AU2013201011B2 - N- (3-amino-quinoxalin-2-yl) -sulfonamide derivatives and their use as phosphatidylinositol 3-kinase inhibitors - Google Patents

Abstract

Abstract The invention relates to compounds of Formula I and a process for their preparation. Compounds of Formula I are small molecule inhibitors of phosphatidylinositol 3 kinase (PI3K), which is associated with a number of malignancies, such as ovarian cancer, breast cancer, colon cancer and others.

Description

PHOSPHATIDYLINOSITOL 3-KINASE INHIBITORS AND METHODS OF THEIR USE FIELD OF THE INVENTION [0001] This invention relates to the field of protein kinases and inhibitors thereof. In particular, the invention relates to inhibitors of phosphatidylinositol 3-kinase (P13K) signaling pathways, and methods of their use. CROSS REFERENCE TO RELATED APPLICATIONS [0002] This is a divisional of Australian Patent Application No. 2006302179, the entire contents of which are incorporated herein by reference. BACKGROUND OF THE INVENTION [0003] The connection between abnormal protein phosphorylation and the cause or consequence of diseases has been known for over 20 years. Accordingly, protein kinases have become a very important group of drug targets. See Cohen, Nature, 1:309-315 (2002). Various protein kinase inhibitors have been used clinically in the treatment of a wide variety of diseases, such as cancer and chronic inflammatory diseases, including diabetes and stroke. See Cohen, Eur. J. Biochem., 268:5001-5010 (2001). [0004] The protein kinases are a large and diverse family of enzymes that catalyze protein phosphorylation and play a critical role in cellular signaling. Protein kinases may exert positive or negative regulatory effects, depending upon their target protein. Protein kinases are involved in specific signaling pathways which regulate cell functions such as, but not limited to, metabolism, cell cycle progression, cell adhesion, vascular function, apoptosis, and angiogenesis. Malfunctions of cellular signaling have been associated with many diseases, the most characterized of which include cancer and diabetes. The regulation of signal transduction by cytokines and the association of signal molecules with protooncogenes and tumor suppressor genes have been well documented. Similarly, the connection between diabetes and related conditions, and deregulated levels of protein kinases, has been demonstrated. See e.g., Sridhar et al. Pharmaceutical Research, 17(11):1345-1353 (2000). Viral infections and the conditions related thereto have also been associated with the regulation of protein kinases. Park et al. Cell 101 (7), 777-787 (2000). [0005] Phosphatidylinositol 3-kinase (P13K or PIK3CA) is composed of an 85 kDa regulatory subunit and a 110 kDa catalytic subunit. The protein encoded by this gene represents the catalytic subunit, which uses ATP to phosphorylate PtdIns, PtdIns4P and Ptdlns(4,5)P2. PTEN, a tumor suppressor which inhibits cell growth through multiple mechanisms, can dephosphorylate PIP3, the major product of PIK3CA. PIP3, in turn, is required for translocation of protein kinase B (AKTL, PKB) to the cell membrane, where it is phosphorylated and activated by upstream kinases. The effect of PTEN on cell death is mediated through the PIK3CA/AKT pathway. [0006] PI3Ko has been implicated in the control of cytoskeletal reorganization, apoptosis, vesicular trafficking, proliferation and differentiation processes. Increased copy number and expression of PIK3CA is associated with a number of malignancies such as ovarian cancer (Campbell et al., Cancer Res 2004, 64, 7678-7681; Levine et al., Clin Cancer Res 2005, 11, 2875-2878; Wang et al., Hum Mutat 2005, 25, 322; Lee et al., Gynecol Oncol 2005, 97, 26-34), cervical cancer, breast cancer (Bachman, et al. Cancer Biol Ther 2004, 3, 772-775; Levine, et al., supra; Li et al., Breast Cancer Res Treat 2006, 96, 91-95; Saal et al., Cancer Res 2005, 65, 2554-2559; Samuels and Velculescu, Cell Cycle 2004, 3, 1221-1224), colorectal cancer (Samuels, et al. Science 2004, 304, 554; Velho et al. Eur J Cancer 2005, 41, 1649-1654), endometrial cancer (Oda et al. Cancer Res. 2005, 65, 10669-10673), gastric carcinomas (Byun et al., Int J Cancer 2003, 104, 318-327; Li et al., supra; Velho et al., supra; Lee et al., Oncogene 2005, 24, 1477-1480), hepatocellular carcinoma (Lee et al., id.), small and non-small cell lung cancer (Tang et al., Lung Cancer 2006, 51, 181-191; Massion et al., Am J Respir Crit Care Med 2004, 170, 1088-1094), thyroid carcinoma (Wu et al., J Clin Endocrinol Metab 2005, 90, 4688-4693), acute myelogenous leukemia (AML) (Sujobert et al., Blood 1997, 106, 1063-1066), chronic myelogenous leukemia (CML) (Hickey and Cotter J Biol Chem 2006, 281, 2441-2450), and glioblastomas (Hartmann et al. A cta Neuropathol (Berl) 2005, 109, 639-642; Samuels et al., supra). (00071 In view of the important role of PI3Ka in biological processes and disease states, inhibitors and/or modulators of this protein kinase are desirable. SUMMARY OF THE INVENTION [00081 The following only summarizes certain aspects of the invention and is not intended to be limiting in nature. These aspects and other aspects and embodiments are described more fully below. All references cited in this specification are hereby incorporated by reference in their entirety. In the event of a discrepancy between the 2 express disclosure of this specification and the references incorporated by reference, the express disclosure of this specification shall control. [0009] The invention comprises compounds of Formula I and Ia that inhibit P13K and pharmaceutical compositions thereof. The invention is also direcetd to methods of inhibiting P13K in a cell, and methods for treating a disease, disorder, or syndrome, [0010] A first aspect of the invention provides a compound of Formula I:

R

52 R" OR 5 ' 'W N NH 0 or a pharmaceutically acceptable salt or solvate thereof, where W', W 2 , W 3 , and W 4 are -C(RO)=; or one or two of W1, W 2 , W 3 , and W 4 are independently N= and the remaining are -C(R 1 )=; and where each R' is independently hydrogen, alkyl, haloalkyl, nitro, alkoxy, haloalkoxy, halo, hydroxy, cyano, amino, alkylamino, or dialkylamino; R is hydrogen or alkyl;

R

52 is hydrogen or halo;

R

0 , R 3 , and R 4 are independently hydrogen, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, hydroxy, alkoxy, alkenyloxy, haloalkoxy, nitro, amino, alkylamino, dialkylamino, -N(R")C(O)-CrCralkylene-N(Rss)Rss, alkylcarbonyl, alkenylcarbonyl, carboxy, alkoxycarbonyl, cyano, alkylthio, -S(O) 2 NRSRssa, or alkylcarbonylamino and where R55 and R55" are indepedently hydrogen, alkyl, or alkenyl and Ra 55 is hydrogen, alkyl, alkenyl, hydroxy, or alkoxy; or RS and R5 4 together with the carbons to which they are attached form a 5- or 6-membered heteroaryl or 5- or 6-membered heterocycloalkyl; B is phenyl substituted with R 3 a and optionally further substituted with one, two, or three R3; or B is heteroaryl optionally substituted with one, two, or three R 3 ;

R

3 a is cyano; hydroxyamino; carboxy; alkoxycarbonyl; alkylamino; dialkylamino; alkylcarbonyl; haloalkoxy; alkylsulfonyl; aminoalkyloxy; alkylaminoalkyloxy; dialkylaminoalkyloxy; or 3 a) -N(R7)C(O)-CrC6-alkylene-N(R7a)(R7 ) where R 7 is hydrogen, alkyl, or alkenyl and

R

7 a and Rh are independently hydrogen, alkyl, alkenyl, hydroxyalkyl, haloalkyl, alkoxy, alkoxyalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl, aryl, arylalkyl, or arylalkyloxy and where the aryl, cycloalkyl, heterocycloalkyl and heteroaryl rings in R 7 a and R 7 " (either alone or as part of arylalkyl, cycloalkylalkyl, heterocycloalkylalkyl and heteroarylalkyl) are independently optionally substituted with 1, 2, or 3 groups independently selected from alkyl, amino, alkylamino, dialkylamino, hydroxy, halo, alkoxy, alkylthio, and oxo); b) -C(O)NRR"' where R' is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, haloalkyl, or haloalkoxy and R 8 ' is hydrogen, alkyl, alkenyl, hydroxyalkyl, cyanoalkyl, alkoxyalkyl, alkylthioalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, aryl, or arylalkyl and where the aryl, cycloalkyl, heteroaryl, and heterocycloalkyl rings in R 8 ' (either alone or as part of arylalkyl, cycloalkylalkyl, heterocycloalkylalkyl and heteroarylalkyl) are independently optionally substituted with 1, 2, or 3 groups independently selected from alkyl, alkenyl, alkoxy, halo, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, oxo, amino, alkylamino, dialkylamino, alkylcarbonyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, alkoxycarbonyl, and -C(O)H; c) -NR 9

C(O)R

9 a where R 9 is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, haloalkyl, or haloalkoxy and R 9 a is hydrogen, C 2

-

6 -alkyl, alkenyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl, aryl, or arylalkyl; where the aryl, cycloalkyl, heteroaryl, and heterocycloalkyl rings in R 9 a (either alone or as part of arylalkyl, cycloalkylalkyl, heterocycloalkylalkyl and heteroarylalkyl) are independently optionally substituted with 1, 2, or 3 groups independently selected from alkyl, alkenyl, alkoxy, hydroxy, hydroxyalkyl, halo, haloalkyl, haloalkoxy, oxo, amino, alkylamino, dialkylamino, alkylcarbonyl, alkoxycarbonyl, -C(O)H, aryl (optionally substituted with one or two halo), arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl, cyloalkyl, cyloalkylalkyl, and cycloalkylcarboiyl; d) -C(0)N(R'")-CrC6-alkylene-N(Ria)R"' where R10a is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, haloalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, or hydroxyalkyl and R 0 and Ri. are independently hydrogen, alkyl, alkenyl, haloalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, or hydroxyalkyl; 4 e) -NRC(O)NRuaRI"b where Rua is hydrogen, alkyl, alkenyl, hydroxy, or alkoxy and R" and R..b are independently hydrogen, alkyl, alkenyl, aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; f) -C(O)R' 2 where R1 is heterocycloalkyl optionally substituted with 1, 2, or 3 groups selected from alkyl, oxo, amino, alkylamino, and heterocycloalkylalkyl; g) -NR 3 C(O)OR1 3 a where R 13 is hydrogen, alkyl, or alkenyl and R 13 is aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, aryl, or arylalkyl; h) -C(O)N(RI 4

)N(R

4 a)(RI 4 b) where R14, R1 4 a, and R1 4 b are independently hydrogen, alkyl, or alkenyl; i) -S(0) 2 N(R"s)-C1.C 6 -alkylene-N(Rlsa)R 5 b where R' 5 , R 15 a, and Rsb are independently hydrogen, alkyl, or alkenyl; j) -C(0)N(R6)-C-alkylene-C(0)OR " where R 1 6 is hydrogen, alkyl, or alkenyl and R 16 a is alkyl or alkenyl; k) heteroaryl optionally substituted with one or two aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; 1) -N(Rl)-C(=N(R 1 7 l)(R7a))(NR74RI 7 d) where R1 7 , R1a, Rl 7 b, R* 17 , and R 7 d are independently hydrogen, alkyl, or alkenyl; m) -N(R")C(0)-Cl-C6-alkylene-N(RII)C(0)R"" where R'a is hydrogen, alkyl, alkenyl, or alkoxy and R1 8 and R"b are independently hydrogen, alkyl, or alkenyl; n) -C(0)N(Rl)-Cl-C6-alkylene-C(0)R9a where R 1 9 is hydrogen, alkyl, or alkenyl and R1 9 a is amino, alkylamino, dialkylamino, or heterocycloalkyl; o) -N(R 20 )C(O)-CI -C 6 -alkylene-C(O)R 2 a Where R 2 0 is hydrogen, alkyl, or alkenyl and

R

2 Oa is cycloalkyl or heterocycloalkfl; p) -NRlS(O) 2

R-C..C

6 -alkylene-N(R 2 1b)Ra where R is hydrogen, alkyl, or alkenyl and R 1 aa and R 2 1b are independently hydrogen, alkyl, or alkenyl; q) -N(R)C(O)-CI.C6-alkylene-N(R 2)-N(lR")(Ra) where R 22 , R 2 a and R 2 2 are independently hydrogen, alkyl, or alkenyl; r) -CO.Cw-alkylene-N(R)-CI.C6-alkylene-N(RE)Raa Where R, R 3 a and R 23 be independently hydrogen, alkyl, or alkenyl; or s) -NR 24 C(O)-CI-C6-alkylene-OR 24 a where R 4 is hydrogen, alkyl, or alkenyl and R 24 a is alkoxyalkyl or aryl optionally substituted with one or two halo or alkyl; and where each of the alkylene in R3a is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, amino, alkylamino, and dialkylamino; and 5 each R 3 (when R 3 is present) is independently alkyl; alkenyl; alkynyl; halo; hydroxy; oxo; alkoxy; cyano; hydroxyamino; carboxy; alkoxycarbonyl; amino; alkylamino; dialkylamino; alkylcarbonyl; haloalkoxy; alkylsulfonyl; aminoalkyloxy; alkylaminoalkyloxy; dialkylaminoalkyloxy; or a) -N(R7)C(O)-C1-Cralkylene-N(R7a)(R 7) where R 7 is hydrogen, alkyl, or alkenyl and

R

7 a and R 7 b are independently hydrogen, alkyl, alkenyl, hydroxyalkyl, haloalkyl, alkoxy, alkoxyalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl, aryl, arylalkyl, or arylalkyloxy and where the aryl, cycloalkyl, heterocycloalkyl and heteroaryl rings in R 7 a and R 7 b (either alone or as part of arylalkyl, cycloalkylalkyl, heterocycloalkylalkyl and heteroarylalkyl) are independently optionally substituted with 1, 2, or 3 groups independently selected from alkyl, amino, alkylamino, dialkylamino, hydroxy, halo, alkoxy, alkylthio, and oxo); b) -C(O)NRRaa where R' is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, haloalkyl, or haloalkoxy and Ra is hydrogen, alkyl, alkenyl, hydroxyalkyl, cyanoalkyl, alkoxyalkyl, alkylthioalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, aryl, or arylalkyl and where the aryl, cycloalkyl, heteroaryl, and heterocycloalkyl rings in Ra (either alone or as part of arylalkyl, cycloalkylalkyl, heterocycloalkylalkyl and heteroarylalkyl) are independently optionally substituted with 1, 2, or 3 groups independently selected from alkyl, alkenyl, alkoxy, halo, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, oxo, amino, alkylamino, dialkylamino, alkylcarbonyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, alkoxycarbonyl, and -C(O)H; c) -NR 9

C(O)R

9 a where R 9 is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, haloalkyl, or haloalkoxy and R 9 a is hydrogen, C 2 6 -alkyl, alkenyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl, aryl, or arylalkyl; where the aryl, cycloalkyl, heteroaryl, and heterocycloalkyl rings in Ra (either alone or as part of arylalkyl, cycloalkylalkyl, heterocycloalkylalkyl and heteroarylalkyl) are independently optionally substituted with 1, 2, or 3 groups independently selected from alkyl, alkenyl, alkoxy, hydroxy, hydroxyalkyl, halo, haloalkyl, haloalkoxy, oxo, amino, alkylamino, dialkylamino, alkylcarbonyl, alkoxycarbonyl, -C(O)H, aryl (optionally substituted with one or two halo), arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl, cyloalkyl, cyloalkylalkyl, and cycloalkylcarbonyl; 6 d) -C(O)N(R")-C1-C6-alkylene-N(Ria)R!'b where R 0 a is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, haloalkyl, or hydroxyalkyl and R" 0 and R... are independently hydrogen, alkyl, alkenyl, haloalkyl, or hydroxyalkyl; e) NRlC(O)NRIUaRIIb where Rua is hydrogen, alkyl, alkenyl, hydroxy, or alkoxy and R" and R"' are independently hydrogen, alkyl, alkenyl, aminoalkyl, alkylaminooalkyl, dialkylaminoalkyl; f) -C(O)R" 2 where R 2 is heterocycloalkyl optionally substituted with 1, 2, or 3 groups selected from alkyl, oxo, amino, alkylamino, and heterocycloalkylalkyl; g) -NR1 3 C(O)ORu 3 a where R1 3 is hydrogen, alkyl, or alkenyl and Ra 13 is aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, aryl, or arylalkyl); h) -C(O)N(RI 4 )N(R14a)(R 4 ') where R1 4 , Ra 14 , and R Mb are independently hydrogen, alkyl, or alkenyl; i) -S(0) 2

N(RI")-C-C

6 -alkylene-N(Rl 5 a)R 5 b where R 15 , R1 5 a, and R 15 b are independently hydrogen, alkyl, or alkenyl; j) -C(O)N(R6)-C I-C 6 -alkylene-C(O)OR 6 a where R 16 is hydrogen, alkyl, or alkenyl and R1 6 a is alkyl or alkenyl; k) heteroaryl optionally substituted with one or two aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; 1) -N(Rl)-C(=N(REb)(R 7 a))(NR" 7 cR1 7 d) where R1 7 , R1 7 a, Rb, R4, and RId are independently hydrogen, alkyl, or alkenyl; m) -N(R")C(0)-Ci-C6-akylene-N(R"')C(O)R"a where R 8 a is hydrogen, alkyl, alkenyl, or alkoxy and R" and R8b are independently hydrogen, alkyl, or alkenyl; n) -C(0)N(Rl)-Ci-C6-alkylene-C(O)R19a where R1 9 is hydrogen, alkyl, or alkenyl and

R

19 a is amino, alkylamino, dialkylamino, or heterocycloalkyl; o) -N(R 2 )C(O)-Ci-C 6 -alkylene-C(O)R 2 0a where R 20 is hydrogen, alkyl, or alkenyl and R20' is cycloalkyl or heterocycloalkyl; p) -NRMlS(0) 2 R-Ci.C 6 -akylene-N(R 2 b)Raa where R 2 ' is hydrogen, alkyl, or alkenyl and RIa and R20' are independently hydrogen, alkyl, or alkenyl; q) -N(Re)C(O)-C1..Chalkylene-N(R2)-N(ReC)(Rna), where R 2 , R 2 a and R 22 ' are independently hydrogen, alkyl, or alkenyl; r) -CO.Cw-aklene-N( )-C..C--aklene-N(R ) a Where R 23 , R 3 a and R 23 b are independently hydrogen, alkyl, or alkenyl; or s) -NR 24 C(O)-C..C-alkylene-OR? 4 a where R 24 is hydrogen, alkyl, or alkenyl and R 24 a is alkoxyalkyl or aryl optionally substituted with one or two halo or alkyl; 7 wherein each of the alkylene in R3 is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, amino, alkylamino, and dialkylamino; and provided that when R 50 and R 52 are hydrogen, R 5 1 is hydrogen or methyl, R 53 is hydrogen or methoxy, and R 4 is hydrogen or methoxy, then B is not 2,3-dihydro-1,4 benzodioxinyl, thien-2-yl, or thien-2-yl substituted with one R 3 where R 3 is halo. [00111 A second aspect of the invention provides a compound of Formula II: A W N Xl

R

4 O II or a pharmaceutically acceptable salt or solvate thereof, wherein W', W 2 , W 3 , and W 4 are -C(R"a)=; or one or two of W', W 2 , W 3 , and W 4 are independently -N= and the remaining are -C(Ria X' is -N(Rsa)_; A is aryl, -S(O)2-aryl, heteroaryl, cycloalkyl, heterocycloalkyl, halo, haloalkyl, haloalkoxy, alkyl, alkoxy, or -alkyl-N(R7)R 7 a, where each of the aryl, heteroaryl, cycloalkyl, heterocycloalkyl, alkyl and alkoxy groups, each either alone or as part of another group within A, are independently optionally substituted with one, two, three, or four R 2 "; or B3 1 is aryl, arylalkyl, alkyl, heteroaryl, or heteroaryalkyl, wherein each of the aryl, heteroaryl and alkyl groups are independently optionally substituted with one, two, three, or four

R

3 ; each RIa is independently selected from hydrogen, alkoxy, alkyl, nitro, halo, cyano, and -Co

C

6 -alkyl-N(R 7

)R

7 a, wherein each of the alkyl and alkoxy groups is optionally substituted with 1, 2, 3, 4, or 5 groups selected from alkyl, alkoxy, halo, haloalkyl, haloalkoxy, nitro, cyano, hydroxy, -N(R8)R'a, and -C(O)OR; each R 2 a (when R 2 a is present) is independently selected from alkyl, alkenyl, -alkenyl

C(O)OR

6 , -OR', -N(R 7

)C(O)R

6 , -N(R 7 )C(O)-Co-C 6 alkyl-N(R)R 7 a, -OC(O)-Co-C 6 alkyl-N(R 7

)R

7 a, -N(R 7

)C(O)-C

1

-C

6 alkylC(O)OR 6 , Co-C 6 -alkyl-C(O)R 6 , oxo, dioxo,

-S(O)

2

-N(R

7

)R

7 a, -C(O)OR 6 , -CH(R 6

)

2

-C(O)OR

6 , -S(O) 2

R

6 , cycloalkyl, heterocycloalkyl, heteroaryl, -C(O)N(R 7 )-alkyl-OR 6 , -Co-C 6 alkyl-C(O)N(R 7 )-Co-C 6 alkyl-C(O)OR 6 , -Co-C 6 -alkyl-C(O)N(R)R 7 a, aryl, arylalkyl, -S-(CI-C 6 alkyl), halo, 8 oxo, nitro, -SCN, cyano, and -Co-C 6 alkyl-N(R)R 7 a, wherein each of the alkyl (including, for example the alkyl within alkoxy), aryl, cycloalkyl, heterocycloalkyl, and heteroaryl groups, either alone or as part of another group within R, is independently optionally substituted with 1, 2, 3, 4, or 5 groups selected from alkyl, halo, haloalkyl, haloalkoxy, oxo, nitro, cyano, hydroxy, -N(Rs)Rsa, alkoxy, and -C(O)OR; each R (when R 3 d is present) is independently oxo, nitro, halo, cyano, alkyl, alkenyl, alkynyl, alkoxy, C 3

-C

6 -cycloalkyl, -Co.C6-alkyl-heterocycloalkyl, -CO.C 6 alkyl

N(R

7 )C(O)-Co-C 6 -alkyl-N(R 7 b)R 7 a, -CO.C 6 alkyl-N(R)C(O)-Co-C 6 -alkyl

N(R

7

)C(O)R

7 a, -Co.C 6 alkyl-C(O)-Co.C 6 -alkyl-N(R)R 7 a, -Co.C6-alkyl-C(O)N(R 7 )-Co

C

6 -alkyl-N(R 7 b)R 7 a, -CO-C6-alkyl-C(O)N(R7)-Cr.CoalkylC(0)OR7a, -Co.C 6 alkyl

N(R

7 )C(O)-Co-C 6 -alkyl-(R 7 a), -CO.C 6 alkyl-N(RI)-Co-C6-alkyl-N(RIb)R7a, -C.C 6 alkyl N(R7)C(O)-CO-C6-alkyl-N(Rlb)-N(R7*)R7a, -Co.C 6 alkyl-N(R 7 )C(O)O-Co-C 6 -alkyl-aryl, -Co.C 6 alkyl-C(O)N(R7)-Co-C6-alkyl-N(Ra)Ra, -CO.C 6 alkyl-N(R)-Co-C 6 alkyl

C(=N(R

7 b) 7 a))( 7 Re 7 d), -Co..C 6 -alkyl-aryl, -Co-C 6 -alkyl-heteroaryl, -Co-C 6 alkyl heterocycloalkyl, -O-C.C 6 alkyl-N(R 7

)R

7 a, -Co-C 6 alkyl-OR 6 , -Co-C 6 alkyl-C(O)OR 6 , Co-C 6 -alkyl-N(R)R 7 a, -CO-C 6 alkyl-C(O)NR 7

R

7 a, -Co-C 6 alkyl-C(O)R 7 , -SR 7 , -S(O) 2

R

7 ,

-S(O)

3

R

7 , -S(O)R 7 , -SO 2

N(R

7

)R

7 a, -SO 2

N(R

7 )-Co.C 6 alkyl-N(R 7 b)R 7 a, -CO-C 6 -alkyl

N(R

7 )-aryl, -CO-C 6 -alkyl-N(R 7 )-heteroaryl, -Co-C 6 -alkyl-N(R)-heterocycloalkyl, -Co-C 6 -alkyl-C(O)N(R 7 )-Co-C 6 -alkyl-cycloalkyl, Co-C 6 -alkyl-C(O)N(R 7 )-Co-C 6 -alkyl aryl, Co-C 6 alkyl-C(O)N(R 7 )-Co-C 6 alkyl-heteroaryl, Co-C 6 alkyl-C(O)N(R 7 )-Co-C 6 alkyl-heterocycloalkyl, -Co-C 6 -alkyl-N(R 7 )C(O)-Co-C 6 -alkyl-cycloalkyl, -Co-C 6 -alkyl

N(R

7 )C(O)-Co-C 6 -alkyl-aryl, Co-C 6 -alkyl-N(RI)C(O)-Co-C 6 -alkyl-heteroaryl, -CO-C 6 alkyl-N(R 7 )C(O)-CO-C6-alkyl-heterocycloalkyl, Co-C 6 -alkyl-N(R 7 )C(O)-Co-C 6 -alkyl heterocycloalkyl-aryl, -N(R 7 )C(O)OR, or -NHC(O)H, wherein each of the alkyl, alkenyl, cycloalkyl, aryl, (including, for example the alkyl within alkoxy), heterocycloalkyl, and-heteroaryl groups, either alone or as part of another group within

R

3 d, is independently optionally substituted with 1, 2, 3, 4, or 5 groups selected from alkyl, alkenyl, -Co-C 6 -alkyl-OR?, cycloalkyl, halo, haloalkyl, haloalkoxy, -C(O)R', nitro, cyano, oxo, -Co-C 6 -alkyl-N(R 8 )Rsa, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, -C(0)OR!, alkylthio, and hydroxyalkyl;

