, C (O) R8, -C (O) OR 8, -OC (O) OR 8, -NR 9 C (O) R 10, -C (O) NR 9 R 10, -NR 9 R 10, C C 6 alkyl, - (CH 2) j (C 6 -C 0 aryl), - ( CH2) t (heterocyclic of d-10 links), (CH2) tO CH2) qOR9 and - (CH2) t OR9, where t is an integer ranging from 0 to 6 and q is a number that oscillates in tre 2 and 6; with the proviso that when R6 and R7 are both bonded to the same nitrogen, then R6 and R7 are not attached to the nitrogen directly through an oxygen; each R8 is independently selected from H, C1-C10 alkyl, - (CH2) t (aryl Ce-Cio) and - (CH2) (heterocyclic of d-10 links), wherein t is an integer ranging from 0 and 6; 0 each R9 and R10 is independently selected from H and CrC6 alkyl; R11 is H, C? -C6 alkyl, -C (0) NR6R9, -C (O) (C6-C? 0 aryl), (CH2) t (CH2) t (aryl Ce-Cio), or - (CH2) t (heterocyclic of d-10 links), wherein t is an integer ranging from 0 to 6, wherein said groups R11 d other than H, are optionally substituted with tert-butyl dimethyl silanyl and with 1 ad groups R5; and R12 is H, C6 alkyl, C (O) (C6-C6 alkoxy), -S (O) j ( C? -C6), -SO2 (CH2) t (CH2) t (C6-C? 0 aryl), (CH2) t (C6-C? 0 aryl), - (CH2) t (heterocyclic d-10 links), - (CH2) tO (CH2) q OR9 or - (CH2) tOR9, where j 0 is an integer ranging from 0 to 2, t is an integer that ranges from 0 and 6 and q is an integer ranging from 2 to 6. The above intermediates of formulas 2d and 26 can be used to prepare the above compounds of formulas 1 and 2.

The invention also relates to a pharmaceutical composition for the treatment of a hyperproliferative disorder in a mammal that contains a therapeutically effective amount of a compound of formula 1 or 2, or a pharmaceutically acceptable salt or hydrate thereof and a pharmaceutically acceptable carrier. In one embodiment, said pharmaceutical composition is for the treatment of cancer, such as brain, lung, squamous cell, bladder, gastric, pancreatic, breast, head and neck, renal, kidney, ovarian, prostate, colorectal, esophageal, gynecological or thyroid. In another embodiment, said pharmaceutical composition 0 is for the treatment of a non-cancerous hyperproliferative disorder, such as benign skin hyperplasia (e.g., psoriasis) or benign prostatic hypertrophy (BPH). The invention also relates to a pharmaceutical composition for the treatment of pancreatitis or kidney disease (including proliferative glomerulonephritis and diabetes-induced renopathy) in a mammal that contains a therapeutically effective amount of a compound of formula 1 or 2 or a pharmaceutically acceptable salt or hydrate thereof and a pharmaceutically acceptable carrier. The invention also relates to a pharmaceutical composition 0 for preventing implantation of the blastocyst in a mammal that includes a therapeutically effective amount of a compound of formula 1 or 2 or a pharmaceutically acceptable salt or hydrate thereof and a pharmaceutically acceptable carrier.

The invention also relates to a pharmaceutical composition for the treatment of a disease related to vasculogenesis or angiogenesis in a mammal that contains a therapeutically effective amount of a compound of formula 1 or 2 or a pharmaceutically acceptable salt or hydrate thereof, and a pharmaceutically acceptable vehicle. In one embodiment, said pharmaceutical composition is for the treatment of a disease selected from the group consisting of tumor angiogenesis, chronic inflammatory disease, such as rheumatoid arthritis, arteriosclerosis, skin diseases, such as, psoriasis, eczema and 0 scleroderma. , diabetes, diabetic retinopathy, retinopathy or prematurity, macular degeneration related to age, hemangioma, glioma, melanoma, Kaposi's sarcoma and breast, lung, pancreatic, prostate, colon and epidermo.de cancer. The invention also relates to a method for the treatment of a hyperproliferative disorder in a mammal comprising administering to said mammal a therapeutically effective amount of a compound of formula 1 or 2 or a pharmaceutically acceptable salt or hydrate thereof. In one embodiment, said method relates to the treatment of cancer such as brain, squamous cell, bladder, gastric, pancreatic, breast, head and neck, esophageal, prostate, colorectal, lung, renal, Kidney, ovarian, gynecological or thyroid. In another embodiment, said method refers to the treatment of a non-cancerous hyperproliferative disorder, such as benign skin hyperplasia (e.g., psoriasis) or prostate hyperplasia (e.g., benign prostatic hypertrophy) (BPH)). The invention also relates to a method for the treatment of a hyperproliferative disorder in a mammal comprising administering to said mammal a therapeutically effective amount of a compound of formula 1 or 2 or a pharmaceutically acceptable salt or hydrate thereof, in combination with an antitumor agent selected from the group consisting of mitotic inhibitors, alkylating agents, antimetabolites, intercalating antibiotics, inhibitors of growth factor, cell cycle inhibitors, enzymes, topoisomerase inhibitors, biological response modifiers, anti- hormones and anti- androgens. The invention also relates to a method for the treatment of pancreatitis or renopathy in a mammal comprising the administration to said mammal of a therapeutically effective amount of a compound of formula 1 or 2 or a pharmaceutically acceptable salt or hydrate thereof. The invention also relates to a method for preventing implantation of the blastocyst in a mammal comprising administering to said mammal a therapeutically effective amount of a compound of formula 1 or 2 or a pharmaceutically acceptable salt or hydrate thereof. The invention also relates to a method for the treatment of diseases related to vasculogenesis or angiogenesis in a mammal comprising the administration to said mammal of an effective amount of a compound of formula 1 or 2 or a pharmaceutically acceptable salt or hydrate thereof. . In an embodiment, said method is for the treatment of a disease selected from group d consisting of tumor angiogenesis, chronic inflammatory disease, such as rheumatoid arthritis, arteriosclerosis, skin diseases, such as, psoriasis, eczema and scleroderma, diabetes , diabetic retinopathy, retinopathy or prematurity, macular degeneration related to age, hemangioma, glioma, melanoma, Kaposi's sarcoma and ovarian cancer, 0 breast, lung, pancreatic, prostate, colon and epidermoid. The patients can be treated with the compounds of formulas 1 or 2 and the pharmaceutically acceptable salts and hydrates of said compounds, according to the methods of this invention, include, for example, patients who have been diagnosed with psoriasis, BPH, cancer. lung cancer, bone cancer, pancreatic cancer, skin cancer, head and neck cancer, cutaneous and intraocular melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, colon cancer, cancer breast, gynecological tumors (eg, uterine sarcomas, fallopian tube carcinoma, endometrial carcinoma, cervix carcinoma, vagina carcinoma or vulvar carcinoma), Hodgkin's disease, esophageal cancer, small bowel cancer, cancer of the endocrine system (for example, cancer of the thyroid, parathyroid or adrenal gland), soft tissue sarcomas, urethral cancer, cancer of the penis, chronic leukemia or acute, childhood solid tumors and lymphocytic lymphomas, bladder cancer, kidney or ureter cancer (eg, renal cell carcinoma, renal pelvis carcinoma) or neoplasms of the central nervous system (eg, primary CNS lymphoma, vertebral axis tumors, brainstem gliomas or pituitary adenomas). The term "halogen", as used herein, unless otherwise indicated, includes fluorine, chlorine, bromine or iodine. The preferred halogen groups are fluorine, chlorine and bromine. The term "alkyl", as used herein, unless otherwise indicated, includes saturated monovalent hydrocarbon radicals having straight chain, cyclic or branched chain radicals. Said "alkyl" group may include a double or triple carbon-carbon bond, wherein said alkyl group contains at least two carbon atoms. It is understood that at least three carbon atoms are required in said alkyl group. The term "alkoxy," as used herein, unless otherwise indicated, includes O-alkyl groups, wherein said "alkyl" is as defined above. The term "aryl", as used herein, unless otherwise indicated, includes an organic radical derived from an aromatic hydrocarbon by removal of a hydrogen, such as phenyl or naphthyl.

The term "d-10-chain heterocyclic" or "d-13-chain heterocyclic", as used herein, unless otherwise indicated, includes aromatic and non-aromatic heterocyclic groups containing one to four heteroatoms, each selected one of O, S and N, in which each heterocyclic group has d-10 or d-13 atoms in its ring system. Heterocyclic groups include benzocondensate ring systems and ring systems substituted with one or two oxo radicals (= O), such as pyrrolidin-2-one. An example of a d-ring heterocyclic group is thiazolyl, an example of a 10-membered heterocyclic group is quinolinyl, and an example of a 13-membered heterocyclic group is a carbazole group. Examples of non-aromatic heterocyclic groups are pyrrolidinyl, piperidino, morpholino, thiomorpholino and piperazinyl. Examples of aromatic heterocyclic groups are pyridinyl, imidazolyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, tetrazolyl, furyl, thienyl, isoxazolyl and thiazolyl. Heterocyclic groups having a condensed benzene ring include benzimidazolyl, benzofuranyl and benzo [1,3] dioxolyl. The phrase "pharmaceutically acceptable salt (s)", as used herein, unless otherwise indicated, includes salts of either acidic or basic groups which may be present in the compounds of the formulas 1 and 2. The compounds of formulas 1 and 2 which are basic in nature are capable of forming a wide variety of salts with various inorganic and organic acids. The acids that can be used to prepare the pharmaceutically acceptable acid addition salts of said basic compounds of formulas 1 and 2 are those which form non-toxic acid addition salts, ie, the salts containing pharmacologically acceptable anions, such as hydrochloride, hydrobromide, d-hydroiodide, nitrate, sulfate, bisulfate, phosphate, acid phosphate, isonicotinate, acetate, lactate, salicylate, citrate, citrate, tartrate, pantothenate, bitartrate, ascorbate, succinate, maleate, gentisinate, fumarate, gluconate , glucaronate, saccharate, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate and pamoate [i.e. 1, 1'-methylene-bis- (2-0-hydroxy-3-naphthoate)]. Those compounds of formulas 1 and 2 which are acidic in nature, are capable of forming basic salts with various pharmacologically acceptable cations. Examples of such salts include the alkali metal or alkaline earth metal salts and, especy, the sodium and d potassium salts. Certain compounds of formula 1 and 2 can have asymmetric centers and, therefore, exist in different enantiomeric forms. This invention relates to the use of all optical isomers and stereoisomers of the compounds of formulas 1 and 2 and mixtures thereof. The compounds of formulas 1 and 2 can also exist as tautomers. This invention relates to the use of said tautomers and mixtures thereof.

SCHEME 1 8 SCHEME 2 SCHEME 3 17 18 twenty DETAILED DESCRIPTION OF THE INVENTION The preparation of the compounds of the present invention is illustrated in the following schemes 1-3. The compounds of the present invention are readily prepared according to synthetic methods familiar to those skilled in the art. Scheme 1 illustrates a general synthetic procedure for the preparation of the compounds of the present invention. Although scheme 1 specifically illustrates the preparation of the compounds of formula 1, it is equally applicable to the preparation of the compounds of formula 2. The compound of formula 7 (wherein X 'is as defined above) can be prepared by one or more methods described in published PCT international applications numbers WO 9d / 19774 (published July 27, 1995), WO 95/19970 (published July 27, 1995) and WO 97/13371 (published April 17, 1995). 1997). Likewise, 4-chlorothieno [3,2-d] pyrimidine is commercially available, such as that of Maybridge Chemical Co. Ltd. A preferred method for the preparation of 4-chlorothieno [3,2-djpyridine is described below with reference to steps 1-3 of scheme 2. In step 1 of scheme 1, the compound of formula 7 can be converted into the corresponding bromo derivative of formula 8 by treating the starting compound with lithium diisopropylamine or n-butyllithium and then 1,2-dibromo-1,1,1,2-tetrafluoroethane or bromine in a non-polar solvent, such as tetrahydrofuran (THF) at a temperature from about -78 ° C for a period of about 15 minutes to half an hour and then gradually heating the mixture to room temperature (20-25 ° C). In step 2 of scheme 1, the compound of formula 8 can be coupled with a compound of formula HNR1R2, wherein R1 and R2 are as defined above, optionally in the presence of a base, such as pyridine, triethylamine or sodium hydride and optionally in the presence of pyridine hydrochloride as a catalyst, in an inert atmosphere, such as nitrogen dry gas, in a solvent, such as C1-C6 alcohol, dimethylformamide (DMF), 1,2-dichloroethane (DCE), N-methylpyrrolidine -2-one 0 (NMP), chloroform, acetonitrile, THF, dimethylsulfoxide (DMSO), 1,4-dioxane or pyridine, or a mixture of two or more of the above solvents, preferably a mixture of t-butyl alcohol and DCE at a temperature from room temperature to reflux, preferably 80-12d ° C for a period of about 2 hours to 72 hours, giving the compound d of formula 9. The above reaction is preferably carried out in a sealed tube. When the compound of formula HNR1R2 is an optionally substituted indole or indoline radical, said compounds may be prepared according to one or more of the methods known to those of skill in the art. Such methods are described in PCT international patent application publication number WO 9d / 23141, cited above and in W.C. Sumpter and F.M. Miller, "Heterocyclic Compounds with Nature and Carbazole Systems" in Volume 8 of "The Chemistry of Heterocyclic Compounds," Interscience Publishers Inc., New York (19d4). Suitable optional substituents may be included before or after the coupling step illustrated in scheme 1. Prior to the coupling step, the primary and secondary amino radicals (other than the aforementioned amine of formula HNR1R2) are preferably protected using a protecting group of nitrogen known to those skilled in the art. Said protective groups and their use are described in T.W. Greene and P.G.M. Wuts, "Protective Groups in Organic Synthesis", Second Edition, John Wiley & amp;; Sons, New York, 1991. 0 In step 3 of scheme 1, the compound of formula 9 can be converted to the compound of formula 1 by coupling the starting compound with a compound of formula R 11 -B (OH) 2 (in the that R11 is as defined above) in the presence of 1,4-bis (diphenylphosphine) butane and a palladium catalyst, such as bis (benzonitrile) -palladium (II) chloride, a base, such as carbonate d sodium or potassium and a solvent, such as toluene, ethanol, THF, DMF, or dimethoxyethane (DME), preferably a mixture of toluene, ethanol and THF, at a temperature in the range of about 50-110 ° C during a period of approximately 1 to 24 hours. This step is analogous to the Suzuki coupling procedure described in N. Miyaura, 0 A. Suzuki, Chem. Rev. 1195, 95, 2457. Alternatively, steps 2 and 3 of scheme 1 can be reversed. That is, the group R11 can be introduced into the compound of formula 7 followed by coupling the resulting compound with the compound of formula HNR1R2 as described above. In another procedure, step 3 of scheme 1 can be carried out by reacting the compound of formula 9 with a compound of formula (trialkylstannyl) -R 11 (in which R 11 is as defined above), such as (tributylstannyl) -R 11, in the presence of copper iodide and trans-benzyl (chloro) -bis d (triphenylphosphine) palladium (II) in DMF at a temperature of about 90 ° C for a period of about 14 hours. The starting compound for this process, specifically (tributylstannyl) -R11, can be prepared from R11-Br by at least three separate procedures. In a first process, R11-Br can be treated with chloride (tributylstannyl) 0 and n-butyl lithium in THF or DMF giving (tributylstannyl) -R11. In a second process, R11-Br can be treated with Bu3Sn-SnBu3, in which Bu represents butyl and sodium metal, giving (tributylstannyl) -R11. And in a third procedure, R1-Br can be treated with Bu3Sn-SnBu3, where Bu represents butyl and Pd (PPh3), where Ph represents phenyl, in toluene, d giving (tributylstannyl) -R11. After or before step 3 of scheme 1, group R11 can be modified to introduce one or more groups R5 (in which R5 is as defined above). In a preferred method, wherein R 11 is a phenyl group that includes an aldehyde group, the aldehyde can be converted to a preferred aminomethyl group. In this process, the starting compound that includes an aldehyde in the group R11 reacts with an amine of the formula HNR6R7 (in which R6 and R7 are as defined above) in the presence of a reducing agent, such as sodium cyanoborohydride or sodium borohydride , in a solvent containing acetic acid and ethanol or methanol at a temperature in the range of 0-100 ° C, preferably at room temperature. This process converts the aldehyde to a radical of the formula R6R7NCH2-. Other methods for modifying the compounds of formula 1 will be obvious to those skilled in the art. The compounds of formula 2 are prepared analogously. Scheme 2 illustrates a process for the preparation of the compounds of formula 1, wherein X 1 is CH. In step 1 of scheme 2, the compound of formula 10 (3-amino-thiophene-2-carboxylic acid methyl ester) is dissolved in sodium hydroxide and refluxed for about 2 hours. The solution is then cooled to 0 ° C and acidified to pH d with concentrated HCl, at which time a precipitate forms. The precipitate is separated and treated with propanol and oxalic acid and the solution is stirred at about 38 ° C for about 4d minutes to give the compound of formula 11 (thiophen-3-ylamine). In step 2 of scheme 2, the compound of formula 11 is dissolved in triethyl orthoformate and stirred at room temperature until the dissolution is complete. Then 2,2-dimethyl- [1, 3] dioxan-4,6-dione at room temperature, forming a precipitate upon completion of the addition. The mixture is then heated to 8d ° C overnight. The resulting precipitate, which is an intermediate (2,2-dimethyl-d- (thiophen-3-ylaminomethylene) - [1,3] dioxane-4,6-dione) is separated and washed. The intermediate is added to the eutectic A (heated to 260 ° C) and the resulting mixture is heated for 30 d2 minutes and then cooled to room temperature to give the compound of formula 12. In step 3 of scheme 2, the compound of formula 12 is added to the oxalyl chloride in a mixture of methylene chloride and DMF and heated to reflux for about two hours to give the compound of formula 13. The compound of formula 13 can be converted to the compound of formula 14 as described above with respect to step 1 of scheme 1. The compound of formula 14 can be converted into the compound of formula 15 as described above with respect to step 2 of scheme 1. The compound of formula 15 can be converted into the compound of formula 16 as described above with respect to step 3 of scheme 1. Scheme 3 illustrates an alternative method of coupling group R11 represented by the compound of formula 18, wherein each radical X is CH or N and R5 is as defined above, with the rest of the compound of formula 1 or 2, the remainder of which is illustrated as the compound of formula 17 corresponds in structure with the compound of formula 1, can be follow the procedure described with respect to scheme 3, to prepare the corresponding compounds of formula 2. In step 1 of scheme 3, the compound of formula 17 is coupled with the compound of formula 18 in DMF in the presence of copper and trans iodide. -benzyl (chloro) bis- (triphenylphosphine) palladium (II) at a temperature from about 90 ° C for about 14 hours to give the compound of formula 19. The compound of formula 19 can then be coupled with compound d3 of formula HNR1R2 , wherein R1 and R2 are those defined above, as described above with respect to step 2 of scheme 1, giving the compound of formula 20. The compounds of the present invention may have carbon atoms d metric Said diastereomeric mixtures can be separated into their individual diastereomers on the basis of their physicochemical differences by methods known to those skilled in the art, for example, by chromatography or fractional crystallization. The enantiomers can be separated by converting the enantiomeric mixtures into a diastereomeric mixture by reaction with an appropriate optically active compound (eg, alcohol), separating the diastereomers and converting (eg, hydrolyzing) the individual diastereomers into the corresponding pure enantiomers. All these isomers, including the mixture of diastereomers and pure enantiomers are considered as part of the invention. The compounds of formulas 1 and 2 which are basic in nature are capable of forming a wide variety of different salts with various inorganic or organic acids. Although such salts must be pharmaceutically acceptable for administration to animals, it is often desired in practice to initially isolate the compound of formula 1 or 2 from the reaction mixture as a pharmaceutically unacceptable salt and then simply convert the latter into the base compound. free by treatment with an alkaline reagent and subsequently converting the last free base d4 into a pharmaceutically acceptable acid addition salt. The acid addition salts of the basic compounds of this invention are readily prepared by treating the basic compound with a substantially equivalent amount of the chosen mineral and organic acid in an aqueous solvent medium or in an appropriate organic solvent, such as methanol or ethanol, By carefully evaporating the solvent, the desired solid salt is easily obtained. The desired acidic salt can also be precipitated in a solution of the free base in an organic solvent by adding an appropriate organic mineral or acid to the solution. 0 Those compounds of formulas 1 and 2, which are acidic in nature, are capable of forming basic salts with various pharmacologically acceptable cations. Examples of said salts include the alkali metal or alkaline earth metal salts and, especially, the sodium and potassium salts. These salts are prepared by conventional techniques. The chemical bases which are used as reagents for preparing the pharmaceutically acceptable salts of this invention are those which form non-toxic basic salts with the acidic compounds of formula 1 and 2. Said non-toxic basic salts include those derived from said pharmacologically acceptable cations as sodium , potassium, calcium and 0 magnesium, etc. These salts can be easily prepared by treating the corresponding acidic compounds with an aqueous solution containing the desired pharmacologically acceptable cations and then evaporating the resulting solution to dryness, preferably under reduced pressure. Alternatively, they can also be prepared by mixing lower alkanolic solutions of the acidic compounds and the desired alkali metal alkoxides and then evaporating the resulting solution to dryness in the same manner as before. In any case, stoichiometric amounts of reagents are preferably employed in order to ensure that the reaction is completed and to obtain maximum yields of the desired final product. The compounds of the present invention are potent inhibitors of the erbB family of tyrosine kinases of oncogenic and proto-oncogenic proteins, such as the epidermal growth factor receptor (EGFR), erb2, HER3 or HER4 and, therefore, all of them are they adapt to therapeutic use as antiprofilerative agents (e.g., anticancer) in mammals, especially humans. The compounds of the present invention are also inhibitors of angiogenesis and / or vasculogenesis. In particular, the compounds of the present invention are useful in the prevention and treatment of a variety of human hyperproliferative disorders, such as malignant and benign tumors of the liver, kidney, bladder, breast, gastric, ovarian, colorectal, prostate , pancreatic, lung, vulvar, thyroid, hepatic carcinomas, or sarcomas, glioblastomas, head and neck and other hyperplastic disorders, such as benign skin hyperplasia (eg, psoriasis) and benign prostatic hyperplasia ( for example, BPH Also, it is expected that a compound of the present invention possesses activity against a range of leukemias and lymphoid malignancies The compounds of the present invention may also be useful in the treatment of other additional disorders in which they are d involved various protein tyrosine kinases related to aberrant expression events in ligand / receptor interactions or in Activation or signaling. Such disorders may include those of a neuronal, glial, astro- cital, hypothalamic nature and others of a glandular, macrophage, epithelial, stromal and blastocoelic nature, in which aberrant function, expression, activation or signaling of the erbB tyrosine kinases are involved. Also, the compounds of the present invention may have a therapeutic utility in inflammatory, angiogenic and immunological disorders, involving both the tyrosine kinases identified and those not yet identified and which are inhibited by the compounds of the present invention. The in vitro activity of the compounds of formulas 1 and 2 in terms of the inhibition of receptor tyrosine kinase (and consequently the proliferative response, eg, cancer) can be determined by the following procedure. The in vitro activity of the compounds of formulas 1 and 2 can be determined by the amount of inhibition of the phosphorylation of an exogenous substrate (for example, Lis3-gastrin or a random copolymer of polyGluTir (4: 1) (I. Posner et al., J. Biol. Chem. 267 (29), 20638-47 (1992) d7 on tyrosine by the epidermal growth factor receptor kinase for a test compound relative to a control. A human EGF receptor with a purified and soluble affinity (96 ng) is obtained according to the procedure described by GN Gill, W. Weber, Methods in Enzymoloqy 146. 82-88 (1987) from A431 cells ( American Collection of Cell Culture Types, Rockville, MD) and preincubated in a microcentrifuge tube with EGF (2 μg / ml) in a phosphorylation buffer + vanadate (PBV: dO mm HEPES, pH 7.4; 12d mm NaCl; 24 mm MgCl 2; 100 μM sodium orthovanadate) in a total volume of 10 μM, for 0 20-30 minutes at room temperature. The test compound, dissolved in dimethyl sulfoxide (DMSO), is diluted in PBV and mixed 10 μM with the EGF / EGF receptor mixture and incubated for 10-30 minutes at 30 ° C. The phosphorylation reaction is initiated with the addition of 20 μl of the 33P-ATP / substrate mixture (120 μM of Lis3-Gastrin (sequence in the code of single letters for amino acids, KKKGPWLEEEEEAYGWLDF), dO mm Hepes pH 7.4, 40 μM ATP, 2 μCi? - [33P] -ATP to the EGFr / EGF mixture and incubate for 20 minutes at room temperature.The reaction is stopped by the addition of 10 μl of stop solution (Od M EDTA, pH 8.2 mm of ATP) and 6 μl of 2N HCl The tubes are centrifuged at 14,000 rpm, 4 ° C, for 10 0 minutes, pipette 3d μl of supernatant from each tube into a 2.d cm circle of Whatman P81 paper, it is washed four times with acetic acid d% in bulk, 1 liter per wash and then air-dried.This produces the binding of the substrate to the paper with loss of free ATP during washing.The d8 [33P] incorporated is measured with a liquid scintillation counter The incorporation in the absence of substrate (eg, lis3-gastrin) is subtracted from all the lores as a background value and the percent inhibition is calculated relative to the controls without the test compound. Said tests, d carried out with a range between the doses of the test compounds, allow the determination of an IC50 value approximately for the in vitro inhibition of the activity of the EGFR kinase. The activity of the compounds of formula 1 and 2, in vivo, can be determined by the amount of inhibition of tumor growth induced by a test compound compared to a control. The inhibitory effects of tumor growth on various inhibitory effects of tumor growth of several compounds are measured according to the methods of Corbett T. H., et al. "Tumor Induction Relationships in Developmental of Transplantable Cancers of the Colon in Mice for Chemotherapy Assays, with a Note on Carcinogen Structure", Cancer Res .. 3d, 2434-2439 (197d) and Corbett, T.H. et al., "A Mouse Colon-tumor Model for Experimental Therapy", Cancer Chemother. Rep. (Part 2). d ^ 169-186 (197d) with slight modifications. The tumors are induced on the left side by s.c. of a 1 x 106 log phase of cultured tumor cells (0 MB-468 human carcinoma cells or HNd head and neck carcinoma cells) suspended in RPMI 0.10 ml 1640. Once enough time has elapsed for the tumors become palpable (2-3 mm in diameter), test animals (nude mice) are treated with the active compound (formulated by d9 solution in DMSO typically with a concentration of dO at 100 mg / ml followed by dilution 1: 9 in saline, or alternatively, 1: 9 dilution in Pluronic ™ P10d in 0.9% saline) per administration twice a day (ie, every 12 hours) intraperitoneally (ip) or orally (po) for dd days Consecutive In order to determine an antitumor effect, the tumor is measured in millimeters with Vernier capillaries in two diameters and the tumor size (mg) is calculated using the formula: tumor weight = (length x [width] 2/2 of according to the methods of Geran Rl et al. "Protocols for Screening Chemical Agents and Natural Products Against Animal Tumors and 0 Other Biological Systems", Third Edition, Cancer Chemother, Rep., 3- 1- 104 (1972). expressed as percent inhibition according to the formula: inhibition (%) = (TuW8ntroi - TuWensayo) / TuWcontroi x 100% The lateral zone of the tumor implantation provides reproducible dose / response effects for a variety of chemotherapeutic agents and The method of measurement (tumor diameter) is a reliable method to determine the rates of tumor growth Other methods for assessing the activity of the compounds of the present invention relate to the application publication PCT International Publication No. WO 9d / 21613 (published August 17, 199d), which is hereby incorporated by reference. The in vitro activity of the compounds of formulas 1 and 2 for inhibiting the KDR / VEGF receptor can be determined by the following method.