R

4 is hydrogen, aryl, -Co-C 6 -alkyl-N(R7)R 7 a, alkoxy, or C 1

-C

6 alkyl, wherein each of the alkyl and aryl groups, either alone or as part of another group in R 4 , is independently 9 optionally substituted with 1, 2, 3, 4, or 5 groups selected from alkyl, halo, haloalkyl, haloalkoxy, nitro, cyano, hydroxy, -N(Rs)Raa, alkoxy, and -C(0)0R 6 ; or

R

4 and X 1 together with the atoms to which they are attached form a heterocycloalkyl or heteroaryl group, wherein Rsa is absent when X is -N(Rsa)-, wherein each of the heterocycloalkyl or heteroaryl is optionally substituted with 1, 2, 3, 4, or 5 groups selected from alkyl, halo, haloalkyl, haloalkoxy, nitro, cyano, hydroxy, -N(R 7

)R

7 a, alkoxy, and -C(0)OR; Rsa is hydrogen, -CI-C 6 alkyl-N(R 7

)R

7 a, alkoxy, alkyl, or aryl, wherein each of the alkyl and aryl is optionally substituted with 1, 2, 3, 4, or 5 groups selected from alkyl, halo, haloalkyl, haloalkoxy, nitro, cyano, hydroxy, -N(R)R"a, C 1

-C

6 alkoxy, or -C(O)OR 6 ; or

R

5 a and R 4 together with the atoms to which they axe attached form a heterocycloalkyl or heteroaryl group, wherein the heterocycloalkyl and heteroaryl is optionally substituted with 1, 2, 3, 4, or 5 groups selected from alkyl, halo, haloalkyl, haloalkoxy, nitro, . cyano, hydroxy, -N(R)R 7 a, C 1

-C

6 alkoxy, and -C(O)OR 6 ;

R

6 and R! are independently hydrogen, hydroxy, alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, hetemcycloalkylalkyl, heteroaryl, heteroarylalkyl, or aryl, each alkyl, aryl, cycloalkyl, heterocycloalkyl, and heteroaryl, either alone or as part of another group within R 6 and R 9 , is independently optionally substituted with 1, 2, 3, 4, or 5 groups independently selected from amino, hydroxy, alkoxy, alkyl, and halo; and

R

7 , R 7 a Rh, R 7 *, R 7 d, R, and R 8 a are independently hydrogen, alkyl, alkenyl, hydroxy, alkyloxy, alkenyloxy, -0-Co-C 6 alkyl-aryl, -Co-C 6 alkyl-C(O)OR 6 , -Co-C 6 alkyl

C(O)R

6 , aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, or heterocycloalkylalkyl, wherein each of the alkyl, aryl, heteroaryl, and heterocycloalkyl, either alone or part of another group within R 7 , R 7 a R 7 ', R 7 , R 7 ',

R

8 , and Ra is independently optionally substituted with 1, 2, 3, 4, or 5 groups selected from amino, alkylamino, dialkylamino, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, -S-C 1

-C

6 alkyl, cyano, nitro, hydroxy, C 1

-C

6 alkoxy, C 1

-C

6 alkyl, halo, aryl, heterocycloalkylalkyl, and heteroaryl optionally substituted with one or two

C

1

-C

6 alkyl. [0012] In a third aspect, the invention is directed to a pharmaceutical composition which comprises a compound of Formula I or a pharmaceutically acceptable salt therof and a pharmaceutically acceptable carrier, excipient, or diluent. 10 [0013] In a fourth aspect, the invention comprises a method of inhibiting P13K in a cell, comprising contacting a cell with a compound of Formula I or II or a pharmaceutically acceptable salt or solvate therof, or with a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula I and a pharmaceutically acceptable carrier, excipient, or diluent. [0014] In a fifth aspect, the Invention provides a method for treating a disease, disorder, or syndrome which method comprises administering to a patient a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula I or II or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula I, Ia, or II and a pharmaceutically acceptable carrier, excipient, or diluent. [0015] A sixth aspect of the invention is directed to a process of preparing a compound of Formula I, comprising: (a) reacting an intermediate of R52 R 3

OR

51

R

54 R5 N- N-1$ LG 0 & 5 where LG is a leaving group such as chloro, and all other groups, are as defined in the Summary of the Invention, with an intermediate of formula NHRaR or HO-C 1

-C

6 alkylene-NHRaRb where Ra and R are independently hydrogen or alkyl to yield, respectively, RW2 R63 OR 5 1 R R50 NH-S B NRaRb H ' 0 1(c) ; and 11 R 6 R6s OR6i R54 R 5 1 N( N NH NS B O-CI-C6-alkylene-NRaRb 1(d); or (b) reacting an intermediate of formula 8 R6 2

R

53 ORB1 R5) R 50 HN 8 where Ra is R, R!, R", R", R 7 , R", R 20 , R 21 , R 22 , or R 24 , each as defined in the Summary of the Invention for a Compound of Formula I and all other groups are as defined in the Summary of the Invention; with an intermediate of formula 9(a), 9(b), 9(c), 9(d), 9(e), 9(f), or 9(g): 9(a) HOC(O)-C1-C-alkylene-N(R 7 a)(R7b) where Ra is R 7 , or a N-protecting group, such as Boc or Fmoc; 9(b) HOC(O)Rla; 9(c) HOC(O)NRu 1 aRilb 9(d) HOC(O)ORua; 9(e) HOC(O)-C1-C 6 -alkylene-N(Ro"b)C(O)Ru a; 9(f) HOC(O)-C1-C-alkylene-C(O)R 2 a; 9(g) LG-S(w)2R-C1.C6-alkylene-N(2)R Where Ra is R 2 1a or a N-protecting group, such as Boc or Fmoc; to yield 12 RU

R

53

OR

51

R

54 R" 11N NH ~0 H BN---

NHR

10 0 0 I(e) where R1 00 is -C(O)Ra, -C(O)NR' aR , -C(O)ORa, -C(O)-C 1

-C

6 -alkylene N(Rsb)C(O)Rsa, -C(O)-C 1

-C

6 -alkylene-C(O)R 2 oa, or -S(O) 2 R-C1.C 6 -alkylene-N(R~e)Ra; or (c) reacting an intermediate of formula 11

R

52 RmORbi R54 R50 N NH N NS C(O)OH 11 with one of the following intermediates NHR8Rsa, NH(Rlo)-Ci-C6-alkylene-N(RIca)R ob, a cyclic amine, NH(R 14

)N(R

4 a 4 , NH(RI 6

)-CI.C

6 -alkylene-C(O)ORsa, and

NH(R

9 )-Cj-C 6 -alkylene-C(O)R1 9 a to yield a Compound of Formula I; or (d) reacting an intermediate of formula 12: R52

R

53

OR

1 RY4 R 60 N NH 0 LG 0 12 12 with an intermediate of formula NH(Reb)R 7 a to yield a Compound of Formula I(f): 13

R

52

R

53

OR

1 R Rwo N NH O NROR 7 b H 1N I(f); or (e) reacting an intermediate of formula 13 where LG is a leaving group, such as chlord, and all other groups are as defined in the Summary of the Invention: .yN LG N -O 13 with an intermediate of formula:

R

52

R

53 Owl R54 R

NH

2 to yield a Compound of Formula I(h):

R

52 R5 3 ORl W4 R 50 . 'QyN NH H 1Q1) I(h); and (f) optionally further resolving individual isomers. DETAILED DESCRIPTION OF THE INVENTION Abbreviations and Definitions [00161 The following abbreviations and terms have the indicated meanings throughout: Abbreviation Meaning br broad "C degrees Celsius 14 Abbreviation Meaning CBZ CarboBenZoxy = benzyloxycarbonyl d doublet dd doublet of doublet dt doublet of triplet EI Electron Impact ionization Et Ethyl g grams) GC gas chromatography h or hr hour(s) HPLC high pressure liquid chromatography L liter(s) molar or molarity m Multiplet mg milligrams) MHz megahertz (frequency) Min minute(s) mL milliliter(s) mM Millimolar mmol millimole(s) mol moles) MS mass spectral analysis normal or normality nM Nanomolar NMR nuclear magnetic resonance spectroscopy q Quartet RT Room temperature Singlet 8- Secondary - Tertiary t or trTriplet 15 Abbreviation Meaning TFA trifluoroacetic acid THF Tetrahydrofuran RL microliter(s) pM Micromole(s) or micromolar [0017] The symbol "-" means a single bond, "=" means a double bond, "i" means a triple bond, and "--" means a single bond and optionally a double bond. When chemical structures are depicted or described, unless explicitly stated otherwise, all carbons are assumed to have hydrogen substitution to conform to a valence of four. [0018] "Administration" and variants thereof (e.g., "administering" a compound) in reference to a compound of the invention means introducing the compound or a prodrug of the compound into the system of the animal in need of treatment. When a compound of the invention or prodrug thereof is provided in combination with one or more other active agents (e.g., surgery, radiation, and chemotherapy, etc.), "administration" and its variants are each understood to include concurrent and sequential introduction of the compound or prodmg thereof and other agents. [00191 "Alkenyl" or "lower alkenyl" means a straight or branched hydrocarbon radical having from 2 to 6 carbon atoms and at least one double bond and includes ethenyl, propenyl, 1 -but-3-enyl, 1 -pent-3-enyl, 1 -hex-5-enyl and the like. [00201 "Alkenylcarbonyl" means a C(0)R group where R is alkenyl, as defined herein. [0021] "Alkenyloxy" or "lower alkenyloxy" means an -OR group where R is alkenyl, as defined herein. Representative examples include methoxy, ethoxy, 1-methoxyprop-1-en 3-yl, propoxy, isopropoxy, cyclopropyloxy, cyclohexyloxy and the like. [0022] "Alkoxy" or "lower alkoxy" means an -OR group where R is alkyl, as defined herein. Representative examples include methoxy, ethoxy, 1 -methoxyprop-1-en-3-yl, propoxy, isopropoxy, cyclopiopyloxy, cyclohexyloxy and the like. [00231 "Alkoxyalkyl" means an alkyl group, as defined herein, substituted with one, two, or three alkoxy groups, as defined herein. [0024] "Akoxycarbonyl" means a-C(O)OR group where R is alkyl as defined herein. [0025] "Alkoxyycarbonylalkyl" means an alkyl group, as defined herein, substituted with one, two, or three alkoxycarbonyl groups, as defined herein. 16 [0026] "Alkyl" or "lower alkyl" means a linear or branched hydrocarbon group having one to six carbon atoms. Examples of lower alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, s-butyl, t-butyl, isobutyl, pentyl, hexyl and the like. A "Co" alkyl (as in "Co-C 6 -alkyl") is a covalent bond. "C 6 alkyl" refers to, for example, n-hexyl, iso-hexyl, and the like. 100271 "Alkylamino" means a -NHR radical where R is alkyl as defied herein, or an N-oxide derivative thereof, e.g., methylamino, ethylamino, n-, iso-propylamino, n-, iso-, tert-butylamino, or methylamino-N-oxide, and the like. [0028] "Alkylaminoalkyl" means an alkyl group substituted with one or two alkylamino groups, as defined herein. [0029] "Alkylaminoalkyloxy" means an -OR group where R is alkylaminoalkyl, as defined herein. [0030] "Alkylcarbonyl" means a C(O)R group where R is alkyl, as defined herein. [0031] "Alkylcarbonylamino" means a -NRC(O)R' group where R is hydrogen or alkyl, as defiend herein, and R' is alkyl, as defiend herein. [0032] "Alkylene" refers to straight or branched divalent hydrocarbon, containing no unsaturation and having from two to eight carbon atoms. Examples of alkylene include eth diyl (-CH 2

CJH

2 -), prop-1,3-diyl (-CH 2

CH

2

CH

2 -), 2,2-dimethylprop-1,3-diyl

(-CH

2

C(CH

3

)

2

CH

2 -), and the like. [0033] "Alkylsulfonyl" means a -S(O) 2 R group where R is lakyl, as defined herien. [0034] "Alkylthio" means a -SR group where R is alkyl, as defined herein. Examples of alkylthio include methylthio and ethylthio, and the like. [00351 "Alkylthioalkyl" means an alkyl group substituted with one or two alkylthio groups, as defined herein, e.g. 2-(methylthio)-ethyl and 2-(ethylthio)-ethyl. [0036] "Alkynyl" or "lower alkynyl" means a straight or branched hydrocarbon radical having from 2 to 6 carbon atoms and at least one triple bond and includes ethynyl, propynyl, butynyl, pentyn-2-yl and the like. [00371 "Amino" means a -NH 2 . [0038] "Aminoalkyl" means an alkyl group subsitutted with at least one, specifically one, two, or three, amino groups. [00391 "Aminoalkyloxy" means an -OR group where R is aminoalkyl, as defined herein. [00401 "Aryl" means a monovalent six- to fourteen-membered, mono- or bi-carbocyclic ring, wherein the monocyclic ring is aromatic and at least one of the rings in the bicyclic 17 ring is aromatic. Representative examples include phenyl, naphthyl, and indanyl, and the like. [0041] "Arylalkyl" means an alkyl group, as defined herein, subsituted with one or two aryl groups, as defined herein. Examples include benzyl, phenethyl, phenylvinyl, phenylallyl and the like. [0042] "Aryloxy"means a -OR group where R is aryl as defined herein. [0043] "Arylalkyloxy" means a -OR group where R is arylalkyl as defined herein. [00441 "Arylsulfonyl" means a -SO 2 R group where R is aryl as defined herein. [0045] "Carboxyalkyl" means an alkyl group, as defined herein, substituted with one, two, or three -C(O)OH groups. [00461 "Carboxy ester" means a -C(O)OR group where R is lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl, aryl or arylalkyl, each of which is defined herein. Representative examples include methoxycarbonyl, ethoxycarbonyl, and benzyloxycarbonyl, and the like. [0047] "Cyanoalkyl" means an alkyl, alkenyl, or alkynyl radical, as defined herein, substituted with at least one, specifically one, two, or three, cyano groups. [0048] "Cycloalkyl" means a monocyclic or polycyclic hydrocarbon radical having three to thirteen carbon atoms. The cycloalkyl can be saturated or partially unsaturated, but cannot contain an aromatic ring. Cycloalkyl includes fused, bridged, and spiro ring systems. Examples of such radicals include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. [0049] "Cycloalkylalkyl" means alkyl group substituted with one or two cycloalkyl group(s), as defined herein. Representative examples include cyclopropylmethyl and 2 cyclobutyl-ethyl, and the like. [00501 "Cycloalkylcarbonyl" means a -C(O)R group where R is cycloalkyl as defined herein. [00511 "Dialkylamino" means a -NRR' radical where R and R' are independently alkyl as defined herein, or an N-oxide derivative, or a protected derivative thereof, e.g., dimethylamino, diethylamino, NN-methylpropylamino or NN-methylethylamino, and the like. [0052] "Dialkylaminoalkyl" means an alkyl group substituted with one or dialkylamino group(s), as defined herein. [00531 "Dialkylaminoalkyloxy" means an -OR group where R is dialkylaminoalkyl, as defined herein. 18 [0054] "Fused ring system" and "fused ring" refer to a polycyclic ring system that contains bridged or fused rings; that is, where two rings have more than one shared atom in their ring structures. In this application, fused-polycyclics and fused ring systems are not necessarily all aromatic ring systems. Typically, but not necessarily, fused-polycyclics share a vicinal set of atoms, for example naphthalene or 1,2,3,4-tetrahydro-naphthalene. A spiro ring system is not a fused-polycyclic by this definition, but fused polycyclic ring systems of the invention may themselves have spiro rings attached thereto via a single ring atom of the fused-polycyclic. In some examples, as appreciated by one of ordinary skill in the art, two adjacent groups on an aromatic system may be fused together to form a ring structure. The fused ring structure may contain heteroatoms and may be optionally substituted with one or more groups. It should additionally be noted that saturated carbons of such fused groups (i.e. saturated ring structures) can contain two substitution groups. [0055] "Haloaloxy" means an -OR' group where R' is haloalkyl as defined herein, e.g., trifluoromethoxy or 2,2,2-trifluoroethoxy, and the like. [0056] "Haloalkoxyalkyl" means an alkyl group, as defined herein, substituted with one, two, or three haloalkoxy, as defined herein. [0057] "Halogen" or "halo" means fluoro, chloro, bromo and iodo. [0058] "Haloalkenyl means an alkenyl group, as defined herein, substituted with one or niore halogens, specifically one to five halo atoms. [0059] "Haloalkyl" means an alkyl group, as defined herein, substituted with one or more halogens, specifically one to five halo atoms. Representative examples includes 2,2 difluoroethyl, trifluoromethyl, and 2-chloro-1 -fluoroethyl, and the like. [0060] "Heteroaryl" means.a monocyclic, fused bicyclic, or fused tricyclic, monovalent radical of 5 to 14 ring atoms containing one or more, specifically one, two, three, or four ring heteroatoms independently selected from -0-, -S(O)- (n is 0, 1, or 2), -N-, -N(R)-, and the remaining ring atoms being carbon, wherein the ring comprising a monocyclic radical is aromatic and wherein at least one of the fused rings comprising a bicyclic or tricyclic radical is aromatic. One or two ring carbon atoms of any nonaromatic rings comprising a bicyclic or tricyclic radical may be replaced by a -C(O)-, -C(S)-, or -C(=NH)- group. R is hydrogen, alkyl, hydroxy, alkoxy, acyl, or alkylsulfonyl. Fused bicyclic radical includes bridged ring systems. Unless stated otherwise, the valency may be located on any atom of any ring of the heteroaryl group, valency rules permitting. In particular, when the point of valency is located on the nitrogen, R is absent. More specifically, the term heteroaryl includes, but is not limited to, 1,2,4-triazolyl, 1,3,5-triazolyl, phthalimidyl, pyridinyl, 19 pyrrolyl, imidazolyl, thienyl, furanyl, indolyl, 2,3-dihydro-lH-indolyl (including, for example, 2,3-dihydro-1H-indol-2-yl or 2,3-dihydro-1H-indol-5-yl, and the like), isoindolyl, indolinyl, isoindolinyl, benzimidazolyl, benzodioxol-4-yl, benzofuranyl, cinnolinyl, indolizinyl, naphthyridin-3-yl, phthalazin-3-yl, phthalazin-4-yl, pteridinyl, purinyl, quinazolinyl, quinoxalinyl, tetrazoyl, pyrazolyl, pyrazinyl, pyrimidinyl, pyridazinyl, oxazolyl, isooxazolyl, oxadiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl, tetrahydroisoquinolinyl (including, for example, tetrahydroisoquinolin-4-yl or tetrahydroisoquinolin-6-yl, and the like), pyrrolo[3,2-c]pyridinyl (including, for example, pyrrolo[3,2-c]pyridin-2-yl or pyrrolo[3,2-c]pyridin-7-yl, and the like), benzopyranyl, thiazolyl, isothiazolyl, thiadiazolyl, benzothiazolyl, benzothienyl, and the derivatives thereof, or N-oxide or a protected derivative thereof. 100611 "Hetereoarylalkyl" means an alkyl group substituted with one or two heteroaryl group(s) as defined herein. [00621 "Heterocycloalkyl" means a saturated or partially unsaturated monovalent monocyclic group of 3 to 8 ring atoms or a saturated or partially unsaturated monovalent fused bicyclic group of 5 to 12 ring atoms in which one or more, specifically one, two, three, or four ring heteroatoms independently selected from -0-, -S(O),- (n is 0, 1, or 2), -N=, -N(R)- (where RY is hydrogen, alkyl, hydroxy, alkoxy, acyl, or alkylsulfonyl), the remaining ring atoms being carbon. One or two ring carbon atoms may be replaced by a -C(O)-, -C(S)-, or -C(=NH)- group. Fused bicyclic radical includes bridged ring systems. Unless otherwise stated, the valency of the group may be located on any atom of any ring within the radical, valency rules permitting. In particular, when the point of valency is located on a nitrogen atom, RY is absent. More specifically the term heterocycloalkyl includes, but is not limited to, azetidinyl, pyrrolidinyl, 2-oxopyrrolidinyl, 2,5-dihydro-1H pyrrolyl, piperidinyl, 4-piperidonyl, morpholinyl, piperazinyl, 2-oxopiperazinyl, tetrahydropyranyl, 2-oxopiperidinyl, thiomorpholinyl, thiamorpholinyl, perhydroazepinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, dihydropyridinyl, tetrahydropyridinyl, oxazolinyl, oxazolidinyl, isoxazolidinyl, thiazolinyl, thiazolidinyl, quinuclidinyl, isothiazolidinyl, octahydroindolyl, octahydroisoindolyl, decahydroisoquinolyl, tetrahydrofuryl, and tetrahydropyranyl, and the derivatives thereof and N-oxide or a protected derivative thereof. [00631 "Heterocycloalkylalkyl" means an alkyl group, as defined herein, substituted with one or two heterocycloalkyl group(s), as defined herein. 20 [0064] "Hydroxyalkyl" means an alkyl radical, as defined herein, substituted with at least one, specifically one, two, or three, hydroxy group(s), provided that if two hydroxy groups are present they are not both on the same carbon atom. Representative examples include, but are not limited to, hydroxymethyl, 2-hydroxyethyl, 2-hydroxypropyl, 3-hydroxypropyl, 1-(hydroxymethyl)-2-methylpropyl, 2-hydroxybutyl, 3-hydroxybutyl, 4-hydroxybutyl, 2,3-dihydroxypropyl, 1-(hydroxymethyl)-2-hydroxyethyl, 2,3 dihydroxybutyl, 3,4-dihydroxybutyl and 2-(hydroxymethyl)-3-hydroxypropyl, specifically 2-hydroxyethyl, 2,3-dihydroxypropyl, or 1-(hydroxymethyl)-2-hydroxyethyl, and the like. [0065], "Hydroxyamino" means a -NH(OH) group. [00661 "Optional" or "optionally" means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where said event or circumstance occurs and instances in which it does not. One of ordinary skill in the art would understand that with respect to any molecule described as containing one or more optional substituents, only sterically practical and/or synthetically feasible compounds are meant to be included. "Optionally substituted " refers to all subsequent modifiers in a term. So, for example, in the term "optionally substituted ary1Ci-g alkyl," both the "Cl-8 alkyl" portion and the "aryl" portion of the molecule may or may not be substituted. A list of exemplary optional substitutions is presented below in the definition of "substituted." [0067] "Optionally substituted alkyl" means an alkyl radical, as defined herein, optionally substituted with one or more group(s), specifically one, two, three, four, or five groups, independently selected from alkylcarbonyl, alkenylcarbonyl, cycloalkylcarbonyl, alkylcarbonyloxy, alkenylcarbonyloxy, amino, alkylamino, dialkylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, cyano, cyanoalkylaminocarbonyl, alkoxy, alkenyloxy, hydroxy, hydroxyalkoxy, carboxy, alkylcarbonylamino, alkylcarbonyloxy, alkyl-S(O)o- 2 -, alkenyl-S(O)o- 2 -, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, alkylsulfonyl-NR*- (where R4 is hydrogen, alkyl, optionally substituted alkenyl, optionally substituted alkynyl, hydroxy, alkoxy, alkenyloxy, or cyanoalkyl), alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylaminoalkyloxy, dialkylaminoalkyloxy, alkoxycarbonyl, alkenyloxycarbonyl, alkoxycarbonylamino, alkylaninocarbonylamino, dialkylaminocarbonylamino, alkoxyalkyloxy, and -C(O)NRaRb (where Ra and Rb are independently hydrogen, alkyl, optionally substituted alkenyl, optionally substituted alkynyl, hydroxy, aikoxy, alkenyloxy, or cyanoalkyl). 21 [00681 "Optionally substituted alkenyl" means an alkenyl radical, as defined herein, optionally substituted with one or more group(s), specifically one, two, or three groups, independently selected from alkylcarbonyl, alkenylcarbonyl, cycloalkylcarbonyl, alkylcarbonyloxy, alkenylcarbonyloxy, amino, alkylamino, dialkylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, cyano, cyanoalkylaminocarbonyl, alkoxy, alkenyloxy, hydroxy, hydroxyalkoxy, carboxy, alkylcarbonylamino, alkylcarbonyloxy, alkyl-S(O)o- 2 -, alkenyl-S(O)o-2-, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, alkylsulfonyl-NR*- (where R* is hydrogen, optionally substituted alkyl, optionally substituted alkynyl, hydroxy, alkoxy, or alkenyloxy), alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylaminoalkyloxy, dialkylaminoalkyloxy, alkoxycarbonyl, alkenyloxycarbonyl, alkoxycarbonylamino, alkylaminocarbonylamino, dialkylaminocarbonylamino, alkoxyalkyloxy, and -C(O)NRaR (where Ra and Rb are independently hydrogen, optionally substituted alkyl, alkenyl, optionally substituted alkynyl, hydroxy, alkoxy, or alkenyloxy). [00691 "Optionally substituted aryl" means an aryl group, as defined herein, which is optionally substituted with one, two, three, four, of five groups selected from halo, haloalkyl, haloalkoxy, hydroxy, lower alkyl, lower alkenyl, lower alkynyl, alkoxy, carboxy, carboxy ester, amino, alkylamino, dialkylamino, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted heteroaryl, -C(O)NR'R" (where R' is hydrogen or alkyl and R" is hydrogen, alkyl, aryl, heteroaryl, or heterocycloalkyl), -NR'C(O)R" (where R' is hydrogen or alkyl and R" is alkyl, aryl, heteroaryl, or heterocycloalkyl), and -NHS(O) 2 R' (where R' is alkyl, aryl, or heteroaryl). [0070] "Optionally substituted heteroaryl" means a heteroaryl group, as defined herein, optionally substituted with one, two, three, four, or five groups selected from halo, haloalkyl, haloalkoxy, lower alkyl, lower alkenyl, lower alkynyl, alkoxy, hydroxy, oxo (valency rules permitting), carboxy, carboxy ester, amino, alkylamino, dialkylamino, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, heteroaryl, optionally substituted aryl, -C(O)NR'R" (where R' is hydrogen or alkyl and R" is hydrogen, alkyl, aryl, heteroaryl, or heterocycloalkyl), -NR'C(O)R" (where R' is hydrogen or alkyl and R" is alkyl, aryl, heteroaryl, or heterocycloalkyl), and -NHS(0) 2 R' (where R' is alkyl, aryl, or heteroaryl). [00711 "Optionally substituted heterocycloalkyl" means a heterocycloalkyl, as defined herein, optionally substituted with one, two, three, four, or five groups selected from halo, haloalkyl, haloalkoxy, hydroxy, oxo, lower alkyl, lower alkenyl, lower alkynyl, alkoxy, 22 optionally substituted cycloalkyl, heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, alkylaminoalkyl, dialkylaminoalkyl, carboxy, carboxy ester, -C(O)NR'R" (where R' is hydrogen or alkyl and R" is hydrogen, alkyl, aryl, heteroaryl, or heterocycloalkyl), -NR'C(O)R" (where R' is hydrogen or alkyl and R" is alkyl, aryl, heteroaryl, or heterocycloalkyl), amino, alkylamino, dialkylamino, and -NHS(O) 2 R' (where R' is alkyl, aryl, or heteroaryl). [0072] "Saturated bridged ring system" refers to a bicyclic or polycyclic ring system that is not aromatic. Such a system may contain isolated or conjugated unsaturation, but not aromatic or heteroaromatic rings in its core structure (but may have aromatic substitution thereon). For example, hexahydro-furo[3,2-b]furan, 2,3,3a,4,7,7a-hexahydro-IH-indene, 7-aza-bicyclo[2.2.1]heptane, and 1,2,3,4,4a,5,8,8a-octahydro-naphthalene are all included in the class "saturated bridged ring system." [0073] "Spirocyclyl" or "spirocyclic ring" refers to a ring originating from a particular annular carbon of another ring. For example, as depicted below, a ring atom of a saturated bridged ring system (rings C and C'), but not a bridgehead atom, can be a shared atom between the saturated bridged ring system and a spirocyclyl (ring D) attached thereto. A spirocyclyl can be carbocyclic or heteroalicyclic. 0 C. [0074] "Patient" for the purposes of the present invention includes humans and other animals, particularly mammals, and other organisms. Thus the methods are applicable to both human therapy and veterinary applications. In a specific embodiment the patient is a mammal, and in a more specific embodiment the patient is human. [0075] "Kinase-dependent diseases or conditions" refer to pathologic conditions that depend on the activity of one or more protein kinases. Kinases either directly or indirectly participate in the signal transduction pathways of a variety of cellular activities including proliferation, adhesion, migration, differentiation and invasion. Diseases associated with kinase activities include tumor growth, the pathologic neovascularization that supports solid tumor growth, and associated with other diseases where excessive local vascularization is involved such as ocular diseases (diabetic retinopathy, age-related macular degeneration, and the like) and inflammation (psoriasis, rheumatoid arthritis, and the like). [0076] While not wishing to be bound to theory, phosphatases can also play a role in "kinase-dependent diseases or conditions" as cognates of kinases; that is, kinases 23 phosphorylate and phosphatases dephosphorylate, for example protein substrates. Therefore compounds of the invention, while modulating kinase activity as described herein, may also modulate, either directly or indirectly, phosphatase activity. This additional modulation, if present, may be synergistic (or not) to activity of compounds of the invention toward a related or otherwise interdependent kinase or kinase family. In any case, as stated previously, the compounds of the invention are useful for treating diseases characterized in part by abnormal levels of cell proliferation (i.e. tumor growth), programmed cell death (apoptosis), cell migration and invasion and angiogenesis associated with tumor growth. [00771 "Therapeutically effective amount" is an amount of a compound of the invention, that when administered to a patient, ameliorates a symptom of the disease. The amount of a compound of the invention which constitutes a "therapeutically effective amount" will vary depending on the compound, the disease state and its severity, the age of the patient to be treated, and the like. The therapeutically effective amount can be determined routinely by one of ordinary skill in the art having regard to their knowledge and to this disclosure. [0078] "Cancer" refers to cellular-proliferative disease states, including but not limited to: Cardiac: sarcoma (angiosarcoma, fibrosarcoma, rhabdomyosarcoma, liposarcoma), myxoma, rhabdomyoma, fibroma, lipoma and teratoma; Lung: bronchogenic carcinoma (squamous cell, undifferentiated small cell, undifferentiated large cell, adenocarcinoma), alveolar (bronchiolar) carcinoma, bronchial adenoma, sarcoma, lymphoma, chondromatous hanlartoma, inesothelioma; Gastrointestinal: esophagus (squamous cell carcinoma, adenocarcinoma, leiomyosarcoma, lymphoma), stomach (carcinoma, lymphoma, leiomyosarcoma), pancreas (ductal adenocarcinoma, insulinorna, glucagonoma, gastrinoma, carcinoid tumors, vipoma), small bowel (adenocarcinorna, lymphoma, carcinoid tumors, Karposi's sarcoma, leiomyoma, hemangioma, lipoma, neurofibroma, fibroma), large bowel (adenocarcinoma, tubular adenoma, villous adenoma, hamartona, leiomyoma); Genitourinary tract: kidney (adenocarcinoma, Wilm's tumor [nephroblastoma], lymphoma, leukemia), bladder and urethra (squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma), prostate (adenocarcinoma, sarcoma), testis (seminoma, teratoma, embryonal carcinoma, teratocarcinoma, choriocarcinoma, sarcoma, interstitial cell carcinoma, fibroma, fibroadenoma, adenomatoid tumors, lipoma); Liver: hepatoma (hepatocellular carcinoma), cholangiocarcinoma, hepatoblastoma, angiosarcoma, hepatocellular adenoma, hemangioma; Bone: osteogenic sarcoma (osteosarcoma), fibrosarcoma, malignant fibrous histiocytoma, chondrosarcoma, Ewing's sarcoma, 24 malignant lymphoma (reticulum cell sarcoma), multiple myeloma, malignant giant cell tumor chordoma, osteochronfroma (osteocartilaginous exostoses), benign chondroma, chondroblastoma, chondromyxofibroma, osteoid osteoma and giant cell tumors; Nervous system: skull (osteoma, hemangioma, granuloma, xanthoma, osteitis defornians), meninges (meningioma, meningiosarcoma, gliomatosis), brain (astrocytoma, medulloblastoma, glioma, ependymoma, germinoma [pinealoma], glioblastorna multiform, oligodendroglioma, schwannoma, retinoblastoma, congenital tumors), spinal cord neurofibroma, meningioma, glioma, sarcoma); Gvnecological: uterus (endometrial carcinoma), cervix (cervical carcinoma, pre-tumor cervical dysplasia), ovaries (ovarian carcinoma [serous cystadenocarcinoma, mucinous cystadenocarcinoma, unclassified carcinoma], granulosa-thecal cell tumors, SertoliLeydig cell tumors, dysgerminoma, malignant teratoma), vulva (squamous cell carcinoma, intraepithelial carcinoma, adenocarcinoma, fibrosarcoma, melanoma), vagina (clear cell carcinoma, squamous cell carcinoma, botryoid sarcoma (embryonal rhabdomyosarcoma], fallopian tubes (carcinoma); Hematologic: blood (myeloid leukemia [acute and chronic], acute lymphoblastic leukemia, chronic lymphocytic leukemia, myeloproliferative diseases, multiple myeloma, myelodysplastic syndrome), Hodgkin's disease, non-Hodgkin's lymphoma [malignant lymphoma]; Skin: malignant melanoma, basal cell carcinoma, squamous cell carcinoma, Karposi's sarcoma, moles dysplastic nevi, lipoma, angioma, dermatofibroma, keloids, psoriasis; and Adrenal glands: neuroblastoma. Thus, the term "cancerous cell" as provided herein, includes a cell afflicted by any one of the above-identified conditions. [00791 A "pharmaceutically acceptable salt" of a compound means a salt that is pharmaceutically acceptable and that possesses the desired pharmacological activity of the parent compound. It is understood that the pharmaceutically acceptable salts are non-toxic. Additional information on suitable pharmaceutically acceptable salts can be found in Remington's Pharmaceutical Sciences, 17 ed., Mack Publishing Company, Easton, PA, 1985, which is incorporated herein by reference or S. M. Berge, et al., "Pharmaceutical Salts," J. Pharm. Sci., 1977;66:1-19 both of which are incorporated herein by reference. [00801 Examples of pharmaceutically acceptable acid addition salts include those formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; as well as organic acids such as acetic acid, trifluoroacetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, 3-(4-hydroxybenzoyl)benzoic 25 acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonic acid, glucoheptonic acid, 4,4'-methylenebis-(3-hydroxy-2-ene-1-carboxylic acid), 3-phenylpropionic acid, trimethylacetic acid, tertiary butylacetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid, p-toluenesulfonic acid, and salicylic acid and the like. [0081] Examples of a pharmaceutically acceptable base addition salts include those formed when an acidic proton present in the parent compound is replaced by a metal ion, such as sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts and the like. Specific salts are the ammonium, potassium, sodium, calcium, and magnesium salts. Salts derived from pharmaceutically acceptable organic non-toxic bases include, but are not limited to, salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins. Examples of organic bases include isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, hydrabamine, choline, betaine, ethylenediamine, glucosamine, methylglucamine, theobromine, purines, piperazine, piperidine, N-ethylpiperidine, trometbamine, N-methylglucamine, polyamine resins, and the like. Exemplary organic bases are isopropylamine, diethylamine, ethanolamine, trimethylamine, dicyclohexylamine, choline, and caffeine. [0082] "Prodrug" refers to compounds that are transformed (typically rapidly) in vivo to yield the active ingredient of the above formulae, for example, by hydrolysis in blood. Common examples of a prodrug include, but are not limited to, ester and amide forms of a compound having an active form bearing a carboxylic acid moiety. Examples of pharmaceutically acceptable esters of the compounds of this invention include, but are not limited to, alkyl esters (for example with between about one and about six carbons) the alkyl group is a straight or branched chain. Acceptable esters also include cycloalkyl esters and arylalkyl esters such as, but not limited to benzyl. Examples of pharmaceutically acceptable amides of the compounds of this invention include, but are not limited to, primary amides, and secondary and tertiary alkyl amides (for example with between about one and about six carbons). 26 [00831 "Metabolite" refers to the break-down or end product of a compound or its salt produced by metabolism or biotransformation in the animal or human body; for example, biotransformation to a more polar molecule such as by oxidation, reduction, or hydrolysis, or to a conjugate (see Goodman and Gilman, "The Pharmacological Basis of Therapeutics" 8.sup.th Ed., Pergamon Press, Gilman et al. (eds), 1990 for a discussion of biotransformation). As used herein, the metabolite of a compound of the invention or its salt may be the biologically active form of the compound in the body. In one example, a prodrug may be used such that the biologically active form, a metabolite, is released in vivo. In another example, a biologically active metabolite is discovered serendipitously, that is, no prodrug design per se was undertaken. An assay for activity of a metabolite of a compound of the present invention is known to one of skill in the art in light of the present disclosure. 10084] "Treating" or "treatment" of a disease, disorder, or syndrome, as used herein, includes (i) preventing the disease, disorder, or syndrome from occurring in a human, i.e. causing the clinical symptoms of the disease, disorder, or syndrome not to develop in an animal that may be exposed to or predisposed to the disease, disorder, or syndrome but does not yet experience or display symptoms of the disease, disorder, or syndrome; (ii) inhibiting the disease, disorder, or syndrome, i.e., arresting its development; and (iii) relieving the disease, disorder, or syndrome, i.e., causing regression of the disease, disorder, or syndrome. As is known in the art, adjustments for systemic versus localized delivery, age, body weight, general health, sex, diet, time of administration, drug interaction and the severity of the condition may be necessary, and will be ascertainable with routine experimentation by one of ordinary skill in the art. Embodiments of the Invention [00851 One embodiment (A) of the invention is directed to a compound of Formula I where W', W 2 , W 3 , and W 4 are -C(R')=; or one or two of W', W 2 , W 3 , and W 4 are independently -N= and the remaining are -C(R)=; where each R1 is independently hydrogen, alkyl, haloalkyl, nitro, alkoxy, haloalkoxy, halo, hydroxy, cyano, amino, alkylamino, or dialkylamino; and all other groups are as defined in the Summary of the Invention. Specifically, W1, W 2 , W 3 , and W 4 are -C(R')= and each R' is independently hydrogen or alkyl; or one of W1 and W 4 is -N= and the other is -C(H)=. More specifically, W1, W 2 , W 3 , and W 4 are -C(R')= where each R1 is independently hydrogen or alkyl. Even more specifically, R 1 is hydrogen. 27 [0086] Another embodiment (B) of the invention is a Compound of Formula I where Rso is hydrogen, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, hydroxy, alkoxy, alkenyloxy, haloalkoxy, nitro, amino, alkylamino, dialkylamino, -N(R 5 5

)C(O)C

1

-C

6 -alkylene N(Rssa)Rssb, alkylcarbonyl, alkenylcarbonyl, carboxy, alkoxycarbonyl, cyano, alkylthio,

-S(O)

2 NRsRssa, or alkylcarbonylamino; where R 5 and Rssb are indepedently hydrogen, alkyl, or alkenyl and R55a is hydrogen, alkyl, alkenyl, hydroxy, or alkoxy; and all other groups are as defined in the Summary of the Invention. Specifically, R is hydrogen. [00871 Another embodiment (C) of the invention is a Compound of Formula I where

R

51 is hydrogen or alkyl; and all other groups are as defined in the Summary of the Invention. Specifically, R 51 is alkyl, More specifically, R5 1 is methyl. [0088] Another embodiment (D) of the invention is a Compound of Formula I where

R

52 is hydrogen or halo; and all other groups are as defined in the Summary of the Invention. Specifically R 5 2 is hydrogen or fluoro. More specifically, R 2 is hydrogen. [0089] Another embodiment (E) of the invention is a Compound of Formula I where Rs 3 is hydrogen, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, hydroxy, alkoxy, alkenyloxy, haloalkoxy, nitro, amino, alkylamino, dialkylamino, -N(R 3

)C(O)-C-C

6 -alkylene N(Rssa)RSWb, alkylcarbonyl, alkenylcarbonyl, carboxy, alkoxycarbonyl, cyano, alkylthio,

-S(O)

2 NRRssa, or alkylcarbonylamino; where R 5 and R sb are indepedently hydrogen, alkyl, or alkenyl and Rssa is hydrogen, alkyl, alkenyl, hydroxy, or alkoxy; and all other groups are as defined in the Summary of the Invention. Specifically, R 3 is hydrogen, alkoxy, nitro, amino, or -N(R")C(O)_-C-alkylene-N(Ra)R75b. More specifically, R 5 ' is hydrogen, methoxy, nitro, amino, or -NHC(Q)CH 2

N(CH

3

)

2 . Even more specifically, R 53 is hydrogen or methoxy. [00901 Another embodiment (F) of the invention is a Compound of Formula I where R 4 is hydrogen, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, hydroxy, alkoxy, alkenyloxy, haloalkoxy, nitro, amino, alkylamino, dialkylamino, -N(R" 5 )C(O)-Ci-C 6 -alkylene N(Rea)Rb, alkylcarbonyl, alkenylcarbonyl, carboxy, alkoxycarbonyl, cyano, alkylthio,

-S(O)

2

NR

5 Rssa, or alkylcarbonylamino; where R 5 5 and R5 5 b are indepedently hydrogen, alkyl, or alkenyl and R 5 5a is hydrogen, alkyl, alkenyl, hydroxy, or alkoxy; and all other groups are as defined in the Summary of the Invention. Specifically, R 54 is hydrogen, alkyl, alkoxy, or halo. More specifically, RM 4 is hydrogen, methyl, methoxy, bromo, or chloro. Even more specifically, R 54 is hydrogen, methoxy, or chloro. 100911 Another embodiment (G) of the invention is directed to a compound of Formula I where R 30 , R 2 , and R are hydrogen and R 4 is halo or alkoxy; R, li 2 , and R7 4 are 28 hydrogen and R 53 is alkoxy; or R 5 ' and R 2 are hydrogen and R 3 and R 4 together with the carbons to which they are attached form a 6-membered heteroaryl; and all other groups are as defined in the Summary of the Invention. More specifically, R 50 , R, and R" are hydrogen and R 4 is chloro or methoxy; RI 0 , R1 2 , and R1 4 are hydrogen and R 53 is methoxy; or R 0 and R 5 are hydrogen and R 5 and R 4 together with the carbons to which they are attached form pyridinyl. Even more speicfically, RsO, Rs 2 , and R53 are hydrogen and R 4 is chloro or methoxy; or R, R 52 , and R 54 are hydrogen and R 3 is methoxy. [0092] In a more specific embodiment (G) of embodiment G is a compound of Formula I where R 51 is methyl. [0093] Another embodiment (H) of the invention is a compound of Formula I where B is phenyl substituted with R 3 a and optionally further substituted with one, two, or three R 3 ; and all other groups are as defined in the Summary of the Invention. Specifically, B is phenyl substituted with Ra. More specifically the Compound is of Formula I(a):

R

52 R)a OR 51 WW N NH R 3 a :11 Vvo (RN o 0 1(a). Even more specifically, B is phenyl substituted with Rsa as depicted in Ia and is not further substituted with R 3 . [0094] Another embodiment of the Invention (J) is directed to a compound of Formula I where. B is heteroaryl optionally substituted with one, two, or three R 3 . Specifically, B is thien-3-yl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, oxazolyl, isoxazolyl, pyrrolyl, imidazolyl, pyrazolyl, or thiazolyl, each of which is optionally substituted with one or two

R

3 . More specifically, B is thien-3-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, imidazol-2-yl, pyrrol 2-yl, pyrrol-3-yl, imidazol-4-yl, imidazol-5-yl, pyrazol-3-yl, pyrazol-4-yl, or pyrazol-5-yl, each of which is optionally substituted with one or two R 3 , Even more specifically, B is thien-3-yl, pyridin-3-yl, pyridin-4-yl, isoxazol-4-yl, or pyrazol-4-yl, each of which is optionally substituted with one or two R 3 . Yet even more specifically, B is pyridin-3-yl, 29 2-hydroxy-pyridin-5-yl, isoxazol-4-yl, or pyrazol-4-yl, each of which is optionally substituted with one or two W 3 . [00951 Another embodiment (K) provides a compound of Formula I or la where R 3 a is cyano; hydroxyamino; carboxy; alkylsulfonyl, aminoalkyloxy; alkylaminoalkyloxy; dialkylaminoalkyloxy; -NeCO-lC-lkln-o'W ) -C(Q)NIRa; -NRC(o)R"a; -CONR)C-6alyeeNRo) 10;NRIJc(o)NRllaRIlb where Rila;

-C(O)R

12 ; -NRl 3 C(O)OR"a; -C(O)N(R 4

)N(RI

4 a)(RI 4 b); -S(O) 2 N(Rl)-C 1

_C

6 -alkylene

N(RI

5 a)R1sb; -C(O)N(Rl)-C.C 6 -alklcyene-C(O)OR 1 6 "; heteroaryl optionally substituted with one or two aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; -N(R 1 7 )_

C(--NR

7 b)(Rl 7 a))(NR 7

GR

7 d); -N(I')C(O)-C 1

_C

6 _alkyleneN(IRllb)C(O)Rla; -C(O)N(R 19

)

CI-C

6 -alkylene-C(O)R 9 a; -N(R2)C(O)-C l-C 6 -alkylefle-N(RPTh-N(R 22 c)(R 22 a); -CO.C 6 alkylene-NR 23 )-Ci.C 6 -alkYlenN( 23 b)R 23 a; or _NR 24 C(O)-C 1.C 6 -alkylene-OR 24 ; where each of the alkylene in R 3 ' is independently optionally futher substituted with 1, 2, 3, 4, or ,5 groups selected from halo, hydroxy, amino, alkylamino, and diaklainino; and all other groups are as defined in the Summary of the Inv ention. 100961 Specifically, W'a is -NHC(O)CH 2

NII(CH

3 ), -NHC(Q)C11 2 N1(CH 2

CH

3 ),

-NHC(O)CH(CH

3 )N1 2 , -NHC(O)C(CH 3

)

2 N1 2 , -NHC(O)CH 2

N(CH

3

)

2 ,

-NHC(O)CH

2

N(CH

3

)CH

2

CH

2

N(CH

3

)

2 , -NHC(O)CH(N1 2

)CH

2

CH

3 ,

-NIIC(O)CH

2

N(CH

3

)CH

2

CH

2

N(CH

3

)

2 , -NHC(O)CH(CH 3 )NI(C1 3 ), -NHC(O)CH 2 NI4 2 , -NHC(O)H, -NHC(O)CH 2 (azetidin-1 -yl), -NI{C(O)qpyrrolidin-2-yl), .. NHC(O)CH(N11 2

)CH

2 OH, -NI{C(O)(azetidin-4-yl), -NHC(O)C(CH 3

)

2 N11(CH 3 ), -NH 2 ,

-NHC(O)CH

2

NH(CH

2 CHzCH 3 ), -NIIC(O)CH 2

CH

2

NH

2 , -NHOH, -NHC(O)(piperidin-3-yl), -NHC(O)C11 2 (4-methyl- 1,4-diazepan-1 -yl), -NIJC(O)CH(NH 2

)(CH

2

CH

3 ),

-NHC(O)CH

2

NH(CH

2

CH(OH)(CH

3 )), -NHC(O)CH 2

NHCH

2

CH

2 F,

-NHC(O)CH

2

NH-(OCH

2

CH(CH

3

)

2 ), -NHC(O)(1 -aminocycloprop-1 -yl),

-NHC(O)CH

2

NH-(CH

2 cyclopropyl), -NHC(O)C11 2 (3-(dimethylamino)-azetidin- l-yl), .NHC(O)(piperidin-2-yl), -NHC(O)(morpholin-4-yl), -N-HC(O)CH 2 (pyrrolidin-1 -31),

-NHC(O)CH(NH

2

)CH

2

CH

2

CH

2

CH

2

N(CH

3

)

2 , -NHC(O)CH 2

N(CH

3

)(CH

2

CH

3 ), -NIIC(O)C11 2 (imidazol-5-yl), -NHC(O)(1 -aminocyclopent-1 -yl),

-NIIC(O)CH

2

NII(CH

2

CH(CH

3

)

2 ), -NHC(O)CH 2

N(CH

3

)(CHZCH

3 ), -NHC(O)(N-(iniidazol 4-ylmethyl)-azetidin-3-yl), -NHC(Q)(N-ethyl-azetidin-3-yl),

-NIICH

2

N(CH

3

)CH

2

CH

2

N(CH

3

)

2 , -NHC(O)CH 2 N(C11 3 )(N-methyl-pyrrolidin-3-yl),

-NIIC(O)CH

2 N(C11 3

)(CH

2

CH

2

N(CH

3

)

2 ), -NHC(O)CH 2 (3-hydroxy-pyrrolidin-1 -yl), -NIIC(O)(1-amino-cyclobut-1 -yI), -NIIC(O)CH 2

NIJ(CH

2

)

3

CH

3 , .. NHC(O)CH2(3-piperidin 30 1-ylazetidin-lyl), -NTIC(O)NH 2 , -NHC(O)(1-hydroxycyclopropyl),

-NHC(O)CH

2 NH-N(C1 3

)

2 , -N[{C(O)NH(CH2)N(CH 3

)

2 , -NHC(O)CH 2 OH, -NHC(O)(pyridazin-4-yl), -NHC(O)(N-methyl-piperidin-4-yl), -NHC(O)CH 2

NHCH(CH

3

)

3 , -NHC(O)C11 2 (3-dimethylamino-pyrrolidin- lyl), -NIIC(O)CH 2

NH(CH

2

)

2

N(CH)

2 , -NHC(O)(1 -cyclopropylmethyl-azetidin-3-yl), -NHC(O)CH 2

NH(CH

3

)

3 , -NIIC(O)(hmidazol-2-yI), -NHC(O)(imidazol-4-yl), -NHC(O)(1 ,2-oxazol-5-yl),

-NHC(O)CH

2

NHCH

2

CF

3 , -NH C(O)CH 2

CH

2 (piperidin- l-yl), .- NHC(O)(3-oxo-cyclopent- 1 yl), -NHC(O)(2-hydroxy-pyridin-6-yl), -NHC(O)CH 2 NH(3-fluoro-4-hydroxyphenyl),

-NHC(O)(CH

2

)

3

N(CH

3

)

2 , -NHC(O)(1 -(furan-2-ylmethyl)-azetidin-3-yl), -NHC(O)(pyriniidin-5-yl), -NHC(O)(pyrrol-2-yl), -NHC(O)CH 2

N(CH

3

)CH(CH

3

)

2 ,

-NHC(O)CH

2

N(CH

2

CH

3

)

2 , -NHC(O)CH 2 (3-methyl-1 ,2-oxazol-5-yl),

-NHC(O)CH

2

NHCH

2 (3-hydroxyphenyl), -NHC(O)(N-methyl-pyrrol-2-yl), -NIIC(O)(2 amino-tetrahydropyran-2-yl), -NHC(O)CH 2 (4-methylamino-piperidin-1 -yl), -NHC(O)(piperidin- 1-yl), -NHC(O)(N-methyl-pyrrolidin-2y), -NHC(O)(thien-3y1), -NHC(O)(N-(cyclopropylcarbonyl)azetidin-3-yl), -NIIC(O)C11 2 (4-methylpiperazin-1 -yl), -NHC(O)(NV-benzylazetidin-3-yl), -NHC(O)(2-chloro-pyridin-3-yl), -NHC(O)CH 2 (pyridin 4 -y 1 ), -NHC(O)CH 2 N(C1 3

)(CH

2

CH=CH

2 ), -NHC(O)CH 2 NH(benzyl), -NHC(O)CH 2

OCH

3 , -NHC(O)[1 -(C(O)CH 2

CH

3 )-azetidin-3-yl], -NIIC(O)(pyridixi-3-yl),

-NIIC(O)CH

2

NIICH

2

CH

2

OCH

3 , -NIIC(O)(1-[C(O)C113]piperidin-4-yl), -NHC(O)C11 2 (2 methyl-pyrrolidin-1-yl), -NIIC(O)(furan-3-yl), -NIIC(O)CH 2

N(CH

3

)

2 , -NIIC(O)(2-chloro pyridin-5-yl), -NIIC(O)(2-chlorophenyl), -NHC(O)C11 2 (pyridin-2-yl), -NHC(O)CH 2 (3 dimethylamino-azetidin-1I-yl), -NHC(O)CH 2 (pyridin-3-yl), -NHC(O)CH 2 (2-cblorophenyl),

-NHC(O)CH

2 N(C1 3

)CH

2

CH

2

CH

2

N(CH

3

)