The ability of the compounds of the present invention to inhibit tyrosine kinase activity can be measured using a recombinant enzyme in an assay that measures the ability of compounds to inhibit phosphorylation of the exogenous substrate, polyGluTir (PGT, Sigma ™, 4: 1 ). The d domain of the KDR receptor kinase? Human EGF (amino acid 80d-13d0) is expressed in Sf9 insect cells as a fusion protein of gluation S-transferase (GST) using the baculovirus expression system, The protein is purified from the lysates of these cells using agarose affinity columns by gluation. The enzymatic assay is performed in 96-well plates that are coated with the PGT substrate (0.62d μg PGT per well). The test compounds are diluted in dimethylsulfoxide (DMSO) and then added to the PGT plates, so that the final concentration of DMSO in the assay is 1.6% (v / v). The recombinant enzyme is diluted in phosphorylation buffer (dO mm of d Hepes, pH 7.3, 12d mm NaCl, 24 mm MgCl 2). The reaction is initiated by the addition of ATP to a final concentration of 10 μm. After a 30 minute incubation at room temperature with stirring, the reaction is aspirated and the plates are washed with phosphate buffer (Tween-20 containing 0.1% PBS). 0 The amount of phosphorylated PGT is quantified by incubation with a PY-d4 antibody conjugated with HRP (HRP is horseradish peroxidase) (Transduction Labs), developed with TMB peroxidase (TMB is 3.3 ', d, d- tetramethylbenzidine) and the reaction is quantified in a BioRad ™ microplate reader at 4d0 nM. The inhibition of the enzymatic kinase activity by the test compound is detected at reduced absorbency and the concentration of the compound that is required to inhibit the signal by d0% is given by the IC50 value for the test compound, d To measure the capacity of compounds for inhibiting KDR tyrosine kinase activity for the full-length protein that exists in a cellular context, porcine aortic endothelial cells (PAE) transformed with human KDR can be used (Waltenberger et al., J. Biol. Chem. 269: 26988, 1994). The cells are transferred to a plate and allowed to grow in 96-well plates in the same medium (Ham's F12) with 10% FBS (fetal bovine serum). The cells are then washed and reduced medium is added again in serum containing 0.1% (v / v) of bovine serum albumin (BSA) and allowed to incubate for 24 hours. Immediately prior to administration of the compound dose, the cells are re-added to the reduced medium in serum (without BSA). The test compounds, dissolved in DMSO, are diluted in the medium (final concentration of DMSO 0.d% (v / v)). At the end of a 2 hour incubation, VEGF165 (dO ng / final ml) is added to the medium for an incubation of 8 minutes. Cells are washed and lysed in HNTG buffer (20 mm Hepes, pH 7.d, 1d0 mm 0 NaCl, 0.2% Triton ™ X-100, 10% glycerol, 0.2 mm PMSF (phenylmethylsulfonyl fluoride), 1 μg / ml, pepstatin, 1 μg / ml leupeptin, 1 μg / ml aprotonin, 2 mm sodium pyrophosphate, 2 mm sodium orthovanadate). The measurement of KDR phosphorylation is measured using an ELISA assay. The 96-well plates are covered with 1 μg per well of goat anti-rabbit antibody. The unbound antibodies are washed from the plate and the remaining sites are blocked with Superblock buffer (Pierce) before the addition of anti-flk-1 C20 antibody (O.d μg per plate, Santa Cruz). All unbound antibodies d are washed from the plates before addition of the cell lysate. After a 2 hour incubation of the lysates with the flk-1 antibody, the phosphotyrosine associated with KDR is quantified by the development with the antibody PY d4 conjugated with HRP and TMB, as described above. The ability of the compounds to inhibit the autophosphorylation reaction stimulated with 0 VEGF by 0%, compared to the controls stimulated with VEGF, is given by the IC 50 value for the test compound. The ability of the compounds to inhibit mitogenesis in human endothelial cells is measured by their ability to inhibit 3 H-thymidine incorporation in HUVE cells (endothelial cells of the human umbilical vein, Clonetics ™). This assay has been well described in the literature (Waltenberger J et al., J. Biol. Chem. 269: 26998, 1994; Cao Y et al. J. Biol. Chem. 271: 31d4, 1996). To summarize, 104 cells are placed in 24-well plates covered with collagen and allowed to attach. Cells are re-added without serum and 24 hours later they are treated with 0 different concentrations of the compound (prepared in DMSO, the final concentration of DMSO in the assay is 0.2% v / v) and 2-30 ng / ml VEGF? 65- During the last 3 hours of the 24 hour treatment with the compound, a pulse is given to the cells with 3H-thymidine (NEN, μCi per well). The media is then removed and the cells carefully washed with Hank's balanced salt solution cooled with ice and then 2 times with ice-cold trichloroacetic acid (10% v / v). The cells are lysed by addition of 0.2 ml of 0.1 N NaOH and the lysates are transferred to scintillation vials. The wells are then washed with 0.2 ml of HCl, 0.1 N and this wash is then transferred to the vials. The degree of incorporation of 3H-thymidine is measured in a scintillation counter. The ability of the compounds to inhibit the incorporation by 0%, compared to the control (VGEF treatment with vehicle or DMSO alone) is given by the IC 50 value for the test compound. The administration of the compounds of the present invention (hereinafter "active compound (s)") can be accomplished by any method that facilitates the release of the compounds at the site of action.These methods include intravenous administration routes. , subcutaneous, intramuscular, intravascular or infusion), topical and rectal. The amount of active compound administered will depend on the subject to be treated, the severity of the disorder or disease, the administration regimen and the opinion of the prescribing physician. However, an effective dose is in the range from about 0.001 to about 100 mg per kg. of body weight per day, preferably about 1 to about 3d mg / kg / day, in single or divided doses. For a 70 kg person, this amount would be from about O.Od to about 7 g / day, preferably from about 0.2 to about 2.d g / day. In some cases, dosage levels below the lower limit of the aforementioned range may be more than adequate although in other chaos higher doses may be employed without causing any detrimental secondary effects, provided that said higher doses are They divide first in several small doses for administration throughout the day. The active compound can be applied with an isolated therapy or it can involve one or more antitumor substances, for example, those selected from among mitotic inhibitors, for example, vinblastine, alkylating agents, for example, cisplatin, carboplatin and cyclophosphamide; antimetabolites, for example, d-fluoracil, cytosine arabinoside and hydroxyurea or, for example, one of the preferred antimetabolites described in European Patent Application No. 239362, such as the acid? / - (5- / - 3,4 -dihydro-2-methyl-d 4-oxoquinazolin-6-ylmethyl) -? / - methylamino] -2-tenoyl) -L-glutamic; growth factor inhibitors; cell cycle inhibitors; intercalating antibiotics, for example, adriamycin and bleomycin; enzymes, for example, interferon; and antihormones, for example, anti-estrogens, such as Nolvadex ™ (tamoxifen) or, for example, anti-androgens, such as Casodex ™ (4'-cyano-3- (4-fluorophenylsulfonyl) -2-hydroxy-2) -methyl-3 '- (trifluoromethyl) propionanilide). Said co-treatment can be carried out by means of the simultaneous, sequential or separate administration of the dose of the individual components of the treatment.

The pharmaceutical composition may for example be in a form suitable for oral administration as a tablet, capsule, pill, powder, sustained release formulations, solution, suspension, for parenteral injection as a sterile solution, suspension or emulsion, d for administration topical as an ointment or cream or for rectal administration as a suppository. The pharmaceutical composition can be in unit dosage form suitable for the single administration of specific dosages. The pharmaceutical composition will include a conventional pharmaceutical carrier or excipient and a compound according to the invention as an active ingredient. It may also include other medicinal or pharmaceutical agents, vehicles, adjuvants, etc. Examples of parenteral administration forms include solutions or suspensions of active compounds in sterile aqueous solutions, for example, aqueous propylene glycol or dextrose solutions. d Such dosage forms can be appropriately buffered if desired. Suitable pharmaceutically acceptable carriers include inert diluents or fillers, water and various organic solvents. The pharmaceutical compositions, if desired, may contain 0 additional ingredients, such as flavoring agents, binders, excipients and the like. Accordingly, for oral administration, tablets containing various excipients, such as starch, alginic acid and certain complex silicates and with binding agents, such as sucrose, gelatin and acacia gum can be used. Additionally lubricating agents, such as magnesium stearate, sodium lauryl sulfate and talc, are often useful for the manufacture of tablets. Solid compositions of the similar type can also be used in soft and hard gelatin d capsules. Preferred materials for this include lactose or milk sugar and high molecular weight polyethylene glycols. When what is desired are aqueous suspensions or elixirs for oral administration, the active component thereof can be combined with various sweetening or flavoring agents, colorants or dyes and, if desired, emulsifiers or suspending agents together with diluents, such as water, ethanol, propylene glycol, glycerin or combinations thereof. Methods of preparing various pharmaceutical compositions with a specific amount of the active compound are known, or will be apparent to those skilled in the art. For more examples, see Remington's Pharmaceutical Sciences, Mack Publishing Company, Easter, Pa, 1st Edition (197d). The examples and preparations given below further illustrate and exemplify the compounds of the present invention and the methods of preparing said compounds. It is understood that the scope of the present invention is not limited to any extent by the scope of the following examples and preparations.

EXAMPLE 1 A. 3-formylamino-thiophene-2-carboxylic acid methyl ester To a solution of the 3-amino-thiophene-2-d-carboxylic acid methyl ester (2d g, 1d9 mmol) in 12d ml of formic acid was added ammonium acetate (1d.9 g, 207 mmol). The reaction mixture was heated to reflux for 3 hours, after which time the solution was cooled to room temperature (20-2d ° C). The solid thus formed was filtered, washed with water and dried under vacuum to give 2d.4 g (86%) of the 3-formylamino-thiophene-2-carboxylic acid methyl ester. 1 H NMR (400 MHz, DMSO) d 10.2 (s, 1 H), 8.3 d (s, 3 H), 7.92 (d, 1 H), 7.91 (d, 1 H), 3.76 (s, 3 H). LC-MS: 186 (MH +); HPLC TR: 2.81 minutes.

B. 3H-T-phenol3,2-d1-pyrimidin-4-one. In a 12d ml round-bottom flask, 3-formylamino-thiophene-2-carboxylic acid methyl ester (dg, 27.0 mmol), ammonium formate were combined. (5.11 g, 81.0 mmol) and formamide (6.40 ml, 162 mmol) and heated to 140 ° C. After 10 hours, the reaction mixture was cooled to room temperature and filtered. The crystalline solid was washed with water and dried under vacuum to give 2.96 g (72%) of 3H-thieno [3,2-d] pyrimidin-4-one. 0 1 H NMR (400 MHz, DMSO) d 8.10 (m, 2H), 7.34 (m, 1 H). LC-MS: 153 (MH +); HPLC TR: 1.21 minutes.

C. 4-Chloro-thienof3,2-d1-pyridine Dimethylformamide (6.6 ml, 8.4 mmol) in dO ml of dichloroethane was cooled to 0 ° C and oxalyl chloride was added slowly (62 ml. mmoles, 2M in dichloromethane) for several hours to form a white gel, d 3H-Thieno [3,2-d] pyrimidin-4-one (d.90 g, 38.8 mmol) was added and the reaction mixture was heated to reflux . After 2.d hours, the mixture was cooled to room temperature and poured into water. The product was extracted into dichloromethane (3 x 100 ml), dried over sodium sulfate and concentrated in vacuo to give d.01 g (76%) of 4-chloro-thieno [3,2-d] pyrimidine. 1 H NMR (400 0 MHz, DMSO) d 8.99 (s, 1 H), d.dd (d, 1 H), 7.71 (d, 1 H). LC-MS: 171 (MH +); HPLC TR; 2.8d minutes D. 6-Bromo-4-chloro-t-ene [3,2-dlpyrimidine] In a 2d0 ml round bottom flask, 6d ml of tetrahydrofuran and lithium diisopropylamine (18.5 ml, 37 mmol, 2M in tetrahydrofuran) were cooled. to -78 ° C, 4-chloro-thieno [3,2-d] pyrimidine (5.26 g, 31 mmol) was dissolved in 37 ml of tetrahydrofuran and added slowly to the reaction mixture for 5 minutes. After 20 minutes, 1,2-dibromo-1,1,1-tetrafluoroethane (4.0d ml, 34 mmol) was slowly added to the anion solution. The temperature was maintained at -78 ° C for 20 minutes and then heated to room temperature for 2 hours. The reaction mixture was poured into water and extracted with chloroform (3 x 100 ml), dried over sodium sulfate and dried under vacuum to give 7J0 g (99%) of 6-bromo-4-chloro-thieno [3, 2-d] pyrimidine. 1 H NMR (400 MHz, DMSO) d 8.97 (s, 1 H), 8.01 (s, 1 H). LC-MS: 249, 2d1 (MH +); HPLC TR: 4.04 minutes.

E. (6-Bromo-thienol [3,2-dlpyridin-4-yl] - (1 H -indol-d-yl) -amine. 6-Bromo-4-chloro- was dissolved. thieno [3,2-b] pyrimidine (7J3 g, 31 mmol) in dO ml of dichloromethane and dO ml of t-butyl alcohol and d-aminoindole 84.09 g, 31 mmol) were added. The reaction mixture was refluxed for 14 hours, cooled to room temperature and concentrated in vacuo to give 13.02 g of (6-bromo-thieno [3,2-d] pyrimidin-4-yl) - ( 1 H-indol-d-yl) -amine. The crude material was used without further purification (purity 83%). 1 H NMR (400 MHz, DMSO) d 11.1 (s, 1 H), 9.62 (s, 1 H), 8.38 (s, 1 H), 7.63 (s, 1 H), 7.49 (s, 1 H), 7.3d (m, 2H), 7.10 (d, 1 H), 6.40 (s, 1 H); LC-MS: 34d, 347 (MH +); HPLC TR: 3J7 minutes.

EXAMPLE 2 (1H-indol-5-yl) - (6-phenyl-thienor3.2-d1-pyridin-4-yl) -amine A mixture of 1,4-bis (diphenylphosphine) butane (50 mg, 0.12 mmol) and bis (benzonitrile) -palladium chloride (ii) (4d mg, 0.12 mmol) was suspended in 12 ml of toluene and made Bubble nitrogen through the solution for 30 seconds. The solution was stirred for 20 minutes and (6-bromo-thieno [3,2-d] pyrimidin-4-yl) - (1 H -indole-d-yl) -amine (400 mg, 1.16 mol) was added, phenylboronic acid (283 mg, 2.32 mmol), sodium carbonate (2.32 ml, 2.32 mmol, 1 M aqueous), 16 ml of tetrahydrofuran and 6 ml of ethanol. Nitrogen was bubbled through the solution for 60 seconds and the mixture was heated to 8d ° C. After 14 hours, the reaction mixture was cooled to room temperature and the pH value was adjusted to 7 by the addition of 1N aqueous hydrochloric acid. The material was then concentrated to dryness and chromatographed through silica gel eluting with methanol: dichloromethane 1-d% to give 194 mg (49%) of (1 H-indol-d-yl) - (6-phenyl) thieno [3,2-d] pyrimidin-4-yl) -amine. 1 H NMR (400 MHz, DMSO) d 11.1 (s, 1 H), 9 J 3 (s, 1 H), 8.49 (s, 1 H), 7 J 9 (m, 4 H), 7.46 (m, 4 H), 7.25 ( d, 1 H), 6.43 (s, 1 H); LC-MS: 343 (MH +); HPLC TR: 4.71 minutes.

EXAMPLE 3 f6- (4-Chloro-phenyl) -thienor3,2-d1-pyrimidin-4-yl) - (1H-indol-5-yl) -amine The title compound was prepared from p-chlorobenzeneboronic acid and (6-bromo-thieno [3,2-d] pyrimidin-4-yl) - (1 H -indol-5-yl) -amine by an analogous procedure to that of Example 2. 1 H NMR (400 MHz, DMSO) d 11.4 (s, 1 H), 8.86 (s, 1 H), 7.d8 (m, 9H), 7.21 (d, 1 H), 6. d0 (s, 1 H). P.F. 190-210 ° C; LC-MS: 377 (MH +); HPLC TR: d.32 minutes.

EXAMPLE 4 r6- (4-Fluoro-phenyl) -thienor3,2-d1-pyrimidin-4-yl) - (1H-indol-5-yl) -amine The title compound was prepared from p-flurobenzeneboronic acid and (6-bromo-thieno [3,2-d] pyrimidin-4-yl) - (1 H -indol-5-yl) -amine by an analogous procedure to that of Example 2. 1 H NMR (400 MHz, DMSO) d 11.4 (s, 1 H), 8.82 (s, 1 H), 7.79 (m, 4 H), 7.41 (m, 5 H), 7.21 (d, 1 H), 6.50 (s, 1 H). P.F. 193-205 ° C; LC-MS: 361 (MH +); HPLC TR: 4.88 minutes.

EXAMPLE 5 (1H-indol-5-yl) - (6-phenyl-thienor-3,2-d-pyrimidin-4-yl) -amine The title compound was prepared from p-methoxybenzeneboronic acid and (6-bromo-thieno [3,2-d] pyrimidin-4-yl) - (1 H -indol-d-yl) -amine by an analogous procedure to that of Example 2. 1 H NMR (400 MHz, DMSO) d 11.4 (s, 1 H), 11.2 (s, 1 H), 8.81 (s, 1 H), 7.55 (m, 6 H), 7.20 (d, 1 H), 7.0d (m, 2H), 6.d0 (s, 1 H), 3.79 (s, 3H). P.F. 1dO-180 ° C; LC-MS: 373 (MH +); HPLC TR: 4.4d minutes.

EXAMPLE 6 (1H-indol-5-yl) - (6-p-tolyl-thienor-3,2-d-pyrimidin-4-yl) -amine The title compound was prepared from p-methylbenzeneboronic acid and (6-bromo-thieno [3,2-d] pyrimidin-4-yl) - (1 H -indol-5-yl) -amine by an analogous procedure Example 2. NMR of 1H (400 MHz, DMSO) d 11.1 (s, 1 H), 9.d0 (s, 1 H), 8.41 (s, 1 H), 7.71 (d, 2H), 7. d9 (s, 2H), 7.24 (m, dH), 6.38 (s, 1 H), 2.29 (s, 3H). P.F. 200-220 ° C; LC-MS: 3d7 (MH +); HPLC TR: 4.d7 minutes.

EXAMPLE 7 4-r4- (1 H-indol-5-yl-amino) -thienor3.2-dlpyrimidin-6-n-benzaldehyde The title compound was prepared from p-formylbenzeneboronic acid and (6-bromo-thieno [3,2-d] pyrimidin-4-yl) - (1 H -indol-d-yl) -amine by an analogous procedure to that of Example 2. 1 H NMR (400 MHz, DMSO) d 11.2 (s, 1 H), 9.9 d (s, 1 H), 8.8 d (s, 1 H), 7.90 (m, 6 H), 7.7 d (s, 1 H), 7.46 (m, 3 H), 7.20 (d, 1 H), 6.49 (s, 1 H). LC-MS: 371 (MH +); HPLC TR: 4.10 minutes.

EXAMPLE 8 (1 H -indole-5-yl) - (6-thiophen-3-yl-thien-3,2-dl-pyrimidin-4-yl) -amine The title compound was prepared from thiophene-3-boronic acid and (6-bromo-thien [3,2-d] pyrimidin-4-yl) - (1 H -indol-5-yl) - amine by a procedure analogous to that of Example 2. 1 H NMR (400 MHz, DMSO) d 11.4 (s, 1 H), 11.2 (s, 1 H), 8.86 (s, 1 H), 8.10 (s, 1 H) ), 7.70 (m, 3H), 7.46 (m, 3H), 7.21 (d, 1 H), 6.49 (s, 1 H); P.F. 178-189 ° C; LC-MS: 349 (MH +); HPLC TR: 4.0d minutes.

EXAMPLE 9 (1H-indol-5-yl) -r6- (4-methylsulfanyl-phenyl) -thienor3,2-d1-pyrimidin-4-yl) -amine The title compound was prepared from 4- (methylthio) benzeneboronic acid and (6-bromo-thieno [3,2-d] pyrimidin-4-yl) - (1 H -indol-d-yl) -amine by a procedure analogous to that of Example 2. 1 H NMR (400 MHz, DMSO) d 11.4 (s, 1 H), 11.2 (s, 1 H), 8.82 (s, 1 H), 7.76 (d, 2H), 7.61 (s, 2H), 7.d1 (m, 2H), 7.3d (d, 2H), 7.22 (d, 1 H), 6.d0 (s, 1 H), 2.49 (s, 3H). P.F. 163-188 ° C; LC-MS: 389 (MH +); HPLC TR: 4.73 minutes.