2 , -NHC(O)C1 2

N(CH

2

CH

3

)CH

2

CH

2 OH,

-NHC(O)CH

2 (2-benzyl-pyrrolidin-1-yl), -NHC(O)(furan-2-yl, -NHC(O)(2-chloro-pyridin 4-yl), -NHC(O)CH 2

NHC(O)CI-

3 , -NHC(O)CH 2

CH

2

CH

3 , -NHC(O)(4-chlorophenyl), -NHC(O)(4-methiyl-phenyl), -NHC(O)CH 2

NHC(O)O(CH

3

)

3 , -NHC(O)(benzo[dJ[ 1,3]dioxol-5-yl), -NIIC(O)CH 2

NIIOCH

2 (2-methoxyphenyl), -NHC(O)(pyridin-4-yl), -NHC(O)CH 2 [4-(3,4-dichlorophenyl)-piperazin-1 -yl],

-NHC(O)CH

2

CH

2 (pyridin-3-yI), -NHC(O)(tetrahydrofuran-3-yl), -NHC(O)CH 2

NHCH

2 (2 methYiphenYl), -NHC(O) CH(CH 3

)CH

2 CH3, -NHC(O)C11 2 (3-fluorophenyl),

-NHC(O)CH

2 C(C11 3

)

2 Phenyl, -NHC(O)(2-methyl-cyoloprop- 1-yl), -NHC(O)(2-methyl 4-methoxyphenyl), -NHC(O)(2-methylpyridin-3-yl), -NHC(O)(4-methoxyphenyl), -NH-C(O)CH2(4-ethylpiperazin- 1-yl), -NHC(O)(thien-2-yl), -NHC(O)(3-fluoro-2 methyiphenyl), -NIIC(O)(2-bromo-tbien-3-yl), -NHC(O)(4-fluorophenyl), -NHC(O)CH 2 (3 31 methylpiperidin-1 -yl), -NHC(Q)CH(CH 3

)

2 , -NHWC (O)(CH 2

)

3

CH

3 , -NHC(O)CH 2

OCH

2

CH

3 ,

-NI{C(O)CH

2 NII(2-fluorophenyl), -NHC(O)(3-dimethylaminophenyl), -NIIC(O)CH 2 (4. methylpiperidin-1 -yl), -NHC(O)CH 2 N-H(2..n-propylphenyl), -NHC(O)phenyl, -NHC(O)(pyrazin2-yl), -NHC(O)(3-fluoro-4.methoxyphenyl), -NHC(O)C(CH 3 2C1 2

CH

3 ,

-NHC(O)CH

2 O(4-fluoropheny1), -Nf{C(O)(1 -methylearbonyl-azetidin-3-yI),

-NHC(O)CH

2 NH(4-methylphenyl), -NI{C(O)CH 2 NH(phenyl), -NHC(O)CH 2 (4-allyl piperazin-I -yl), -NHC(O)(2-methylphenyl), -NHC(O)CH 2 CHzOCH 3 , -NHC(O)(3-.methy1 furan-2-yI), -NHC(O)C(CH 3

)

3 , -NHC(O)CH 2 NHObenzyl,

-NHC(O)CH

2 NH(3-chlorophenyl), -NHC(O)cyclobutyl, -N-HC(O)CH 2 (3-methoxyphenyl), -NIHC(O)(1-methylcycloprop-1 -yI), -NHC(O)(3-flurophenyl), -NHC(O)(4-dimethylaniinophenyl), -NHC(O)(3,4-dlichlorophenyl),

-NHC(O)CH

2

NHCH

2 (2-methylthiophenyl), -NHC(O)CH 2 (2-fluorophenyl), 4'JHC(O)CH 2

N(CH

2

CH

3

)CH(CH

3

)

2 , -NHC(O)(thiazol-4-yl), .. NIC(O)CH 2

N(CH

3 )benzyl,

-NHC(O)CH

2

NHCH

2 (tbien-2-yl), -NHC(O)CH 2

NH-CH

2 (pyridin-2-yl), -NHC(O)(3 methoxyphenyl), -NHC(O)CH 2

NHCH

2 (3-chloro-4-methylphenyl),

-NHC(O)CH(CH

3

)CH

2

CH

2

CH

3 , -NH~C(O)CH 2 (4-chlorophenyl), -NHC(O)(3-fluoro-4 methyiphenyl), -NHC(O)C11 2 0(2-methlylphenyl), -NHC(O)CH 2 (cyclohexyl), -NHC(O)(2 phenlyl-r-yeloprop-1 -yl), -NHC(O)(3-chlorophenyl), -NHC(O)CH 2 (2-methoxyphenyl),

-NHC(O)CH

2

CH

2 (3-methoxyphenyl), -NHC(O)CI 2 NII(2-fluoro-4-methyl-phenyl),

-NHC(O)CH

2

NHCH

2 (3-fluoro-phenyl), -NHC(O)CH 2 (4-methioxy-phenyl), -NHC(O)benzyl, -NHC(O)(2,4-dichlorophenyl), -NIIC(O)(3-oxo-cyclohex-1-yl),

-NHC(O)CH

2 NI{(3-fluorophenyl), -N-HC(O)CH 2 (3..chlorophenyl),

-NHC(O)CH

2

NHCH

2 CH(CHs)phenyl, -NHC(O)CH 2

NI{CH

2 (2,4-dimethylphenyl),

-NHC(O)CH

2 (2-methyl-piperidin- 1-yl), -NJIC(O)CH 2 NH(2-methoxyph enyl),

-NHC(O)CH

2 (1 ,2,3,4-tetrahydroisoquinolin-2-yl), -NHC(O)CH 2

CFI

2

CH=CH

2 ,

-NHC(O)CH

2 zNH(2-methylphenyl), ..NHC(O)CH 2 (4-oxo-piperidin-1-yl), -NEIC(O)(2 fluorophenlyl), -NHC(O)CH 2

NHCH(CH

3 )phenyl, -NHC(O)(2-fluoro-6-methoxyphenyl),

-NHC(O)CH

2 NH(2-isopropylphenyl), -NI{C(O)CH 2

CH

2 (2-methoxyphenyl),

-NHC(O)CH

2

CH

2

CH(CH

3

)

2 , .. NIC(O)C11 2 (2-phenlyl-morpholin-4-yI),

-NHC(O)CH

2

CH

2 (4-methioxyphenyl), -NHC(O)CIL 2 N(allyl)cyclopentyl,

-NHC(O)CH

2

N(CH

3

)CH

2

CH

2

OCH

3 , -NHC(O)CH 2

CH

2 C(O)cyclopropyl,

-NHC(O)CH

2 NH(3-tert-butylphenyl), -NHC(O)CH2N(n-propyl)(cyclopropylmethyl),

-NHC(O)CH

2 (2-oxo-cyclopentyl), -NIIC(O)CH 2 NFI(4-chlorophenyl), -NHC(O)CH 2 (4. piperidin-1-ylpiperidin-1 -yl), -NHC(O)CH 2 (4-cyclopentylpiperazin-1 -yl), -NHC(O)C11 2 (2 32 methyiphenyl), -NHC(O)CH 2

NTICI

2 (3-fluoro-6-methylphenyl), -NHC(Q)CH 2 C(C1 3

)

3 ,

-NIIC(Q)CH

2 NH(2-chlorophenyl), -NHC(O)(3-fluoro-6-methylphenyl), -NHC(O)(4-fluoro 3-methylphenyl), .. NIC(O)(2,3-dichlorophenyl), -NHC(O)Cll 2 OphenyI,

-NHC(Q)CH

2 NH(2,3-dimethylphenyl), -NI{C(O)(2-fluoro-5-methylphenyl), -NHC (O)CH 2

NHOCLI

2 (4-rnethylphenyl), -NHC(O)C11 2 (4-isopropylpiperazin-1-yI),

-NHC(O)CH

2 (4-fluorophenyl), -NHC(Q)CH 2 CH(C1 3

)

2 , -NIIC(O)(2-rnethoxy 4-methyiphenyl), -NHC(O)CH2(4-n-propylpiperidin-1 -yI), -NHC(O)CHzO(3 methyiphenyl), -NHC(Q)(tetrahydrofuran-2-yl), .. NHC(O)CH 2 (3-hycroxymethylpiperidin. 1-yl), -NHC(O)(1 -tert-butoxycarbonylpipeicin-2-yl), -NHC(O)CH 2 N(C1 3 )C11 2 (pyridin-3 yl), -NIIC(O)CH 2

N(CH

2

CII

3 )phenyl, -NWC(O)CHzOCH 2

CII

2 00H 3 , -NHC(O)C1 2 C11 2 (cyclopentyl), .. NIC(Q)(2,5-dichlorophenyl), -NFJC(O)C11 2 (4 methylearbonylpiperazin- l-yl), -NHC(Q)(5-fluoro-2-niethoxyphenyl),

-NHC(O)CH

2 N(C1 2 C11 3 )eyclohexyl, -NHC(O)(5-methyl-1 ,2-oxazol-3-yl), -NHC(O)(3 methylpyridin-3-yI), -NHC(Q)(2-methoxypyridin-3-yI), -NHC(O)(3,5-dichlorophenyl),

-NHC(O)CH

2 (thiazolidin3-yl), -NHC(Q)CH 2 (4-[C(O)H]-piperazin-1 -yI), .- NHC(O)CH 2 (2 pyridin-4-ylpiperidin-1-yl), -NHC(O)(2-methoxyphenyl),

-NHC(O)CI

2 N(C1 3

)CH

2

CJJ(CH

3

)

2 , -NIIC(O)C11 2 (4-[C(O)LII-homopiperazin-1-yl), -NEC (O)(1 -phenylcycloprop-1 -yl), .. NHC(O)C11 2 (2,6-dimethylmorpholin-4-yl), NHC(O)C11 2 (2-phenylpyrrolidin-1 -yI), -NHC(O)CH 2 (morpholin-4-yl),

-C(O)NHCI(CH

3

)CH

2

N(CH

3

)

2 , -C(O)NHCHzCHzN(CH 3

)

2 , -C(O)NH(pyrrolidin-3-yl),

-C(Q)NHCI

2 C1 2 (pyrrolidin- 1-yI), -C(Q)NHCH 2

CH

2

NH

2 , -C(O)N(CH 3

)CH

2

CH

2

N(CH

3

)

2 ,

-C(Q)NHCII

2 (piperidin-2-yI), -C(O)NH(l-methylazetidin-3-yl),

-C(Q)NHC~HCH

2 (piperidin-1 -yl), -C(O)NHCI 2

CH

2 N(CH2C1 3

)

2 , -C(O)NHII methylpiperidin-3-yI), -C(O)NII(piperidin-3-yI), -C(O)NHCH 2 (1 -methylpiperilin-3-yl),

-C(O)NHCH

2

CH

2

N(CII

2 CHzOH) 2 , -C(Q)NH(1 -ethylpiperidin-3-yl), -C(Q)NH 2 , -C(O)(3 aminopyrrolidin-1 -yl), -C(O)(3-methylaminopyfrolidin- l-yI), -C(O)OH,

-C(Q)NHCLI

2

CH

2 Qnorpholin-4-Yl), -C(O)NETCH 2 (1 -ethylpyrrolidiri-2-yl), -C(O)(4-ainino 3-oxo-pyrazolidin-1 -yl), -C(O)NI{CH 3 , -C(O)(3-aininoeyclobut-1-yl),

-C(Q)NIICH

2 (pyridin-3-yl), -C(Q)NHCH 2

CH

2 OII, -C(O)NH(3-oxo-pyrazolidin-4-yl),

-NHCH

2

CH

2 (itnidazol-4-yI), -C(O)(3-dirnethylaininopyrrolidin- l-yl),

-C(Q)NHCII

2 (pyridin-4-yl), -C(O)N(C11 3 )(1 -methyl-pyrrolidin-3-yl), -C(O)(3 diethylanainopyrrolidin-1 -yl), -C(O)NH(pyrrol- 1-yl), -C(O)NHCTI 2

CII

2

CH

2 (pyrrolidin-1 yl), -C(O)N(C1 3 )C-1 2 C1-IzCN, -C(O)NHCH 2

CII

2

OCH

3 , -C(O)N(CH2CH 3

)CH

2

CII

2 CN, -C(O)(3-aminopiperidin-1 -yl), -C(Q)NHCH 2

CH

2

CH

2

N(CH

3

)

2 , -C(Q)NH-(morpholin-4-yl), 33 -C(O)NJIN(C1 3

)

2 , -C(O)NHCH 2

CH

2

CH

2 (imidazol- l-yl),

-C(O)NLICH

2

CH

2

CH

2

N(CH

2

CH

3

)

2 , -C(O)NCH 2

CH

2 CNh~, -C(O)NITCH 2

CH

2

C(Q)OCH

3 ,

-C(O)NHCH

2

CH

2

SCH

3 , -C(O)NHCH 2

CH

2

SCH

2

CH

3 , -C(O)(CH 2

CH

3

)CH

2

CH

2

(CH

3

)

2 ,

-C(O)NHCH

2

CH

2

CH

2 (2-oxo-pyrroliclin- Il-yl), -C(O)NIHCH 2

CH

2 (pyridin-4-y1),

-C(O)NHCH

2

CH

2

CH

2

OCH

2

CH

3 , -C(O)NHCH 2

CH

2

CH

2 (morpholin-4-yl)I

-C(O)NHCH

2

CH

2

CH

2

OCH

3 , -C(O)N(CH 3

)CH

2

CH

2

CH

2

(CH

3

)

2 ,

-C(O)NHCH

2

CH

2

CH

2

OCH

2

CH

2

CH

3 , -C(O)N1HCH 2

CH

2

C(O)OCH

2

CH

3 ,

-C(O)NIICH

2

CTA

2

CH

2 00H(0H 3

)

2 , -C(O)NHC(0H 3

)

2 0H 2 (piperidin-1 -yl),

-C(O)N(CH

3

)CH

2

CH

2

CH

3 , -C(O)NH(piperidin-1 -yl), -C(O)NHCH(CH 3

)CH

2

OCH

3 , -C(O)NIIC(C11 3

)

2

CH

2 (morpholin-4-yl), -C(O)(2-dimethylaminomethylpiperidin- Il-yl),

-C(O)NH(CH

2

)

3 0(CH 2

)

3

CH

3 , -C(O)NHCH(CH 3

)(CH

2

)

3

N(CH

2 dH 3

)

2 ,

-C(O)NHC(CH

3

)

2 C(O)(piperidin-1 -yl), -C(Q)(4-miethylpiperazin-l -yl), -C(O)(2-piperidin 1 -ylmethayl-piperidia-1-yl), cyano, -NHCH 3 , -CH(0H 3

)NHCH

2

CH

2 N(C1 3

)

2 ,, -C(O)CH 3 ,

-S(O)

2

NHCH

2

CH

2

N(CH

3

)

2 , -S(O) 2

NH(CH

2

)

3

N(CH

3

)

2 , 5-(NN-dimethylaminomethyl) 1,3 ,4-oxadiazol-2-yl, -NHCI{ 2

CH

2

N(CH

3

)

2 , -N(CH 3

)

2 , -OCH 2

CH

2

N(CH

3

)

2 , -NHC[N(0H 3

)

2 1[=N(CH 3

)

2 ], -OCHF 2 , -S(Q) 2 0H 3 , -OCF 3 , Or -NHC(O)CH 2 (4 dimethylaminopiperidin- l-yl). 10097] In a more specific embodiment (L), the compound of Formula I or la is that where RWais hydroxyamino, -NR)()C-6-keeNe() -C(O)NRR a

-NR

9

C(O)R

9 a, -CONR)C-6akieNR~)Ib -NR''c(O)NR' laRilb, _NW)()C.6aklnp~)Nec(C,) _NR I1C(O)OR 13 a, _N(R' 8

)C(O)-C

1

-C

6 allcylene-N(Rl8b)C(O)Rlaa , _NR 24 C(O)_C I..C 6 alkYlene-OR 2 a, Or -N(R 20

)C(O)-C

1

-C

6 alkylene-C(O)ROa; where each of the alkylene in Wsa is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, and amino; and all other groups are as defined in the Summary of the Invention. Specifically, W"a is

-NHC(O)CH

2 NH(0H 3 ), -NIIC(O)CH(CH 3

)NH

2 , -NHC(O)C(CH 3

)

2 N1l 2 ,

-NHIC(Q)CH

2

N(CH

3

)

2 , -NHC(O)CH 2

(CH

3

)CI

2

CI

2

N(CH

3

)

2 , -NIIC(O)CH(NH 2

)CH

2

CH

3 ,

-NHC(Q)CH

2

N(CH

3

)CH

2

CH

2

N(CH

3

)

2 , -NHC(O)CII(CH 3

)N{(CH

3 ), -NHC(O)H,

-NHC(Q)CH

2 (azetidin-1-yl), -NJ*C(O)(pyrrolidin-2-yl), -NHC(O)CH(N11 2

)CH

2 OH, -NHC(Q)(azetidin-4-yl), -NIIC(O)C(CH 3

)

2

NH(CH

3 ), -NH 2 ,

-NHC(O)CH

2

NU(CH

2

CH

2

CH

3 ), -NHC(O)CH 2

CI

2

N{

2 , -NHOH, or -NHC(O)(piperidin-3 yl). 100981 In a more specific embodiment (No the compound is of Formula I or la and W 3 8

-N(R

7 )C(O)-C -C 6 -allene-N(R 7 a)(R1h); and R7 is hydrogen or alkyl and R7' and R 7 b are 34 independently hydrogen, alkyl, aminoallcyl, alkylaminoalkyl, or dialkylaniinoalkyl; and all other groups are as defied in the Summary of the Invention. More specifically, R 3 a is .- NI{C(O)CH 2

NTI(CH

3 ), -NHC(O)CI(CH 3

)NH

2 , -NHC(O)C(CH 3

)

2

NH

2 ,

-NH~C(O)CH

2

N(CH

3

)

2 , -NHC(O)CH 2

N(CH

3

)CII

2

CH

2

N(CH

3

)

2 , -NHC(O)CH(NH 2

)CH

2

CH

3 ,

-NHC(O)CH

2

N(CH

3

)CH

2

CH

2 N(C1 3

)

2 , or .- NHIC(O)CH(CH 3

)NH(CH

3 ). 10099] Embodiment (N) provides a compound of Formula I where each R3~ is independently halo; cyano; alkyl; ailkenyl; alkoxy; hydroxyamino; carboxy; ailcylsulfonyl, aminoalkyloxy; alkylaminoalkyloxy; dialkylaminoalkyloxy; -N(R 7 )C(O)-Cl-C 6 -alkylene N(RWa)(R7h); -C(Q)NRB~; -NR!C(O)Ra; -CONR)C-6ayceNRRO -NR1"c(oYNR1 R11 where R' 1a; _C(O)R 12 ; -NR 1 3 C(O)QR1 3 a; _C(O)N(Rl 4 )N(Rl1a)q(l1b); -S02("-lC-lyeeNRs) "b C(O)N(RI 6 )-Ci..C 6 -alkylene-C(O)OR 1 6 ; heteroaryl optionally substituted with one or two aminoalkyl, alkylaminoalkyl, or dialkylaMinoalkyl; _N(Rl 7 )_C(=-N(Rl 7 b)(R 1 7 a))(NR 7 c'R 7 d); -N(R' 8 )C(O)-Cl-C 6 -alkylene-' N(R' Sb)C(O)RlSa ; -CONR)C-6al~eeCORa _N(R 22 )C(O)-C i.C 6 -alkylene N(Rllb)_N(R 22 WXfa); -Co..C 6 -akylene-N(R 23 )-C-C-akyeneN(R 2 1~)R 3 "; or -NR 24 C(O)_

CIC

6 -alkylene-QR 2 4 a; where each of the alkylene in R3~ is independently optionally ffirther substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, amino, alkylamino, and dialkylamino; and all other groups are as defined in the Summary of the Invention. [001001 Specifically, each R3~ is independently methyl, bromo, chioro, fluoro,

-NUC(O)CH

2

NH(CH

3 ), -NHC(O)CH 2

NI{(CH

2

CH

3 ), -NHC(O)CH(CH 3

)NH

2 ,

-NHC(O)C(CH

3

)

2

NW

2 , -NHC(O)CH 2

N(CH

3

)

2 , -NHC(O)CH 2

N(CH

3

)CH

2

CII

2

N(CH

3

)

2 ,

-NHC(O)CH(NH

2

)CH

2

CH

3 , -NFIC(O)CH- 2

N(CH

3

)CH

2

CII

2

N(CH

3

)

2 ,

-NHC(O)CH(CH

3

)NIJ(CH

3 ), -NHC(O)CH 2

NH

2 , -NHC(O)H, -MIC(O)CH 2 (azetidin-1-yl), .. NHC(O)(pyrrolidin-2-yl), -NHC(O)CH(NH 2

)CH

2 OH, -NHC(O)(azetidin-4-yl),

-NHC(O)C(CH

3

)

2

NH(CH

3 ), -NH 2 , -NHC(O)CH 2

NH(CH

2

CH

2

CH

3 ), -NH-C(O)CH 2

CH

2

NH

2 , -NHOH, -NHC(O)(iperidin-3-y), -NHC(O)CH 2 (4-methyl-1I,4-diazepan-1 -yl), -NI{C(O)CH(N11 2

)(CH

2

CH

3 ), -NHIC(O)CH 2

NH(CH

2

CH(OH)(CH

3 )),

-NHC(O)CH

2

NHCH

2

CII

2 F, -NHC(O)CII 2

NH(OCH

2

CH(CH

3

)

2 ), -NI C(O)(l aminocycloprop-1 -yl), -NHC(O)CH 2 NH(Cll2cyclopropyl), -NEC(O)CH 2 (3 (dixnethylamino)-azetidin-1 -yl), -NHC(O)(piperidixi-2-yl), -NHC(O)(morpholin-4-yl), -NHC(O)CH2(pyrrolidin-1 -yI), -NI{C(O)CH(N11 2

)CH

2

CH

2

CH

2

CH

2

N(CH

3

)

2 ,

-NHC(O)CH

2

N(CH

3 )(CH2CH 3 ), -NHC(O)CH2(imidazol-5-yl), -NHC(O)( 1 arminocyclopent- 1-yl), -NHC(O)CH 2 NHi(CH2CH(CH 3

)

2 ), -N-HC(O)CH 2

N(CH

3

)(CH

2

CH

3 ), -NI{C(O)(N-(imidazol-4-ylmethyl)-azetidin-3-yl), -NHC(O)(N-ethyl-azetidin-3-yl), 35

-NHCH

2

N(CH

3

)CH

2

CH

2

N(CH

3

)

2 , -N}IC(O)CH 2

N(CH

3 )(N-miethiyl-pyrrolidin-3-yl),

-NE{C(O)CH

2

N(CH

3

)(CH

2

CH

2 N(C H 3

)

2 ), -NHC(O)CH 2 (3-hydroxy-pyrrolidin-1 -yl), -NIIC(O)(1-amino-cyclobut-1 -yl), -NHC(O)CH 2

NFI(CH

2

)

3

CH

3 , -NIHC(O)CH 2 (3-piperidin 1-ylazetidin-lyl), -NIIC(O)NH 2 , -NHC(O)(1-hydroxycyclopropyl),

-NHC(O)CH

2

NHN(CH

3

)

2 , -NTLC(O)NH(CH 2

)

2

N(CH

3

)

2 , -. NHC(O)CH 2 OH, -NHC(O)(pyridazin-4-yl), -NHC(O)(N-methyl-piperidin-4-yl), -NHC(O)CH 2

NHCH(CH

3

)

3 ,

-NHC(O)CH

2 (3-dimethylaimino-pyrrolidin-lyl), -NHC(O)CH 2

NH(CH

2

)

2

N(CH

3

)

2 , -NHC(O)(1-cyclopropylmethyl-azetidin-3-yl), -NHC(O)CH 2

NE{(CH

3

)

3 , -NUC(O)(imidazol-2-yl), -NHC(O)(imidazol-4-yl), -NHC(O)(1,2-oxazol-5-yl),'

-N}{C(O)CH

2

NHCH

2

CF

3 , -NHC(O)CHzCH 2 (piperidin- l-yl), -NI{C(O)(3-oxo-cyclopent- 1 yl), -NHC(O)(2-hydroxy-pyridin-6-yl), -NHC(O)CH 2 NH(3-fluoro-4-hydroxyphenyl),

-NHC(O)(CH

2

)

3

N(CH

3

)

2 , -NHC(O)(1-(fUran-2-ylmethyl)-azetidin-3-yl), -NHC(O)(pyrimidin-5-yl), -NHC(O)(pyrrol-2-yl), -NHC(O)CH 2

N(CH

3

)CH(CH

3

)

2 ,

-NHC(O)CH

2

N(CH

2

CH

3

)

2 , -NIIC(O)CH 2 (3-methyl-1 ,2-oxazol-5-yl), -N'HC(O)CHaNHCH 2 (3-hydroxyphenyl), -NHC(O)(N-methyl-pyrrol-2-yl), -NHC(O)(2 amino-tetrahydropyran-2-yi), -NHC(O)CH 2 (4-methylamino-piperidin-1-yl),, -NHC(O)(piperidin-1-yi), -NHC(O)(N-methyl-pyrrolidin-2y1), -NHC(O)(thien-3y1), -NIIC(O)(N-(cyclopropylcarbonyl)azetidin-3-y), -NHC(O)CH 2 (4-rnethylpiperazin-1 -yl), -NHC(O)(N-benzylazetidln-3-yl), -NHC(O)(2-cbloro-pyridin-3-yl), -NHC(O)CH 2 (pyridin 4-yl), -NI{C(O)CH 2

N(CH

3

)(CH

2 CJ4=0H 2 ), -NHC(O)CH 2 NH(benzyl), -NI{C(O)CH 2

OCH

3 , -NHC(O)[1 -(C(O)CH 2

CH

3 )-azetidin-3-yl], -NHC(O)(jpyridin-3-yl),

-NHC(O)CH

2

NI{CH

2

CH

2

OCH

3 , -NHC(O)(1 -[C(O)CH 3 ]piperidin-4-yl), -NHC(O)CH 2 (2 methyl-pyrrolidin-1 -yl), -NMC(O)(furan-3-yl), -NIIC(O)CH 2

N(CH

3

)

2 , -NHC(O)(2-chloro pyridin-5-yl), -NHC(O)(2-cbloroplienyl), .. NIC(O)CH 2 (pyridin-2-yl), -NHC(O)CH 2 (3 dimethylaniino-azetidin- l-yl), -NHC(O)CH 2 (pyridin-3-yl) -NHC(O)CH 2 (2-cblorophenyl),

-NHC(O)CH

2

N(CH

3

)CH

2

CH

2

CH

2

N(CH

3

)

2 , -NHC(O)CH 2

N(CH

2

CH

3

)CH

2

CH

2 oH, -NIIC(O)CH2(2-benzyl-pyrrolidin-1 -yl), -NHC(O)(furan-2-yI, -NHC(O)(2-thloro-pyridin 4 -yl), -NI{C(O)CH 2

NI{C(O)CH

3 , -NHC(O)CH 2

CH

2

CH

3 , -NHC(O)(4-cblorophenyl), -NHC(O)(4-methyl-phenyl), -NHC(O)CH 2

NHC(O)O(CH

3

)

3 , -NHC(O)(benzo[d][1 ,3ldioxol-5-yl), -NHC(O)CH 2

NIIOCH

2 (2-methoxyphenyl), -NHC(O)(pyridn-4-yl), -NHC(O)CH 2 [4-(3,4-dichlorophenyl)-piperazin-1-yl], -NHC(O)CHzCH 2 (pyridin-3-yl), -NHC(O)(tetrahydrofuran-3-yi), -NHC(O)CH 2

NFICH

2 (2 methyiplienyl), -NHC(O)CH(CH 3

)CH

2

CH

3 , -NHC(O)CH2(3-fluorophenyl), -NHC(O)CH2C(CH 3

)

2 phenyl, -NHC(O)(2-methyl-cycloprop-1 -yI), .. NHC(O)(2-methyl 36 4.-methoxyphenyl), -NIIC(O)(2-methylpyridin-3-yl), -NHC(O)(4-methoxyphenyl), -NHC(O)C11 2 (4-ethylpiperazin-1-yl), -NHC(O)(thien-2-yl), -NIIC(O)(3-fluoro-2 methyiphenyl), -NHC(O)(2-bromo-thien-3-yl), -NHC(O)(4..fluorophenyl), -NHC(O)CH 2 (3 methylpiperidin-1 -yl), -NHC(O)CH(CH 3

)

2 , -N1IC(O)(CH 2 )3CH 3 , -NIIC(O)CH 2

OCI

2

C-

3 ,

-NHC(O)CH

2 MI(2-fluorophenyl), -NHC(O)(3-dimethylaminophenyl), -NHC(O)CH 2 (4 methylpiperidin-1 -yl), -NHC(O)CH 2 NH(2-n-propylphenyl), -NHC(O)phenyl, -NHC(O)(pyrazin2-yl), -NEIC(O)(3-fluoro-4..methioxypheniyl), -NHC(O)C(11 3

)

2

CH

2

CH

3 ,

-NHC(O)CH

2 0(4-fluorophenyl), -NHlC(O)(1 -methylcarbonylkazetidin-3-yl),

-NHC(O)CH

2 NEI(4-methylphe~nyl), -NI{C(O)CH 2 NiI(phenyl), -NHC(O)CH 2 (4-al]Yl piperazin-1 -yl), -NIIC(O)(2-methylphenyl), -NHC(O)CH 2

CH

2

OCH

3 , -NHC(O)(3-methyl furan-2-yl), -NIIC(O)C(CH 3

)

3 , -NH4C(O)CH 2 NilObenzyl,

-NHC(O)CH

2 NH(3-cblorophenyl), -NHC(O)cyclobutyl, -NHC(O)CH 2 (3-methoxyphenyl), -INHC(O)(1-methylcycloprop-1-yl), -NHC(O)(3-flurophenyl), -NHC(O)(4-dimethylaminophenyl), -NHC(O)(3,4-dichlorophenyl),

-NHC(O)CH

2

NHCH

2 (2-methylthiophenyl), -NHC(O)CH 2 (2-fluorophenyl),

-NIIC(O)CH

2

N(CH

2

CH

3

)CH(CH

3

)

2 , -NIIC(O)(thiazol-4-yl), -NH-C(O)CH 2 N(C11 3 )benzyl,

-NHC(O)CH

2

NHCH

2 (thien-2-yl), -NIIC(O)CH 2

NHCH

2 (pyridin-2-yl), -NHC(O)(3 methoxyphenyl), -NHC(O)CH 2

NHCH

2 (3-chloro-4-methylphenyl),

-NIIC(O)CH(CH

3

)CH

2

CH

2

CH

3 , -NUC(O)CH 2 (4-chlorophenyl), -NHC(O)(3-fluoro-4 methyiphenyl), -NHC(O)CH 2 O(2-methylphenyl), -NHC(O)CH 2 (cyclohexyl), -NHC(O)(2 phenyl-cycloprop-1-yl), -NHC(O)(3-cblorophenyl), -NHC(O)CH 2 (2-methoxyphenyl),

-NIIC(O)CH

2

CH

2 (3-methoxyphenyl), -NHC(O)CH 2 NII(2-fluoro-4-methyl-phenyl),

-NHC(O)CH

2

NIICI

2 (3-fluoro-phenyl), -NHC(O)CH 2 (4-methioxy-phenyl), -NIIC(O)benzyl, -NIIC(O)(2,4-dichlorophenyl), -NHC(O)(3-oxo-cyclohex- l-yl),

-NHC(O)CH

2 NH(3-fluorophenyl), -NHC(O)CH 2 (3-cblorophenyl), -NI4C(O)CH 2

NHCH

2

CH(CH

3 )phenyl, -NIIC(O)CII 2

NHCH

2 (2,4-dimethylphenyl), -NHC(O)C11 2 (2-methyl-piperidin-1 -yl), -NIIC(O)CH 2 NH(2-methoxyphenyl),

-N[IC(O)CH

2 (1,2,3,4-tetrahydroisoquinolin-2-yl), -NHC(O)CH 2

CH

2

CH=CH

2 ,

-NIIC(O)CH

2 NH4(2-methylphenyl), -NHlC(O)CH 2 (4-oxo-.piperidin-1-y1), -NHC(O)(2 fluorophenyl), -NH4C(O)CH 2

NHCH(CH

3 )phenyl, -NIIC(O)(2-fluoro-6-methoxyphenyl),

-NHC(O)CH

2 NH(2-isopropylphenyl), -NHC(O)CH 2 CH2(2-methioxyphenyl),

-NHC(O)CH

2

CH

2

CH(CH

3

)

2 , -NIHC(O)CH 2 (2-phenyl-morpholin-4-yl),

-NHC(O)CH

2

CH

2 (4-methoxyphenyl), -NIHC(O)CH 2 N(allyl)cyclopentyl, -NI4C(O)CH 2

N(CH

3

)CH

2

CH

2

OCH

3 , -NHC(O)CH 2

CH

2 C(O)cyclopropyl, 37

-NHC(O)CH

2 NH(3-tert-butylphenyl), -NHC(O)CH2N(n-PropYl)(cYcloPropyhnethYl),

-NI{C(O)CH

2 (2-oxo--cyclopentyl), -NHC(O)CH 2 NH(4-chlorophenyl), -NI{C(O)CH 2 (4 piperidin-1 -ylpiperidin-1 -yl), -N[JC(O)CH 2 (4-cyclopentylpiperazin-1 -y 1 ), -NHC(O)CH 2 (2 methyiphenyl), -NHC(O)CH 2

NIICH

2 (3-fluoro-6-methylphenyl), -INHC(O)CII 2

C(CH

3

)

3 ,

-NHC(O)CH

2 NH(2-chlonophenyl), -NHC(O)(3-fluoro-6-methylpbenyl), -NHC(O)(4-fluoro 3-methyiphenyl), -N}{C(O)(2,3-dichlorophenyl), -NHC(O)CH 2 Ophenyl,

-NHC(O)CH

2 NH(2,3-dimethylphenyl), -NHC(O)(2-fluoro-5-methylphenyl),

-NHC(O)CH

2

NHOCH

2 (4-methylphenyl), -NHC(O)CH2(4-isopropylpiperazin- 1-yl),

-NHC(O)CH

2 (4-fluorophenyl), -NHC(O)CH 2

CH(CH

3 )2, -NHC(O)(2-methoxy 4-methyiphenyl), -NHC(O)CH 2 (4-n-propylpiperidin-1 -yl), -NHC(O)CH 2 O(3 methyiphenyl), -NHC(O)(tetr~hydrofiiran-2-y1), -NHC(O)CH 2 (3-hydroxymethylpiperidin l-yl), -NHC(O)( 1-tert-butoxycarbonylpiperidin-2-yI), -NHC(O)CH 2

LN(CH

3 )C11 2 (pyridin-3 yl), -NHC(O)CH 2

N(CH

2

CH

3 )phenyl, -NHC(O)CH 2

OCH

2

CH

2

OCH

3 ,

-NHC(O)CH

2

CH

2 (cyclopentyl), -NHC(O)(2,5-dicblorophenyl), -NHC(O)CH 2 (4 methylcarbonylpiperazin-1 -yl), -NHC(O)(5-fluoro-2-methoxyphenyl),

-NHC(O)CH

2

N(CH

2

CH

3 )cyclohexyl, -NHC(O)(5-methyl- 1,2-oxazol-3-yl), -NHC(O)(3 methylpyridin-3-yl), -NLIC(O)(2-methoxypyridin-3-yl), -NHC(O)(3,5-dichlorophenyl),

-NHC(O)CH

2 (thiazolidin3 -yl), -NHC(O)CH 2 (4-[C(O)H]-piperazin-1-yl), -NHC(O)CH 2 (2 * pyridin-4-ylpiperidin-1 -yl), -N}{C(O)(2-methoxyphenyl),

-NHC(O)CH

2

N(CH

3

)CH

2

CH(CH-

3

)

2 , -NHC(O)CH 2 (4-[C(O)H]-hoinopiperazin-1-yl), -NHC(O)(1 -phenylcycloprop-1 -yl), -NHC(O)CH 2 (2,6-dimethylniorpholin-4-yl),

NHC(O)CH

2 (2-phenylpyrrolidin- 1-yl), -NHC(O)CH 2 (morpholin-4-yl),

-C(O)NHCH(CH

3

)CH

2

N(CH

3

)

2 , -C(O)NHCHzCH 2

N(CH

3

)

2 , -C(O)N}{(pyrrolidin-3-yl), * C(O)NHCH 2

CH

2 (pyrrolidin-1 -yl), -C(O)NHCH 2

CH

2 NH2, -C(O)N(CH 3

)CH

2

CH

2

N(CH

3

)

2 ,

-C(O)NHCH

2 (piperidin-2-yl), -C(O)NH(1-methylazetidin-3-y), * C(O)NHCH 2

CH

2 (piperidin-1 -yl), -C(O)NHCH 2

CH

2

N(CH

2

CH

3

)

2 , -C(O)NLI methylpiperidin-3-yl), -C(O)N}{(piperidin-3-yl), -C(O)NHCI- 2 (1-methylpiperidini-3-yl),

-C(O)NHCH

2

CH

2

N(CH

2

CH

2

OH)

2 , -C(O)NH(1-ethylpiperidin-3-yl), -C(O)N}{ 2 , -C(O)(3 aininopyrrolidin-1 -yl), -C(O)(3-methylaminopyrrolidin- l-yl), -C(0)0O4,

-C(O)NHCH

2

CH

2 (morpholin-4-yl), -C(O)NHCH 2 (1 -ethylpyrrolidin-2-yl), -C(O)(4-amino 3-oxo-pyrazolidin- l-yl), -C(O)NHCH 3 , -C(O)(3-aminocyclobut-1-yl),

-C(O)NHCH

2 (pyridin-3-yl), -C(O)NHCH 2

CH

2 OH, -C(O)NH(3-oxo-pyrazolidin-4-yl),

-NIICH

2

CH

2 (imidazol-4-yl), -C(O)(3-dimethylaminopyrrolidin- l-yI),

-C(O)NHCH

2 (PYridin-4-Yl), -C(O)N(C11 3 )(1 -methyl-pyrrolidin-3-yl), -C(O)(3 38 diethylaminopyrrolidin- l-yl), -C(O)NH(pyrrol-l -yl), -C(O)NHCH 2

CH

2

CH

2 (pyrrolidin-1 yl), -C(Q)X(CH 3

)CI{

2

CH

2 CN, -C(O)NHCH 2

CH

2 00H 3 , -C(O)N(CH 2

CJI

3

)CH

2

CI{

2 CN, -C(O)(3-aininopiperidin- 1-yl), -C(O)NIICH 2

CH

2

CH

2

N(C{

3

)

2 , -C(O)NII(morpholin-4-yl),

-C(O)NIIN(CH

3

)

2 , -C(O)NHCH 2 CH2CH 2 (imnidazol-1 -yl),

-C(O)NHCH

2

CH

2

CH

2

X(CH

2

CH

3

)

2 , -C(O)NHCH 2

CH

2 CN, -C(O)NHCH 2

CH

2

C(O)OCH

3 ,

-C(O)NHCI{

2

CH

2

SCH

3 , -C(O)NIICH 2

CH

2

SCH

2

CH

3 , -C(O)X(CH 2

CH

3

)CH

2

CH

2

X(CI{

3

)

2 ,

-C(O)NHCH

2

CLI

2

CH

2 (2-oxo-pyrrolidin-1-yl), -C(Q)NIICH 2

CH

2 (pyridin-4-yl), -C(O)NfICL 2

CLI

2

CH

2

OCH

2

CH

3 , -C(Q)NHCH 2

CH

2

CH

2 (Morpholin-4-yl),

-C(Q)NHCH-

2 C1{ 2 C1 2 0CH 3 , -C(O)N(CH 3

)CH

2

CH

2

CLI

2

N(CH

3

)

2 ,

-C(Q)NI{CH

2

CI{

2

CH

2

OCH

2

CH

2

CH

3 , -C(O)NHCH 2

CH

2

C(Q)OCH

2

CH

3 ,

-C(Q)NHCH

2

CH

2

CH

2

QCH(CH

3

)

2 , -C(O)NIIC(CH3) 2

CH

2 (piperidin-1 -yl),

-C(O)X(CH

3

)CH

2

CH

2

CH

3 , -C(O)NII(piperidin-1 -yl), -C(Q)NHCH(CH 3

)CH

2

QCH

3 , -C(O)NHC(CH3) 2

CH

2 (Morpholin-4-yl), -C(O)(2-dimethylaminomethylpiperidin-I -yl),

-C(O)NU(CH

2

)

3 0(CH 2

)

3

CH

3 , -C(O)NHCH(CH 3

)(CH

2

)

3

N(CH

2

CH

3

)

2 ,

-C(O)NHC(CH

3

)

2 C(Q)(piperidin-1 -yl), -C(O)(4-methylpiperazin-1-yl), -C(O)(2-piperidin 1 -ylmethyl-piperidin-1-yl), cyano, -NHCH 3 , -CH(CI{ 3

)NHCH

2

CH

2

N(CH

3

)

2 , -C(O)CH 3 ,

-S(O)

2

NHCH

2

CH

2

X(CH

3

)

2 , -S(O) 2

NH(CH

2

)

3

X(CH

3

)

2 , 5-(NN-dimethylaniinomethyl) 1,3,4-oxadiazol-2-yl, -NHCH 2

CH

2

N(CH

3

)

2 , -N(CH 3

)

2 , -QCH 2 cH 2

N(CH

3

)

2 ,

-MIC[N(CH

3

)

2 ] [=X(CH 3

)

2 ], -OCHF 2 , -CF 3 , -S(O)2C1{3, -OCF 3 , -NJIC(O)CH 2 (4 diniethylaminopiperidin- 1-yl), or methoxy. [00101] In a more specific embodiment (P), the Compound of Formula I is that where each W 3 is independently halo, alkyl, hydroxyamino, -N(R 7 )C(O)-C1-C 6 -alkylene N(Ra)(Re), -C(O)NRR ~N 9 )~, -C(O)N(R 1 0

)-C

1

-C

6 -alkylene N(R0a )RIOb-NRII C(O)NR' IaRI b, _N 2CO_ -6akleeN bOco~ -NR 1 3 C(O)OR1 3 a, -N(R' 8 )C(O)-C I-C 6 -alklene-N(R' 8 b)C(Q)R~a , -NR? 4 C(o)-Cl-C 6 akene-OR? .a, or -NROCO.lC-akln-() a where each of 'the alkylene in R 3 is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, and amino; and all other groups are as defined in the Summary of the Invention. Specifically, each W 3 is independently methyl, chioro, -NHC(O)CH 2

NH(CH

3 ),

-NHC(O)CH(CH

3

)N{

2 , -NI{C(O)C(CH 3

)

2

XH

2 , -NHC(Q)CLI 2

N(CH

3

)

2 ,

-NHC(O)CH

2

N(C{

3

)CH

2

CH

2

N(CH

3

)

2 , -NIJC(O)CH(NH 2

)CH

2

CH

3 ,

-NIIC(O)CH

2

X(CH

3

)CH

2

CH

2

N(CH

3

)

2 , -NHC(O)CH(CH 3 )NH(C1 3 ), -NHC(O)H, -. NHC (0) C12(azeti din-i -yl), -NHC(O)(pyrrolidin-2-yl), -NHC(O)CH(NH 2

)CH

2 0H, -NHC(0)(azetidin-4-yl), -NHC(O)C(CH 3

)

2 NH(CH1 3 ), -NH 2 , 39

-NHC(O)CH

2

NH(CH

2

CH

2

CH

3 ), -NHC(0)CH 2

CH

2

NH

2 , -NHOH, or -NHC(0)(piperidin-3 yl). [001021 In a more specific embodiment (Q), the Compound of Formula I is that where R 3 is alkyl or -N(R7)C(O)-CrC6-alkylene-N(R7a)(R7); and R 7 is hydrogen or alkyl and R 7 ' and R 7 b are independently hydrogen, alkyl, aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; and all other groups are as defined in the Summary of the Invention. More specifically, each R 3 is independently methyl, -NHC(O)CH 2

NH(CH

3 ),

-NHC(O)CH(CH

3

)NH

2 , -NHC(O)C(CH 3

)

2

NH

2 , -NHC(O)CH 2

N(CH

3

)

2 ,

-NHC(O)CH

2

N(CH

3

)CH

2

CH

2

N(CH

3

)

2 , -NHC(O)CH(NH2)CH 2

CH

3 ,

-NHC(O)CH

2

N(CH

3

)CH

2

CH

2

N(CH

3

)

2 , or -NHC(O)CH(CH 3

)NH(CH

3 ). [00103] In another specific embodiment (R), the Compound of Formula I is that where B is phenyl, R? is not present or R 3 is halo, alkyl, or alkoxy; R3a is -C(0)NRRaa

-NR

9

C(O)R

9 a, -N(R)C(O)-CrC6-alkylene-N(a)(R71), or -C(O)N(RIO)-C 1

-C

6 -alkylene N(Rca)R4b where each of the alkylene in Ra is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, and amino; and all other groups are as defined in the Summary of the Invention. [001041 In a more specific embodiment (RI) of embodiment R, the compound is that where Rso, R 2 , and R 3 are hydrogen and R 54 is halo or alkoxy; R 5 , Rs 2 , and R 4 are hydrogen and Rs 3 is alkoxy; or R 50 and Rs 2 are hydrogen and R 53 and R 54 together with the carbons to which they are attached form a 6-membered heteroaryl; and all other groups are as defined in the Summary of the Invention. Specifically, R", R , and R are hydrogen and R5 4 is halo or alkoxy; or R" 0 , R 5 ', and R are hydrogen and R 53 is alkoxy. [001051 In a more specific embodiment of (R2) of embodiment R, the compound is that where R 1 is methyl. [001061 In a more specific embodiment (S), the compound of Formula Ia:

R

53 OR' RNN R"0 0 1(a) 40 is that where R 3 is not present or R 3 is alkyl and R 3 ' is -N(R 7 )C(O)-C-Cs-alkylene

N(R

7 a)(R 7 b), -C(O)NRRa , -NR C(O)Ra, or -C(O)N(R'O)-C1-C6-alkylene-N(Rioa)R' O where each of the alkylene in Ra is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, and amino; and all other groups are as defined in the Summary of the Invention. Specifically, R 3 is is not present or is methyl. More specifically, R 3 is is not present. [001071 In a more specific embodiment (Sl) of embodiment S is that where R 7 is hydrogen or alkyl and R 7 a, and R are independently hydrogen, alkyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; R is hydrogen or alkyl and Ra is heterocycloalkyl or heterocycloalkylalkyl; R 9 is hydrogen or alkyl and R 9 a is hydrogen, heterocycloalkyl, or heterocycloalkylalkyl; and R10, Rioa, and Ri"' are independently hydrogen, alkyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl. [001081 In a more specific embodiment (S2) of embodiment S is that where R 0 , R 52 , and R are hydrogen and R 54 is halo or alkoxy; or R 50 , R 52 , and R 54 are hydrogen and R 53 is alkoxy; or R 50 and R 2 are hydrogen and R 53 and Rm together with the carbons to which they are attached form a 6-membered heteroaryl. Specifically, R", R 2 , and R 3 are hydrogen and R 54 is halo or alkoxy; or R", Rs 2 , and R 54 are hydrogen and R 3 is alkoxy. [00109] In a more specific embodiment of (S3) of embodiment S, the compound is that where R is methyl. [00110] In another specific embodiment (T), the Compound of Formula I is that where B is heteroaryl, one R 3 is halo, alkyl, or alkoxy and a second R 3 is -C(O)NRRa,

-NR

9

C(O)R

9 a, -N(R)C(O)-C1-C6-alkylene-N(R)(RE, or -C(O)N(R 1 0

)-C

1

-C

6 -alkylene N(Rioa)Rob where each of the alkylene in R 3 is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, and amino; and all other groups are as defined in the Summary of the Invention. [00111] In another specific embodiment (Ti) of embodiment T, the compound is that where R 7 is hydrogen or alkyl and R 7 a, and R*b are independently hydrogen, alkyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, -or dialkylaminoalkyl; R is hydrogen or alkyl and R 8 a is heterocycloalkyl or heterocycloalkylalkyl; R 9 is hydrogen or alkyl and R 9 ' is hydrogen, heterocycloalkyl, or heterocycloalkylalkyl; R" 0 , Rioa, and R10b are independently hydrogen, alkyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl. [00112] In another specific embodiment U, the compound of Formula I is that where B is 41 (R)O-2

(R

3

)

0

-

2 (R 3 )- 0R 3 )3 ( -2 N% OH N , 0 or R301 ; each R 3 (when R 3 is present) is independently halo, alkyl, alkoxy, aminoalkyloxy, alkylaminoalkyloxy, dialkylaminoalkyloxy, alkylamino, dialkylamino, -C(O)NRRaa, -NR 9 C(O)Ra, -N(R 7

)C(O)

Co-C6-alkylene-N(Ra)(R7), Or -C(O)N(Rl)-Ci-C6-alkylene-N(Rioa)R'O'; and all other groups are as defined in the Summary of the Invention. [00113] In a more specific embodiment (U1) of embodiment U, the compound of Formula I is that where RsO, Rs 2 , and R 53 are hydrogen and R 4 is halo or alkoxy; R 5 0 , Rs 2 , and R 4 are hydrogen and R 53 is alkoxy; or R 50 and R 52 are hydrogen and R 53 and R 54 together with the carbons to which they are attached form a 6-membered heteroaryl; and all other groups are as defined in the Summary of the Invention. Specifically, RI 0 , Rs 2 , and R are hydrogen and R 4 is halo or alkoxy; or R 0 , R 52 , and R are hydrogen and R 53 is alkoxy. [00114] In a more specific embodiment (U2) of embodiment Ul, the compound of Formula I is that where R 5 1 is methyl. [00115] In another specific embodiment (U3) of embodiment U, the Compound of Formula I is that where R7 is hydrogen or alkyl and R 7 a, and R 7 ' are independently hydrogen, alkyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; R 8 is hydrogen or alkyl and Ra is heterocycloalkyl or heterocycloalkylalkyl; R 9 is hydrogen or alkyl and R9a is hydrogen, heterocycloalkyl, or heterocycloalkylalkyl; R 10 , R10a, and RiOb are independently hydrogen, alkyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl [00116] In another embodiment of the Invention (V) the Compound of Formula I is that whereW', V 2 , W, and W 4 are -C(H)=; or W 2 and W 3 are -C(H)= and one of W' and W 4 is -N= and the other is -C(H)=;

R

50 is hydrogen; Rsi is hydrogen or alkyl;

R

52 is hydrogen;

R

53 is hydrogen, alkoxy, nitro, amino, or -N(R)C(O)-C1-C6-alkylene-N(Rssa)R 5b; and R1 4 is hydrogen, alkyl, alkoxy, or halo; or R 53 and R together with the carbons to which they are attached form a 6-membered heteroaryl; B is phenyl substituted with R 3 a and optionally further substituted with one R 3 ; or B is heteroaryl optionally substituted with one or two R 3 ; 42 R is cyano; hydroxyamino; carboxy; alkylsulfonyl, aminoalkyloxy; alkylaminoalkyloxy; dialkylaminoalkyloxy; -N(R7)C(0)-C -C6-alkylene-N(Ra)(R7b); -C(O)NRIRa;

-NR

9

C(O)R

9 A; -C(O)N(R")-Cl-C-akylene-N(Rwa)R'b; -NRIjC(O)NR' aRJIb where Ru 1a; -C(O)R 2 ; -NRl 3 C(O)ORl 3 a; -C(O)N(R 4 )N(Ra)(R 4 b); -S(0) 2

N(R")-C

1

.C

6 alkylene-N(R 5 a)R1b; -C(O)N(R)-Ci.C 6 -alkylene-C(O)OR1aa; heteroaryl optionally substituted with one or two aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; -N(Rl 7 )-C(=N(R1 7 b)(RI 7 a))(NR1 7 cRI 7 d); -N(R8)C(O)-Cl-C6-aklene-N(R")C(0)Ra -C(O)N(R")-Cl-C6-alkylene-C(O)R 9 a; -N(R 2 )C(O)-C .. C 6 -alkylene-N(RW 2

)

N(R

22 e)( 2 2 a); -CO.C-alklene-N(R3)-C1.C6-alkylene-N(R3U)Raa; or -NR? 4

C(O)