EXAMPLE 10 (1H-indol-5-yl) -r6- (3-nitro-pheny1) -thienor3,2-dlpyrimidin-4-yl) -amine The title compound was prepared from 3-nitrobenzeneboronic acid and (6-bromo-thieno [3,2-d] pyrimidin-4-yl) - (1 H -indol-5-yl) -amine by a procedure analogous to that of Example 2. 1 H NMR (400 MHz, DMSO) d 11.3 (s, 2 H), 8.83 (s, 1 H), 8.47 (s, 1 H), 8.31 (m, 1 H), 8.0 d (m, 2H), 7.77 (m, 2H), 7.47 (m, 2H), 7.2d (m, 1 H), 6.d0 (s, 1 H). P.F. 17d-183 ° C; LC-MS: 388 (MH +); HPLC TR: 4.80 minutes.

EXAMPLE 11 (1H-indol-5-yl) -r6- (4-trifluoromethyl-phenyl) -t-inof3,2-dl-pyrimidin-4-yl) -amine The title compound was prepared from 3-trifluoromethylbenzeneboronic acid and ^ (6-bromo-thieno [3,2-d] pyrimidin-4-yl) - (1 H -indole-d-yl) -amine by a procedure analogous to that of example 2. PF 181-194 ° C; LC-MS: 411 (MH +); HPLC TR: 4.88 minutes.

EXAMPLE 12 f6- (3-Chloro-4-fluoro-phenyl-thienof3.2-dlpyrimidin-4-yl- (1H-indol-5-yl) -amine The title compound was prepared from 3-chloro-4-fluoromethylbenzeneboronic acid and (6-bromo-thieno [3,2-d] pyrimidin-4-yl) - (1 H-indol-7d d-il) amine by a procedure analogous to that of Example 2. PF 175-183 ° C; LC-MS: 39d (MH +); HPLC TR: d.33 minutes.

EXAMPLE 13 [6- (4-ethyl-phenyl) -thieno r3,2-dlpyrimidin-4-yl1-f1H-indol-5-yl) -amine The title compound was prepared from 4-ethylbenzeneboronic acid and (6-bromo-thieno [3,2-d] pyrimidin-4-yl) - (1 H -indol-5-yl) -amine by a procedure analogous to that of example 2. PF 171-182 ° C; LC-MS: 371 (MH +); HPLC TR: 5.13 minutes.

EXAMPLE 14 (1H-indol-5-yl) -6- (4-thiophen-2-yl-phenyl) -thieno r3,2-dlpyrimidin-4-ip-amine The title compound was prepared from thiophene-2-boronic acid and (6-bromo-thieno [3,2-d] pyrimidin-4-yl) - (1 H -indol-d-yl) -amine by a procedure analogous to that of example 2. PF 16d-178 ° C; LC-MS: 349 (MH +); HPLC TR: 4.dd minutes.

EXAMPLE 15 (1H-indol-5-yl) -r6- (3-methoxy-phenyl) -thienof3,2-d1-pyridin-4-n-amine The title compound was prepared from 3-d-methoxybenzeneboronic acid and (6-bromo-thieno [3,2-d] pyrimidin-4-yl) - (1 H -indol-d-yl) -amine by a procedure analogous to that of example 2. PF 160-168 ° C; LC-MS: 373 (MH +); HPLC TR: 4.7d minutes.

EXAMPLE 16 0 f6- (3,4-dimethoxy-phenyl) -thienor3,2-d1-pyrimidin-4-M1- (1H-indol-5-yl) -amine The title compound was prepared from 3,4-dimethoxybenzeneboronic acid and (6-bromo-thieno [3,2-d] pyrimidin-4-yl) - (1 H -indol-5-yl) - amine by a procedure analogous to that of Example 2. PF 171-78 ° C; d LC-MS: 403 (MH +); HPLC TR: 4.11 minutes.

EXAMPLE 17 3- (4-R4- (1 H -Indol-5-ylamino) -thienor3,2-d1-pyrimidin-6-yl-benzylamino) -propionic acid methyl ester 0-methyl aminopropionic acid methyl ester (261 mg) 1.7 mmol) was dissolved in 3 ml of methyl alcohol and the pH was adjusted to 6 with concentrated acetic acid. 4- [4- (1 H -indol-5-ylamino) -thieno [3,2-d] pyrimidine-6-yl] -benzaldehyde (11 mg, 0.17 mmol) was added to the solution followed by sodium cyanoborohydride ( 11 mg, 0.17 mmol). After 14 hours, the reaction mixture was poured into water and diluted with chloroform. The aqueous layer was separated and the pH was adjusted to 8.5 with 1 N sodium hydroxide. The desired product was extracted from the aqueous layer with chloroform (3 x 20 ml), the combined organic extracts were dried over sodium sulfate, filtered and dried in vacuo giving 8d mg (41%) of the 3- methyl ester. { 4- [4- (1 H -indol-d-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzylamino) -propionic acid. The product was converted to the HCl salt by stirring with 1 equivalent of 1 N HCl in ether and the resulting yellow solid was dried in vacuo. P.F. 105-118 ° C; LC-MS: 4d8 (MH +); HPLC TR; 3.86 minutes EXAMPLE 18 N- (4-β4- (1H-indol-5-ylamino) -thinomer3.2-dlpyridin-6-in-benzyl> -N.N'-dimethyl-ethanol- 1, 2-diamine The title compound was prepared from N, N-dimethylethylenediamine and 4- [4- (1 H -indole-5-yl-amino) -thieno [3,2-d] pyrimidin-6-yl) ] -benzaldehyde by a procedure analogous to that of Example 17. PF 170-183 ° C; LC-MS: 443 (MH +); HPLC TR: 3.02 minutes.

EXAMPLE 19 N-. { 4-r4- (1H-indol-5-ylamino) -thieno [3,2-d1-pyrimidin-6-n-benzyl > -N, N'-methyl-ethane-1,2-diamine The title compound was prepared from N-methylethylenediamine and 4- [4- (1 H -indol-d-yl-amino) -thieno [3,2-d] pyrimidin-6-yl] - benzaldehyde by a procedure analogous to that of example 17. The product was converted to the mesylate salt analogously to that of example 17, becoming the HCl salt. P.F. 93-10d ° C; LC-MS: 429 (MH +); HPLC TR: 3.46 minutes.

EXAMPLE 20 (1 H -indole-5-yl) - (6-. {4-r 2 -methoxy-ethylamino) -methyl-phenyl > -thienor3,2- d1pyrimidin-4-yl) -amine The title compound was prepared from 2-aminoethanol and 4- [3- (1 H -indol-5-yl-amino) -thieno [3,2-d] pyrimidin-6-yl] -benzaldehyde by a procedure analogous to that of example 17. PF 170-190 ° C; LC-MS: 416 (MH +); HPLC TR: 2.91 minutes.

EXAMPLE 21 (1H-indol-5-yl) -r6- (4-propylaminoethyl-phenyl) -thienor3,2-d1-pyrimidin-4-n-amine The title compound was prepared from propylamine and 4- [4- (1 H-indol-d-yl-amino) -thieno [3,2-d] pyrimidin-6-yl] -benzaldehyde by a procedure analogous to that of example 17. PF 190-20d ° C; LC-MS: 414 (MH +); HPLC TR: 4.1 d minutes.

EXAMPLE 22 (1 H -indole-5-in- (6- (4-r (3-methoxy-propylamino-methyl-phenyl-t-inor-3-d-pyrimidin-4-yl) -amine) The title compound was prepared from 3-methoxypropylamine and 4- [4- (1 H -indol-5-yl-amino) -thieno [3,2-d] pyrimidin-6-yl] - benzaldehyde by a procedure analogous to that of example 17. PF 160-175 ° C; LC-MS: 444 (MH +); HPLC TR: 3.92 minutes.

EXAMPLE 23 (1H-indol-5-in-r6- (4-r (2-piperazin-1-yl-ethylammon) -metn-phenyl-thienor -3.2-dl pyrimidin-4 -sheet The title compound was prepared from N- (2-aminoethyl) -piperazine and 4- [4- (1 H indol-d-yl-amino) -thieno [3,2-d] pyrimidine-6-) il] - benzaldehyde by a procedure analogous to that of Example 17. PF 178-191 ° C; LC-MS: 484 (MH +); HPLC TR: 4.23 minutes.

EXAMPLE 24 (1 H -indole-5-n- (6 4-r (2-morpholin-4-yl-ethylamino) -metn-phenol> -thienof3.2- d1-pyrimidin-4-yl) -amine The title compound was prepared from N- (2-aminoethyl) morpholine and 4- [4- (1 H -indol-5-yl-amino) -thieno [3,2-d] pyrimidin-6-) il] -benzaldehyde by a procedure analogous to that of Example 17. PF 100-111 ° C; LC-MS: 48d (MH +); HPLC TR: 4.23 minutes.

EXAMPLE 25 (1H-indol-5-yl) - (6- (4-methylaminomethyl-phenyl) -thienor-3,2-d-pyrimidin-4-yl) -amine The title compound was prepared from methylamine and the 4- [4- (1 H-indol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzaldehyde by a procedure analogous to that of example 17. The product was converted to the salt mesylate analogously to example 17, becoming the HCl salt. P.F. 140-147 ° C; LC-MS: 386 (MH +); HPLC TR: 3.d4 minutes.

EXAMPLE 26 (1H-indol-5-ylW6-r4- (4-methy1-piperazin-1-ylmethyl) -phenyl-t-ene3.2-dlpyrimidin-4-yl -amine The title compound was prepared from N-methylpiperazine and 4- [4- (1 H -indol-d-yl-amino) -thieno [3,2-d] pyrimidin-6-yl] - benzaldehyde by a procedure analogous to that of example 17. The product was converted to the mesylate salt analogously to example 17, converting it into the HCl salt. P.F. 143-1 dO ° C; LC-MS: 4dd (MH +); HPLC TR: 4.23 minutes.

EXAMPLE 27 2- (4-r4- (1H-indol-5-yl) -t-inor3,2-d1-pyrimidin-6-illbenzylamino > -propan-1,3-diol The title compound was prepared from serinol and 4- [4- (1 H-indol-5-yl-amino) -thieno [3,2-d] pyrimidin-6-yl] -benzaldehyde by an analogous procedure to that of example 17. The product was converted to the mesylate salt analogously to that of example 17, becoming the HCl salt. 1 H NMR (400 MHz, MeOH) d 8.37 (s, 1 H), 7.67 (s, 1 H), 7.d 9 (d, 2 H), 7.49 (s, 1 H), 7.41 (m, d H), 7.30 (d, 1 H), 7.19 (dd, 1 H), 6.48 (d, 1 H), 3.8 d (s, 2 H), 3.d9 (m, 4 H), 2.72 (m, 1 H); LC-MS: 446 (MH +); HPLC TR: 3.2 minutes.

EXAMPLE 28 3-f4-f4- (1H-indol-5-yl) -thienor3,2-d1-pyrimidin-6-yl) -benzylamino) -propan-1-ol The title compound was prepared from 3-amino-propanol and 4- [4- (1 H -indol-d-yl-amino) -thieno [3,2-d] pyrimidin-6-yl] -benzaldehyde by a procedure analogous to that of example 17. The product was converted to the mesylate salt analogously to that of example 17, becoming the HCl salt. 1 H NMR (400 MHz, MeOH) d 11.1 (s, 1 H), 9.d4 (s, 1 H), 8.44 (s, 1 H), 7.7d (dd, 4H), 7.42 (m, 4H) , 7.23 (m, 1 H), 6.41 (s, 1 H), 3.67 (s, 2H), 3.30 (s, 2H), 1.54 (m, 2H); LC-MS: 430 (MH +); HPLC TR: 3.34 minutes.

EXAMPLE 29 2 - ((2-Hydroxy-ethyl) - (4-r4- (1H-indol-5-yl) -thienor3.2-dlpyrimidn-6-ylbenzyl> - aminol -ethanol The title compound was prepared from 2- (2-hydroxy-ethylamino) -ethanol and 4- [4- (1 H -indol-5-yl-amino) -thieno [3,2-d] pyrimidine- 6-yl] -benzaldehyde by a procedure analogous to that of example 17. The product was converted to the mesylate salt analogously to that of example 17, becoming the HCl salt. P.F. 110-127 ° C; LC-MS: 460 (MH +); HPLC TR: 3.d0 minutes.

EXAMPLE 30 2- (2- (4-i4- (1 H-indol-5-n-thienof3.2-dlpyrimidin-6-n-benzyllamine > -ethoxy) -ethanol The title compound was prepared from 2- (2-amino-ethoxy) -ethanol and 4- [4- (1 H -indol-5-yl-amino) -thieno [3,2-d] py! 4-yl] -benzaldehyde by a procedure analogous to that of Example 17. The product was converted to the mesylate salt analogously to that of Example 17, becoming the HCl salt. P.F. 111-119 ° C; LC-MS: 460 (MH +); HPLC TR: 3.40 minutes.

EXAMPLE 31 2- (2- (4-r4- (1H-indol-5-yl) -thienor3.2-dlpyrimidin-6-n-benzylamine) -ethylamino) -ethanol The title compound was prepared from 2- (2-amino-ethylamino) -ethanol and 4- [4- (1 H -indol-5-yl-amino) -thieno [3,2-d] pyrimidine- 6-yl] -benzaldehyde by a procedure analogous to that of example 17. The product was converted to the mesylate salt analogously to that of example 17, becoming the HCl salt. P.F. 78-9d ° C; LC-MS: 4d9 (MH +); MPLC TR: 3.74 minutes.

EXAMPLE 32 f6- (4-ff2- (4H-imydazol-4-yl) -eti-lamino-1-methyl-2-phenyl) -thienof3,2-d1-pyrimidin-4-yl) - (1 H-indole -5-l) -amine The title compound was prepared from histamine and 4- [4- (1 H-indol-d-yl-amino) -thieno [3,2-d] pyrimidin-6-yl] -benzaldehyde by an analogous procedure to that of example 17. The product was converted to the mesylate salt analogously to that of example 17, becoming the HCl salt. 1 H NMR (400 MHz, DMSO) d 11.1 (s, 1 H), 9.61 (s, 1 H), 8.47 (s, 1 H), 7.83 (m, 3 H), 7.66 (s, 1 H), 7 .d7 (m, 2H), 7.38 (m, 2H), 7.24 (m, 1 H), 6.9d (s, 1 H), 6.42 (s, 1 H), 4.22 (s, 2H), 3.1 d ( m, 2H), 2.82 (m, 2H); LC-MS: 466 (MH +); HPLC TR: 3.76 minutes.

EXAMPLE 33 (1 H -indole-5-n-r 6 - (4-fr (thieno-2-ylmethyl-amino-1-methyl > -phenyl) -thienor 3-2-dlpyrimidin-4-yl) - amine The title compound was prepared from C-thiophen-2-yl-methylamine and 4- [4- (1 H -indol-5-yl-amino) -thieno [3,2-d] pyrimidin-6 -l] -benzaldehyde by a procedure analogous to that of example 17. The product was converted to the mesylate salt analogously to that of example 17, becoming the HCl salt. P.F. 111-121 ° C; LC-MS: 468 (MH +); HPLC TR: 4.44 minutes. 8d EXAMPLE 34 r6- (4- (r (furan-2-methyl-amino-1-methyl-phenyl) -thienof3.2-dlpyrimidin-4-yl- (1 H- indol-5-yl) -amine The title compound was prepared from C-furan-2-yl-methylamine and 4- [4- (1 H -indol-d-yl-amino) -thieno [3,2-d] primidin-6 -yl] -benzaldehyde by a procedure analogous to that of example 17. PF 125-134 ° C; LC-MS: 452 (MH +); HPLC TR: 4.51 minutes.

EXAMPLE 35 1- (3- (4-r4- (1H-indol-5-yl) -t-inor3,2-dlpyrimidin-6-ill-benzylamino) -propyl) -pyrrolidin-2-one The title compound was prepared from 1- (3-aminopropyl) -pyrrolidin-2-one and 4- [4- (1 H -indol-d-yl-amino) -thieno [3,2-d] ] pyrimidin-6-yl] -benzaldehyde by a procedure analogous to that of Example 17. PF 139-146 ° C; LC-MS: 497 (MH +); HPLC TR: 4.01 minutes.

EXAMPLE 36 N- (4-r4- (1H-indol-5-ylamino) -t-inor3.2-d1-pyrimidin-6-yl-benzyl-N '- N'-dimethylpropane-1, 3- diamine The title compound was prepared from N, N-dimethylpropylenediamine and 4- [4- (1 H-indol-d-yl-amino) -thieno- [3,2-d] pyrimidin-6-yl] -benzaldehyde by a procedure analogous to that of example 17. PF 148-160 ° C; LC-MS: 4d7 (MH +); HPLC TR: 3.84 minutes.

EXAMPLE 37 (1 H-indol-5-ylH6- (4- (morpholin-4-ylmethyl-phenyl) -thienor3,2-dlpyrimidin-4-yl-amine The title compound was prepared from morpholine and 4- [4- (1-indol-d-yl-amino) -thieno [3,2-d] pyrimidin-6-yl] -benzaldehyde by an analogous procedure to that of example 17. PF 141-1d2 ° C; LC-MS: 422 (MH +); HPLC TR: 4.10 minutes.

EXAMPLE 38 Ethyl ester of 2- (4. 4M - (1 H -indole-5-ylamino) -thione-2,3-d.-pyrimidin-6-yl-benzylamino} -acetylamino) -acetic acid The title compound was prepared from the ethyl ester of (2-amino-acetylamino) -acetic acid and 4- [4- (1-ynol-5-yl-amino) -thieno [3,2-d] pyrimidin-6-yl] -benzaldehyde by a procedure analogous to that of Example 17. PF 98-11d ° C; LC-MS: 515 (MH +); HPLC TR: 3.88 minutes.

EXAMPLE 39 1- (4-f4-r4- (1H-indol-5-ylamino) -thiomer3,2-d1-pyrimidin-6-ill-benzyl> -piperazin-1-yl) - Etanone The title compound was prepared from 1-piperazin-1-yl-ethanone and 4- [4- (1-indole-d-yl-amino) -thieno [3,2-d] pyrimidine-6-) il] -benzaldehyde by a procedure analogous to that of Example 17. PF 163-180 ° C; LC-MS: 483 (MH +); HPLC TR: 4.24 minutes.

EXAMPLE 40 r6- (4-Cyclopropylaminoethyl-phenyl) -thienor3,2-dlpyrimidin-4-yn- (1 H -indol-5-yl) -amine The title compound was prepared from cyclopropylamine and 4- [4- (1 H -indol-d-yl-amino) -thieno [3,2-d] pyrimidin-6-yl] -benzaldehyde by a procedure analogous to that of example 17. PF 176-180 ° C; LC-MS: 412 (MH +); HPLC TR: 4.10 minutes.

EXAMPLE 41 2-4-r4- (1H-indol-5-ylamino) -thienor3,2-d1-pyrimidin-6-n-benzylamino) -propan-1-yl The title compound was prepared from 2-amino-propan-1-ol and 4- [4- (1 H-indol-d-yl-amino) -thieno [3,2-d] pyrimidine-6-) il] -benzaldehyde by a procedure analogous to that of Example 17. PF 160-17d ° C; LC-MS: 444 (MH +); HPLC TR: 3.90 minutes.

EXAMPLE 42 f1H-indol-5-ylammon) - (6-r4- (2-methoxymethyl-pyrrolidin-1-ylmethyl) -phenyin-3-F3,2-dl-pyrimidin-4-yl} -amine The title compound was prepared from 2-methoxymethyl-pyrrolidone and 4- [4- (1 H -indol-d-yl-amino) -thieno [3,2-d] pyrimidin-6-yl] - benzaldehyde by a procedure analogous to that of example 17. PF 161-177 ° C; LC-MS: 470 (MH +); HPLC TR: 4.dd minutes.

EXAMPLE 43 N- (2-f4-r4-f1H-indol-5-ylamino) -thienor3,2-d1-pyrimidin-6-inbenzylamino > -ethyl) - acetamide The title compound was prepared from N- (2-amino-ethyl) -acetamide and 4- [4- (1 H -indol-d-yl-amino) -thieno [3,2-d] pyrim D, n-6-yl] -benzaldehyde by a procedure analogous to that of Example 17. PF 142-1dd ° C; LC-MS: 4d7 (MH +); HPLC TR: 3.3d minutes.

EXAMPLE 44 1-f4-r4- (1 H-indol-5-ylammon) -thienor3,2-d1-pyrimidin-6-ill-benzyl > -piperidine-4-carboxylic acid The title compound was prepared from the piperidine-4-carboxylic acid amide and 4- [4- (1 H -indole-d-1-amino) -thieno [3,2-d] pyrimidine) 6-yl] -benzaldehyde by a procedure analogous to that of Example 17. PF 198-20d ° C; LC-MS: 483 (MH +); HPLC TR: 3.d6 minutes.

EXAMPLE 45 N- (2-f4-r4- (1 H -indol-5-ylammon) -thienof3.2-d-pyrimidin-6-inbenzyl> -N'-N'-dimethyl-hexane- 1, 6-diamine The title compound was prepared from the amide of N'-N'-dimethylhexane-1,6-diamine and 4- [4- (1 H -indol-d-yl-amino) -thieno [ 3,2-d] pyrimidin-6-yl] -benzaldehyde by a procedure analogous to that of Example 17. 1 H NMR (400 MHz, DMSO) d; P.F. 134-148 ° C; CL-EM: 499 (MH +); HPLC TR: 4.12 minutes.

EXAMPLE 46 Furan-2-yl- (4-f4-f1H-indol-5-ylamino) -thienor3,2-dlpyrimidin-6-ill-benzyl > - piperazin-1 -yl) -metanone The title compound was prepared from furan-2-yl-piperazin-1-yl-methanone and 4- [4- (1H-indol-d-yl-amino) -thieno [3,2- d] pyrimidin-6-yl] -benzaldehyde by a procedure analogous to that of Example 17. 1 H NMR (400 MHz, DMSO) d; P.F. 167-174 ° C; LC-MS: d3d (MH +); HPLC TR: d.24 minutes.

EXAMPLE 47 A. Thiophene-3-ylamine 3-Amino-thiophene-2-carboxylic acid methyl ester (2d g, 1d9 mmol) was dissolved in 160 ml of 2N sodium hydroxide and refluxed for 2 hours. The solution was cooled to 0 ° C and acidified to pH d with concentrated HCl, at which time a precipitate formed. The precipitate was washed with water and then dissolved in acetone, dried over magnesium sulfate and concentrated to near dryness at room temperature. To the residue were added dO ml of propanol and oxalic acid (1 d.8 g, 17 d mmoles) and the solution was stirred at 38 ° C for 4 d minutes. The mixture was cooled and ether was added. The precipitate that formed was filtered, washed with ether and dried to give 16.7 g of the crude material. The solid was suspended in 300 ml of water and the pH was adjusted to 9 with saturated aqueous ammonium hydroxide. The solution was extracted with methylene chloride (4 x 100 ml), dried over sodium sulfate, filtered and concentrated in vacuo giving 6.37 g (40%) of thiophene-3-ylamine. d B. 4H-thienol [3.2-b1pyridin-7-one dimethyl- [1, 3] -dioxan-4,6-dione (d, 0 g, 34.6 mmol) was combined with triethylene orthoformate (20d ml, 138 mmol ) and stirred at 30 ° C for 1 hour. Thiophen-3-ylamine (2.81 g, 28.3 mmol) was added in small portions at room temperature, at which time it precipitated. The mixture was heated at 8d ° C overnight. The reaction mixture was cooled to room temperature and isopropyl ether was added and the suspension was stirred for one hour. The precipitate was filtered and washed with ethylpropionate and dried in vacuo. The intermediate product was dissolved in methylene chloride and potassium carbonate was added and the suspension was stirred for 30 minutes. The solid was filtered and the solution was concentrated giving the, 2-dimethyl-d- (thiophen-3-ylaminomethylene) - [1, 3] dioxan-4,6-dione as the free base. In a single round-bottom flask, the eutectic A (1d ml) was heated to 260 ° C and small portions of 2,2-dimethyl-d- (thiophen-3-ylaminomethylene) - [1, 3] dioxan- were added in small portions. 4,6-0 diona. The mixture was heated for 30 minutes and then cooled to room temperature and isopropyl ether was added and the suspension was stirred for one hour. The precipitate was filtered and washed with isopropyl ether and dried under vacuum to give 3.43 g (79%) of 4H-thieno [3,2-b] pyridinone. 1 H NMR (400 MHz, DMSO) d 7.93 (d, 1 H), 7 J 9 (d, 1 H), 7.21 (d, 1 H), d.99 (d, 1 H); LC-MS: 1 d2 (MH +); HPLC TR: 1.21.