CI.C

6 -alkylene-ORua; where each of the alkylene in R 3 " is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, and amino; each R 3 (when R 3 is present) is independently halo; cyano; alkyl; alkenyl; alkoxy; hydroxyamino; carboxy; alkylsulfonyl, aminoalkyloxy; alkylaminoalkyloxy; dialkylaminoalkyloxy; -N(Rc)C(O)-C1-Co-alkylene-N(R a)(RI); -C(O)NRRaa;

-NR

9

C(O)R

9 a; -C(O)N(RN")-CrC6-alkylene-N(Rioa)RR _ IIC(O)NRuaRi Lb where Rua; -C(0)RII; -NR1C(O)O3a; -C(0)N(RII)N(Ra~a)(Ru4); -S(O)2N(R15)-Cl.o alkylene-N(RI 5 a)Risb; -C(O)N(R')-C .C,-alkylene-C(O)ORu 6 a; heteroaryl optionally substituted with one or two aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; -N(Rl)-C(=N(Rll)(Rlla))(NRR17,l0); -N(R]8)C(O)-CrC -alkylene-N(Rl56)C(0)R aa -C(O)N(R-)-CrC6-alkylene-C(O)Rwa; -N(Re 2

)C(O)-C

1

.C

6 -alkylene-N(Re)

N(R

22 c)(R 22 a); -Co.C 6 -alkylene-N(R 2 e)-C 1 C..alkylene-N(Re)Ra; or -NReC(O)

CI.C

6 -a1kylene-OR 4 a; where each of the alkylene in R 3 is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, and amino; provided that when R 0 and 'Rs 2 are hydrogen, R 5 1 is hydrogen or methyl, R 53 is hydrogen or methoxy, and R 54 is hydrogen or methoxy, then B is not 2,3-dihydro- 1,4 benzodioxinyl, thien-2-yl, or thien-2-yl substituted with one R 3 where R is halo. [00117] Another embodiment (W) of the invention is a Compound of Formula I where

R

0 , R1 3 , and R" 4 are independently hydrogen, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, hydroxy, alkoxy, alkenyloxy, haloalkoxy, nitro, amino, alkylamino, dialkylamino, -N(R")C(O)-CrC6-alkylene-N(Rsa)R3b, alkylcarbonyl, alkenylcarbonyl, carboxy, alkoxycarbonyl, cyano, alkylthio, -S(0) 2

NR"R

5 a, or alkylcarbonylamino and where R, and R 5 b are indepedently hydrogen, alkyl, or alkenyl and R5a is hydrogen, alkyl, alkenyl, hydroxy, or alkoxy; or R 5 3 and R 4 together with the carbons to which they are attached form a 5- or 6-membered heteroaryl or 5- or 6-membered heterocycloalkyl. 43 [00118] Another embodiment (X) of the invention is a Compound of Formula I where

R

3 and R 4 together with the carbons to which they are attached form a 5- or 6-membered heteroaryl or 5- or 6-membered heterocycloalkyl. [001191 Another specific embodiment of the invention is a pharmaceutical composition comprising a compound of Formula I, Formula Ia, or a compound according the above Embodiments A-X and a pharmaceutically acceptable carrier, excipient, or diluent. [00120] Another specific embodiment of the invention is a method of inhibiting P13K in a cell, comprising contacting a cell in which inhibition of P13K is desired with a compound of Formula I, Ia, or II or a compound according to Embodiments A-X. Specifically, the Compound is of Formula I or Ia. [001211 Another specific embodiment of the invention is a method of treating a disease, disorder, or syndrome mediated by P13K which method comprises administering to a patient a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula I, Ia, or II or a compound according to embodiments A-X. Specifically, the Compound is of Formula I or Ia. More specifically, the Compound is of Formula Ia. [001221 More specifically, the disease is cancer. Even more specifically, the cancer is breast cancer, colon cancer, rectal cancer, endometrial cancer, gastric carcinoma, glioblastoma, hepatocellular carcinoma, small cell lung cancer, non-small cell lung cancer, melanoma, ovarian cancer, cervical cancer, pancreatic cancer, prostate carcinoma, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), or thyroid carcinoma. Even more specifically, the cancer is ovarian cancer, cervical cancer, breast cancer, colon cancer, rectal cancer, or glioblastoma. [001231 Another aspect of the Invention is directed to employing the compounds of the invention in a method of screening for candidate agents that bind to, for example P13K. In that method, the protein is bound to a support, and a compound of the invention is added to the assay. Alternatively, the compound of the invention is bound to the support and the protein is added. Classes of candidate agents among which novel binding agents may be sought include specific antibodies, non-natural binding agents identified in screens of chemical libraries, peptide analogs, etc. Of particular interest are screening assays for candidate agents that have a low toxicity for human cells. A wide variety of assays may be used for this purpose, including labeled in vitro protein-protein binding assays, electrophoretic mobility shift assays, immunoassays for protein binding, functional assays (phosphorylation assays, etc.) and the like. 44 [00124] The determination of the binding of the candidate agent to, for example, P13K may be done in a number of ways. In one example, the candidate agent (the compound of the invention) is labeled, for example, with a fluorescent or radioactive moiety and binding determined directly. For example, this may be done by attaching all or a portion of the P13K protein to a solid support, adding a labeled agent (for example a compound of the invention in which at least one atom has been replaced by a detectable isotope), washing off excess reagent, and determining whether the amount of the label is that present on the solid support. Various blocking and washing steps may be utilized as is known in the art. [00125] The term "labeled" as used herein is meant to include both direct and indirect labeling with a compound that provides a detectable signal, for example, radioisotope, fluorescent tag, enzyme, antibodies, particles such as magnetic particles, chemiluminescent tag, or specific binding molecules, and the like. Specific binding molecules include pairs, such as biotin and streptavidin, digoxin and antidigoxin, and the like. For the specific binding members, the complementary member would normally be labeled with a molecule which provides for detection, in accordance with known procedures, as outlined above. The label can directly or indirectly provide a detectable signal. [00126] In some embodiments, only one of the components is labeled. For example, P13K protein may be labeled at tyrosine positions using 1251, or with fluorophores. Alternatively, more than one component may be labeled with different labels; using 1251 for the proteins, for example, and a fluorophor for the candidate agents. [00127] The compounds of the invention may also be used as competitors to screen for additional drug candidates. The terms "candidate bioactive agent" or "drug candidate" or grammatical equivalents as used herein describe any molecule, e.g., protein, oligopeptide, small organic molecule, polysaccharide, polynucleotide, etc., to be tested-for bioactivity. They may be capable of directly or indirectly altering the cellular proliferation phenotype or the expression of a cellular proliferation sequence, including both nucleic acid sequences and protein sequences. In other cases, alteration of cellular proliferation protein binding and/or activity is screened. In the case where protein binding or activity is screened, some embodiments exclude molecules already known to bind to that particular protein. Exemplary embodiments of assays described herein include candidate agents, which do not bind the target protein in its endogenous native state, termed herein as "exogenous" agents. In one example, exogenous agents further exclude antibodies to P13K. [00128] Candidate agents can encompass numerous chemical classes, though typically they are organic molecules having a molecular weight of more than about 100 and less than 45 about 2,500 daltons. Candidate agents comprise functional groups necessary for structural interaction with proteins, particularly hydrogen bonding and lipophilic binding, and typically include at least an amine, carbonyl, hydroxyl, ether, or carboxyl group, for example at least two of the functional chemical groups. The candidate agents often comprise cyclical carbon or heterocycloalkyl structures and/or aromatic or heteroaromatic structures substituted with one or more of the above functional groups. Candidate agents are also found among biomolecules including peptides, saccharides, fatty acids, steroids, purines, pyrimidines, derivatives, structural analogs, or combinations thereof. [00129] Candidate agents are obtained from a wide variety of sources including libraries of synthetic or natural compounds. For example, numerous means are available for random and directed synthesis of a wide variety of organic compounds and biomolecules, including expression of randomized oligonucleotides. Alternatively, libraries of natural compounds in the form of bacterial, fungal, plant and animal extracts are available or readily produced. Additionally, natural or synthetically produced libraries and compounds are readily modified through conventional chemical, physical and biochemical means. Known pharmacological agents may be subjected to directed or random chemical modifications, such as acylation, alkylation, esterification, amidification to produce structural analogs. [001301 In one example, the binding of the candidate agent is determined through the use of competitive binding assays. In this example, the competitor is a binding moiety known to bind to IGFIR, such as an antibody, peptide, binding partner, ligand, etc. Under certain circumstances, there may be competitive binding as between the candidate agent and the binding moiety, with the binding moiety displacing the candidate agent. [001311 In some embodiments, the candidate agent is labeled. Either the candidate agent, .or the competitor, or both, is added first to P13K protein for a time sufficient to allow binding, if present. Incubations may be performed at any temperature that facilitates optimal activity, typically between 4 0 C and 40 0 C. [001321 Incubation periods are selected for optimum activity, but may also be optimized to facilitate rapid high throughput screening. Typically between 0.1 and I hour will be sufficient. Excess reagent is generally removed or washed away. The second component is then added, and the presence or absence of the labeled component is followed, to indicate binding. [001331 In one example, the competitor is added first, followed by the candidate agent.. Displacement of the competitor is an indication the candidate agent is binding to P13K and thus is capable of binding to, and potentially modulating, the activity of the P13K. In this 46 embodiment, either component can be labeled. Thus, for example, if the competitor is labeled, the presence of label in the wash solution indicates displacement by the agent. Alternatively, if the candidate agent is labeled, the presence of the label on the support indicates displacement. [00134] In an alternative embodiment, the candidate agent is added first, with incubation and washing, followed by the competitor. The absence of binding by the competitor may indicate the candidate agent is bound to P13K with a higher affinity. Thus, if the candidate agent is labeled, the presence of the label on the support, coupled with a lack of competitor binding, may indicate the candidate agent is capable of binding to P13K. 100135] It may be of value to identify the binding site of P13K. This can be done in a variety of ways. In one embodiment, once PI3K is identified as binding to the candidate agent, the P13K is fragmented or modified and the assays repeated to identify the necessary components for binding. 100136] Modulation is tested by screening for candidate agents capable of modulating the activity of P13K comprising the steps of combining a candidate agent with P13K, as above, and determining an alteration in the biological activity of the P13K. Thus, in this embodiment, the candidate agent should both bind to (although this may not be necessary), and alter its biological oi biochemical activity as defined herein. The methods include both in vitro screening methods and in vivo screening of cells for alterations in cell viability, morphology, and the like. [00137] Alternatively, differential screening may be used to identify drug candidates that bind to native P13K, but cannot bind to modified P13K. [00138] Positive controls and negative controls can be used in the assays. For example, all control and test samples are performed in at least triplicate to obtain statistically significant results. Incubation of samples is for a time sufficient for the binding of tie agent to the protein. Following incubation, samples are washed free of non-specifically bound material and the amount of bound, generally labeled agent determined. For example, where a radiolabel is employed, the samples can be counted in a scintillation counter to determine the amount of bound compound. [00139] A variety of other reagents can be included in the screening assays. These include reagents like salts, neutral proteins, e.g., albumin, detergents, etc which may be used to facilitate optimal protein-protein binding and/or reduce non-specific or background interactions. Also reagents that otherwise improve the efficiency of the assay, such as 47 protease inhibitors, nuclease inhibitors, anti-microbial agents, etc., may be used. The mixture of components can be added in any order that provides for the requisite binding. [00140] One of ordinary skill in the art would understand that certain crystallized, protein-ligand complexes, in particular PI3K-ligand complexes, and their corresponding x ray structure coordinates can be used to reveal new structural information useful for understanding the biological activity of kinases as described herein. As well, the key structural features of the aforementioned proteins, particularly, the shape of the ligand binding site, are useful in methods for designing or identifying selective modulators of kinases and in solving the structures of other proteins with similar features. Such protein ligand complexes, having compounds of the invention as their ligand component, are an aspect of the invention. [001411 Another aspect of the invention is directed to suitable x-ray quality crystals, and one of ordinary skill in the art would appreciate that they can be used as part of a method of identifying a candidate agent capable of binding to and modulating the activity of kinases. Such methods may be characterized by the following aspects: a) introducing into a suitable computer program, information defining a ligand binding domain of a kinase in a conformation (e.g. as defined by x-ray structure coordinates obtained from suitable x-ray quality crystals as described above) wherein the computer program creates a model of the three dimensional structures of the ligand binding domain, b) introducing a model of the three dimensional structure of a candidate agent in the computer program, c) superimposing the model of the candidate agent on the model of the ligand binding domain, and d) assessing whether the candidate agent model fits spatially into the ligand binding domain. Aspects a-d are not necessarily carried out in the aforementioned order. Such methods may further entail: performing rational drug design with the model of the three-dimensional structure, and selecting a potential candidate agent in conjunction with computer modeling. [001421 Additionally, one skilled in the art would appreciate that such methods may further entail: employing a candidate agent, so-determined to fit spatially into the ligand binding domain, in a biological activity assay for kinase modulation, and determining whether said candidate agent modulates kinase activity in the assay. Such methods may also include administering the candidate agent, determined to modulate kinase activity, to a mammal suffering from a condition treatable by kinase modulation, such as those described above. [001431 Also, one skilled in the art would appreciate that compounds of the invention can be used in a method of evaluating the ability of a test agent to associate with a molecule or 48 molecular complex comprising a ligand binding domain of a kinase. Such a method may be characterized by the following aspects: a) creating a computer model of a kinase binding pocket using structure coordinates obtained from suitable x-ray quality crystals of the kinase, b) employing computational algorithms to perform a fitting operation between the test agent and the computer model of the binding pocket, and c) analyzing the results of the fitting operation to quantify the association between the test agent and the computer model of the binding pocket. Representative Compounds [00144] Representative compounds of Formula I and/or II are depicted below. The examples are merely illustrative and do not limit the scope of the invention in any way. Compounds of the invention are named according to systematic application of the nomenclature rules agreed upon by the International Union of Pure and Applied Chemistry (IUPAC), International Union of Biochemistry and Molecular Biology (IUBMB), and the Chemical Abstracts Service (CAS). Names in Table 1 were generated using ACD/Labs naming software 8.00 release, product version 8.08 with the exception of Compound 374 which was named using ChemDraw v. 9.0.1. Table 1 Cpd. No. Structure Name

CH

3 O= HN H 1 CH3 1 (methoxy)phenyl]amino}quinoxalin-2-yl) ami no]sulfonyl}phenyl) acetamide 4-bromo-N-[3-(phenylamino)quinoxalin-2-y] 2 benzene sulfonamide d H. Br 4-bromo-N-{3-[(2 3 . methylphenyl)amino]quinoxalin-2-yl}benzene sulfonamide Ha_ - 4-bromo-N-(3-{[4 4 (methoxy)phenyl]amino}quinoxalin-2-y) benzene sulfonamide 49 Table 1 Cpd. No. Structure Name 5I 4-chloro-N-{3-[(4-chlorophenyl)amino]-6 Im NH(methoxy)quinoxalin-2-yl~benzenesulfonamide "1 0 ___________ 0 HN) , N-(4-{[3-{[(4-cblorophenyl)sulfonyl amino) -7 6 (motboxy)quinoxalin-2-yl]amino) phenyl) 0N~~NNH /\ c~ acetamide u ~N NH NT N,- 4j H 0 0 N HN< 8 N ~4chlorohNyl;slfbyl(mnox quin2oxai-2,-yl N - NH y~~~~amino]henleaid-y~enesufam 0 N N~~~~~1-{3-[(3,{4-eblbnlainj6 10 mpethyl~slylmnquinoxalin-2-yl}--eblezn Nx NH cl sloamiey~ctmd

N

4 05 ________Table 1 Cpd. No. Structure Name 11 NI (dimethylaniino)phenyl]amino}quinoxalin-2 0 yl)-4-mothylbenzene sulfonamide H 0 '0c,\' 4-mothyl-NV-{6-mothyl-3-[(4 12 methylphenyl)aminojquinoxalin-2-yl} benzene H~c-f 9 CHsulfonamide CH, OL A-{ 3-f(4-hydroxyphenyl)amino]-6 13 N\/ methylquinoxalin-2-yl}-4-methylbenzene sulfonamide CH, 14 N-{3-[(2,5-dinietbylphenyl)amino]quinoxalin-2

H

3 C yl}-4-methylbenzenesulfonanide 16 ~ ~ ~ rNH2 N-{3o-[(3-nphaen-2-i~qioain2y} 15 cl ylamin4-chlor o xi--benzenesulfonamide 0 NH 2 17 ,'Nc (minosulfophenyljamino~quinoxalin-2-yl) 4-chtrobenzenesulfonaiide -(3o--{3[4 18 chisloro nyl)pnino~quinolinoxl-y) N N c~ ylntbenzenesulfonaide NN 51 Table 1 Cpd. No. Structure Name Hl 4-chloro-N-{3-[(4 19 ci methylphenyl)amino]quinoxalin-2 yl}benzenesulfonamide CH . 4-chloro-N-(3-[(2 20 NH methylphenyl)amino]quinoxalin-2-yl) N Y benzenesulfonamide methyl 4-[(3-{[(4 21 chlorophenyl)sulfonyl]amino) quinoxalin-2-yl) I N XN bamino]benZoate methyl 2-chloro-5-[(3-{[(4 22 NH H methylphenyl)sulfonyl]amino}quinoxalin-2-yl) N \ amino]benzoate CH, \11 lV-{4-[(7-methyl-3-{[(4 23 methylphenyl)sulfonyl]amino}quinoxalin-2-yl) amino]phenyl}acetamide ',CH, C4-methyl-N-(6-methyl-3-{[2 24 H,O, NH /o C' (methoxy)phenyl]amino} quinoxalin-2 N syl)benzenesulfonamide 25 e NH -{3-[(phenylmethyl)amino]quinoxalin-2 N 0 H yl}benzenesulfonamide N O H 26 ' H 4-({3-[(phenyisulfonyl)amino]quinoxalin-2 2N H yl}amino)benzoic acid 52 Table 1 Cpd. No. Structure Name 27 10I =< -) 3.{{3.{(phenylsulfonyl)amino]quinoxalin.2 0 '

H

2 N'S' N N 0 , j N-{3-[(1,5-dimethyl-3-oxo-2-phenyl-2,3 28 dfiydro-1H-pyrazol-4-yl)amino]quinoxalin-2 0 CH3 CH3 30 N H V1311(4-hydroxyphenyl)aminoquinoxalin.2 31, N I , H N-(4-hnosuo yphenylaminoquinoxalin-2-) 30 L N Y' yl4-methylbenzenesulfonamide 0 32 N N 0 (mthyupheny)uhnyl~amino~quinoxain-2-y) -4N NO -So - yl-mniinobenzenoiaid e H 53 Table 1 Cpd. No. Structure Name 33 0 =0 N-[4-({[3-(phenylamnino)quinoxalin-2 33 yl]amino}sufonyl)phenylacetamide HN yCH 0 N N N-(4-{[(3-{[4 34 o (aminosulfonyl)phenyl]amino}quinoxalin-2 HN-F \-o N) N- So yl)amino]sulfonyl}phenyl)acetamide 0 OH 3 0 f H 2 N CN:H 35 0=0 N-[4-({[3-(naphthalen-1-ylamino)quinoxalin-2 yl]amino)sulfonyl)phenyl]acetamide HNYCHa 0 H-CH, 36 CH, methylphenyl)sulfonyl]amino}quinoxalin-2 yl)amino]phenyl}acetamide 37 0-- (aminosulfonyl)phenyl]amino}quinoxalin-2-yl) 4-bromobenzenesulfonamide

-

CH, 3 HO N-{3-[(3-hydroxyphenyl)amino]quinoxalin-2 yl}-4-methylbenzenesulfonamide O OH OH 4-{(3-{[(4 39 ci chlorophenyl)sulfonyllamino}quinoxalin-2 yl)amino]-2-hydroxybenzoic acid 54 Table 1 Cpd. No. Structure Name HC, 40 N-(3 -[4-(methoxy)phenylaminolquinoxalin-2 II N H yl)-3-nitrobenzenosulfonamide a 41 N N CI chlorophenyl)sufonyljaminolquinoxalin-2 X~1NR i yl)amino~bevzoic acid 19 42 cl(aniinosulfbnyl)phenyljamino)quinoxalin-2-yl) ir 4-chiorobenzenesulfonamide 43N (aniinosulfonyl)phenyl]amino)quinoxalin-2-yl) Q1~XS4-chlorobenzenesulfonamide 44 y I2 9,. N-[3-(naphthalen-2-ylamino)quinoxalin-2-yJ-4 N, NH N, nitrobenzeniesulfonanude ~N NE N-(3-{ [3-(methoxy)phenyllamino~quinoxalin-2 45 yJ)benzonesulfonamide er 46 A-{3-[(4-bromophenyl)amino]quinoxalin-2-yI) (N' 01-3-nitrobenzenesuffoniamide 55 Table 1 Cpd. No. Structure Name 0 4712 nitrophenyl)sulfonyl]amino~quinoxalin-2 frN NH 0 N yl)amino]benzoic acid 48 N N a * 4-nitro-N.{3-(phenylamino)quinoxalin-2 yljbenzenesulfonamide 49 cl 4-chloro-N-[3-(phenylamino)quinoxalin-2 frty N"0yJ~benzenesulfonamide 50 3-nitro-N-[3- (phenylamino)quinoxalin-2 ,a N N.11ylbenzenesulfoanide 51 0- nitrophenyl)sulfonyl]amino~quinoxalin-2 9, yI)amnino]benzoic acid N rb 52 N-[3-(naphthalen-2-ylamino)quinoxalln-2-yl]-3 ryN N.Hnitrobeozenesulfonamide 9H 3 N NH 4-methyl-N-(3-{[3 53 N NH (methoxy)phenyljamino~quinoxalin-2 yl)benzenesulfonainide CH, ycI N NH N-(3-{[3-chloro-4. 54 (methoxy)pheny]amninolquinoxain-2 Ct~ t, 4"yl)benzenesulfonamide ___ 6 _ _ _ _ _ _ _ _ _ _ 56 Table 1 Cpd. No. Structure Name F N-{3-[(3-chloro-4 55 N H fluorophenyl)amino]quinoxalin-2 yl}benzenesulfonamide N CHa methyl 2-chloro-5-({3 56 N NH [(phenylsulfonyl)amino]quinoxalin-2 ,-,, N; Jyl}amino)benzoate OH 4-chloro-N-{3-[(3 57 NH hydroxyphenyl)amino]quirioxalin-2 yl}benzenesulfonamide HC Y;- N X N NH 4-methyl-N-[6-methyl-3 58 0s0 (phenylamino)quinoxalin-2 yIlbenzenesulfonamide CH 59 6 N NH N-{4-[({3-[(4-methylphenyl)amino]quinoxalin N l N 2-yl}amino)sulfonyl]phenyl}acetamide N CH, H o 0 CH, CH, 1-methylethyl 4-[(3-([(4 60 N chlorophenyl)sulfonyl]amino}-7 N Kmethylquinoxalin-2-yl)amino]benzoate N 0 61 N H N-{3-[(4-methylphenyl)amino]quinoxalin-2 N H yl}benzenesulfonamide 57 Table I Cpd. No. Structure Name 62, O N)-NH N-{3 -[(3 -methylphenyl)amnino]quinoxalin-2 y1lbenzenesulfonamide 63 I NLN N-{ 3-[(4-bromophenyl)azninojquinoxalin-2-yl} 4-methylbenzenesulIfanamide P H 3 H 4-methyl-N-{3-[(3 64 00methylphenyl)amino]quinoxalin-2 yl yIbenzenesulfonamide CH, 65 '- N N,4-methyl-N-[3-(naphthalen-1 ylamino)quinoxalin-2-yljbenzenesulfonarnide N, H 3 NN N-{4-[({3-[(4-chlorophenyl)aminolquinoxalin 66 2-yI~amino)sulfonyflphenyl~acetamide HN yCH3 0 58 Table 1 Cpd. No. Structure Name 0 67 0=N 0(aminosulfonyl)phenyl]amino}quinoxalin-2 yl)amino]sulfonyllphenyl)acetamide I-J CH, 9 -R 4-methyl-N-{3 68 Mv N 0[(phenylmethyl)amino]quioxalin-2 yl}benzenesulfonamide H HO b," / 4-[(3{1[(4 69 0 N\12 bromophenyl)sulfonyl]amino~quinoxalin-2 yl)amino]-2-hydroxybenzoic acid 0 4-bromo-N-{3-[(4 70 N /N methylphenyl)anino]quinoxalin-2 yl~benzenesulfonaimide H~C 4-bromo-N-{3-[(3 71 0methylphenyl)amino]quinoxali-2 yl}benzenesulfonamide

H

3 C 72 O~/ IIXN-{4-[({ 3-[(2-hydroxyethyl)amino]quinoxalin 2-yI~araino)sulfonyl]phenyl~acetwinde 4-bromo-N-[3-(naphthal en-i 73 8 -1V,\/,ylamino)quinoxalin-2-yllbenzenesulfonamide o oH 4-[(3-f[(4 74NH o chlorophenyl)sulfonyflamino~quinoxalin-2 Yl)aminolbenzoic acid 59 Table 1 Cpd. No. Structure Name 0 OH 3-[(3-{[(3 75 r, NN H nitrophenyl)sulfonyl]amino}quinoxalin-2 AN A -o yl)amino]benzoic acid 76 N-3-[(2-methylphenyl)amino]quinoxalin-2 -0o1o yllbenzenesulfonamide 6 -NH2 4-({3-[(phenylsulfonyl)amino]quinoxalin-2 yl} amino)benzenesulfonamide 0 78 N N N-[3-(naphthalen-l-ylamino)quino alin2-yl]-3

N-

0 nitrobenzenesulfonamide N ~ N NH2 N-(3-f[3 79 . NjNH , (aminosulfonyl)phenyl]amino}quinoxalin-2-yl) Nr NH 3-nitrobenzenesulfonamide o=S 0 80 N-{3-[(4-bromophenyl)amino]quinoxalin-2-yl} 4-nitrobenzenesulfonamide 81 N H 4-chloro-N-[3-(naphthalen-1 o= 0 ylamino)quinoxalin-2-yl]benzenesulfonamide 60 Table 1 Cpd. No. Structure Name yN NH0 NX NH N.{14-f({3-[(phenylmethyl)aminolquinoxalin-2 82 0=S0 yl~amino)sulfonyljphenyl~acetamide CH, H 3 83 0= N-[4-({[3-(butylamino)quinoxalin-2 yI]amino~sulfonyl)phenyl]acetamide 0Y NH CH, N4 NN-[3-(butylamino)quinoxalin-2-yJ-4 H HNmethylbenzenesulfonamide 0 85 N N N[3(cycohexyamino)quinoxain-2 07--~. yl~benzenesulfonamide N' 0 1-(phenylsulfonyl)-3-[4-(pyrrolidin-l 86 H, ylsulfonyl)phenyl]-2,3-dihydro-1H-imidazo[4,5 N N b]quinoxaline _ 0 N-, 1-(phenylsulfonyl)-3-[4-(piperidin-1 87 ylsulfonyl)phenyl]-2,3-dihydro-IH-imidazo[4,5 0 biquinoxaline 61 Table 1 Cpd. No. Structure Name 88 N 2,5-dichloro-N-[3-(3,4-dihydroquinolin-1(2H) SNH yl)quinoxalin-2-yl]benzenesulfonamide 06o cl CA ethyl 2-[(3-{[(4 89 Nmethylphenyl)sulfonyljaminolquinoxalin-2 N yl)amino]-4,5,6,7-tetrahydro-l-benzothiophene 3-carboxylate H30 2,5-dichloro-N-{3-[(2-morpholin-4 90 a N N H. ylphenyl)aminolquinoxaIin-2 cz yl}benzenesulfonamide 91NH N-{4-[({3-[(3-methylphenyl)amino]quinoxalin 91 2-yl}amino)sulfonyl]phenyl}acetamide 4-chloro-N-{3-[(3-chloro-4-piperidin-l 92 ylpheny)amino]-6-methylquinoxalin-2

H,

3 C0C, N C yl)benzeneulfonmnide H ; 93H 3-nitro-N-[3-(quinolin-6-ylamino)quinoxalin-2 N N - yl)benzenesulfonamide 62 Table 1 Cpd. No. Structure Name 0 Y~ N P- HY N0 butyl N-[[4-([3 94 0) YEM(phenylsulfonyl)amino]quinoxalin-2 iN NHyllamino)phenyl]carbonyl~glycinate N N 4-nitro-N-(3-[[3 95 /\(trifluorometbyl)phenylamino}quinoxalin-2 ,N -(F\\)-SNH HN yl)benzonesulfonamide o 0 FF HN OH 3 96 fDN-[4-({3-[(phenylsulfbnyl)amino~quinoxalin-2 I yl}amino)phenyl]acetamide H C 0 H 97 qmnethylphenyl)sulfonyi]amino)quinioxalin-2 NH yI)amino~phenyl)acetamide 0 Hsqao FF L~J ethyl 3,3,3-trifluoro-2-hydroxy-2-{4-[(3-{ E(4 98 NH methylphenyi)sulfonyl]ainino~quinoxalin-2 ~N~NHyl)amino]phonyl~propanoate 00 __ l /j0 N-13-[(4-([(2,6-dimetbylpyrimidin-4 99 /0 '0 o"r+ yl)amino]sulfonyl~phenyl)ainino]quinoxalin-2 N= - wto y]) -3-nitrobenzenesulfonamide 63 Table I Cpd. No. Structure Name CH, CH 100 cl 4-chloro-N-{3-[(3,4-dimethylphenyl)amino)-6 HC N_ H methylquinoxalin-2-yl}benzenesulfonamide N W' ~ OCH 3 4-chloro-N-(6-methyl-3-([3 101 HC NH V- (methoxy)pheny]]amino)quinoxalin-2 N s ~yl)benzenesulfonamide o O, CH 102 butyl 4-[(3-{[(4-chlorophenyl)sulfonyl]amino} Ha NH C 7-methylquinoxalin-2-yI)amino]benzoate CH, 4-chloro-N-{3-[(3-chloro-4 103 N NH C methylphenyI)amino]quinoxalin-2 yl}benzenesulfonamide INX 0 OG>H3 1-methylethyl 4-[(3-{[(4 104 Cl chlorophenyl)sulfonyl]amino}quinoxalin-2 yl)amino]benzoate

H

3 C 9? CH N-{3-[(2,5-dimethylphenyl)amino]-6 105 gN NH nitroquinoxalin-2-yl}-4 N0 methylbenzenesulfonamide 0N CH, N-[3-(cyclohexylamino)-6-nitroquinoxalin-2 1 N yl)-4-methylbenzenesulfonamide H 0 64 Table 1 Cpd. No. Structure Name CH, 1130 107 N NH -CH 3 N-{3-[(2,4-dimethylphenyl)amino]quinoxalin-2 yl}-4-methylbenzenesulfonamide H 0 0 N-(3-{[4-(ethyloxy)phenyl]amino}-6 108 methylquinoxalin-2-yl)-4 HC osxNNI jCHa methylbenzenesulfonamide N OH - r~ 3-({3-[({4 109 1 [hydroxy(oxido)amino]phenyl)sulfonyl)amino] NH quinoxalin-2-yl}amino)benzoic acid 110 OH N-{[4-({3-[(phenylsulfonyl)amino]quinoxalin NH o 2-yl}amino)phenyl]carbonyl}glycine CHa 11Cli 3 N-{3-[(3-{[(4-chlorophenyl)sulfonyl]amino}-7 HC k NH methylquinoxalin-2-yl)anino]phenylI acetamide

H

3 C' CH, 4-chloro-N-(3-[(3,5-dimethyl-1H-pyrazol-4 112 HaC ,, N C yl)amino]-6-methylquinoxalin-2 N -yl}benzenesulfonamide N ' N 0 113 N= 4-bromo-N-{3-[(4'-nitrobiphenyl-3 0 NH yl)amino]quinoxalin-2-yl}benzenesulfonamide 65 E -dN.Structure Tbe1Name 'J'XCi 4-bromo-N-{3-[(2 114 N NHchlorophenyl)amino]quinoxalin-2 -N NH yl~benzenesulfonamide 0 N-{ 3-[(4-butyphenyl)amino]-6 115 H N methylquinoxalin-2-y} -4 NH chlorobenzenesulfonamide 0 HNACH, 116 I'1 N-{4-[(3-{[(4-ohlorophenyl)sulfonyl]amino) -7 HC c clmethylquinoxalin-2-yl)aminolphenyllacetamide N 4-chloro-N-{6-methyl-3-[(2-oxo-2,3-dihydro 117 HCIH C H-benzimidazol-5-yI)aniinolquinoxalin-2 :( 'C y)benzonesulfonamide aN propyl 4-[(3-f{((4 118 C (NH chloroplienyl)sulfonyljamino)-7

N

3 NN~~ )~ mtylunoai-2-y1)aminolbenzoate 4-chloro-N-{3-[(4 119 ,-,N N fluorophenyl)amino]quinoxalin-2 " N Nyl~benzenesuffonamide 120 HN 0 N-[4-({E3-(naphthalen-2-ylamino)quinoxalin-2 cc -Nr -'--yllamino~sulfonylphenyl]acetamide 66 Table 1 Cpd. No. Structure Name q HN Br 4-bromo-N-(3-[4 121 NHH . (phenylamino)phenyl]amino}quinoxalin-2 s, yl)benzenesulfonamide 00 HN O 2-hydroxy-4-({3 122 HO . y N [(phenylgulfonyl)amino]quinoxalin-2 HO;XC NT yl)amino)benzoic acid O

CH

3 123* N-(3-{[3 123 (aminosulfonyl)phenyl]amino}quinoxalin-2-yl) 4-methylbenzenesulfbnamide N ~ 4-[(3-{[(3 124 nitrophenyl)sulfonyl]amino}quinoxalin-2 Ho- yl)amino]benZOic acid CH, N-(3-{[3-(butyloxy)phenyi]amino}quinoxalin 2 NH 2-yl)-4-methylbenzenesulfonamide c F 126 NH O N-{3-[(4-fluorophenyl)aminolquinoxalin-2-yl} NH6 NH + - 3-nitrobenzenesulfonamide 67 Table 1 Cpd. No. Structure Name CH,4-(3-([4 127 (acetylaniino)phenyljsulfonyl)amino)quinoxalin -2-yI]aminol-2-hydroxybeiizoic acid 128 ~ L 1~ 0 N-43-(naphthalei-l-ylamino)quinoxalin-2-y]-4 ) -I-- Nnitrobenzenesutfonamide HN',4-(3[[4 129 Nbromophenyt)sulfonytlaminolquinoxalin-2 Ho.I Jya yl)aminolbenzoic acid 0H lIN' %% N(-1(-[3 130 _r -I-- N hydroxyphenyl)amino]quinoxalin-2 'O- r 4 yIlaniino)sulfonyl]phenyl~acetamlde H HN 4 131 o-~~'~ N bromophenyl)sulfonyllamino~quinoxalin-2 l[~J ~yI)ainino~benzoic acid 4-bromo-N-(3-{[3. 132 N(butyloxy)phenyljaininolquinoxalin-2 ol 14HyI)benzenenuIfonamide 9< 4-bromo-N-(3-(13 133 ~ ~ ~ H(trifluoromethyl)pheniyllaminolquinoxali-2 L)LA yIobenzenesulfonainide 0 68 Table I Cpd. No. Structure Name q. 134 4-methyl-N-(3.{(4'-nitrobiphenyl-3 p3 yl)aminojquinoxalin-2-y1}benzenesulfonamide F (PI _ N 4-chloro-N{3-[(3 135 fluorophenyl)amino]quinoxalin-2 NH yl}benzenesulfonamide 0 Pcl 136 N NH N-{3-[(2-chlorophenyl)amino]quinoxalin-2 1=6 yl)benzenesulfonamide 90 6 N NH 137 ",NNN 4-bromo-N-[3-(quinolin-5-ylamino)quinoxain 13 oo 2-yl]benzenesulfonamide Sr YF N NH N-{3-[(3-fluorophenyl)amino]quinoxalin-2-yl} 138 4-methylbenzenesulfonamide NO= CHa 0 139 N V-{3-[(4-fluorophenyl)amino]quinoxalin-2-yl} 4-methylbenzenesulfonamide 0=6 69 Table 1 Cpd. No. Structure Name NF N NH 3-nitro-N-(3-{[3 140 N NH (trifluoromethyl)phenyl]amino}quinoxalin-2 yl)benzenesulfonamide 0. .0 'H HRs 2-hydroxy-4-[(3-{[(3 141 Ho 0 nitrophenyl)sulfonyl]amino}quinoxalin-2 H0.K(% N yI)amino]benzole acid HOP N nbe 142 NH N-{3-[(3-chlorophenyl)aminoquinoxalin-2-yl} 4-methylbenzenesulfonamide Nob CH, O HBr 143 s N-[3-(1,3-benzodioxol-5-ylamino)quinoxalin-2 .3 N I yl]-4-bromobenzenesulfonamide HaC 0 144 N-{3-[(3-acetylphenyl)amino]quinoxalin-2-yl} s- 4-chlorobenzenesulfonanide NO N IN 3-nitro-N-(3-{[4-(9H-xanthen-9 145 yl)phenyl]amino}quinoxalin-2 -N HN yl)benzenesulfonamide 0 70 ________Table 1 Cpd. No. Structure Name 146 NH4-chloro-N-{34(4'-nitrobiphenyl-3 0 " NH yl)amino]quinoxain-2-yIlbenzenesulfonamide CI 147 NV-[3-(2,1,3-benzothiadiazol-5 N N ylamino)quinoxalin-2-yl]-4-tolylsulfonamide N o CH, N-(3-((2-methyl-1,3-dioxo-2,3-dihydro-IH 148 rN M isoindol-5-yi)amino]quinoxalin-2 N Ix NHyi~benzenesulfonainide 0 149 HH 4-methyl-N-[3-(quinolin-5-ylamino)quinoxalin 14 H 0p 2-yl]benzenesufonanide t4~4-methy[-N-{3[(Ivoxo-1 ,3-dihydro.2 150 XtHbenzofuran-5-y)amino]quinoxalin-2. CHN 151 ~ JN NH chlorophenyl)aminojquinoxain-2 CXNIX yl~benzenesufonamide 0 N~\P 2-hydroxy-5-[(3-{[R4 152 / - methylphenyl)sullnyl]aminoj quinoxalin-2 CH \ - H H OH yi)amino]benzoic acid 00 1 0 HO 71 Table 1 Cpd. No. Structure Name OH N-(3-{[3,5-bis(1,1 -dimethylethyl)-4 153 , NNH hydroxyphenyl]amino}quinoxalin-2 .1~~ yi)benzenesulfonamide N Si - FF N NH N-[3-({2 154 [(trifluoromethyl)thio]phenyl}amino)quinoxalin N NH -2-yl]benzenesulfonamide HN N-{4-[({3[ 155 hydroxyphenyl)amino]quinoxalin-2 HO-IC yI}amino)sulfonyl]phenyl}acetamide CHNH CH 156 N N-[3-(1,3-benzodioxol-5-yamino)quinoxalin-2 5W1 yi]-4-methylbenzenesulfonamide 0 3 eN NH 6H3 N-(3-{[2,5 157 N NH bis(methoxy)phenyl]amino}quinoxalin-2 0= y)benzenesulfonamide 15 NI H N-{3-[(2,4-dichlorophenyl)ainino]quinoxalin-2 N1H yi}benzenesulfonamide O=8=o 72 Table 1 Cpd. No. Structure Name gro N-[4-(f [3 -(2,3-dihydro-1,4-benzodioxin-6 159 NH H ylaniino)quinoxalin-2 NN . 1 yl]amirio~sulfonyl)phenyllacetamide b-"~~AN~CH 3 roc X N NH 4-ch]Qro-N-{3-[(3,4 160 -- NxV dimethylphenyl)aminolquinoxalin-2 O=S=O yl~benzenesulfonamide ~N,,NH ON N-f{[,5 161 NN bis(methoxy)phrnyllatnino~quinoxalin-2-y)-3 C~5C nitrobenzenesulfonamide ~~CH3 I~N 4-bromo-N-f 3-[(3,4 162 N NH dimcothylphenyl)aminolquinoxalin-2 o= 0 yi),benzenesulfonamide Br f~OH 163. o*'l N (acetylamino)phenyllsulfonyl~amino)quinoxalin ' N H-2-yljaniino}-2-hydroxybenzoic acid 0 0 3 .N XNH6, 164 N H bis(methoxy)phenyllamino~quinoxalin-2-yl)-4 O0O chlorobenzenesulfonamide CI 73 Table 1 Cpd. No. Structure Name a(NNH CH 3 165 N= NH bis(methoxy)phenyl]amino~quinoxalin-2-yl)-4 methylbenzenesulfonamide

CH

3 0 N fNH 166 N H N-{ 3-(2,4-dichlorophenyl)axnino]quinoxalin-2 o4~o yi}-4-methylbenzenesulfonamide CH, (N- H4-bromo-N-3-[(3 167 N fluorophenyl)amino]quinoxalin-2 yl} beazenesulfonamide Br HN' 168 0 (acetylamino)phenyl]sulfonyl~amino)quinoxalin -2-yl] amino} benzoic acid QNH 169 NN-{3.{(2-fluorophenyl)arninolquinoxalin-2-yl} 169 )[~ ~4-methylbenzenesulfonianide IJJ

CH

3 I N.43-(2,3-dihydro-1,4-benzodioxin.6 170 CHylainino)quinoxalin-2-ylj-4 N NH'a methylbenzenesulfonamide 74 Table 1I __________________ Cpd. No. Structure Name ~~CH1 171 ~N NH N-{3-[(3,4-dimethylphenyl)aminojquinoxalin-2 a ~NNH yI~benzenesulfonamide 120N N/VN 4-mothyl-N-(3-{[3 172 /(trifluoromethyl)phenyl]amino}quinoxalin-2 0H/ N H _~ yI)benzenesulfonmd F 173 -chlorophenyl)sulfonyl~aminolquinoxalin-2 CI /S H HN O yI)amnino]-2-hydroxybenzoic acid 0 0 HO NN 3-nitro-N-(3-[(1-oxo-I ,3-dihydro-2-benzofuraii 174 0 A5-yl)aminolquinoxalin-2 ~-F yl} benzenesulfonamide 0 CIIXNHN-{4-IX{3-[(2-bromo-4 175 0= " methylphenyJ~aminolquinoxalin-2 I ~yI) arino)sulf'onyllphenyl} acetamide 0 Nli NH pN-{3-[(2-fluoropheny)aninolquinoxalin-2-y) 176 N-I'- 4-nitrobenzenesulfonamide N 0 75 Table 1 Cpd. No. Structure Name N-{3-[(2-methyl-1,3-dioxo-2,3-dihydro-1H 177 N NH isoindol-5-yl)amino]quinoxalin-2-y}-3 o-s=o nitrobenzenesulfonamide 0 N H4-chloro-N-{3-[(1-oxo-1,3-dihydro-2 178 NXNH benzofuran-5-yl)amino]quinoxalin-2 o .o yl}benzenesulfonamide Ci 179 N H N-{3-[(I-oxo-1,3-dihydro-2-benzofuran-5 a N 'H yl)amino]quinoxalin-2-ylj benZenesulfonamide F ZN NH ISO N NH N-{3-[(2-fluorophenyl)amino]quinoxalin-2-y} o0o 3-nitrobenzenesulfonamide N. 0 0 HN O

H

0 C N-[2-(butyloxy)-2-.hydroxyethyl]-4-({3 181 [(phenylsulfonyl)amino]quinoxalin-2 H yI}amino)benzamide 0=7 76 Table 1 Cp.N.Structure- Name 3-nitro-N-(3-f[4 182 (pbenylamino)pbenyljamnino~quinoxalin-2 N NH yl)benzenesulfonamide N 0 (X "I 4-bromo-N-{3-[(4 183 NNH fluoropbenyl)amino~quinoxalin-2 0= =0 yl}benzenesulfonamide Br oNN 4-methyl-A"-(3-({2 14 CH S Y NHLFN-p)/ [(trifluoromethyl)thiojphenyll ainino)quinoxalin 11 -2-ylbenzenesulfonamide F F SN'OCH, N-[4-({3-(2-(methoxy)pbenylj-2,3-dihydro-1H 185 C N > zimidazo[4,5-b]quinoxalin-1 -()- royl~sulfonyl)pbenyllacetaniide o

H

3 C ~OH 4-(3-{[4-(acetylamino)pbeinyllsulfonyl} -2,3 186 -~N .N\ dihydro-1H-imidazo[4,5-b~quinoxalin-l 1, yl)benzoic acid 0i

H

3 C 77 Table I Cpd. No. Structure Name 187 1-naphthalen-2-yl-3-[(3-nitropheny)sulfonyl] 187Vj 2,3-dihydro-1H-imidazo[4,5-b]quinoxaline ,Csa 0 N> N-[4-({3-[4-(methoxy)phenyl]-2,3-dihydro-H 188 imidazo[4,5-b]quinoxalin-1 oj yl}sulfbnyl)phenyl]acetsmide CHa

CH

3 1-(3-methylphenyl)-3-[(4 189 N 0 methylphenyl)sulfonyl]-2,3-dihydro-IH imidazo[4,5-b]quinoxaline H, N-(4-{[3-(4-methylphenyl)-2,3-dihydro-1H 190 imidazo[4,5-b]quinoxalin-1 yl]sulfonyl}phenyl)acetanide C4 3 191 o N-{4-[(3-phenyl-2,3-dihydro-lH-imidazo[4,5 bjquinoxalin-1-yl)sulfonyl]phenyl}acetamide C7 3 78 Table I Cpd. No. Structure Name X'> N-(4-{[3-(3-methylphenyl)-2,3-dihydro'1H 192 0: imidazo[4,5-b~quinoxalin-1 Q yljsulfonyl)phonyl)acetamide 083 1-[4-(methoxy)phenyl]-3-[(4 193 mnethylphenyl)suifonyl]-2,3-dihydro-lH -o imidazo[4,5-bJquinoxaline CCX~ !C>-(4-{[3-(2-methylphenyl)-2,3-dibydro-FT 194 08imidazo[4,5-blquinoxalin-1 yljsulfbnyl)phnylacctamidc 195 I NII ] 1-(3-methylphenyl)-3 -(3-nitropbenyl)sulfonyl] 2,3-dihydro-1H--imidazot4,5-b]quinoxaline 0 196,N 1.-(4-methylphenyl)-3-[(3-nitrophenyl)sulfonyl] 196 N CN2,3-dihydro-1H-imidazo[4,5-bjquinoxaline 0 a N , ~t N-{3-I(4-methylphenyI)amino]quinoxalin2 1~7 yl}-3-(1H-tetrazol-1-yI)bcnzenesulfonamide P* N% 79 Table 1 Cpd. No. Structure Name ( Ha H 198 ,0N-(3-{([2-(ethyloxy)phenyl]amino~quinoxalin-2 N l yi)-4-inethylbenzenesulfonamide N %H H 199 N-{44[({3-[(4-ethylphenyl)amino]quinoxalin-2 d 0 yJ~amino)sulfonyllphenyi~acetamide 4-bromo-N-(3-{f3 200C (methoxy)phenyl]amninolquinoxalin-2 N N 0 yl)benzenesulfonaniide

~H

3 201 (ethiyloxy)pheny1]amino~quinoxain-2 1 0 Yl)aminolsuffonyf~phenyl)acetamide H~I3. 202 N-{4-[({3-[(2-ethylphenyl)arninolquinoxalin-2 0 yl) amino)sulfanyllphenyl} acetamide 203 (ethY]Oxy)plienyllamino~quinoxain-2 Yl)aminolsulfony~phenyf)acetamide 80 Table 1 Cpd. No. Structure Namte 204 -NX.NH A-3-[(4-nitrophenyl)amino~quinoxalin-2 yl~benzonesulfonamide

H

3 c. 205 tlk4-(ethyloxy)-N-(3-{[4 205 (methoxy)phenyl]amino) quinoxalin-2 H yl)benzenesuffonamide OyN methyl N-acetyl-N-[4-({3. 206 NH [(phenylsulfonyl)aminolquinoxalin-2 Y yl)amino)phonyl]-beta-alaninate gH3 0 N clmethyl N-acety)-N.{44(3.{[(4 207 IHH-% (\ chlorophenyl)sulfonyljamino)quinoxalin-2 d'~Oyl)amninojphenyl}-beta-alaninate 208 NX NH NV-{3-(3-chloro-5 20 1N0 methylphenyl)amino]quinoxalin-2-yl}-4 O~5O mpthylbenzenesulfonamide 209 NHN-{3-[(3-acetylphenyl)aminojquinoxalin-2-yl) N , ,3-nitrobenzonesulfonamjde N 81 Table 1 Cpd. No. Structure Name 4-{[3-({[4 210 - s NN (acetylamino)phenyl]sulfonyl}amino)quinoxalin -2-yl]amino}-N-[4-(methoxy)phenyl]benzamide HC H OH N H 2-hydroxy-5-({3 211 N NH [(phenylsulfonyl)aminojquinoxalin-2 yl}amino)benzoic acid o" . 0 N-[3-(2,3-dihydro-1,4-benzodioxin-6 212 ylamino)quinoxalin-2-yl]-3 N NH nitrobenzenesulfonamide NH N-[4-(methoxy)phenyl]-4-[(3-{[(4 213 N nitrophenyl)sulfonyl]amino}quinoxalin-2 *' yl)amino]benzamide HN 4-chloro-N-{3-[(2-oxo-2,3-dihydro-IH 214 benzimidazol-5-yl)amino]quinoxalin-2 N CI yl}benzenesulfonamide (N O 215 ~ N- N CH, 4-methyl-N-{3 215 [methyl(phenylmethyl)amino]quinoxalin-2 O~0 yl}benzenesulfonamide CH, 82 Table 1 Cpd. No. Structure Name N NrqA-[3-(3,4-dihydroisoquinolin-2(IB 216 -11 HyI)quinoxalin-2-yl]-2 0=8=0 methylbenzenesulfonamide N-[4-({j3-(2,1,3-benzothiadiazol-5 217 ylamnino)quinoxalin-2 HN yIjaminolsulfonyl)phenyljacetamide "-' NN-'Nl 218 N 1 H4-bromo-N-{3-[(4-phenylquinolin-8 N NH yl)aminajquinaxalin-2-yllbenzenesulfonamide o=8'=0 Br 219 - 4-methyl-N-{3-[(4-phe~nylquinolin P-HHN yl)amino~quinoxalin-2-yl~benzenesulfoanide 1-j(4-chloropbenyl)sulfonyl]73-j4-(pyrrolidin-1 220 ylsulfonyl)phenyl]-2,3-dihydro-1H-imidazo[4,5 N Jul'biquinoxaline 83 Table 1 d. No. Structure Name 221 N 1-(4-morpholin-4-ylphenyl)-3-(phenylsulfonyl) N 2,3-dihydro-1H-imidazo[4,5-b]quinoxaline HPS CH yN NH 0 methyl 4,5-dimethyl-2-((3 222 N NH [(phenylsulfonyl)aminojquinoxalin-2 0== yljamino)thiophene-3-carboxylate o ,OH, ethyl 6-methyl-2-[(3-{[(2 223N methylphenyl)sulfonyllaminolquinoxalin-2 H3 yl)amino]-4,5,6,7-tetrahydro-1-benzothiophene 3-carboxylate ethyl 2-{[3-({[4 224 (acetylamino)phenyl]sulfonyl}amino)quinoxalin k-LN NH -2-yl]amino}-6-phenyl-4,5,6,7-tetrahydro-1 0s benzothiophene-3-carboxylate o NH CHa NHN CH 3 ethyl 6-methyl-2-[(3-{[(4 225 methylphenyl)sulfonyl]amino)quinoxalin-2 N NH yl)aminoj-4,5,6,7-tetrahydro-1-benzothiophene 0=s=o 3-carboxylate HC propyl 4-[(3-{[(4 226 - chlorophenyl)sulfonyl]amino}quinoxalin-2 - Cyl)aminolbenzoate O8a 84 Table 1 Cpd. No. Structure Name

H

3 227 NJL~ 1 -N-{3-[(4-butylphenyl)aminojquinoxalin-2-yl} HadI 4-chloroberizonesulfanamide eo ocI 228N 1 NNH N-{3-1(2-cblorophenyl)onino]quinaxatin-2-yI) 228 0 4-methylbenzenesulfonamide

OH

3 229 c 2 XNNH N-{3-1(2,3-dimethyLphenyl)aminojquinoxalin-2 0O8=0 yl}-4-methylbenzenesulfonamide N MN 230 QQXN N-{3-[(3,4-dimethylpheriyl)aminojquirioxalin-2 " -- oyi-3-nitrobenzeesulfonamide 0 N N N-f 4-[((3-[(2,3 231 CH N\i dimethylpheriyl)aminojquinoxalin-2 HN-F \j--NH HN--'~ yl)amino)sufoy1]jpheriyl~acetamide

CH

3 Cl-I N NH 4-chlaro-N-{3-[(2,3 232 a l xdimethylpheriyl)aminojquiioxaliri-2 N NHyl)benzenesuffoiamide 0 c 85 CIH y\l13-nitrobeNzenesulfonami 2363 H S"N 9 N dismethyphenyllamoqinoquxain-2 It / - \ yl~aminoensulfonlmphey~ctm 00 N NH ethlo -(3-[(4 23 a XV chlorophnyl)uffonyljainoxquinon-2 ybenzenesulfonamide cl CH86 Table 1 Cpd. No. Structure Name 0, 0 , " ethyl 2-[(3-([(2 239 , zmethylphenyl)sulfonyl]amino~quinoxalin-2 yl)aminoj-4,5,6,7-tetrahydro-l-benzothiophene S-NH 3-carboxylate C1 CI 4-bromo-N-(3-[(2,4 240 N Hdichlorophenyl)amino]quinoxalin-2 I yl~benzenesulfonamide

H

2 C. i ?~I ethyl 5-ethyl-2-[3-{ [(3 241 -_ /nitrophenyl)sulfonyl]amino) quinoxalin-2 HC\, s yl)amino]thiophene-3-carboxylate N' N-(3-{ [3 -(morpholin4 242 0ylsulfonyl)phenyl]amino~quinoxalin-2 yl)benzenesulfonamide 0 HC Op ethyl 2-[(3-{[(4 243 0 f ON~q~ Br bromophenyl)sulfonyl]amino) quinoxalin-2 yI)amino]-4,5,6,7-tetrahydro-l-benzothiophene C ~ 1 3-carboxylate PH 4-methyl-N-(3-{[3-(Piperidin-1 244 N. Cylsulfonyl)phenyljamino~quinoxaini-2 yl)benzenesulfonamide 9"o H J0\4-chloro-N-(3-{[4-(morpholin-4 245 CI N -0( ylsulfonyl)phenyl]aniino}quinoxalin-2 N ;, Pyl)benzenesulfonamide 0 87 Table 1 Cpd. No. Structure Name 4-chloro-N-(3-{[3-(morpholin-4 246 ylsulfonyl)phenyl]amino}quinoxalin-2 yl)benzenesulfonamide 247 N CHa 4-methyl-N-[3-(quinolin-6-ylamino)quinoxalin 2-yl]benzenesulfonamide N8 NH N-(3-{[3-(piperidin-1 248 Nylsulfonyl)phenyl]amino}quinoxalin-2 yl)benzenesulfonamide N, 9 -(3-{[4 249 N (phenylamino)phenyl]amino) quinoxalin-2 yl)benzenesulfonamide 0 PH3 BrN-3{25 250 - bis(methoxy)phenyl]amino}quinoxalin-2-yl)-4 bromobenzenesulfonamide ethyl 2-[(3-{[(3 2 Mnitrophenyl)sulfonyllamino)quinoxalin-2 251 -N/ yl)amino]-5,6-dihydro-4H NH H+O ' cyclopenta[b]thiophene-3-carboxylate PN N\ N -{3 -[(4'-nitrobiphenyl-4-yl)amino]quinoxalin R01 / NH H o 2-yl)benzenesulfonamide N .