D. 7-chloro-thieno [3,2-b1-pyridine d 100 ml with methylene chloride and dimethylformamide (6.1 ml, 78.6 mmol) were combined in a 2 d0 ml round bottom flask and cooled to 0 ° C. Oxalyl chloride (d7 ml, 114 mmol) was added dropwise over several minutes. 4H-Thieno [3,2-b] pyridin-7-one (d.4 g, 3d.7 mmoles) was added and the solution was heated to reflux. After 2 hours, the flask was cooled to room temperature and the resulting solid was filtered and dried under vacuum to give 6.29 g (100%) of 7-chloro-thieno [3,2-b] pyridine as a yellow solid. 1 H NMR (400 MHz, DMSO) d 9.67 (d, 1 H), 8.29 (d, 1 H), 7.66 (d, 1 H), 7.61 (d, 1 H); LC-MS: 171 (MH +); HPLC TR: 4.19. d E. 2-bromo-7-chloro-thieno [3,2-blpyridine] A solution of 90 ml of tetrahydrofuran and diisopropylamine (4.6 ml, 32.9 mmoles) was cooled to -78 ° C and added dropwise n - Butyllithium (12.2 ml, 30.3 mmol) in hexane. The solution was heated to 0 ° C for 10 minutes, cooled again to -78 ° C and 7-chloro-0-thieno [3,2-b] pyridine (4.29 g, 2d.2 mmol) was added. The anion was stirred for 10 minutes and 1,2-dibromo-1,1,1,2-tetrafluoroethane (3.3 ml, 27.8 mmol) was added. The solution was stirred for another 20 minutes and then allowed to warm to room temperature. After 1 hour, the reaction mixture was poured into water and extracted with chloroform (3 x 100 ml). The combined organic portions were dried over magnesium sulfate, filtered and dried to give 4.6d g (74%) of 2-bromo-7-chloro-thien [3,2-b] pyridine. 1 H NMR (400 MHz, DMSO) d 8.64 (d, 1 H), 7.91 (s, 1 H), 7.6d (d, 1 H); LC-MS: 171 (MH +); d HPLC TR: 5.49.

F. (1 H-indol-5-yl) - (2-phenyl-thienor-2,3-b-pyridin-7-yl) -amine In a sealed tube, 2-bromo-7-chloro- thieno [2,3-bjpyridine (1.01 g, 4.08 mmol) in 1 d ml of dichloroethane and 1 d ml of t-0 butyl alcohol. D-amino-indole (d40 mg, 4.08 mmol) was added, the tube was sealed and the contents heated to 8d ° C for 36 hours. The solution was cooled and filtered, the solid was washed with methylene chloride and dried in vacuo to give 1.96 g of the crude product. A portion of the material (100 mg, 0.29 mmol) was coupled with benzeneboronic acid in a procedure analogous to that of Example 2 d to give 37.1 mg (38%) of (1 H-indol-d-yl) :( 2-phenyl-t. Eno [2,3-b] pyrimidin-7-yl) -amine. 1 H NMR (400 MHz, DMSO) d 11.1 (s, 1 H), 8.69 (s, 1 H), 8.15 (d, 1 H), 7J8 (m, 3 H), 7.41 (m, 6 H), 6.98 ( d, 1 H), 6.53 (d, 1 H), 6.41 (s, 1 H); LC-MS: 342 (MH +); HPLC TR: 4.81.

EXAMPLE 48 4-r7- (1H-indol-5-ylamino) -thienof3,2-b1pyridin-2-n-benzaldehyde The title compound was prepared from 4-formylbenzeneboronic acid and (2-bromo-thieno [3,2-d] pyridin-7-yl) - (1 H -indol-5-yl) -amine by a procedure analogous to that of Example 17. 1 H NMR (400 MHz, DMSO) d 11.1 (s, 1 H), 9.98 (s, 1 H), 8.21 (d, 1 H), 8.05 (s, 1 H), 7.95 ( s, 3H), 7.82 (d, 1 H), 7.60 (m, 3H), 7.00 (d, 1 H), 6.d8 (s, 1 H), 6.40 (s, 1 H); LC-MS: 370 (MH +); HPLC TR: 4.83 minutes.

EXAMPLE 49 f1H-indol-5-yl) -f2-thiophen-2-yl-t-ene3.2-blpyridin-7-n-amine The title compound was prepared from thiophene-2-boronic acid and (2-bromo-t-ene [3,2-d] pyridin-7-yl) - (1 H -indole-d-1) -amine by a procedure analogous to that of example 17. 1 H NMR (400 MHz, DMSO) d 11. 1 (s, 2H), 8.27 (d, 1 H), 7.73 (s, 1 H), 7.48 (m, dH), 7.19 (m, 1 H), 7.03 (d, 1 H), 6. d0 (s, 1 H); LC-MS: 348 (MH +); HPLC TR: 5.11 minutes.

EXAMPLE 50 (1H-indol-5-ip-r2- (4-methoxy-phenyl) -thienor3.2-b1pyridin-7-in-amine The title compound was prepared from 4-d-methoxybenzeneboronic acid and (2-bromo-t-ene [3,2-d] pyridin-7-yl) - (1 H-indol-d-yl) - amine by a procedure analogous to that of Example 17. 1 H NMR (400 MHz, DMSO) d 11.3 (s, 1 H), 10.6 (s, 1 H), 8.21 (d, 1 H), 7.6d (m, dH), 7.00 (m, dH), 6.43 (d, 1 H ), 3.80 (s, 3H); LC-MS: 372 (MH +); HPLC TR: d.45 minutes.

EXAMPLE 51 (1H-indol-5-yl) -r2-f4-methylsulfanyl-phenyl) -thienof3,2-b1pyridin-7-p-amine The title compound was prepared from 4- (methylthio) benzeneboronic acid and (2-bromo-thieno [3,2-d] pyridin-7-yl) - (1 H -indol-5-yl) -d amine by a procedure analogous to that of Example 17. 1 H NMR (400 MHz, DMSO) d 11.4 (s, 1 H), 10.6 (s, 1 H), 8.30 (d, 1 H), 7.d3 (m, 9H), 7.0d (d, dH), 6.43 (s, 1 H), 2.48 (m, 3H); LC-MS: 388 (MH +); HPLC TR: 6.07 minutes.

EXAMPLE 52 0 r2- (4-fluoro-phenin-thienor3.2-b1pyridin-7-in-f1H-indol-5-yl) -amine The title compound was prepared from 4-fluorobenzeneboronic acid and (2-bromo-t-ene [3,2-d] pyridin-7-yl) - (1 H -indole-5-yl) amine by a procedure analogous to that of Example 17. 1 H NMR (400 MHz, DMSO) d 11.4 (s, 1 H), 10.7 (s, 1 H), 8.28 (d, 1 H), 7.d0 (m) , 9H), 7.0d (d, 1 H), 6.49 (s, 1 H); LC-MS: 360 (MH +); HPLC TR: d.40 minutes.

EXAMPLE 53 2- (4-r7-f1H-indol-5-8-amino) -thienor3,2-b1-pyridin-2-p-phenoxy > -ethanol The title compound was prepared from 4- [2-tert-butyl-dimethyl-silanyloxy) -ethoxy] -benzoicboronic acid and (2-bromo-thieno [3,2-d] pyridin-7-yl] - (1 H-indol-5-yl) -amine by a procedure analogous to that of example 17. 1 H NMR (400 MHz, DMSO) d 11.4 (s, 1 H), 10.7 (s, 1 H), 8.24 (d , 1H), 7.d3 (m, 9H), 7.08 (m, 1 H), 6.49 (s, 1 H), 4.02 (t, 2H), 3.70 (t, 2H), LC-MS: 402 (MH + ); HPLC TR: 3.9d minutes.

EXAMPLE 54 2- (2-f4-f7- (1 H -indol-5-ylamino) -thieno-3,2-b1-pyridin-2-in-benzylamino> -ethoxy) -ethanol The title compound was prepared from 2- (amino-ethoxy) -ethanol and 4- [7- (1 H -indol-5-ylamino) -thieno [3,2-d] pyridin-2- il] -benzaldehyde by a procedure analogous to that of example 17. LC-MS: 4d9 (MH +); HPLC TR: 3.48 minutes.

EXAMPLE 55 2-f4-r7- (1H-indol-5-ylamino) -thienof3,2-blpyridin-2-yl-benzylamino > -ethanol The title compound was prepared from 2-aminoethanol and 4- [7- (1 H -indol-d-ylamino) -thieno [3,2-d] pyridin-2-yl] -benzaldehyde by an analogous procedure to that of example 17. LC-MS: 415 (MH +); HPLC TR: 3.40 minutes.

EXAMPLE 56 Amide of 1-f4-r7- (1H-indol-5-ylamino) -thienor3,2-blpiridin-2-benzyl acid} -piperadin-4-carboxylic The title compound was prepared from the piperidine-4-carboxylic acid amide and the 4- [7- (1 H -indol-5-ylamino) -thieno [3,2-b] pyridin-2-amide il] -benzaldehyde by a procedure analogous to that of example 17. LC-MS: 482 (MH +); HPLC TR: 3.d6 minutes.

EXAMPLE 57 N- (4-r7- (1H-indol-5-ylamnol-t-inor3.2-blpyridin-2-in-benzyl) -N'-N'-dimethy1- hexane-1, 6-diamino The title compound was prepared from N, N-dimethyl-hexane-1,6-diamine and 4- [7- (1 H -indol-d-ylamino) -thione [3,2-b] ] pyridin-2-yl] -benzaldehyde by a procedure analogous to that of example 17. LC-MS: 498 (MH +); HPLC TR: 3.93 minutes.

EXAMPLE 58 2- ( { - 4-f7-f1H-indol-5-ylamino) -thienor3.2-blpyridin-2-yl-benzyl > -methyl-amino) - ethanol The title compound was prepared from methylaminoethanol and 4- [7- (1 H -indole-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzaldehyde by a procedure analogous to from example 17. LC-MS: 429 (MH +); HPLC TR: 3.d3 minutes.

EXAMPLE 59 (1 H -indole-5-n- (2- (4-r (2-piperazin-1-yl-ethylamino) -methyl-phenytimide3.2- blpyridin-7-iD- amine The title compound was prepared from 2-piperazin-1-yl-ethylamine and 4- [7- (1 H -indol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzaldehyde by a procedure analogous to that of example 17. LC-MS: 483 (MH +); HPLC TR: 3.41 minutes.

EXAMPLE 60 (1H-indol-5-ylamino) - (2-pyridin-2-yl-thienof3,2-blpyridin-7-yl) -amine In a sealed tube were combined (2-bromo-tJeno [3,2-b] pyridin-7-yl) - (1 H -indole-d-1) -amina (1d0 mg, 0.29 mmol) and - (tributylstannyl) pyridine (118 mg, 1.1 mmol) in 3 ml of dimethylformamide together with copper iodide (3 mg, 0.01 d mmol). Nitrogen was bubbled into the solution and trans-benzyl (chloro) bis- (triphenylphosphine) palladium (II) (33 mg, 0.044 mmol) was added, the tube was sealed and heated to 90 ° C. After 14 hours, the solution was cooled and concentrated to dryness. Chromatography on 1d g of silica gel with CH 2 Cl 2 / MeOH (5-20%) gave 30.3 mg (28%) of the title compound. LC-MS: 343 (MH +); HPLC TR: 3.94 minutes.

EXAMPLE 61 2-methoxy-N- (4-phenyl) -N '- (6-phenyl-thienor-3,2-d1-pyrimidin-4-yl) -benzene-1,4-diamine To 4-chloro-6-phenyl-thieno [3,2-b] pyrimidine (150 mg, 0.608 mmol) in t-butane (2.d ml) and in dichloromethane (2.d ml) was added 2-methoxy -N- (4-phenyl) -benzene-1,4-diamine (130 mg, 0.608 mmol) and the mixture was heated in an oil bath at 80 ° C overnight. The reaction was cooled to room temperature and isopropyl ester was added. The product was filtered giving a tan solid (200 mg, 78% yield). RP18-HPLC TR: 6.261 minutes; AP MS: 424, d2 (MH +); P.F .: 201-203 ° C.

EXAMPLE 62 N- (4-methoxy-phenyl) -N'-f6-phenyl-thienof3.2-dlpyrimidin-4-yl) -benzene-1,4-diamine To 4-chloro-6-phenyl-thieno [3,2-b] pyrimidine (1d0 mg, 0.608 mmol) in t-butane (2.d ml) and in dichloromethane (2.d ml) was added 2-methoxy -N- (4-phenyl) -benzene-1,4-diamine (1d2 mg, 0.608 mmol) and the mixture was heated in an oil bath at 80 ° C overnight. The reaction was cooled to room temperature and isopropyl ester was added. The product was filtered giving a tan solid (248 mg, 96% yield). RP18-HPLC TR: 6.228 minutes; AP MS: 424, d2 (MH +); P.F .: 210-211 ° C.

EXAMPLE 63 A. Preparation of Nm-tolyl-benzene-1,4-diamnan To a mixture of 4-nitro-fluorobenzene (250 mg, 1.77 mmol) and 3-methylaniline (190 mg, 1.77 mmol) in 4 ml of water in a sealed tube was added magnesium oxide (86 mg, 2.126 mmol). The suspension was stirred at 200 ° C for 2 days. The reaction was cooled to room temperature and the suspension was diluted with water and filtered to remove the insoluble material. The aqueous layer was extracted 3 times with ethyl acetate (dO ml) and the combined organic layers were washed with a solution of boronic acid (d%, dO ml) and water, dried over magnesium sulfate and concentrated in vacuo to give the (4-Nitro-phenyl) -m-tolyl-amine (190 mg, 47% yield). RP18-HCPL d TR: 7,020 minutes; API EM: 229.20 (M + 1). To a solution of (4-nitro-phenyl) -m-tolyl-amine (180 mg, 0.88 mmol) in toluene (10 ml) was added 18 mg of palladium on carbon (10%) in a Parr flask. The mixture was hydrogenated at 3d psi (2.46 kg / cm2) with stirring for 12 hours and then filtered and concentrated in vacuo to give N- (6-0 phenyl-thieno ^ -bjpyrimidin ^ -ilj-N'-m-tolyl- benzene-1-diamine with a quantitative yield as a yellow solid, API API: 199.20 (M + 1).

B. N- (6-phenyl-thienof3,2-dlpyrimidin-4-yl) -N'-m-tolyl-benzene-1,4-diamine d Using a procedure analogous to that described in example 61, prepared the title compound in 21% yield from N-m-tolyl-benzene-1,4-diamine (230 mg, 1.16 mmol) and 4-chloro-6-phenyl-thieno [3,2- b) pyrimidine (2d0 mg, 1.16 mmol). RP18-HPLC TR: 7.432 minutes; API EM: 409.1 (MH +); P.F .: 170-171 ° C.

EXAMPLE 64 A. Preparation of Np-tolyl-benzene-1,4-diamnan To a mixture of 4-nitro-fluorobenzene (2d0 mg, 1.77 mmol) and 4-d amino-toluene (19d mg, 1.77 mmol) in 4 ml of water in a sealed tube was added magnesium oxide (86 mg, 2.126 mmol). The suspension was stirred at 200 ° C for 2 days. The reaction was cooled to room temperature and the suspension was diluted with water and filtered to remove the insoluble material. The aqueous layer was extracted 3 times with ethyl acetate (dO ml) and the combined organic layers were washed with boronic acid (d%, dO ml) and water, dried over magnesium sulfate and concentrated in vacuo to give the sodium hydroxide solution. -nitro-phenyl) -p-tolyl-amine (190 mg, 47% yield). API EM: 229.20 (M + 1). To a solution of (4-nitro-phenyl) -p-tolyl-amine (180 mg, 0.788 mmol) in toluene (10 ml) was added 18 mg of palladium on carbon (10%) d in a Parr flask. The mixture was hydrogenated at 3d psi with stirring for 12 hours and then filtered and concentrated in vacuo to give N- (6-phenyl-thienop ^ -bjpyrimidin ^ -ylj-N'-p-tolyl-benzene-diamine in a yield quantitative as a yellow solid, API API: 199.20 (M + 1). 0 B. N- (6-phenyl-thienof3.2-dlpyrimidin-4-yl) -N'-p-tolyl-benzene-1,4-diamine Using a procedure analogous to that described in example 61 , the title compound was prepared in a 27% yield from N-m-tolyl-benzene-1,4-diamine (100 mg, 0.4 d mmol) and 4-chloro-6-phenyl-thieno [3 2- djpyrimidine (80 mg, 0.4d mmol). RP18-HPLC TR: 7.468 minutes; API EM: 409.1 (MH +); P.F .: 221-222 ° C.

EXAMPLE 65 A. Preparation of 2,3-dimethoxy-N- (4-phenyl-P-benzene-1,4-diamine Following the procedure described in Example 63 this intermediate was prepared with an overall yield of 40% from of 4-nitro-fluorobenzene (376 mg, 3.54 mmol) and of 4-amino-1,2-dimethoxy-benzene (542 mg, 3.54 mmol) followed by hydrogenation in ethanol. RP18-HPLC TR: 6.10 minutes; API EM: 246.10 (M + 1). d B. N- (3,4-d¡methoxy-phenyl) -N '- (6-phenyl-thieno [3.2-blp-r, m, d-n-4-yl) -benzene-1, 4 -diamine Using the procedure analogous to that described in example 61, the title compound was prepared in a yield of 21% from the 2,3-dimethoxy-N- (4-phenyl) -benzene-1,4-diamine (191 mg, 0.696 mmol) and 4-0 chloro-phenyl-thieno- [3,2-b] pyrimidine (172 mg, 0.696 mmol). RP18-HPLC TR: 6. d12 minutes; EM API: 4d4.dd (M + 1). P.F. 160-161 ° C.

EXAMPLE 66 A. Preparation of N- (3-methoxy-phenyl) -benzene-1,4-diamine Following the procedure described in example 63, this intermediate was prepared with an overall yield of d3% from 4% onwards. Nitro-fluorobenzene (199 mg, 1.77 mmol) and 3-methoxyaniline (2d0 mg, 1.77 mmol) followed by hydrogenation in ethanol. API EM: 216.28 (M + 1).

B. N- (3-methoxy-phenyl) -N '- (6-phenyl-phenol-3,2-birpyrimidin-4-yl) -benzene-1,4-diamine Using an analogous procedure to that described in Example 61, the title compound with a 17% yield from the added N- (3-methoxy-phenyl) -benzene-1,4-diamine (100 mg, 0.40d mmol) and 4-chloro-6 phenyl-thieno [3,2-d] pyrimidine (100 mg, 0.40d mmol). RP18-HPLC TR: 6,833 minutes; EM API: 42d.d3 (M + 1); P.F. 189-191 ° C.

EXAMPLE 67 A. Preparation of N- (4- (N, N-dimethyl) -amina-phenyl-benzene-1,4-diamine Following the procedure described in Example 63, this intermediate was prepared with a yield overall 44% from 4-nitro-fluorobenzene (2d0 mg, 1.77 mmol) and 4- (N, N-dimethyl) -amine-aniline (228 mg, 1 J7 mmol) followed by hydrogenation in ethanol. RP18- HPLC TR: d.2d minutes; API EM: 216.28 (M + 1).

B. 4- (N, N-dimethylamine) -N- (4-phenyl) -N '- (6-phenyl-thienor-3-d-pyrimidin-4-yl) -benzene -1,4-diamine Using a procedure analogous to that described in Example 61, the title compound was prepared in a 31% yield from N- (4- (N, N-dimethyl) amine-phenyl) - added benzene-1, 4-diamine (100 mg, 0.40d mmol) and 4-chloro-6-phenyl-thieno [3,2-d] pyrimidine (93 mg, 0.406 mmol). RP18-0 HPLC TR: 7.066 minutes; API EM: 438.4d (M + 1); PF: 198-199 ° C.

EXAMPLE 68 A. Preparation of 2-methyl-d-aminoindole d To a mixture of 2-methyl-d-nitroindole (200 mg, 1.13 mmol) and palladium on carbon (20 mg, 10%) in 10 ml of ethanol was added hydrazine ( 100 mg, 3.4 mmol) and heated at 80 ° C for 16 hours. The reaction mixture was filtered through celite and concentrated in vacuo to give a red-brown solid which was used without further purification. RP18-HPLC TR: 1.278 0 minutes; API EM: 147.1 (M + 1).

B. (2-methyl-1 H -indole-d-yl) - (6-phenyl-thieno [3,2-d1-pyrimidin-4-yl] -amine) 2-Phenyl-7-chloro was dissolved in a sealed tube. -tiene [3,2- djpyrimidine (1 dO mg, 0.608 mmol) in 1 d ml of dichloroethane and 1 d ml of t-butyl alcohol. 2-Methyl-d-aminoindole (89 mg, 0.608 mmol) was added, the tube was sealed d and the contents heated to 8d ° C for 36 hours. The solution was cooled and filtered, the solid was washed with methylene chloride and dried under vacuum to give 123 mg (61% yield) of the title compound. RP18-HPLC TR: d.407 minutes; API EM: 357.1 (M + 1); P.F. 218-220 ° C. 0 EXAMPLE 69 A. Preparation of 1-benzenesulfonyl-1-H-indol-5-yl-amine To a mixture of d-nitroindole (30 g, 18 d mmoles) in dry THF (300 ml) was added potassium t-butoxide ( 24.26 g, 204 mmol). The reaction was stirred at room temperature for 30 minutes. Benzenesulfonyl chloride was added in one portion (28.33 g, 222 mmol) and the reaction changed from dark black to an orange suspension. The reaction was stirred at room temperature for 24 hours. The reaction mixture was partitioned between water and ethyl acetate and the aqueous layer was extracted 3 times with ethyl acetate. The organic extracts were combined and dried over magnesium sulfate and concentrated in vacuo. The crude residue recrystallized from hexane to give dO g (91%) of the nitro intermediate. PR18-HPLC TR: d.13 minutes.

The nitro intermediate was dissolved in 90 ml of THF and palladium on carbon (dOO mg, 10%) was added. The mixture was hydrogenated at room temperature at 1.2 atmospheres of pressure. The reaction was filtered and concentrated in vacuo to give the title compound as a yellow residue, which was used for further purification. RP18-HPLC TR: 4.261 minutes.

B. Preparation of [1-benzenesulfonyl-1 H-indol-d-yl-1- (6-phenylethieno [3,2-dlpyrimidin-4-yl] -amine In a sealed tube 2-phenyl- was dissolved 7-chloro-thieno [3,2-0 djpyrimidine (1000 mg, 4.0 d mmoles) in 1 d ml of dichloroethane and 1 d ml of t-butyl alcohol. 1-Benzenesulfonyl-1 H-indol-d-yl-amine (1100 mg, 4.0 d mmoles) was added, the tube was sealed and the contents heated to 8d ° C for 36 hours. The solution was cooled and filtered, the solid was washed with methylene chloride and dried under vacuum to give 1723 mg (89% yield) of title compound d. RP18-HPLC TR: 6,629 minutes; EM API: 483.4d (M + 1).

C. H - (2-morpholin-4-yl-ethyl) -1 H -indol-5-yl-6-phenyl-thienor-3-dl-pyridin-4-yl) -amin A a suspension of NaH (486 mg, 0.642 mmol) in dioxane was added [1-benzenesulfonyl-1 H-indol-5-yl] - (6-phenyl-thieno [3,2-d] pyrimidin-4-) sheet (246 mg, 1.00 mmol) and the reaction was stirred for 30 minutes at room temperature. Hydroxyethyl morpholine (46 mg, 1.0 mmol) was added and the reaction was refluxed overnight. The reaction mixture was partitioned between water and ethyl acetate and the layer was extracted 3 times with ethyl acetate. The organic extracts were combined and dried over magnesium sulfate and concentrated in vacuo. The crude residue is chromatographed on silica gel with 1% methanol / methylene chloride to give 26 mg (16%) of the title compound. RP18-HPLC TR: d.d86 minutes. API EM: 342.43 (M + 1). P.F .: 22d-266 ° C.

EXAMPLE 70 Ri-F3-Diethylamino-propyl) -1H-indol-5-in- (6-phenyl-thienor-3,2-blpyrimidin-4-yl) -amine The title compound was prepared from [1-benzenesulfonyl-1 H-indol-5-yl] - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine (246 mg, 1.00 mmol) and diethylamino-propanol (120 mg, 0.939 mmol) by a procedure analogous to that of Example 96. RP18-HPLC RT: 4.5 d minutes; MS API: 45d.63 (M + 1): 178-180 ° C.

EXAMPLE 71 A. Preparation of (1 H-indol-d-1) - (2-methyl-6-phenyl-tethenic-3, 2-dlp-r, r, 4-yl-4-yl) -amine To a solution of methyl 3-amino-d-phenylthiophene-2-carboxylate (1.0 g, 4.28 mmol) in 6 ml of acetonitrile a dry stream of HCl gas was bubbled in for 30 minutes. The reaction was poured into ice water and the pH was adjusted to 9 with ammonium hydroxide. The product was filtered and recrystallized from dioxane to give the product as a white solid. 100 ml of methylene chloride and dimethylformamide (0.247 ml, 3.19 mmol) were combined in a 2 d0 ml round bottom flask and cooled to 0 ° C. Oxalyl chloride (2.33 ml, 4.66 mmol) was added dropwise over several minutes. 2-Methyl-6-phenyl-4H-thieno [3,2- b] pyrimidin-7-one (3d3 mg, 1.45 mmol) was added and the solution was heated to reflux. After 2 hours, the flask was cooled to room temperature and the resulting solid was filtered and dried under vacuum to give 400 mg (100%) of 7-chloro-0-thieno [3,2-b] pyrimidine as a solid green. LC-MS: 261 (MH +).

B. Preparation of (1 H-indol-5-yl) - (2-methyl-6-phenyl-ene-2,3-dl-pyrimidin-4-ip-amine In a sealed tube, 2-phenyl-d- was dissolved methyl-7-chloro-thieno [3,2-d bjpyrimidine (200 mg, 0J67 mmol) in 1d ml of dichloroethane and 1d ml of f-butyl alcohol 1 H-indole-d-yl-amine (843 mg , 0.767 mmol), the tube was sealed and the contents heated to 8d ° C for 36 hours.The solution was cooled and filtered, the solid was washed with methylene chloride and dried under vacuum to give 190 mg (62% yield ) of the title compound RP18-HPLC TR: d.46 minutes; EM API: 3d6.47 (M + 1); PF: 20d-210 ° C.

EXAMPLE 72 N- (4-Methoxy-phenyl) -N '- (2-methyl-6-phenyl-thienor-3,2-d1-pyrimidin-4-yl) -benzene-1,4-diamine d The title compound was prepared from 2-phenyl-d-methyl-7-chloro-thieno [3,2-b] pyrimidine (200 mg, 0.767 mmol) and N- (4-methoxy-phenyl) - benzene-1, 4-diamine (843 mg, 0.767 mmol) by an analogous procedure to that of Example 71. RP18-HPLC TR: 6.7d minutes; API EM: 438.68 (M + 1); PF: 181-18d ° C. 0 EXAMPLE 73 A. Preparation of N- (6-phenyl-thieno [2,3-d1-pyrimidin-4-yl) -benzene-1,4-diamine d) 2-phenyl-7-chloro-thieno was dissolved in a sealed tube [3,2 - bjpyrimidine (600 mg, 2026 mmol) in 1 d ml of dichloroethane and 1 d ml of butyl alcohol. 4-Nitroaniline (279 mg, 2026 mmol) was added, the tube was sealed and the contents heated to 8d ° C for 36 hours. The solution was cooled and filtered, the solid was washed with methylene chloride and dried under vacuum to give 0 400 mg (67% yield) of the title compound. RP18-HPLC TR: d.46.47607 minutes; API EM: 367.1348.38 (M + 1); PF: 210-211 ° C. To a mixture of (4-nitro-phenyl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine (400 mg, 1.48 mmol) and palladium on carbon (40 mg, 10% ) in 10 ml of ethanol was added hydrazine (200 mg, 3.4 mmol) and heated at 80 ° C for 16 hours. The reaction mixture was filtered through celite and concentrated in vacuo to give a red-brown solid, which was used without further purification. RP18-HPLC TR: 4.816 minutes; API EM: 319.38 (M + 1). d B. N- (2-Benzyl-oxyl) -N '- (6-phenolyl-ene3,2-blpyrimidin-4-benzene-1,4-diamine The title compound was prepared from benzyloxyacetaldehyde (12 mg, 0.079 mmol) and N- (6-phenyl-t-ene [3,2-b] pyrimidin-4-yl) -benzene-1,4-diamine (160 mg, 0.471 mmol) by an analogous procedure to that of Example 17. RP18-HPLC TR: 7.062 minutes; API EM: 4d2.d8 (M + 1); PF: 201-203 ° C.

EXAMPLE 74 d 5- (6-Phenyl-thienop3,2-b1-pyrimidin-4-ylamino) -1H-indol-3-carbaldehyde To a solution of (1 H-indol-d-yl) - (6-phenyl-thieno [3,2-b] pyrimidin-4-yl) -amine (481 mg, 1.4 mmol) in 3 ml of methylene chloride in a 3-neck flask with a dropping funnel, under nitrogen at 0 ° C, 0 titanium tetrachloride (461 mg, 4.2 mmol) was added dropwise. The mixture was stirred for 30 minutes and dichloromethoxymethane (380 ml, 4.2 mmol) was added dropwise. The reaction was warmed to room temperature and concentrated in vacuo. The resulting residue was preabsorbed on the silica gel (10 mg) and purified by ultrafast chromatography using methanol / methylene chloride d% to give the title compound in 92% yield. RP18-HPLC TR: 4.80 minutes; MS API: 371.20 (M + 1); PF: 174-175 ° C.

EXAMPLE 75 f3-Bromo-1H-indol-5-yl) - (6-phenylthienor3,2-dlpyrimidin-4-yl) -amine To a solution of (1H-indol-5-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) amine (160 mg, 0.438 mmol) in methylene chloride was added N-bromosuccinimide (86 mg, 0.482 mmol). The reaction mixture was stirred for 2 days at room temperature and then concentrated in vacuo. The orange residue was chromatographed by preparative reverse phase HPLC using a 200 nM acetate buffer and a gradient of acetonitrile to give the pure product (yield 17%). RP18-HPLC TR: 6,377 minutes; API EM: 371.2 (M + 1); PF: 201 -303 ° C.

EXAMPLE 76 N- (1 H -indole-3-ylmethyl) -N '- (6-phenyl-thienor-3,2-dlpyrimidin-4-in-benzene-1,4-diamine The title compound was prepared from 1 H-indole-3-carbaldehyde (12 mg, 0.079 mmol) and N- (6-phenyl-thieno [3,2-b] pyrimidin-4-yl) - benzene-1,4-diamine (150 mg, 0.471 mmol) by a procedure analogous to that of Example 73. RP18-HPLC TR: 6.932 minutes; API EM: 448.20 (M + 1); PF: 259-261 ° C.

EXAMPLE 77 N- (6-Bromo-thienor-3,2-d-pyrimidin-4-yl) -N'-4-methoxy-phenyl) -benzene-1,4-diamine The title compound was prepared from 2-bromo-7-chloro-thieno [3,2-b] pyridine (1.8 g, 7.26 mmol) and N- (4-methoxy-phenyl) -benzene-1 , 4-diamine (1.7 mg, 0.767 mmol) by a procedure analogous to that of Example 1. RP18-HPLC TR: d.7d minutes; API EM: 426.26 (M + 1).

EXAMPLE 78 N- (4-Methoxy-phenyl) -N'-r6- (2-nitro-phenyl) -thienor3,2-dlpyrimidin-4-ill-benzene-1,4-diamine The title compound was prepared from 2-nitrobenzeneboronic acid and N- (6-bromo-thieno [3,2-d] pyrimidin-4-yl) -N '- (4-methoxy-phenyl) -benzene -1,4-diamine by a procedure analogous to that of example 2. PF 228-237 ° C; LC-MS: 383.56 (MH +); HPLC TR: 6,885 minutes.

EXAMPLE 79 N-84-Methoxy-phenyl) -N, -r6- (4-methoxy-phenyl) -thienor3,2-dlpyrimidin-4-benzene-1,4-diamine d The title compound was prepared from 2-methoxybenzeneboronic acid and from N- (6-bromo-thieno [3,2-d] pyrimidin-4-yl) -N '- (4-methoxy-phenyl) - benzene-1, 4-diamine by a procedure analogous to that of example 2. PF 159-169 ° C; LC-MS: 453.31 (MH +); HPLC TR: 7,003 minutes. 0 EXAMPLE 80 N- (4-Methoxy-phenin-N'-r6- (6-methoxy-pyridn-3-n-inen3.2-dlprr -4-benzene-1,4-diamine The title compound was prepared from 2-methoxy-d-pyridyl-d-boronic acid and from N- (6-bromo-thieno [3,2-d] pyrimidin-4-yl) -N '- (4 -methoxyphenyl) -benzene-1,4-diamine by a procedure analogous to that of example 2. PF 149-169 ° C; LC-MS: 466.29 (MH +); HPLC TR: 6,747 minutes.

EXAMPLE 81 N- (4-Methoxy-phenyl) -N '- (6-thiophen-2-yl-thienor-3,2-dl-pyrimidin-4-n-benzene-1,4-diamine The title compound was prepared from 2-thiophenebenzoboronic acid and N- (6-bromo-thieno [3,2-d] pyrimidin-4-yl) -N '- (4-methoxy-phenyl) -benzene -1,4-diamine by a procedure analogous to that of example 2. PF 231-240 ° C; LC-MS: 431 (MH +); HPLC TR: 6,740 minutes.

EXAMPLE 82 f3-Methyl-1H-indol-5-yl) - (6-phenyl-thienor-3,2-dlpyrimidin-4-yl) -amine A suspension of 5- (6-phenyl-t-ene [3,2-d-pyrimidin-4-ylamino) -1H-indole-3-carbaldehyde (75 mg, 0.203 mmol) in 5 ml of methylene chloride was added zinc iodide (97 mg, 0.303 mmol) and sodium cyanoborohydride (97 mg, 1522 mmol). The reaction mixture was refluxed for 24 hours and then cooled to room temperature and poured into an ice-cooled saturated ammonium chloride mixture. The solution was then neutralized with 6N HCl and extracted with ethyl acetate (3x, 50 ml). The organic extracts were dried over magnesium sulfate and concentrated in vacuo. The residue was chromatographed using a Biotage Autoflash 40 system and MeOH / CH 2 Cl 2 1% yielding the title compound (22 mg, 31% yield). RP18-HPLC TR: 6.071 minutes; MS API: 357.10 (M + 1); PF: 221-223 ° C.

EXAMPLE 83 N ^ -Metoxy-phenin-N '^ - O-nitro-phenyD-thienoyl S ^ -dlpyridin ^ -ill-benzene-l-diamine The title compound was prepared from 2-nitrobenzeneboronic acid and N- (6-bromo-thien [3,2-d] pyrimidin-4-yl) -N '- (4-methoxy-phenyl) ) -benzene-1,4-diamine by a procedure analogous to that of example 2. PF 175-184 ° C; LC-MS: 4dd.29 (MH +); HPLC TR: 6,646 minutes.

EXAMPLE 84 (7-Methoxy-1H-indol-5-in- (2-phenyl-t-ene [3,2-blpyridin-7-yl] -amine) The title compound was prepared according to a procedure that is analogous to the procedure described in the previous examples.

EXAMPLE 85 N- (4-methoxy-phenyl) -N'-thienor3,2-dlpyrimidin-4-yl-benzene-1,4-diamine The title compound was prepared from 7-chloro-thieno [3,2-b-pyridine (3.65 g, 14.64 mmol) and N- (4-methoxy-phenyl) -benzene-1,4-diamine (3.13 g. , 14.64 mmoles) by a procedure analogous to that of Example 1. RP18-HPLC TR: 6.070 minutes; PF: 181-186 ° C; API EM: 428 (M + 1).

EXAMPLE 86 (1H-indol-5-yl) -r6-f6-methoxy-pyridin-3-yl) -thienof3,2-d1-pyrimidin-4-yn-amine In a sealed tube, (2-bromo-thieno [3,2-b] pyrimidin-7-yl) -1H-indol-5-yl) -amine (150 mg, 0.29 mmol) and 3-pyridyl-diethylborane were combined. (133 mg, 0.869 mmol) in 3 ml of dimethylformamide together with copper iodide (3 mg, 0.015 mmol). Nitrogen was bubbled through the solution and rans-benzyl (chloro) bis-triphenylphosphine) palladium (II) (33 mg, 0.044 mmol) was added, the tube was sealed and heated to 90 ° C. After 14 hours, the solution was cooled and concentrated to dryness. Chromatography on 15 g of silica gel with CH 2 Cl 2 / MeOH (5-20%) gave 71 mg (44%) of the title compound. LC-MS: 374 (MH +); P.F. 243-249 ° C; HPLC TR: 5.396 minutes.

EXAMPLE 87 N- (4-Methoxy-phenin-N'-r2- (6-methoxy-pyridin-3-yl) -t-inor3.2-b1-pyridin-7-illbenzene-1, 4- diamine The title compound was prepared from 2-methoxy-pyridyl-5-boronic acid and from N- (6-bromo-thieno [3,2-d] pyridin-4-yl) -N '- (4 -methoxy-phenyl) -benzene-1,4-diamine by a procedure analogous to that of example 2. PF 175-184 ° C; LC-MS: 455.29 (MH +); HPLC TR: 6,646 minutes.

EXAMPLE 88 (6-Chloro-1H-indol-5-yl) - (6-phenyl-thienor-3,2-d-pyrimidin-4-yl) -amine The title compound was prepared according to a procedure that is analogous to the procedure described in the previous examples.

EXAMPLE 89 A. Preparation of 4- [7- (2-methy1-H-indole-d-ylamino) -thieno [312-b1pyridin-2-p-benzaldehyde] The title compound was prepared at from 4-formylbenzeneboronic acid and (2-bromo-thieno [3,2-b] pyridin-7-yl) - (2-methyl-1 H-indol-d-yl) -amine by a procedure analogous to from Example 17. RP18-HPLC TR: d.391 minutes; EM API: 384.29 (M + 1).

B. Preparation of 2-bromo-t-inof3,2-b1pyridin-7-yl) - (2-methyl-1H-indol-5-yl) -amine In a sealed tube was dissolved 2-bromo-7-chloro-thieno [3,2-bjpyridine (736 mg, 2.96 mmol) in 15 ml of dichloroethane and 15 ml of f-butyl alcohol. 2-Methyl-5-aminoindole (480 mg, 3.26 mmol) was added, the tube was sealed and the contents heated to 8d ° C for 36 hours. The solution was cooled and filtered, the solid was washed with methanol and dried under vacuum to give 1.96 mg (quantitative yield) of the title compound, which was used without further purification. RP18-HPLC TR: 6,827 minutes; EM API: 369.08 (M + 1).

C. 2- (4- [7- (2-methyl-1 H-indol-d-amyl) -thione [3,2-blp¡r¡din-2-n-benzylamino) - Ethanol The title compound was prepared from 4- [7- (2-methyl-1 H -indol-5-ylammon) -thieno [3,2-b] pyridin-2-yl] - benzaldehyde (60 mg, 0.156 mmol) and 2-Hydroxyethylamine (57 mg, 0.939 mmol) by a procedure analogous to that of Example 82. RP18-HPLC TR: 4.078 minutes; EM API: 465.0 (M + 1).

EXAMPLE 90 (2-methyl-1H-indol-5-in-r2- (4-morpholin-4-ylmethyl-phenyl) -thienor2.3-b1-pyridin-7-yl-amine The title compound was prepared from 4- [7- (2-methyl-1 H -indol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzaldehyde (60 mg, 0.156 mmol) and morpholine (82 mg, 0.939 mmol) by a procedure analogous to that of Example 89. RP18-HPLC TR: 4,652 minutes; API EM: 454.69 (M + 1).

EXAMPLE 91 (1H-indol-5-yl) - (6-phenyl-thienoyl-3,2-d1-pyrimidin-4-yl) -amine In a 12d ml single-neck round bottom flask with a reflux condenser, 4-hydroxy- (6-phenyl) -thieno [3,2-d] pyrimidine was combined with triphenylphosphine polymers (900 mg, 2.7 mmol) , carbon tetrachloride (1.1 ml, 11 mmol) and dichloroethane (1d ml). Boiling chips were added and the mixture was refluxed for 18 hours. The mixture was cooled to room temperature and filtered in a second single-neck bottom flask. The polymer was washed with 26 ml of 10% dichloroethane / tert-butanol. The organic layers were combined and d-amino-indole (212 mg, 1.6 mmol) was added and the resulting solution was refluxed for 18 hours. The reaction mixture was cooled to room temperature and concentrated to give a green-brown residue. The residue was partitioned between 1 N NaOH and 2-propanol / 15% chloroform. The aqueous layer was extracted 2 times with 15 ml 15% isopropanol / CHCl3. The organic layers were combined and dried over sodium sulfate and concentrated to give a black residue. The residue was triturated with methanol giving 57 mg of the product. PF: 2dd-268 ° C (dec); anal. RP18-HPLC TR: 4.38 minutes; TS-MS: 343 (M + 1).

EXAMPLE 92 (6-phenyl-thienor-3,2-dl-pyrimidin-4-yl) -m-tolyl-amine Following the procedure of example 91, the title product was prepared in a 61% yield from 4-hydroxy-6-phenyl-thieno [3,2-d-pyrimidine (1.0 eq) and m-toluidine (1.5 eq) in butanol. The HCl salt was prepared from the purified free base by dissolving the free base in minimal methanol and a solution of HCl (g) bubbled in 2 ml Et 2 O was added dropwise until the mixture became turbid. The precipitated HCl salt was dried in vacuo, washed once with Et 2 O and dried in vacuo to give a constant mass. P.F. 238-241 ° C; 318 (MH +); anal. RP18-HPLC TR: 4.96 minutes.

EXAMPLES 93-97 Examples 93-97 were prepared according to the method of Example 91 from 4-hydroxy-6-phenyl-thieno [3,2-b] pyrimidine and the appropriate amine starting materials.

EXAMPLES 98-105 The compounds of Examples 98-105 were prepared according to the method of Example 91 from 4-hydroxy-6- (4-methoxy-phenyl) -thieno [3,2-d] pyridine and the appropriate amine starting materials.

EXAMPLES 106-113 The compounds of Examples 106-113 were prepared according to the method of Example 91 from 4-hydroxy-d- (2,4-dimethoxy-phenyl) -thieno [3,2-d] pyrimidine and the materials amine starting materials.

EXAMPLE 114 N, N-dimethyl-NY4-r7- (2-methy1-1H-indol-5-ylamino) -thieno-f3,2-blp¡r¡d¡n-2- illbenzyl) -propane- 1, 3-diamino The title compound was prepared from 4 - [] 7- (2-methyl-1 H-indol-d-ylamino) -thieno [3,2-b] pyridn-2-yl] -benzaldehyde (63 mg, 0.166 mmol) and 3- (dimethylamine) -propylamine (102 mg, 0.994 mmol) by a procedure analogous to that of Example 89. RP18-HPLC TR: 4.35 minutes; API EM: 69.66 (M + 1) MP: 167 ° C (mild, 275 ° C dec.).

EXAMPLES 115-146 The compounds of Example 115-146 were synthesized by a method analogous to that of Example 61 starting from 4-chloro-6-phenyl-thieno [3,2-bjpirimide (1.49 ml, 66.9 mm solution in DCE: tBuOH) and 110 mmol of the corresponding amines.

EXAMPLE 147 6-vodo-4-chloro-thienor-2,3-d-pyridine In a 500 ml round bottom flask, 120 ml of tetrahydrofuran was cooled with 13 grams of 4-chloro-thieno [3,2-d] pyridine (76.6 mmol) to -78 ° C. To the stirring solution was added dropwise n-butyllithium (191.6 mmol, 2.5 M in hexane) over a period of 20 minutes. After stirring for another 20 minutes, iodine (48.3 g, 191.6 mmol) in 80 ml of THF was added dropwise, so that the internal temperature did not exceed -78 ° C. After the addition was complete, the reaction was allowed to warm slowly to room temperature. The reaction mixture was quenched by diluting with chloroform and extracted with H20 (2x250 ml), followed by extraction of the aqueous material combined with CHCl3 (1x100 ml). The organic portions were then washed with Na2S203 (2x200 ml), H20 (2x200 ml), dried over MgSO4, filtered and dried. The resulting residue was suspended in a minimal amount of chloroform and an excess of water was added. The solid obtained was filtered and washed with ether. The mother liquor was concentrated and more material was isolated in the same way. The two collected portions of crystals were combined giving 11.8 g (52%) of 6-iodo-4-chloro-thieno [3,2-d] pyridine which was greater than 90% pure. 1 H NMR (400 MHz, CDCl 3) d 8.51 (d, 1 H), 7.83 (s, 1 H), 7.24 (d, 1 H). LC-MS: 259.9, 297.9 (MH +); HPLC TR: 6.45 min.

EXAMPLE 148 A.2-r2- (tert-butyl-dimethyl-silanyl) -3-methyl-3H-imidazole-4-in-7-chloro-thienor3,2-blpyridine 2- (I-butyl) -dimethyl-silane) -1-methyl-1H-imidazole (1.3 g, 6.74 mmol) was dissolved in 15 ml of tetrahydrofuran and cooled to -78 ° C was added dropwise n-butyl lithium (2.8 ml, 2.5 M in hexane). The cold bath was removed and the mixture was stirred at room temperature for 3 hours. The solution was re-cooled to -78 ° C and zinc chloride (14.9 ml, 0.5 M in THF) was added and the reaction mixture was warmed to room temperature. After 1 hour, 6-iodo-4-chloro-thieno [3,2-d] pyridine (1.0 g, 3.37 mmol) in 7 ml of THF was added followed by tetrakis (390 mg, 0.337 mmol) and the solution was dissolved. heated to reflux for 3 hours. The mixture was cooled to room temperature, diluted with water and extracted with chloroform (3 x 50 ml). The organic extracts were dried over Na 2 SO 4, filtered and concentrated. Chromatography on 50 g of silica gel with methanol / 2% methylene chloride gave 912 mg (74%) of 2- [2- (tert-butyl-dimethylsilanyl) -3-methyl-3H-imi. dazol-4-yl] -7-chloro-thieno [3,2-b] pyridine. 1 H NMR (400 MHz, CD3OD) d 8.58 (d, 1 H), 7.69 (s, 1 H), 7.51 (s, 1 H), 7.47 (d, 1 H), 3.97 (s, 3 H), 0.98 (s, 9H), 0.47 (s, 6H). LC-MS: 364, 366 (MH +); HPLC TR: 6.65 min.

B. 7-chloro-2- (3-methy1-3H-imidazole-4-p-thienor3.2-bipyridine. 2- [2- (ert-Butyl) -dimethyl-silanyl) was dissolved. 3-methyl-3H-imidazol-4-yl] -7-chloro-thieno [3, 2-b] pyridine (912 mg, 2.60 mmol) in 15 ml of methanol and 10 ml of 1N aqueous hydrochloric acid and heated to 35 ° C overnight. The solution was cooled, diluted with water and extracted with ethyl acetate (3x30 ml). The aqueous layer was basified (pH 9) with 1N aqueous sodium hydroxide and extracted with chloroform (3x30 ml). The combined organic extracts were dried over Na2SO4, filtered and concentrated to give 628 mg (84%) of 7-chloro-2- (3-methyl-3H-ylazol-4-yl) -thieno [3,2-b ] pyridine. 1 H NMR (400 MHz, CD 3 OD) d 8.58 (d, 1 H), 7.84 (s, 1 H), 7.68 (s, 1 H), 7.42 (s, 1 H), 3.93 (s, 3 H). LC-MS: 250.1, 252 (MH +): HPLC TR: 4.40 min.

C.r2- (3-methy1-3H-imidazol-4-ynt-inof3.2-blp-rdin-7-ill- (2-methyl-1 H -indole-5-yl) - amine 7-Chloro-2- (3-methyl-3H-imidazol-4-yl) -thieno [3,2-bjpyridine (600 mg, 2.40 mmol) and 2-methyl-5-aminoindole (422 mg, 2.89 g. mmoles) in 20 ml of tert-butanol and 20 ml of dichloroethane and heated to 85 ° C. The solvent was allowed to evaporate overnight and was replaced the next day by the same amounts as in the initial reaction mixture together with 90 ml. additional mg of indole The solution was heated an additional 24 hours and allowed to dry as before. Chromatography of the residue with methanol: ethyl acetate 30-5% gave 142 mg (16%) of [2- (3-methyl- 3H-imidazol-4-yl) -thieno [3,2-b] pyridin-7-yl] - (2-methyl-1 H -indol-5-yl) -amine 1 H NMR (400 MHz, CD3OD) d 8.14 (d, 1 H), 7J9 (s, 1 H), 7.45 (s, 1 H), 7.40 (s, 1 H), 7.43 (d, 1 H), 7.29 (s, 1 H), 6.99 (d, 1 H), 6J2 (d, 1 H), 6.17 (s, 1 H), 3.84 (s, 3H), 2.44 (s, 3H), LC-MS: 360, 361 (MH +), HPLC- TR: 3.96 min.

EXAMPLE 149 A. 2-r5- (7-Chloro-thienor3.2-b1pyridin-2-in-1-methyl-1 H-imidazole-2-ill-propan-2-ol) In a round bottom flask of 50 ml were cooled to 7 ml of tetrahydrofuran and n-butyllithium (0.88 ml, 2.5 M in hexane) to -40 ° C. A suspension of 7-chloro-2- (3-methyl-3H-) was added dropwise. imidazol-4-yl) -thieno [3,2-d] pyridine (500 mg, 2.00 mmol) in 9 ml of tetrahydrofuran to the solution and stirred for 40 minutes Acetone (0.79 ml, 3.00 mmol) was added to the anion and the reaction mixture was allowed to warm to room temperature overnight The mixture was diluted with water and extracted with chloroform (3 x 50 ml) The combined extracts were dried over NaSO, filtered and concentrated. 60 g of silica gel with methanol: methylene chloride d% gave 191 mg (31%) of 2- [d- (7-chloro-thieno [3,2- b] pyridin-2-yl) -1-methyl -1 H-imidazol-2-yl] -propan-2-ol, 1 H NMR (400 MHz, CDCl 3) d 8.68 (d, 1 H), 7.61 (s, 1 H), 7.28 (d, 1 H) , 7.24 (s, 1 H), 4.02 (s, 3H), 1 77 (s, 6H) LC-MS: 308.1, 310.1 (MH +); HPLC TR: 4.18 min.

B.2-11 -methyl-d-IJ- (2-methyl-1 H -indol-d-ylammon) -thinyenoic -3.2-blpyridin-1-p-1 H-imidazole-2 -l} -propan-2-ol 2- [d- (7-Chloro-thieno [3,2-b] pyridin-2-yl) -1-methyl-1 H -amidazol-2-yl] -propan- 2-ol (190 mg, 0.62 mmol) and 2-methyl-d-aminoindole (108 mg, 0J14 mmol) in 3 ml of tert-butyl alcohol and 3 ml of dichloroethane and the solution was heated to 8d ° C. After allowing the reaction to dry overnight, solvent was added along with another 45 mg of indole and the solution was heated for another 18 hours. Chromatography of the residue with 20% methylene methochloride gave 166 mg of 2-. { 1-methyl-5- [7- (2-methyl-1 H -indol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -1 H -imidazol-2-yl} -propan-2-ol 1 H NMR (400 MHz, CD3OD) d 8.17 (d, 1 H), 7.51 (s, 1 H), 7.44 (s, 1 H), 7.40 (d, 1 H), 7.02 (d, 1 H), 6.84 (s, 1 H), 6.20 (s, 1 H), 3.33 (s, 3H), 2.44 (s, 3H), 1.64 (s, 6H). LC-MS: 418, 419 (MH +); HPLC TR: 3.98 min.

EXAMPLE 150 A. 7-Chloro-2- (1-methyl-1 H -amidazol-2-yl) -t-inof3,2-b1pyridine 1-Methylimidazole (0.54 mL, 6.74 mmol) was dissolved in 15 mL of tetrahydrofuran and cooled to -78 ° C and n-butyllithium (2.8 mL, 2.5 M in hexane) was added dropwise. After stirring for 30 minutes at -78 ° C, zinc chloride (14.9 ml, 7.42 mmol) was added and the solution was allowed to warm to room temperature. After 1 hour, 6-iodo-4-chloro-thieno [3,2-d] pyridine (1.0 g, 3.37 mmol) in 7 ml of THF was added followed by tetrakis (390 mg, 0.337 mmol) at reflux for 3 hours. hours. The mixture was cooled to room temperature, diluted with water and extracted with chloroform (3 x 60 ml). The organic extracts were dried over Na 2 SO 4, filtered and concentrated. Chromatography on 60 g of silica gel with 2% methylene methochloride gave 458 mg (5d%) of 7-chloro-2- (1-methyl-1 H-imidazol-2-yl) -thieno [3,2- b] pyridine. 1 H NMR (400 MHz, CD3OD) d 8.68 (d, 1 H), 7.69 (s, 1 H), 7.61 (s, 1 H), 7.47 (d, 1 H), 3.97 (s, 3 H), 0.98 (s, 9H), 0.47 (s, 6H). LC-MS: 364, 366 (MH +); HPLC TR: 6.65 min.

B. [2- (1-methyl-1 H-imidazol-2-yl) -thienof3.2-blpyridin-7-n- (2-methyl-1 H -indole-5-yl) -amine They were dissolved 7-chloro-2- (1-methyl-1 H -imidazol-2-yl) -thieno [3,2-bjpyridine (1.0 g, 4.0 mmol) and 2-methyl-5-aminoindole (732 mg, 5.0 mmol) in 7 ml of butyl alcohol and 7 ml of dichloroethane and the solution was heated to 85 ° C. After allowing the reaction to dry overnight, the reaction mixture was cooled and absorbed on silica gel. Chromatography of the residue with 20% methylene methochloride gave 991 mg (69%) of [2- (1-methyl-1 H-imidazol-2-yl) -thieno [3,2-b] pyridin-7-yl. ] - (2-methyl-1 H-indol-5-yl) -amine. 1 H NMR (400 MHz, CD3OD) d 8.26 (d, 1 H), 7.95 (s, 1 H), 7.62 (s, 1 H), 7.48 (m, 2 H), 7.39 (d, 1 H), 7.04 (m, 2H), 6.20 (s, 1 H), 3.33 (s, 3H), 2.43 (s, 3H). LC-MS: 360 (MH +); HPLC TR: 4.15 min.

EXAMPLE 151 A. 7-chloro-2-thiazol-2-yl-t-ene [3,2-blpyridine] 6-Bromo-4-chloro-thieno [3,2-d] pyridine (3.72 g, 15 mmol) was combined ) and 2-tributylstannaylthiazole (14 g, 37.4 mmol) with copper iodide (I) (285 mg, 1.5 mmol), frans-benzyl (chloro) (triphenylphosphine) palladium (II) (3.4 g, 4.5 mmol) in 22 ml of dimethylformamide. The reaction mixture was heated to 90 ° C and stirred for 1 hour. The mixture was cooled, concentrated and absorbed on silica gel. Chromatography with 10% ethyl acetate: methylene chloride gave 1.6 g (42%) of 7-chloro-2-thiazol-2-yl-thieno [3,2-b] pyridine. NMR of H (400 MHz, CDCl 3) d 8.59 (d, 1 H), 7.93 (s, 1 H), 7.89 (d, 1 H), 7.45 (d, 1 H), 7.30 (d, 1 H). LC-MS: 263 (MH +): HPLC TR: d.7d min.

B. (2-methyl-1 H -indole-d-in- (2-thiazole-2-yl-inor3,2-blpridine-7-in-amino) 7-chloro-2- was dissolved thiazol-2-yl-thieno [3,2-b] pyridine (400 mg, 1.58 mmol) and 2-methyl-5-aminoindole (231 mg, 1.68 mmol) in 6 ml of t-butyl alcohol and 6 ml of dichloroethane and the solution was heated to 8d ° C. After allowing the reaction to dry overnight, the reaction mixture was cooled and taken up on silica gel.Chartyping the residue with methanol methylene chloride d% gave 374 mg (68%) of (2-methyl-1 H-indol-5-yl) - (2-thiazol-2-yl-thieno [3,2-b] pyridin-7-yl) -amine. (400 MHz, DMSO) d 8J8 (s, 1 H), 8.18 (d, 1 H), 7.84 (m, 2H), 7.27 (m, 2H), 6.90 (d, 1 H), 7.39 (d, 1) H), 6.59 (d, 1 H), 6.10 (s, 1 H), 2.36 (s, 3 H) LC-MS: 363 (MH +); HPLC TR: 5.01 min.

EXAMPLE 152 A. 2-r2- (7-Chloro-thieno-2,3-b1-pyridin-2-in-thiazole-d-1-propan-2-ol) In a 2-ml round bottom flask, 2 ml were cooled of tetrahydrofuran and diisopropylamine (0.14 ml, 1.0 mmol) to -78 ° C and n-butyllithium (0.38 ml, 0.95 mmol) was added.The solution was warmed to 0 ° C for 10 minutes, then cooled again to -78 ° C. A solution of 7-chloro-2-thiazol-2-yl-thieno [3,2-b] pyridine (200 mg, 0.79 mmol) in 2 ml of tetrahydrofuran and the solution was added dropwise. The resulting mixture was stirred for 30 minutes, acetone (0.88 ml, 1.19 mmol) was added to the anion and the reaction mixture was allowed to warm to room temperature overnight.The mixture was diluted with water and extracted with chloroform (3 x 50 ml. The combined organic extracts were dried over NaSO 4, filtered and concentrated, chromatography on 50 g of silica gel with ethyl acetate: methylene chloride 30% gave 129 mg (52%) of 2- [2- ( 7-chloro-thieno [3,2-b] pyridin- 2-yl) -thiazol-5-yl] -propan-2-ol. 1 H NMR (400 MHz, CD3OD) d 8.56 (d, 1 H), 7.95 (s, 1 H), 7.71 (s, 1 H), 7.50 (d, 1 H), 1.66 (s, 6 H). LC-MS: 308.1, 311 (MH +): HPLC TR: 5.32 min.

B.2-. { 2-f7- (2-methyl-1 H -indol-5-ylamino) -thioenoic -3.2-blpyridin-2-p-thiazol-5-yl) -propan-2-ol 2- [2 - (7-chloro-thieno [3,2-b] pyridin-2-yl) -thiazol-d-yl] -propan-2-ol (129 mg, 0.42 mmol), 2-methyl-d-aminoindole (72 mg, O.dO mmol), potassium carbonate (138 mg, 8.84 mmol) and triethylamine (0.12 mmol, 0.84 mmol) in 2 ml of f-butyl alcohol and 2 ml of dichloroethane and the solution was heated to 8d ° C. After allowing the reaction to dry overnight, solvent was dissolved together with another 36 mg of indole and the solution was heated for another 18 hours. Chromatography of the residue with 20% methane-methochloride gave 166 mg (40%) of 2-. { 2- [7- (2-methyl-1 H -indol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -thiazole-5-yl} -propan-2-ol 1 H NMR (400 MHz, CD3OD) d 8.13 (d, 1 H), 7J1 (s, 1 H), 7.62 (s, 1 H), 7.35 (d, 1 H), 7.30 (d, 1 H), 6.99 (d, 1 H), 6.64 (d, 1 H), 6.13 (s, 1 H), 2.43 (s, 3H), 1.65 (s, 6H). LC-MS: 421 (MH +); HPLC TR: 4J5 min.

EXAMPLE 153 f6- (4-Fluoro-phenyl) -thienor3,2-dlpyrimidin-4-yn- (1H-indol-5-yl) -amine The title compound was prepared from 4-pyridylboronic acid and (6-bromo-thieno [3,2-d] pyrimidin-4-N) - (1 H -indol-5-yl-amine) by the procedure analogous to that of Example 2 above. P.F. 208-213 ° C; LC-MS: 343 (MH +); HPLC TR: 4,967 minutes.

EXAMPLE 154 4-r7 - (2-methyl-1 H -indole-5-ylamino) -thienor3,2, -b1-pyridin-2-yl-benzaldehyde The title compound was prepared from 4-pyridylboronic acid and (2-bromo-thieno [3,2-b] pyridin-7-yl) - (2-methyl-1 H-indol-d-yl-amine ) by the procedure analogous to that of Example 17 above. RP18-HPLC TR: 4.36 minutes; API EM: 357 (M + 1); P.F. 223-240 ° C.

Claims

NOVELTY OF THE INVENTION CLAIMS

1. - A compound of formula 1 or 2 or a pharmaceutically acceptable salt or hydrate thereof, wherein X1 is N or CH; R1 is H, d-C6 alkyl or -C (O) (C6-C6 alkyl); R 2 is C 6 -C 0 aryl or a 5-13 membered heterocycle, wherein said R 2 groups are optionally substituted with 1 to 5 R 5 substituents; each R 3 is independently selected from H, -C (O) OR 9 and C C β alkyl, wherein said alkyl is optionally substituted with 1 to 3 R 5 groups; R4 is R3, -OR9 or -NR9R10; each R5 is independently selected from halogen, cyano, nitro, trifluoromethoxy, trifluoromethyl, azido, -C (O) R8, -C (O) OR8, -OC (O) R8, -OC (O) OR8, -NR6C (0 ) R7, -C (O) NR6R7, -NR6R7, OR9, -S02-NR6R7, d-C6 alkyl, - (CH2) J0 (CH2) qNR6R7, - (CH2) tO (CH2) qOR9, - (CH2) tOR9 , -S (0) j (C6 alkyl), - (CH2) t (C6-C? 0 aryl), - (CH2) t (5-10 membered heterocyclic), -C (O) - (CH2) t (aryl C6-C? 0), - (CH2) tO (CH2) j (aryl C6-C? 0) - (CH2) tO (CH2) q (heterocyclic of 5-10 links), C (O) ( CH2) t (CH2) t (5-10 membered heterocyclic), (CH2) jNR7 (CH2) qNR6R7, - (CH2) jNR7 (CH2C (0) NR6R7, (CH2) jNR7 (CH2) qNR9C (0) R8, - (CH2) jNR7 (CH2) tO (CH2) qOR9, (CH2) jNR7 (CH2) qS (0) j (C6 alkyl), - (CH2) jNR7 (CH2) tR6, -S02 (CH2) t- ( C6-C10 aryl) and -S02 (CH2) t (5-10-membered heterocyclic), where j is an integer ranging from 0 to 2, t is an integer ranging from 0 to 6, q is an integer ranging from 2 to 6, optionally including the radicals - (CH2) q and - (CH2) t- of the above groups R5 a double or triple carbon-carbon bond, where t is an integer between 2 and 6, and the alkyl, aryl and heterocyclic radicals of the above groups R5 are optionally substituted with 1 to 3 substituents independently selected from halogen, cyano, nitro , trifluoromethyl, azido, -C (0) R8, -C (0) OR8, -OC (0) R8, -OC (0) OR8, -NR6C (0) R7, - C (0) NR6R7, - (CH2 ) tNR6R7, C? -C6 alkyl, - (CH2) t (aryl CC? o), - (CH2) t (heterocyclic 5-10 links), - (CH2) tO (CH2) q OR9 and - (CH2) tOR9 , where t is an integer that ranges from 0 to 6 and q is an integer that ranges from 2 to 6; each R6 and R7 is independently selected from H, C6 alkyl, - (CH2) t (C6-C ?0 aryl), - (CH2) t- (5-10 heterocyclic link), - (CH2) tO (CH2) qOR9 and - (CH2) tOR9, wherein t is an integer ranging from 0 to 6 and q is an integer ranging from 2 to 6 and the alkyl, aryl and heterocyclic radicals of the above groups R6 and R7 are optionally substituted with 1 to 3 substituents independently selected from halogen, cyano, nitro, trifluoromethyl, azido, -C (0) R8, -C (0) OR8, -CO (0) R8, -OC (0) OR8, -NR9C ( 0) R10, - C (0) NR9R10, - NR9R10, CrC6 alkyl, - (CH2) t (C6-C? 0 aryl), - (CH2) t (5-10 membered heterocyclic), - (CH2) tO ( CH2) qOR9 and - (CH2) tOR9, where t is an integer ranging from 0 to 6 and q is an integer ranging from 2 to 6; with the proviso that when R6 and R7 are both bonded to the same nitrogen, then R6 and R7 are not linked to the same nitrogen directly through an oxygen; each R 8 is independently selected from H, C 1 -C 10 alkyl, - (CH 2) t (C 6 -C 6 aryl) -y (CH 2) t (heterocyclic d-10 links), wherein t is a whole number that ranges between 0 and 6; Each R 9 and R 10 is independently selected from H and C C β alkyl; R11 is H, CrC6 alkyl; -C (0) NR6R9, -C (O) (aryl C6-C? 0), - (CH2) t (aryl C6-? O) o), - (CH2) t (heterocyclic 5-10 links), in that t is an integer ranging from 0 to 6, wherein said R11 groups, other than H, are optionally substituted with 1 to 5 R5 groups; and R 2 is H, C? -C6 alkyl, -C (O) (C? -C6 alkoxy), -S (0) j (C6 alkyl), -S (0) 2 (CH2) t (aryl) C6-C? 0),), -, (CH2) t (aryl C6-? O) or - (CH2) t (heterocyclic 5-10 links), - (CH2) tO (CH2) qOR9 and - (CH2) tOR9 , wherein j is an integer ranging from 0 to 2, t is an integer ranging from 0 to 6 and q is an integer ranging from 2 to 6.

2. A compound according to claim 1 , wherein said compound is a compound of formula 1 wherein R11 is - (CH2) t (aryl CT-CIO) or - (CH2) t (5-10 membered heterocyclic), wherein t is a number an integer ranging from 0 to 6, wherein said R11 groups are optionally substituted with 1 to 5 R5 groups.

3. - A compound according to claim 2, wherein R11 is phenyl or pyridyl, wherein said phenyl and pyridyl are optionally substituted with 1 to 5 R5 groups.

4. A compound according to claim 1, wherein said compound is a compound of formula 1, wherein X1 is CH.

5. A compound according to claim 1, wherein said compound is a compound of formula 1, wherein R2 is phenyl optionally substituted with 1 to 5 substituents R5.

6. A compound according to claim 1, wherein said compound is a compound of formula 1, wherein R2 is a group of the formula: wherein X2 is -S- or -N (R6) -, X3 is N or CH, the dotted line in formula 3 represents an optional double bond, and the above R2 groups of formulas 3 and 5 are optionally substituted by from 1 to 5 substituents R5 and groups R2 of formulas 4 and 6 are optionally substituted by 1 to 3 substituents R5.

7. A compound according to claim 6, wherein R2 is a group of formula 3 above in which said group is optionally substituted by 1 to 5 substituents R5.

8. A compound according to claim 1, wherein said compound is selected from the group consisting of: (3-Ethinyl-phenyl) - (6-phenyl-thieno [3,2-d] pyrimidin-4) -l) -amina; (3-Ethinyl-phenyl) - [6- (4-methoxy-phenyl) -thieno [3,2-d] pyrimidin-4-yl] -amine; Benzo [b] thiophen-d-yl- (6-phenyl-thieno [3,2-d] -pyrimidin-4-yl) -amine; (1 H-indol-d-yl) - [6- (4-methoxy-phenyl) -thieno [3,2-d] pyrimidin-4-yl-amine; (1 H-lndol-5-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; (6-Phenyl-t-ene [3,2-d] pyrimidin-4-yl) - (2-pyrrol-1-yl-phenyl) -amine; (d-Phenyl-1 H -pyrazol-3-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; (5-Phenyl-1 H -pyrazol-3-yl) -thieno [3,2-d] pyrimidin-4-yl) -amine; (I H-lndol-d-yl) -thieno [3,2-d] pyrimidin-4-yl-amine; N- (5-Phenyl) -1- (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -1 H- [1, 2,4] triazole-3,5-diamine; 3- [3-Phenyl] -5- (6-phenyl] -thieno [3,2-d] pyrimidin-4-ylamino) -pyrazol-1-yl] -propionitrile; (d- Furan-2-yl-2H-pyrazol-3-yl) - (6-phenyl-t-ene- [3,2-d] pyrimidin-4-yl-amine; (6-phenyl-thieno [ 3,2-d] pyrimidin-4-yl) - (5-thiophen-2-yl-2H-pyrazol-3-yl) -amine; N- (6-phenyl-thieno [3,2-d] pyrimidin-4) -yl) -benzene-1, 4-diamine; N- [4- (6-Phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -phenyl] -benzamide; N-Methyl-NYT-phenyl- tienoß ^ -djpyrimidin ^ -yl) -benzene-1,4-diamine; (1 H-indazol-5-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; [d- (4-chloro-phenyl) -2H-pyrazol-3-yl] -6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; Benzothiazol-6-yl- (6-phenyl-thieno [3-2-d] pyrimidin-4-yl) -amina; 4- (6-Phenyl-thieno [3,2- d] pyridimin-4-ylamino) -benzamide; 4-Methyl-N- [4- (6-phenyl-thieno [3-2-d] pyridimidin-4-ylamino) -phenyl] -benzenesulfonamide; N-Phenyl-N '- (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -benzene-1,4-diamine; (6-Phenol-thieno [3,2-d] pyrimidin-4-yl) - (2H-pyrazol-3-yl) -amine; (1 H-ldazol-6-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; N, N -Dimethyl-N 6-phenyl-t-ene [3,2-d] pyridin-4-yl) -benzene-1,4-diamine; (2,3-Dimethyl-1 H-indol-d-yl) - (6-phenyl-thieno [3,2-d] pyridimidin-4-yl) -amine; N-Ethyl-N '- (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -benzene-1,4-diamine; [4- (1 H-lndol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -phenyl-methanone; (1 H-lndol-5-yl) - (6-p-tolyl-thieno [3,2-d] pyrimidin-4-yl) -amine; (5-Furan-2-yl-2H-pyrazol-3-yl) -thieno [3,2-d] pyrimidin-4-ylamine; Thieno [3,2-d] pyridimin-4-yl- (d-thiophen-2-yl-2H-pyrazol-3-yl) -amine; [d- (4-Chloro-phenyl) -2H-pyrazol-3-yl] -thieno [3,2-d] pyrimidin-4-yl-amine; (2H-Pyrazol-3-yl) -thieno [3,2-d] pyrimidin-4-yl-amine; Tieno [3,2-d] pyrimidin-4-yl- (5-p-tolyl-2H-pyrazol-3-yl) -amina; 4- [4-1 H-lndol-d -lamino) -thieno [3,2-d] pyrimidin-6-yl] -benzaldehyde; [6- (4-Chloro-phenyl) -thione [3,2-d] pyrimidin-4-yl] - (1 H-indol-d-yl-amine; [6- (4-Fluoro- phenyl) -thione [3,2-d] pyrimidin-4-yl] - (1 H-indol-d-yl-amine; (1 H-lndol-d-yl) - (6-thiophen-3-yl) il-thieno [3,2-d] pyrimidin-4-yl) -amine; 2- [3- (4-chloro-phenyl) -5- (thieno [3,2-d] pyrimidin-4-ylamino) - pyrazol-1-yl] -ethanol; (1 H-lndol-d-yl) - [6- (4-trifluoromethyl-phenyl) -thieno [3,2-d] pyrimidin-4-yl] -amine; (1 H-lndol-5-yl) - [6- (4-methylsulfanyl-phenyl) -thieno [3,2-d] pyrimidin-4-yl] -amine; (1 H-lndol-d-yl) - [6- (3-nitro-phenyl) -thieno [3,2-d] pyrimidin-4-yl] -amine; [6- (3-Chloro-4-fluoro-phenyl) -thione [3,2-d] pyrimidin-4-yl] - (1 H -indol-5-yl) -amine; [d- (4-Methoxy-phenyl) -2H-pyrazol-3-yl] -thieno [3,2-d] pyrimidin-4-yl-amine; 4- [5- (T-ene [3,2-d] pyrimidin-4-ylamino) -1 H -pyrazol-3-yl] -benzoic acid methyl ester; (d-Methyl-2H-pyrazol-3-yl) -thieno [3,2-d] pyrimidin-4-yl-amine; Ethyl ester of d- (6-Phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -1H-indole-2-carboxylic acid; (6- Benzofuran-2-l-thieno [3,2-d] pyrimidin-4-yl) - (1 H -indole-d-yl-amine; Tieno [3,2- d] pyrimidin-4 -yl- (5-m-toyl-2H-pyrazol-3-yl) -amine; [5- (3-chloro-phenyl) -2H-pyrazol-3-yl] -thione [3,2-d] ] pyrimidin-4-yl-amine; [6- (4-Ethyl-pheny] -thieno [3,2-d] pyrimidin-4-yl] - (1 Hd indol-d-yl) -amine; 4- [4- (1 H-lndol-5-ylamino) -thieno [3,2- d] pyrimidin-6-yl] -benzoic acid methyl; 4- [d- (Tetin [3,2 -d] pyrimidin-4-ylamino) -1H-pyrazol-3-yl] -benzoic acid (1 H-indol-d-yl) - (6-thiophen-2-yl-thieno [3,2- d] pyrimidin-4-yl) -amine; [5- (2-Chloro-phenyl) -2H-pyrazol-3-yl] -thieno [3,2-d] pyrimidin-4-yl-amine; - lndol-5-yl) - (6-pyridin-3-yl-thieno [3,2-d] pyrimidin-4-yl) -amine; (1 H-lndol-5-yl) - [6- (3 -0-methoxy-phenyl) -thieno [3,2-d] pyrimidin-4-yl-amine; {. 4- [4- (1 H-Indol-d-ylamino) -thieno [3,2-d] pyrimidin-6-ill-phenyl.} - methanol; [6- (3,4-dimethoxy-phenyl) -thieno [3,2- d] pyrimidin-4-yl] - (1 H-indol-5-yl) ) -amine; [6- (4-Dimethylamino-phenyl) -thieno [3,2- d] pyrimidin-4-yl] - (1 H -indol-5-yl) -amine; [4- (1 H- lndol-d-ylamino) - thieno [3,2- d] pyrimidin-6-yl] -phenyl-methanol; 4- (1 H-lndol-d-5-ylamino) -thieno [3,2-d] pyrimidine-6-carboxylic acid (2-dimethylamino-ethyl) -amide; (1 H-lndol-5-yl) - [6- (4-trifluoromethoxy-phenyl) -thieno [3,2-d] pyrimidin-4-yl] -amine; (1 H-lndol-d-yl) - [6- (2-methoxy-phenyl) -thieno [3,2-d] pyrimidin-4-yl] -amine; 4- [4- (1 H-lndol-d-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -phenol; [6- (5-Diethoxymethyl-thiophen-2-yl) -thieno [3,2-d] pyrimidin-4-yl] - (1 H -indol-d-yl) -amine; 4- (1 H-lndol-d-ylamino) -0-thieno [3,2-d] pyrimidine-6-carboxylic acid (2-methoxy-ethyl) -amide; N-. { 4- [4- (1 H-lndol-5-ylamino) -thieno [3,2- d] pyrimidin-6-yl] -benzyl} -N ', N'-dimethyl-ethane-1,2-diamine; (1 H-lndol-5-yl) - (6- { 4- [(2-methoxy-ethylamino) -methyl] -phenyl} -thieno [3,2-d] pyrimidine- 4-yl) -amine; (1 H-lndol-5-yl) -. { 6- [2- (4-methyl-piperazin-1-yl) -phenyl] -thieno [3,2-d] pyrimidin-4-yl-amine; 4- (1 H-lndol-5-ylamino) -thione [3,2-d] pyrimidine-6-carboxylic acid propylamide; 2-. { 4- [4- (1 H-lndol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzylamino] -ethanol; [6- (2,4-Dimethoxy-phenyl) -thieno [3,2-d] pyrimidin-4-yl] - (1 H -indol-d-yl) -amine; [6- (4-diethylamino-phenyl) -thieno [3,2-d] pyrimidin-4-yl] - (1 H -indole-d-yl) -amine; [6- (4-Ethoxy-d-phenyl) -thione [3,2-d] pyrimidin-4-yl] - (1 H -indol-d-yl) -amine; 3-. { 4- [4- (1 H-lndol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzylamino} -propane-1,2-diol; (1 H-lndol-5-yl) - [6- (4-propylaminomethyl-phenyl) -thieno [3,2-d] pyrimidin-4-yl] -amine; (1 H-lndol-5-yl) - (6- { 4 - [(3-methoxy-propylamino) -methyl] -phenyl} - thieno [3,2-d] pyrimidin-4-yl) -amine; [6- (3-Fluoro-4-methoxy-phenyl) -thieno [3,2-d] pyrimidin-4-yl] - (1 H -indol-5-yl) -amine; (1 H-0 lndol-d-yl) - [6- (3-methylsulfanyl-phenyl) -thieno [3,2-d] pyrimidin-4-yl-amine; (1 H-Indol-d- 1) - [6- (d-methyl-thiophen-2-yl) -thieno [3,2-d] pyrimidin-4-yl-amine; (1 H-lndol-d-yl) - (6- { 4- [(2-piperazin-1-yl-ethylamino) -methyl] -phenyl} -thieno [3,2-d] pyrimidin-4-yl) -amine; (6- Benzo [1, 3] dioxol-5-yl-thieno [3,2-d] pyrimidin-4-yl) - (1 H -indol-d-yl) -amine; . { 6- [4- (1-Ethoxy-ethoxy) -phenyl-thieno [3,2-d] pyrimidin-4-yl} - (1 H-indol-5-yl) -amine; (1 H-Indol-d-il) -d. { 6- [4- (2-pyrroline-1-l-ethoxy) -pheny] -thieno [3,2-d] pyrimidin-4-yl} -amine; (1 H-lndol-5-yl) -. { 6- [4- (2-methoxy-ethoxy) -phenyl] -thieno [3,2-d] pyrimidin-4-yl} -amine; (1 H-lndol-d-yl) - (6- { 4 - [(2-morpholin-4-yl-ethylamino) -methyl-phenyl} -thieno [3,2-d] pyrimidine -4-yl) -amine; . { 6- [4- (2-Dimethylamino-ethoxy) -phenyl] -thieno [3,2-d] pyrimidin-4-yl} - (1 H-indol-d-yl) -amine; (1 H-lndol-d-yl) - [6- (4-methylaminomethyl-phenyl) -thieno [3,2-d] pyrimidin-4-yl] -amine; 5-0 (6-Phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -1,3-dihydro-indol-2-one; (1 H- Benzotriazol-5-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; (6-Phenyl-thieno [3,2- d] pyrimidin-4-yl) - [4- (2 H -tetrazol-d-yl) -phenyl] -amine; N-. { 4- [4- (1 H-lndol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzyl} -N'-methyl-etaneo-1,2 diamine; (1- Benzenesulfonyl-1 H -indole-5-yl-6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; 3-. { 4- [4- (1 H-lndol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzylamino} -propan-1-ol; (1 H-lndol-5-1) -. { 6- [4- (4-Methyl-p-piperazin-1-ylmethyl) -phenyl] -thieno [3,2-d] pyrimidin-4-yl} -amine; 2-. { 4- [4- (1 H-lndol-d -lamino) -thieno [3,2-d] pyrimidin-6-yl] -benzylamino} -propane-1,3-diol; 2 ((2-Hydroxy-ethyl) -. {4- [4- (1 H -indole-d-ylamino) -thieno [3,2-d] pyrimidin-6-yl-benzyl}. .amino) -ethanol; . { 5- [4- (1 H-lndol-d-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -thiophen-2-yl} -methanol; 2- (2-. {4- [4- (1 H-lndol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] benzylamino] -ethoxy-ethanol 2- ( 2- {4- [4- (1 H-lndol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] benzylamino} -ethylamino) -ethanol; [6- (4 - { [2- (1 H-lmidazol-4-yl) -ethylamino-methyl] -phenyl) -thieno [3,2-d] pyrimidin-4-yl] - (1 H-indol-d -yl) -amine; (1 H-lndol-5-yl) - { 6- [4-morpholin-4-yl-ethoxy) -phenyl] -thieno [3,2-d] pyrimidin-4-yl } amine; 2-. { 4- [4- (1 H-lndol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -phenoxy} -ethanol; [4- (2-Ethyl-oxazol-5-yl) -phenyl] - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; N- (2-Methoxy-phenyl) -N '- (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -benzene-1,4-diamine; N- (4-Methoxy-phenyl) -N '- (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -benzene-1,4-diamine; d- [4- (1 H-lndol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] thio-phene-2-carbaldehyde; [5- (6-Phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -1 H -indol-2-yl] -methanol; (2-Phenyl-1 H-indol-3-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; (9H-Carbazol-3-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; (2-Methyl-1 H -indol-5-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; (1-Phenylethyl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; (1 H-lndol-5-yl) - [6- (4-. {[[(Thiophen-2-ylmethyl) -amino] -methyl]} - phenyl) -thieno [3,2-d] pyrimidine -4-yl] -amine; Acid methyl ester 3-. { 4- [4- (1 H-lndol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzylaminoj-propionic acid; [6- (4-. {[[(Furan-2-ylmethyl) -amino] -methyl]. Phenyl) -thieno [3,2- d] pyrimidin-4-yl] - (1 H-indole) 5-yl) -amine; 1 - (3- { 4- [4- (1 H-lndol-d-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzylamino.} - propyl) -pyrrolidin-2 -one; N-. { 4- [4- (1 H-lndol-5-ylaminoHienoIS ^ -dJpyrimidin-e-ill-benzyl-N ', N'-dimethyl-propane-1,3-diamine; (1 H-lndol-5-yl) - [6- (4-morpholin-4-ylmethyl-phenyl) -thieno [3,2-d] pyrimidin-4-yl] -amine; (2- {4- [4- (1 H-lndol-d-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzylaminol-acetylamino) -acetic acid ethyl ester; 1 - (4- { 4- [4- (1 H-lndol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzyl}. -piperazin-1-yl) -etanone; (6- { 4 - [(2,2-Diphenyl-ethylamino) -methyl] -phenyl] -thieno [3,2-d] pyrimidin-4-yl) - (1 H-indole) 5-yl) -amine; (1 H-lndol-d-il) -. { 6- [4- (2-methoxymethyl-pyrrolidin-1-ylmethyl) -phenyl] -thieno [3,2-d] pyrimidin-4-yl} -amine; N- (2- {4- [4- (1 H-lndol-d-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzylamino} -ethyl) -acetamide; [6- (4-Cyclopropylaminomethyl-phenyl) -thieno [3,2-d] pyrimidin-4-yl] - (1 H -indol-d-yl) -amine; 2-. { 4- [4- (1 H-lndol-d-ylamino) -thieno [3,2-d] -thieno [3,2-d] pyrimidin-6-yl] -benzylamino} -butan-1-ol; 2- ( { D- [4- (1 H-lndol-d-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -thiophen-2-ylmethyl] -amino) -ethanol; (1 H-lndol-5-yl) - (6- { 4 - [(2-pyrrolidin-1-yl-ethylamino) -methyl] -phenyl} -thieno [3,2-d] pyrimidine- 4-yl) -amine; . { 6- [4- (Benzylamino.methyl) -phenyl] -thione [3,2-d] pyrimidin-4-yl} - (1 H-indol-d-yl) amine; Amide of acid 1-. { 4- [4- (1 H-lndol-d-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzyl} -piperidine-4-carboxylic acid; (1 H-lndol-5-yl) -. { 6- [4- (pyrrolidin-3-ylaminomethyl) -phenyl] -thieno [3,2-d] pyrimidin-4-yl} -amine; (6- { 4 - [(3-1-imidazol-1-yl-propylamino) -methyl] -phenyl} -thieno [3,2-d] pyrimidin-4-yl) - (1 H- indole-d-yl) -amine; N-. { 4- [4- (1 H-Indol-d-ylammon) -thieno [3,2-d] pyrimidn-6-yl] -benzyl} -N ', N'-dimethyl-hexane-1,6-diamine; (1-Allyl-1 H-lol-5-yl) - (6-phenyl-t-ene [3,2-d] pyrimidin-4-yl) -amine; (1 -Methyl-1 H-indol-5-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; (1 H-lndol-5-yl) -. { 6- [4- (4-phenyl-piperazin-1-ylmethyl) -phenyl] -thieno [3,2-d] pyrimidin-4-yl} -amine; N-. { d- [4- (1 H-lndol-d-ylamino) -thieno tienofS ^ -djpyrimidin-β-yl-thiophen ^ -ylmethyl-N ', N'-dimethyl-ethane-1,2-diamine; N-. { 5- [4- (1 H-lndol-d-ylamino) -thione [3,2-d] pyrimidin-6-yl] -thiophen-2-ylmethyl} -N'-methyl-ethane-1,2-diamine; (1 H-lndol-d-yl) - (6- { 5 - [(2-methoxy-ethylamino) -methyl] -thiophen-2-yl}. -thieno [3,2-d] pyrimidin-4-yl) -amine; Methyl ester of 2-amino-3- (3. {4- [4- (1 H -indol-5-ylamino) -thieno [3,2-d] pyrimidn-6-yl- benzyl.} - 3 H -imidazol-4-yl) -propionic; 3-. { 4- [4- (1 H-lndol-d-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzylamino} -2,2-dimethyl-propan-1-ol; (9-Ethyl-9H-carbazol-3-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; [1 - (2-Diethylamino-ethyl) -1 H -indol-5-yl] - (6-phenyl] -thieno [3,2-d] pyrimidin-4-yl) -amine; [1 - (3-diethylamino-propyl) -1 H-indol-d-yl] - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; (2-Bromo-thieno [3,2-b] pyrimidin-7-yl) - (1 H -indol-d-N) -amine; [6- (4-Amomethyl-phenyl) -thieno [3,2-d] pyrimidin-4-yl] - (1 H -indol-5-yl) -amine; 3-Hydroxy-2- methyl acid ester. { 4- [4- (1 H-indol-d-ylamino) -thione [3,2-d] pyrimidin-6-yl] -benzylamino} -propionic; Furan-2-yl- (4- { 4- [4- (1 H -indol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzyl} -piperazin- 1 -yl) -metanone; [6- (4-Dimethylaminomethyl-phenyl) -thione [3,2-d] pyrimidin-4-yl] - (1 H -indol-5-yl) -amine; 2- (. {4- [4- (1 H-lndol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl] -benzyl] -methyl-amino) -ethanol; (1 -. {4- [4- (1 H-lndol-5-ylammon) -thione [3,2-d] pyrimidin-6-yl] -benzyl} -pyrrolidin-2- il) -methanol; 2- [2- (4- { 4- [4- (1 H-lndol-5-ylamino) -thione [3,2-d] pyrimidin-6-yl] -benzyl .} - piperazin-1-yl) -ethoxy] -ethanol; 4- [4- (1 H-lndol-5-ylamino) -thieno [3,2-d] pyrimidin-6-yl-benzoic acid; (3-Methyl-1 H -indole-5-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; (1 H-lndol-5-yl) - (2-methyl-6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; N- (4-Methoxy-phenyl) -N '- (2-methyl-6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -benzene-1,4-diamine; (2-Benzyloxy-ethyl) -N '- (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -benzene-1,4-diamine; d- (6-Phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -1 H -indole-3-carbaldehyde; (3-Bromo-1 H-indol-d-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; N- (1 H-lndol-3-ylmethyl) -N '- (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -benzene-1,4-diamine; N- (6-Bromo-thieno [3,2-d] pyrimidin-4-yl) -N '- (4-methoxy-phenyl) -benzene-1,4-diamine; N- (4-Methoxy-phenyl) -N '- [6- (2-nitro-phenyl) -thieno [3,2-d] pyrimidin-4-yl] -benzene-1,4-diamine; N- (4-Methoxy-phenyl) -N '- [6- (4-methoxy-phenyl) -thione [3,2-d] pyrimidin-4-yl] -benzene-1,4-diamine; N- (4-Mey-phenyl) -N-6-thiophen-2-yl-t-ene [3,2-d] pyridn-4-yl) -benzene-1, 4- diamine; N- (4-Mey-phenyl) -N '- ^ ->? - mey-pyridine-Si-thienop ^ -dl-pyrimidine ^ -ill-benzene-l-diamine; (1 H-lndol-5-yl) - [ 6- (4-thiomorpholin-4-ylmethyl-phenyl) -thieno [3,2-d] pyrimidin-4-yl] -amine; 6- (6-phenyl-thieno [3,2-d] pyrimidin-4-) ilamino) -benzothiazole-2-thiol; N- (4-mey-phenyl) -N, -thieno [3,2-d] pyrimidin-4-yl-benzene-1,4-diamine; N- (2 -Metoxy-pheni-NYT-phenyl-thienofS ^ -dlpyrimidin ^ -ylJ-benzene-l-diamine; N- (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -N ' -o-totl-benzene-1,4-diamine; N- (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -N'-p-tolyl-benzene-1 , 4-diamine; N- (3,4-dimey-phenyl) -N '- (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -benzene-1, 4- diamine; N- (6-Phenyl-thieno [3,2-dlpyrimidin ^ -i-N'-IS-3-dimey-phene-benzene-1-diamine; N- (6-phenyl-thieno [3, 2-d] pyrimidin-4-yl) -N'-m-tolyl-benzene-1,4-diamine; N- (4-chloro-phenyl) -N '- (6-phenyl-thieno [3, 2-d] pyrimidin-4-yl) -benzene-1,4-diamine; (1 H-lndol-5-yl) - [6- (6-mey-pyridin-3-yl) -thieno [ 3,2-d] pyrimidin-4-yl] -amine; N- (4-dimethylamino-phenyl) -N '- (6-phenyl-thieno [3,2-d] pyri) midin-4-yl) -benzene-1,4-diamine; N- (3-Mey-phenyl) -N '- (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -benzene-1,4-diamine; (1,3-Dibromo-1 H-indol-d-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; (6-Chloro-1 H-indol-5-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; [5- (6-Phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -1 H -indol-3-yl] -methanol; (6-Phenyl-thieno [3,2-d] pyrimidin-4-yl) -. { 3 - [(3-pyrazol-1-yl-propylamino) -methyl-1 H-indol-d-yl} -amine; Methyl ester of acid. { [5- (6-Phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -1 H -indol-3-ylmethyl] -amino} -acetic; 2-. { [5- (6-Phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -1 H -indol-3-ylmethyl] -amino) -ethanol; D- (6-Phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -1 H -indole-3-carbaldehyde oxime; (3-Methyliminomethyl-1 H -indol-5-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; [3- (2-Nitro-vinyl) -1 H -indole-5-yl] - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; 4- [4- (6-Phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -phenylamino] -phenol; d-Methyl-1 - [4- (6-phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -phenyl] -1,2-dihydro-pyrazol-3-one; (2-Methyl-benzothiazol-6-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amina; (3-Methylaminomethyl-1 H -indol-5-yl) - (6-phenyl-teno [3,2-d] pyrimidin-4-yl) -amine; (4-Mey-2-methyl-phenyl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; [4- (4-Chloro-phenoxy) -phenyl] - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; 6- (6-Phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -1 H -benzofd] [1,3] oxazine-2,4-dione; 2-Diethylaminomethyl-4- (6-phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -phenol; 5-Methyl-1- [4- (6-phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -phenyl] -1,2-dihydro-pyrazol-3-one; [4- (4, d-Dichloro-imidazol-1-yl) -phenyl] - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amina; (6-Phenyl-thieno [3,2-d] pyrimidin-4-yl) - [4- (3-trifluoromethyl-pyrazol-1-yl) -phenyl] -amine; [4- (4-Methyl-piperazin-1-yl) -phenyl] - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; [4- (4-Methyl-piperidin-1-yl) -phenyl] - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; 1- [4- (6-Phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -phenyl] -1 H-tetrazole-d-thiol; 3- (6-Phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -benzenesulfonamide; (2-Methyl-benzothiazol-6-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; [4- (Morpholine-4-sulfonyl) -phenyl] - (6-phenyl-t-ene [3,2-d] pyrimidin-4-yl) -amine; [3,5-Dimethyl-4- (thiophen-3-ylmey) -phenyl] - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; [4,5-Dimey-2- (1 H -tetrazol-d-yl) -phenyl] - (6-phenyl-t-ene [3,2-d] pyrimidin-4-yl) -amine; 5- [4- (6-Phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -phenyl] -oxazolidine-2,4-dione; 1-Ethyl-5- (6-phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -1,3-dihydro-indol-2-one; 6- (6-Phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -3H-benzooxazol-2-one; Dibenzothiophen-4-yl- (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; N- (6-Phenyl-thieno [3,2-d] pyrimidin-4-yl) -N'-p-tolyl-benzene-1,2-diamine; (2-Furan-2-yl-1-methyl-1 H-benzoimidazol-5-yl) - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; d- (6-Phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -benzo [b] thiophene-2-carbonitrile; (6-Phenyl-thieno [3,2-d] pyrimidin-4-yl) - (2-pyridin-4-yl-1 H-benzoimidazol-5-yl) -amine; [4- (1-Methyl-1 H-imidazol-2-ylsulfanyl) -phenyl] - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; (6-Phenyl-thieno [3,2-d] pyrimidin-4-yl) - [4- (pyridin-2-yloxy) -phenyl] -amine; [4- (5-Methyl-tetrazol-1-yl) -phenyl] - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; 1 - [3- (6-Phenyl-thieno [3,2-d] pyrimidin-4-ylamino) -phenyl] -1 H-tetrazole-d-thiol; 4- [4- (6-Phenol-thieno [3,2-d] pyrimidin-4-ylammon) -phenylamino] -phenol; [3- (3-Methyl-4,5-dihydro-pyrazol-1-yl) -phenyl] - (6-phenyl-thieno [3,2-d] pyrimidin-4-yl) -amine; [6- (4-Fluoro-phenyl) -thieno [3,2-d] pyrimidin-4-yl] - (1 H -indol-d-yl) -amine; Benzo [1,2,3] thiadiazol-6-yl- (6-phenyllothieno [3,2-d] pyrimidin-4-yl) -amine; and the pharmaceutically acceptable salts and hydrates of the above compounds.

9. A compound according to claim 1 selected from the group consisting of: [2- (4-Fluoro-phenyl) -thieno [3,2-b] pyridin-7-yl] - (1 H-indole -5-yl) -amine; (1 H-indol-d-yl) - (2-thiophen-2-yl-thieno [3,2-b] pyridin-7-yl) -amine; 4- [7- (1H-lndol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -161-benzaldehyde; (1 H-lndol-d-yl) - [2- (4-methylsulfanyl-phenyl) -thieno [3,2-b] pyridin-7-yl-amine; (1 H-lndol-5-yl) -thieno [3,2-b] pyridin-7-yl-amine; 2-. { 4- [7- (1 H-Indol-d-ylamino) -thieno [3,2-b] pyridin-2-yl] -phenoxy} -ethanol; [2- (4-Dimethylamino-phenyl) -thieno [3,2-b] pyridin-7-yl] - (1 H -indol-d-yl) -amina; 4- [7- (1 H-lndol-d-ylammon) -thieno [3,2-b] pyridin-2-yl] -benzoic acid methyl ester; (1 H-lndol-5-yl) - (2-thiophen-3-yl-thieno [3,2-b] pyridin-7-yl) -amine; (1 H-lndol-d-yl) - (2- { 4 - [(2-methoxy-ethylamino) -methyl] -phenyl} -thieno [3,2-b] pyridin-7-yl) -amine; Furan-2-yl- (4- { 4- [7- (1 H -indol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzyl} .piperazin-1-yl) -methanone; 4- [7- (1 H -indole-d-ylamino) -thieno [3,2-b] pyridin-2-yl] -phenol; 2- (2- { 4- [7- (1 H-lndol-d-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamino} -ethoxy) -ethanol; 2-. { 4- [7- (1 H-lndol-d-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamine} -ethanol; N-. { 4- [7- (1 H-lndol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzyl} -N ', N'-dimethyl-hexane-1,6-diamine; 2- ( { 4- [7- (1 H -Indol-d-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzyl] -methyl-amino) -ethanol; (1 H-indol-d-yl) - (2- { 4 - [(2-piperazin-1-yl-ethylamino) -methyl] -phenyl] -thieno [3, 2-b] pyridin-7-yl) -amine; (2- {4 - [(3-lmidazol-1-yl-propylamino) -methyl] -phenyl} -thieno [3,2-b] pyridin-7-yl) - (1 H-indole) d-il) -amine; 2 - ((2-Hydroxy-ethyl) -. {4- [7- (1 H -indol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzyl}. amino) -ethanol; [2- (4-D-methylaminomethyl-pheny] -thieno [3,2-b] pyridin-7-yl] - (1 H -indol-d-yl) -amine; N-. { 4- [7- (1 H-lndol-d-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzyl} -N ', N'-dimethyl-ethane-1,2-diamine; (1 - { 4- [7- (1 H-lndol-d-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzyl] -pyrrolidin-2-yl) -methanol; 2- (4- { 4- [7- (1 H-lndol-5-ylamino) -thione [3,2-b] pyridin-2-yl] -benzyl.} - piperazin-1 - il) -ethanol; (1 H-lndol-d-il) -. { 2- [4- (2-morpholin-4-yl-ethoxy) -phenyl] -thieno [3,2-b] pyridin-7-yl} -amine; Amide of acid 1-. { 4- [7- (1 H-lndol-5-ylammon) -thieno [3,2-b] pyridin-2-yl] -benzyl} -piperidine-4-carboxylic acid; . { 4- 162 [7- (1 H-lndol-d-ylamino) -thieno [3,2-b] pyridin-2-yl] -phenyl} -methanol; 2-. { 4- [7- (1 H-Indol-d-ylammon) -thieno [3,2-b] pyridin-2-yl] -benzylamino} -butan-1-ol; N-. { 4- [7- (1 H-lndol-5-lamino) -thieno [3,2-b] pyridin-2-yl] -benzyl} -N'-methyl-ethane-1,2-diamine; (1 H-Indol-d-yl) - [2- (4-morpholin-4-ylmethyl-phenyl) -thieno [3,2-b] pyridin-7-yl-amine; 3-. { 4- [7- (1 H-lndol-d-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamino} -propan-1-ol; 1- (3- { 4- [7- (1 H-lndol-d-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamino} -propyl) -pyrrolidin -2-ona; (1 H-lndol-5-yl) -. { 2- [4- (2-methoxy-ethoxy) -phenyl] -thieno [3,2-b] pyridin-7-yl} amine; 2- (2- { 4- [7- (1 H-lndol-d-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamino] -ethylamino) -ethanol; 3-. { 4- [7- (1 H-lndol-5-ylammon) -thieno [3,2-b] pyridin-2-yl] -benzylamine} -2,2-dimethyl-0 propan-1-ol; 3-. { 4- [7- (1 H-lndol-d-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamino} - propane-1,2-diol; [2- (4- { [2- (1 H-lmidazol-4-yl) -ethylamino] -methyl} - phenyl) -thione [3,2- b] pyridin-7-yl] - (1 H-indol-d-yl) -amine; N- (2- { 4- [7- (1 H-lndol-d-ylamino) -thieno [3,2- b] pyridin-2-yl] -benzylamino.} -etl) -acetam gives; 2-. { 4- [7- (1 H-lndol-d-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamine} -acetamida; 2-. { 4- [7- (1 H-lndol-5-ylamino) -d-thieno [3,2-b] pyridin-2-yl] -benzylamino} -propane-1,3-diol; N- (4-Methoxy-phenyl) -N '- [2- (3-n-t-phenyl) -thieno [3,2-b] pyridin-7-yl] -benzene-1,4-diamine; (7-Methoxy-1 H-indol-d-yl) - (2-phenyl-thieno [3,2-b] pyridin-7-yl) -amine; (1 H-lndol-5-yl) - [2- (4-methylaminomethyl-phenyl) -thieno [3,2-b] pyridin-7-yl] -amine; N-. { 4- [7- (1 H-lndol-d-ylamino) -thieno [3,2- b] pyridin-2-yl] -benzyl} -ethane-1, 2-d-amines; Methyl ester of acid. { 4- [7- (1 H-0 lndol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamino} -acetic; N-. { 4- [7- (1 H-Indol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzyl} -N ', N'-dimethyl-propane-1,3-diamine; (1 H-lndol-d-yl) - (2-pyridin-2-yl-t-ene [3,2-b] pyridin-7-yl) -amine; (1 H-lndol-5-yl) - (2- {4- [(2-morpholin-4-yl-ethylamino) -methyl] -phenyl} -thieno [3,2-b] ] pyridin-7-yl) -amine; (1H-indol-5-yl) -. { 2- [4- (pyrrolidin-3-aminomethyl) -phenyl-t-ene [3,2-b] pyridin-7-yl} -amine; 1- (4- { 4- [7- (1 H-lndol-d-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzyl}. -piperazin-1- L) -ethanone; Amide of acid 1-. { 4- [7- (1 H-lndol-d-ylamino) -thione [3,2-b] pyridin-2-yl] -benzyl} -pyrrolidine-2-carboxylic acid; N- (4-Methoxy-phenyl) -N '- [2- (6-methoxy-pyridin-3-yl) -thieno [3,2-b] pyridin-7-yl] -benzene-1,4-diamine; (1 H-lndol-5-yl) - (2-pyridin-3-yl-thieno [3,2-b] pyridin-7-yl) -amine; 4- [7- (1 H-lndol-d -lamino) -thieno [3,2-b] pyridin-2-yl-but-3-yn-1-yl; N- (4-Methoxy-phenyl) -N '- (2-thiophen-2-yl-thieno [3,2- b] pyridin-7-yl) -benzene-1,4-diamine; N- (2-Hydroxy-ethyl) -4- [7- (1 H -indol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzamide; N- (3-lmidazol-1-yl-propyl) -4- [7- (1 H -indol-d-ylamino) -thieno [3,2- b] pyridin-2-yl] benzamide; 3- [4- (4- { 4- [7- (1 H-lndol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamino} -butyl) - piperazin-1 -yl] -propan-1 -ol; (1 H-lndol-d-yl) - [2- (4-. {[4- (4-methyl-piperazin-1-yl) -butylamino] -methyl} -phenyl) -thieno [3, 2-b] pyridin-7-yl] -amine; 2- [4- (4- { 4- [7- (1 H-lndol-d -lamino) -thieno [3,2-b] pyridin-2-yl] -benzylamino}. -butyl) -piperazin-1 -yl] -ethanol; 1-lidazol-1-yl-3-. { 4- [7- (1 H -indol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamino} propan-2-ol; 5-. { 4- [7- (1 H-lndol-d-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamino} -pentan-1 -ol; 2- [2- (4- { 4- [7- (1 H-lndol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzyl}. -piperazin-1 -yl-ethoxy] -ethanol; (1 H-lndol-d-yl) - (2. {4 - [(2-methylsulfanyl-et -lamino) -methyl] -phenyl} -thieno [3, 2-b] pyridin-7-yl) -amine; 2 - [(2-hydroxy-ethyl) - (3. {4- [7- (1 H -indol-5-ylamino) -thieno [3, 2-b] pyridin-2-yl] -benzylamino.}. -propyl) -amino] -ethanol; N- (2-Amino-ethyl) -N'- { 4- [7- (1 H-indole -d-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzyl.} ethane-1,2-diamine; 2- (3-. {4- [7- (1 H- Indole-d-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamine.}. -propylamine) -ethanol; N- { 4- [7- (1 H-indol-d-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzyl] -hexane-1,6-diamine; (2-Methyl-1 H-indole-164) 5-l) - [2- (4-morpholin-4-ylmethyl-phenyl) -thieno [3,2-b] pyridin-7-yl-amine; 2- { 4- [7 - (2-Methyl-1 H -indole-d-ylamine) -thieno [3,2-b] pyridin-2-yl] -benzylamino] -ethanol; (1 H-lndol-5-yl) - [2- (6-methoxy-pyridin-3-yl) -thieno [3,2-b] pyridin-7-yl] -amine; {. 5- [7- (1 H-lndol-d -ylamino) -thieno [3,2-b] pyridin-2-yl] -pyridin-2-yl.} - methanol; N, N-Dimethyl-N'-. { 4- [7- (2-methyl-1 H-indol-d-ylammon) -thieno [3,2-b] pyridin-2-yl] -benzyl} -propane-1, 3-diamine; 2 - [(2-Hydroxy-ethyl) - (3- { 4- [7- (2-methyl-1 H -indole-d-ylamino) -thieno [3,2-b] pyridin-2- il] -benzylamino.}. -propyl) -amino] -ethanol; 2-. { 4- [7- (2-Methyl-1 H -indol-5-ylamino) -thione [3,2-b] pyridin-2-yl-benzylamino} -propane-1,3-diol; 1,2-diol; 3-. { 4- [7- (2-Methyl-1 H -indol-d-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamino) -propane; 1 - (3- { 4- [7- (2-Methyl-1 H -indol-d-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamino.}. -propyl) pyrrolidin-2-one; N- (2-Amino-ethyl) -N'-. { 4- [7- (2-methyl-1 H-indol-d-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzyl} -ethane-1, 2-diamine; 2- (2- { 4- [7- (2-Methyl-1 H -indol-5-ylamino) -thieno [3,2-b] pyridin-2-yl-benzylamino} ethylamino) - ethanol; 3-. { 4- [7- (2-Methyl-1 H-indol-d -lamino) -thieno [3,2-b] pyridin-2-yl] -benzylamino} -propan-1-ol; Amide of acid 1-. { 4- [7- (2-Methyl-1 H -indol-d-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzyl} -piperidine-4-carboxylic acid; 2- (2- { 4- [7- (2-Methyl-1 H -indol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamino} ethoxy) - ethanol; 2- (Methyl-. {4- [7- (2-methyl-1 H-indol-d-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzyl}. amine) -ethanol; N- (methyl-N'- { 4- [7- (2-methyl-1 H -indol-5-ylamino) -thione [3,2-b] pyridin-2-yl] - benzyl.} ethane-1,2-diamine; (1 H-indol-d-yl) - [2- (3-nitro-phenyl) -thieno [3,2-b] pyridin-7-yl] -amine; N- { 4- [7- (2-methyl-1 H -indol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzyl} -ethane- 1,2-diamine; (2-methyl-1 H-indol-d-yl) - (2-. {4 - [(2-piperazin-1-yl-ethylamino) -methyl] -phenol .}.-thieno [3,2-b] pyridin-7-yl) -amine; N, Nd-methyl-N'- { 4- [7- (2-methyl-1 H-indole- d-ylammon) -thieno [3,2-b] pyridin-2-yl] -benzyl.} ethane-1,2-diamine; 2-. { 4- [7- (2-methyl-1 H -indol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamino} -butan-1 -ol; (2-methyl-1 H-indol-5-yl]) - (2. {4 - [(2-morpholin-4-yl-ethylamino) -methyl] -phenyl} -thieno [3 , 2-b] pyridin-7-yl) -amina; (2-methyl-1 H-indol-d-yl) -. { 2- [4- (pyrrolidin-3-ylaminomethyl) -phenyl] -thieno [3,2-b] pyridin-7-yl} -amina; . { 6- [7- (1 H-indol-d-ylamino) -thieno [3,2-b] pyridin-2-yl] pyridin-3-yl} -methanol; . { 6- [7- (2-methyl-1H-indol-d-ylamino) -thieno [3,2-b] pyridin-2-yl] -pyridin-3-yl} -methanol; 3- [4- (4- { 4- [7- (2-methyl-1 H -indole-d-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamino}. -butyl) -piperazin-1 -yl] -propan-1 -ol; 2- [4- (4- { 4- [7- (2-methyl-1 H -indol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamine} -butyl) -piperazin-1-yl] -ethanol; (2- {4 - [(3-Midazol-1-yl-propylamino) -methyl-phenyl} -thieno [3,2-b] pyridin-7-yl) - (2-methyl- 1 H-indol-d-yl) -amine; 1-imidazol-1-yl-3-. { 4- [7- (2-methyl-1 H-indol-d-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzylamino} -propan-2-ol; 2 - [(2-hydroxy-ethyl) - (4- { 4- [7- (2-methyl-1 H -indol-5-ylamino) -thieno [3,2-b] pyridin-2-yl ] -benzylamino.} - butyl) -amino] -ethanol; N, N-diethyl-N'-. { 4- [7- (2-methyl-1 H -indole-d-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzyl} -propane-1, 3-diamine; [2- (3-amino-phenyl) -thione [3,2-b] pyridin-7-yl] - (1 H -indole-5-yl) -amine; (2-methyl-1 H-indol-d-yl) - (2- {4 - [(3-morpholin-4-yl-propylamino) -methyl] -phenyl} -thieno [3,2- b] pyridin-7-yl) -amine; [2- (4-d.methylaminomethyl-phenyl) -thieno [3,2-b] pyridin-7-yl] - (2-methyl-1 H -indol-d-yl) -amine; 1 - [d- (2-pyridin-2-yl-thieno [3,2-b] pyridin-7-ylamino) -2,3-dihydro-indol-1-yl] -ethanone; (2,3-dihydro-1 H-indol-d-yl) - (2-pyridin-2-yl-thieno [3,2-b] pyridin-7-yl) -amine; (1 H-benzotriazol-d-yl) - (2-pyridin-2-yl-thieno [3,2-b] pyridin-7-yl) -amine; 5- (2-phenyl-thieno [3,2-b] pyridin-7-ylammon) -1 H -indole-3-carbaldehyde; (1 H -ndazol-d-yl) - (2-pyridin-2-yl-thieno [3,2-b] pyridin-7-yl) -amine; (2-methyl-1 H-indol-d-yl) -166 (2-pyridin-2-yl-thieno [3,2-b] pyridin-7-yl) -amine; (1 H-benzoimidazol-5-yl) - (2-phenyl-thieno [3,2-b] pyridin-7-yl) -amine; dimethylamide of d- (2-pyridin-2-yl-thieno [3,2-b] pyridin-7-ylamino) -1H-indole-2-carboxylic acid; . { d- [7- (2-methyl-1 H-indol-d-ylamino) -thieno [3,2-b] pyridin-2-yl} -methanol; N- (3-imidazol-1-yl-propyl) -6- [7- (1 H -indol-5-ylamino) -thieno [3,2-b] pyridin-2-yl] -nicotinamide; N- (3-hydroxy-propyl) -6- [7- (2-methyl-1 H -indole-d-ylamino) -thieno [3,2-b] pyridin-2-yl] -n-sn-acinamide; [2- (5-amino-pyridin-2-yl) -thieno [3,2-b] pyridin-7-yl] - (2-methyl-1 H -indol-5-yl) -amine; N- [2- (2-hydroxy-ethoxy) -ethyl] -6- [7- (2-methyl-1 H -indol-d-ylaminium) -thieno [3,2-b] pyridin-2-yl] -nicotinamide; [2- (3-methyl-3H-imidazol-4-yl) -thieno [3,2-b] pyridin-7-yl] - (2-methyl-1 H -indol-d-yl) -aminia; 2-. { 1-methyl-5- [7- (2-methyl-1 H-indol-d-ylamino) -thieno [3,2-b] pyridin-2-yl] -1 H -imidazol-2-yl} -propan-2-ol; [2- (1-methyl-1 H-imidazol-2-yl) -thieno [3,2-b] pyridin-7-yl] - (2-methyl-1 H -indol-5-yl) -amine; (2-methyl-1 H-indol-d-yl) - (2-thiazol-2-yl-thieno [3,2-b] pyridin-7-yl) -amine; 2-. { 2- [7- (2-methyl-1 H -indol-d-ylamino) -thieno [3,2-b] pyridin-2-yl] -thiazol-d-yl] -propan-2-ol; 4- [7- (2-methyl-1 H -indole-d-ylamino) -thieno [3,2-b] pyridin-2-yl] -benzaldehyde; and the pharmaceutically acceptable salts and hydrates thereof.

10. A compound of formula 2d or 26 25 26 167 or a pharmaceutically acceptable salt or hydrate thereof, wherein X 1 is N or CH; Z1 is halogen and Z2 is -NR1R2, or Z1 is R11 and Z2 is halogen; or Z1 and Z2 are independently halogen or R1 is H, Ci-Cß alkyl or -C (0) (Cr Cß alkyl); R2 is Ce-Cry or heterocyclic aryl of d-13 elements, wherein said R2 groups are optionally substituted with 1 to 5 R5 substituents, each R3 is independently selected from, H, -C (0) OR9 and Ci-Cß alkyl , wherein said alkyl is optionally substituted with 1 to 3 R5 groups; each R5 is independently selected from halogen, cyano, nitro, trifluoromethoxy, trifluoromethyl, azido, -C (0) R8, -C (0) OR8, -OC (0) R8, -OC (0) OR8, -NR6C (0 ) R7 ,. -C (0) NR6R7, -NR6R7, -OR9. -S02NR6R7, C alquilo-C6 alkyl, - (CH2) jO (CH2) qNR6R7, - (CH2) tO (CH2) qOR9, - (CH2) tOR9, -S (0) j (C6 alkyl), - ( CH2) t (aryl C6-C? O), - (CH2) t (heterocyclic of d-10 links), -C (0) - (CH2) t (aryl C6-C? 0), - (CH2) tO (CH2) j (C6-C aryl 0), - (CH2) tO (CH2) q (5-10 membered heterocyclic), -C (0) (CH2) t (CH2) t (5-10 heterocyclic) links), - (CH2) tNR7 (CH2) qNR6R7, - (CH2) tNR7CH2C (0) NR6R7, - (CH2) jNR7 (CH2) qNR9C (0) R8, (CH2) jNR7 (CH2) tO (CH2) qOR9, - (CH2) JNR7 (CH2) qS (0) j (alkyl d-C6), - (CH2) jNR7 (CH2) tR6, -S02 (CH2) t (C6-C? 0 aryl) and -S02 (CH2) t (5-10-membered heterocyclic), where j is a whole number which oscillates between 0 and 2, t is an integer ranging from 0 to 6, q is an integer ranging from 2 to 6, optionally including the radicals - (CH2) q- and - (CH2) t- of the previous R5 groups a double or a triple carbon-carbon bond, where t is an integer between 2 and 6, and the alkyl, aryl and heterocyclic radicals of the above groups R5 are optionally substituted with 1 to 3 168 independently selected substituents between halogen, cyano, nitro, trifluoromethyl, azido, -C (0) R8, -C (0) OR8, -OC (0) R8, -OC (0) OR8, NR6C (0) R7, -C (0) NR6R7, - (CH2) tNR6R7, C6 alkyl, - (CH2) t (C6-C10 aryl), - (CH2) t (heterocyclic d-10 links), - (CH2) tO (CH2) qOR9, and - ( CH2) tOR9, where t is an integer ranging from 0 to 6 and q is an integer ranging from 2 to 6; each R6 and R7 is independently selected from H, (C? -C6 alkyl), - (CH2) t (Ce-Cio aryl), - (CH2) t (d-10-membered heterocyclic), - (CH2) tO ( CH2) qOR9, and - (CH2) tOR9, wherein t is an integer ranging from 0 to 6 and q is an integer ranging from 2 to 6 and the alkyl, aryl and heterocyclic radicals of the above groups R6 and R7 are optionally substituted with 1 to 3 substituents independently selected from halogen, cyano, nitro, trifluoromethyl, azido, -C (0) R8, -C (0) OR8, -OC (0) OR8, NR9C (0) R10, - C (0) NR9R10, -NR9R10, C6 alkyl, - (CH2) t (C6-C10 aryl), - (CH2) t (heterocyclic 5-10 links), - (CH2) tO (CH2) qOR9 and - ( CH2) tOR9, where t is an integer ranging from 0 to 6 and q is an integer ranging from 2 to 6; with the proviso that when R6 and R7 are both attached to the same nitrogen, then R6 and R7 are not attached to the nitrogen directly through an oxygen; each R8 is independently selected from H, C1-C10 alkyl, - (CH2) t (aryl Ce-Cio) and - (CH2) t (heterocyclic d-10 links), wherein t is an integer ranging from 0 and 6; each R9 and R10 is independently selected from H and C6C6 alkyl; R11 is H, d-C6 alkyl, -C (0) NR6R9, -C (0) (aryl Ce-Cio), - (CH2) t (aryl C6-C? 0) or - (CH2) t (heterocyclic) -10 links), wherein t is a whole number ranging from 0 to 6, wherein said R11 groups other than H, are optionally substituted with fer- t-butyl-dimethyl-silanyl and with 1 to 5 R5 groups; and R12 is H, alkyl dC6, -C (0) (alkoxy CrC6), -S (0) j (alkyl CrC6), -S02 (CH2) t (aryl C6-C? 0), (CH2) t (aryl C6-C? 0), - (CH2) t (heterocyclic d-10 links), - (CH2) tO (CH2) qOR9 or - (CH2) tOR9, where j is an integer ranging from 0 and 2, t is an integer that ranges from 0 to 6 and q is an integer that ranges from 2 to 6.

11. - A pharmaceutical composition for the treatment of a hyperproliferative disorder in a mammal, which contains a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.

12. - The pharmaceutical composition according to claim 11, wherein said proliferative disorder is cancer.

13. - The pharmaceutical composition according to claim 12, wherein said cancer is brain, lung, kidney, kidney, ovarian, squamous cell, bladder, gastric, pancreatic, breast, head and neck cancer. , esophageal, gynecological, prostate, colorectal or thyroid.

14. - The pharmaceutical composition according to claim 11, wherein said hyperproliferative disorder is non-cancerous.

15. - The pharmaceutical composition according to claim 14, wherein said disorder is a benign hyperplasia of the skin or prostate.

16. A pharmaceutical composition for the treatment of a hyperproliferative disorder in a mammal that contains a therapeutically effective amount of a compound of claim 1 in combination with an antitumor agent selected from the group consisting of mitotic inhibitors, alkylating agents, anti-metabolites, intercalating antibiotics, enzymes, topoisomerase inhibitors, biological response modifiers, antihormones and antiandrogens and a pharmaceutically acceptable carrier.

17. - A pharmaceutical composition for the treatment of pancreatitis or renal disease in a mammal containing a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.

18. - A pharmaceutical composition for blastocyst implantation in a mammal that includes a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.

19. - A pharmaceutical composition for the treatment of a disease related to vasculogenesis or angiogenesis in a mammal that contains a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.

20. The pharmaceutical composition according to claim 19, wherein said disease is selected from the group consisting of tumor angiogenesis, chronic inflammatory disease, such as rheumatoid arthritis, atherosclerosis, skin diseases, such as psoriasis, eczema and scleroderma , diabetes, diabetic retinopathy, retinopathy of prematurity, age-related macular degeneration, hemangioma, glioma, melanoma, Kaposi's sarcoma and ovarian, breast, lung, pancreatic, colon and epidermoid prostate cancer.

21. The use of a compound of claim 1 for the manufacture of a medicament for the treatment of a hyperproliferative disorder in a mammal.

22. The use according to claim 21, wherein said hyperproliferative disorder is cancer.

23. - The use according to claim 22, wherein said cancer is brain, lung, squamous, renal, kidney, ovarian, bladder, gastric, pancreatic, breast, head and neck, esophageal , prostate, colorectal, gynecological or thyroid.

24. - The use according to claim 21, is that said hyperproliferative disorder is non-cancerous.

25. The use according to claim 24, wherein said disorder is a benign hyperplasia of the skin or prostate.

26. - The use of a compound of claim 1, in combination with an antitumor agent selected from the group consisting of mitotic inhibitors, alkylating agents, anti-metabolites, intercalating antibiotics, growth factor inhibitors, cell cycle inhibitors, enzymes, topoisomerase inhibitors, biological response modifiers, anti-hormones and anti-androgens for the manufacture of a medicament for the treatment of a hyperproliferative disorder in a mammal.

27. The use of a compound of claim 1 for the manufacture of a medicament for the treatment of pancreatitis or renal disease in a mammal.

28. The use of a compound of claim 1 for the manufacture of a medicament for the prevention of blastocyst implantation in a mammal.

29. The use of a compound of claim 1 for the manufacture of a medicament for the treatment of a disease related to vasculogenesis or angiogenesis in a mammal.

30. The use according to claim 29, wherein said disease is selected from the group consisting of tumor angiogenesis, chronic inflammatory disease, such as rheumatoid arthritis, atherosclerosis, skin diseases, such as psoriasis, eczema and scleroderma, diabetes, diabetic retinopathy, retinopathy of prematurity, age-related macular degeneration, hemangioma, glioma, melanoma, Kaposi's sarcoma and ovarian, breast, lung, pancreatic, prostate, colon and epidermoid cancer.