88 Table 1 Cpd. No. Structure Name H,C A o) P -ethyl 2-[(3-{[(3 253 N... \ nitrophenyl)sulfonyl]amino}quinoxalin-2 2N H D0NO yl)amino]-4,5,6,7-tetrahydro-1-benzothiophene s 0 3-carboxylate N NN-(3-{[4-chloro-3-(morpholin-4 254 ylsulfonyl)phenyl]amino)quinoxalin-2 p 0 yl)benzenesulfonamide 0 H ,C\ - o N-ethyl 5-ethyl-2-({3 255 [(phenylsulfonyl)amino]quinoxalin-2 H 0 yl}amino)thiophene-3-carboxylate HaC S H N-[4-({[3-(quinolin-6-ylamino)quinoxalin-2 256 yl]amino}sulfonyl)phenylacetamide H O ethyl 2-[(3-{ [(2 257 methylphenyl)sulfonyl]amino}quinoxalin-2 -NH yl)amino]-5,6-dihydro-4H s 0 HC cyclopenta[b]thiophene-3-carboxylate -S 258 C1 3,4-dichloro-N-[3-(naphthalen-1 N NH ,. ylamino)quinoxalin-2-yl]benzenesulfonamide 2 H9 r - ethyl 2-{[3-({[4-(acetylamino)-3,5 259CH 3 dibromophenyllsulfonyl)amino)quinoxalin-2 s r yl]amino)-4,5,6,7-tetrahydro-1-benzothiophene 3-carboxylate 89 Table 1 Cpd. No. Structure Name HaC.C' ethyl 2-[(3-{[(2-chloro-5 260 9' nitrophenyl)sulfonyl]amino}quinoxalin-2 N 10, W UNyl)amino]-4,5,6,7-tetrahydro-1-benzothiophene s ~3-carboxylate 261 N-{3-[(3-fluorophenyl)amino]quinoxalin-2 261r yl}benzenesulfonamide F 9"o0 H 0 N-(3-{[4-(morpholin-4 262 N -0 0ylsulfonyl)phenyl]amino}quinoxalin-2 N O yl)benzenesulfonamide HaC H H a N ~ ethyl 2-L ({ 263 o .C* (acetylamino)phenyl]sulfonyl}amino)quinoxalin NH -2-yl]amino}-4,5,6,7-tetrahydro-1 s benzothiophene-3-carboxylate o N ethyl 2-[(3-{[(4 264 chlorophenyl)sulfonyl]amiino)quinoxalin-2 HaC s- NH oyl)aminoj-5-ethylthiophene-3-carboxylate HC N NH C~aH NN-diethyl-4-(-[(4 265 _3 methylphenyl)sulfonyl]amino}quinoxalin-2 yl)amino]benzenesulfonamide 0 HC -NH ethyl 2-{[3-({[4 266 N H (acetylamino)phenyllsulfonyl} amino)quinoxalin HaC NH H 0 -2-yl]amino}-5-ethylthiophene-3-carboxylate 90 Table I Cpd. No. Structure Name ethyl2-3-[4 267 0 ~~9~)..Ichlorophenyf)sulfonyllamnino) quinoxalin-2 yJ)amino-4,5,6,7-tera1ydro- I -benzothiophene V 3-carboxylate

H

3 C 0 0 N ethyl 2-({3-1(phenylsulfonyl)aniinolquinoxalin 268 2-yl~amino)-4,5,6,7-tetahydro-l \ - H 0benzothiophone-3 -carb oxylate p AN-[4-(methoxy)phonyl]-4-[(3-{ [(3 269 H nitrophenyl)sulfonyljamino~quinoxalin-2 jPIH 9Wt 0 yI)amino]benzamide 270 HNaminophenyl)oxy~phenyllamino)quinoxalin-2 0 yll-4-chlorobenzenesulfonamide 271 amninophenyl)oxylphenyl~amino)quinoxalln-2 N NH yl~aiino~sulfonyl)phenyl]acetarniide c ~~CH3 N H 272 ( N NY IjC3 methylphenyl)sulfonyl]amino~quinoxalin-2 ,Cf yJ)amino]phonyl~prop-2-enoic acid NV-{3-[(9-ethy]-9H-=abazol-3. 273 yl)amino]quinoxalin-2-yI}.3 0 4 NH Nt nitrobenzenesulfonamide 91 Table 1 Cpd. No. Structure Name N a2 N-[3-({4-[(4 274 aminophenyl)oxy]phenyl}amino)quinoxalin-2 yl]benzenesulfonamide a0 275 4-bromo-N-{3-[(9-ethyl-9H-carbazol-3 H75 yoamino]quinoxalin-2-yl}benzenesulfonamide o H 276 N-{3-[(9-ethyl-9H-carbazol-3 N Ayl)amino]quinoxalin-2-yl}benzenesulfonamide

H

3 C~ N NH 277 N-{3-[(2-iodophenyl)amino]quinoxalin-2 N H y])benzenesulfonamide N N 278 NN-{3-[(-phenylethyl)amino]quinoxalin-2 278 N = H yl)benzenesulfonamide 4-bromo-N-{3-[(4 279 N t\ bromophenyl)amino]quinoxalin-2 yljbenzenesulfonamide 0 0 a4-bromo-N-{3-[(4 280 chlorophenyl)amino]quinoxalin-2 yl)benzenesulfonamide 92 Table 1 Cpd. No. Structure Name 281 CjPI4.- N iI -8r 4-bromo-N-[3-(naphthalen-2 ylamino)quinoxalin-2-yl]benzenesulfonamide

H

3 CN( O N-{3-r(2,3-dimethylphenyl)amino]-6 282 3C~Q y~O'methylbenzenesulfonamiide Y< 4-chloro-N-{3-f (2 283 tcHK l' 0 iodophenyl)amino]quinoxalin-2 tr yllbenzenesulfonamide 284 HN' N-(3-{[4-(octyloxy)phenyl]aminolquinoxalin-2 Y N yI)benzenesulfonamide 28 NN N NO 43 ..- (2,1,3-benzothiadiazo 1-5 N%.. / -NH HNS nitroberizenesuffonamide 5' 0 'N CH, M NHN-{3-[(2-bromo-4 286 L)JI\X metbylphenyl) amino] quinoxalin-2 0=8=0yI~benzenesulfonamide P CiI0aNH N-[-(4-63 287 NH2 v-N*L -'s. aminophenyl)sulfonyl]phenyl~amino)quinoxalin N d'O-2-yI]-4-chlorobenzenesulfonandde 93 Table 1 Cpd. No. Structure Name H N-[3-({2 288 [(difluoromethyl)oxy]phenyl}amino)quinoxalin 2-yl]-3-nitrobenzenesulfonamide 0 OH 8-[(3-{[(4 289 NH methylphenyl)sulfonyl]amino}quinoxalin-2 yl)amino]quinoline-2-carboxylic acid al ~CH, F ethyl 3,3,3-trifluoro-2-hydroxy-2-{4-[(3-{[(3 290 N nitrophenyl)sulfonyflamino}quinoxalin-2 N YH yl)ammlo]phenyl}propanoate 0 H 291 N-[3-(quinolin-6-ylamino)quinoxalin-2 ylJbenzenesulfonamide NH 292 N (acetylamino)phenyl]sulfonyl}amino)quinoxalin -2-yl]amino}phenyl thiocyanate o NH cH aI~ N o -[3-({[4 293 (acetylamino)phenylsulfonyl}amino)quinoxalin -2-yl]-4-methylpyridinium. HaC NH 0 94 ________Table 1 -Cpd. No. Structure Name 294 &N-{3-[(2-chlorophenyl)amino~quinoxalin-2-yl} WH HN- /3-nitrobenzenesulfonamide 0 295 N' N 4-methyl-N-[3-(phenylamino)quinoxalin-2 ylllbenzenesulfonamjde 296 '-- 'N4-methyl-N-{3-[(2 296 methylphenyl)aminojquinoxalin-2 yllbenzenesulfonamide 4-methyl-N-{ 3+E4 297 ~ Hmethylphenyi)aniino]quinoxaMi-2 O'S0 yl~benzenesulfonamide 298 N NN-{3-[(4-,chlorophenyl)amino~quinoxain-2-y} 0 4-methylbenzenesulfonamide 299 Nr7NN4-methyl-N.{3-(naphthalen-2 i ylamino)quinoxalin-2-yl]benzenesulfonamide 95 Table 1 Cpd. No. Structure Name NH 300 N-{4-[({3-[(4-bromophenyl)amino~quinoxalin 2 -yl} amino)sulfonyllphenyl}acetamide HN~rN Y:;CH3 N " 301N.- N-{4-[({3-[(2-methylphenyl)amino]quinoxalin 301 -=02-yIlamino)sulfonyljphenyl~acetamide 302 'INX~HN-{3-[bis(phcnylmethyl)ainino]quinoxalin-2 ozs=o yl~bonzenesulfonamide HO 0 >/ & _S- 4-[(3-{[(4 303 mothylphonyl)sulfonyl] amino quinoxalin-2 yl)aniinolbcnzoic acid VG 011,2-hydroxy-4-[(3-{[(4 304 o \O methylphenyl)sulfonyl] amino) quinoxalin-2 & yl)amino]benzoic acid 0CH 3 4-bromo-N-(3-[f2 305 (methoxy)phenyl]amino~quinoxalin-2 yl)benzonesulfonamnide 30 HO yl~bonzenesulfonamide 307 N-[3-(naphthalen-l-ylamino)quinoxalin-2 307 N yIlbnzenesulfonamde 96 Table 1 Cpd. No. Structure Name foly- , CH3 1XN( NH 3-methyl-1-(3-([(4 308 0 methylphenyl)sulfonyl]amino}quinoxalin-2 yl)pyridinium

H

3 N-(3-{[3-{[(4-chlorophenyl)sulfonyl]amino)-7 309 (methoxy)quinoxalin-2 0 Ci yl]amino}phenyl)acetamide 0 o . CH, N-{3-[(3-{ [(4 310 NN a chlorophenyl)sulfonyl]amino}quinoxalin-2 N , t.J yl)amino]phenyl)acetamide N-{3-[(4-bromophenyl)aminolquinoxalin-2-yl} 3 T c 4-chlorobenzenesulfonamide Ha N-{3-[(2,4-dimethylpheny)amino]-6 312 H ac CH methylquinoxalin-2-y)-4 Ha N j methylbenZenesulfonamide CH I )N-{3-[(3,4-dimethylpheny)amino]quinoxalin-2 313 "C H yl)-4-methylbenzenesulfonamide H C CH, N-(3-[(2,5-dimethylphenyl)amino]-6 314 HC ,NHKCN4 methylquinoxalin-2-yl)-4 N methylbenzenesulfonamide 0 Oy CH, I ethyl 4-[(3-{[(4 315 01 chlorophenyl)sulfonyl]amino}quinoxalin-2 yl)amino]benzoate 97 Table I Cpd. No. Structure Name cHa 4-chloro-N-{3-[(4 316 c ethylphenyl)amino]quinoxalin-2 yl}benzenesulfonamide N r%~ CH 4-chloro-N-(6-nethyI-3-{[4 317 . (methoxy)phenyl]amino}quinoxalin-2 HN yl)benzenesulfonamide el 318 c4-chloro-N-{3-[(4-chlorophenyl)amino]-6 Hc NH - methylquinoxalin-2-yl}benzenesulfonanide N, NH HN-(3-{[4-chloro-2,:5 319 N Hbis(methoxy)phenyl]amino)quinoxalin-2 o= =0 yl)benzenesulfonamide H, 0.CH, 32 a N -1NH N-(3([,5 320 N NH bis(methoxy)phenyllamino)quinoxalin-2 1-'-0 yl)benzenesulfbnamide CH, 321 N NFP bis(methoxy)phenyl]amino}quinoxalin-2-y)-4 methylbenzenesulfonamide OMeO OMS -N N9 Noa N-(3-{[3,5 322 N bis(nethoxy)phenyl]amino~quinoxalin-2-yl)-3 nitrobenzenesulfonamide 98 Cpd. No. Structure______Name_ 324 , N-(2-oomethoxy-phenylamino)n N~H quinxali2yJbenzensulfonamide RQ( NHN-mi1N(3{34 325 H 0 is-3(etho 5-hoyphenylamino)ai 324 CQ:Q quylnonzeeln-2 idzelo nmd QN PNH H X CH 3 n'({[(3[3,5 327 ~ N NH bis(methoxy)phenyljaminojquinoxalin-2 H~~CQI~t&QCH~ yl)aminzensulfonlmphey~ctm 328 NH NI-(3-{f4-hoo 326 bs~(methoxy)phenyljminoquinoxalin-2-y)4 0 cylbenznesulfonamide 99 Table 1 Cpd. No. Structure Name F o' CH, N-(3-{[4-fluoro-3 329 N NH (methoxy)phenyl]amino}quinoxalin-2 NH yl)benzenesulfonamide No' NH2 3-amino-N-(3-{[2,5 330 - xJbis(methoxy)phenyljamino}quinoxalin-2 Hac yl)benzenesulfonamide Br N-(3-{[3,5 331 N NW bis(methoxy)phenyl]amino}quinoxalin-2-yl)-4 bromobenzenesulfonamide H CO& , CH, c N-(3-{[2-chloro-5, 332 NH NO2 (methoxy)phenyl]amino}quinoxalin-2-yl)-3 nitrobenzenesulfonamide 0 C1 3-amino-N-(3-{ [2-chloro-5 333 N NH H 2 (methoxy)phenyl]amino}quinoxalin-2 N yl)benzenesulfonamide -- (CH3-{[(3-{[3,5 334 wCH bis(methoxy)phenylJamino)quinoxalin-2 0O yl)amino]sulfonyl)phenyl)-N-2-,N-2 HC O oCHa dimethylglycinamide HC N 335 Ha N I N-(3-{[2,5-bis(methoxy)phenyl]amino)-7 HaC I methylquinoxalin-2-yl)benzenesulfonamnide cCH,1H OC~e N-(3-{[2,5 336 bis(methoxy)phenyl]amino}quinoxalin-2-yl)-4 (methoxy)benzenesulfonamide 100 Table 1 Cpd. No. Structure Name IP -OCH3N-(3-{E2,5 337 ~ N NH 37Br bis(methoxy)phenytl amino) quinoxalin-2-yi)-3 CN bromobenzenesulfonamnide 338 <sNz . N NH bis(methoxy)phenyl]amnino~quinoxalin-2-yl)-3 L~~,~I~H , F fluorobenzenesulfonamide F 339 C C Hbis(methoxy)phenyl]amino}quinoxalin-2-yI)-2 fluorobenzenesulfonamide 340 . N NHbis(methoxy)phenyl]aniino}quinoxalin-2-yl)-4 - N N, H(methoxy)benzenesulfonainide -1 341 . N NHbis(methoxy)phenyl]amino~quinoxalin-2-yl)-3 ;2 r bromobenzenesulfonamide ,0H 3 342 NH-% 0 \ . bis(methoxy)phenyl]anino~quinoxalin-2 NN 0 yl)ainino]sulfonyl~phenyl)-l-metbylpiperidine H3C' )OI.CH, 4-carboxamide 343 N NH 8 -2bis(methoxy)phenyl]amino} quirioxalin-2 34 yl)amino]sulfonyl~phenyl)-3-piperidin-l

H

3

C

0 I1~.

0

.CH

3 ylpropanaxnide 101 Table 1 Cpd. No. Structure Name SH N-(3-{[(3-{[3,5 344 bis(methoxy)phenyl]amino}quinoxalin-2 HC ,JCH yl)amino]sulfonyl}phenyl)-4 (dimethylamino)butanamide N OH N-(3-{[3,5 345 N bis(methoxy)phenyllamino}quinoxalin-2-yl)-3 (hydroxyamino)benzenesulfonamide H C, CH, \ / N-(3-{[(3-{[3,5 346 ~ N NHbis(methoxy)phenyl]amino)quinoxalin-2 yl)amino]sulfonyl)phenyl)-2-morpholin-4

H

3 C, I , OCH 3 ylacetamide cl N-(3-f[(3-f[2-chloro-5 37N N H H (methoxy)phenyl]amino)quinoxalin-2 34N N .I-c yl)amlno]sulfonyl)-4-methylphenyl)-N-2 N H methylglycinamide c : ci N-(3-{[(3-{[2-chloro-5 348 NH NH 2 (methoxy)phenyl]amino}quinoxalin-2 yI)amino]sulfonyl}-4-methylpheny)-L NH ~ OCH 3 alaninamide c CN-(3-{[(3-{[2-chloro-5 349 N(methoxy)phenyl]amino}quinoxalin-2 yl)amino]sulfonyl}-4-methylphenyl)-2 _ ~>Nmethylalaninamide NH2 102 Table 1 Cpd. No. Structure Name H Cl N-(3-{[(3-{(2-chloro-5 350 (methoxy)phenyl]amino}quinoxalin-2 (:: N< NH yl)aminolsulfonyl)-4-methylphenyl)-N-2-,N 2-dimethylglycinamide o' N NH N-(3-([(3-{[3,5 351 bis(methoxy)phenyl]amino}quinoxalin-2 NH CH3 yl)amino]sulfonyl}phenyl)-D-alaninamide O NH2 cI N-(3-{[(3-{[2-chloro-5 352 (methoxy)phenyllamino}quinoxalin-2 N NH yl)amino]sulfonyl)phenyl)-N-2 H methylglycinamide N ci N-(3-{[(3-{[2-chloro-5 353 NH N (methoxy)phenyl]amino}quinoxalin-2 yl)amino]sulfonyl}-4-methylphenyl)-D N 3 NH alaninamide N V INN-(3-{[(3-{[3,5 5 N Nbis(methoxy)pheny]]aniino}quinoxalin-2 354N HH N-&- Q;yl)amino]sulfonyl}phenyl)-N-2 0 Hmethylglycinamide N-(3-{[(3-{[2-chloro-5 355 N NH (methoxy)phenyl]amino)quinoxalin-2 yl)amino]sulfonyl)phenyl)-L-alaninamide N 1H 103 Table 1 Cpd. No. Structure Name 6N NH N-(3-{[(3-{(2-chloro-5 356 (methoxy)phenyl]amino)quinoxalin-2 N 0yl)amino]sulfonyl~phenyl)-D-alaninamide o ~ rLNH 2 N N N-(3-([(3-{[2-chloro-5 7 NH (methoxy)phenyl]amino}quinoxalin-2 N NH yl)amino]sulfonyl)phenyl)-2 H H methylalaninamide Oe: C r'-'::NH2

-

A N-(3-f [(3-f [3,5 358 bis(methoxy)phenyl]amino}quinoxalin-2 O CNINH yl)amino]sulfonyl}phenyl)-2 methylalaninamide N-(3-{{(3-{{3,5 359 N NH bis(methoxy)phenyl]amino~quinoxalin-2 C (N': NHyl)aminolsulfonyl}-4-methylpheny1)-N-2-,N 2-dimethylglycinamide N-(3-{[(3-{ [2-chloro-5 H (methoxy)phenyl]amino}quinoxalin-2 360 yl)amino]sulfonyl)phenyl)-N-2-[2 o H(dimethylamino)ethyl]-N-2 N methylglycinamide (2S)-2-amino-N-(3-((3-{[2-chloro-5 361 N H (methoxy)phenyl]amino}quinoxalin-2 M-CNH NH 2 yl)amino]sulfonyl)phenyl)butanamide N-(3-{[(3-{[3,5 Q H H QObis(methoxy)phenyl]amino)quinoxalin-2 362 yl)amino]sulfonyl)phnyl)-N-2-[2 (dinethylamino)ethyl]-N-2 -methylglycinamide 104 Table 1 Cpd. No. Structure Name 9 N-(3-{[(3-{[2-chloro-5 363 N NH H (methoxy)phenyl]amino)quinoxalin-2 yl)aminojsulfonyl}phenyl)-N-2-,N-2 dimethylglycinamide 364 NH bis(methoxy)phenyl]amino}quinoxalin-2 yl)amino]sulfony}pheny)-N-2-methyl-L alaninamide K-NH _ _ _ _ _ _ _ ,0,N NH N-(3-{[(3-{{2-chloro-5 365 (methoxy)phenyl]anino}quinoxalin-2 NH yl)amino]sulfonyl}phenyl)glycinamide 0o NH2-(3-{[(3-{[3,5 366 N'NH HN bis(methoxy)phenyl]amino}quinoxalin-2 yl)amino]sulfonyl}phenyl)glycinamide c I N-(2-chloro-5-([(3-{[2-chloro-5 367 N (methoxy)phenyl]amino}quinoxalin-2 yoamino]sulfonyl}phenyl)-N-2 N ~methylglycinamide 0 H -N 0 NH 2-(dimethylamino)-N-(3-(N-(3-(3-(2 368 N 9 (dimethyia'mino)acetamido)-5 00 methoxyphenylamino)quinoxalin-2 N KNH yl)sulfamoyl)phenyl)acetamide NH 0 N-(3-{{(3-(2-acetyl-5 369 NH (methoxy)phenyl]amino}quinoxalin-2 yl)amino]sulfonyl}phenyl)-N-2-,N-2 NN )rdimethylglycinamide 105 Table 1 Cpd. No. Structure Namie 370 N N-(3-{2-chloro-5 370 (methoxy)phenyl]amino~quinoxalin-2-yl)-3 N~NH (formylamino)benzenesulfonandde

_HN

M~qN\HN-(3-{E(3-{[2-chloro-5 371 cIIIi 0 (methoxy)phenyllamino~quinoxalin-2 N NH yI)aminojsulfonyljphenyl)-N-2 I cl thylglycinamide 37 NH bis(methoxy)phenyl]amino~quinoxalin-2 372 ANX:NH yl)amino]sulfonyl} -2 01 H methylphenyl)glycinandde III N-2-azetidin-1-yl-N-(3- {[(3-{[2-chloro-5 373 (methoxy)phenyllamino~quinoxalin-2 yl)arninolsulfonyl} phenyl)acetamnide ci N-(3-{[(3-{[2-chloro-5 374 ,,_, NH (methoxy)phenyl]aminolquinoxalin-2 k~ok-XN HNyJ)amino]sulfonyllphenyl)-L-prolinarnide HN-Q_ " N - 0HN - 2 -, N 2 d m t y - - 3{[( 3 -{[2 b6 -o 5 376NH (methoxy)quinl~inoIqinoxquinox-2 37 N -yl)amino]sulfonyI~phenyt)-~cNaniid 10 Table I Cpd. No. Structure Name CH 3 O I~ OCHs3 0 ~ NH N-(3-{[(3-{[,5 377 bis(methoxy)phenyl]amino}quinoxalin-2 N NH yl)aTnino]sulfonyl}phenyl)-L-alaninamide &~ykNHz

CH

3 NH N-(3-{([(3-{[2-chloro-5 378 (methoxy)phenyl]amino}quinoxalin-2 NH yl)amino]sulfonyl)phenyl)-N-2-methyl-D alaninamide ~9H Hs N-(3-{[(3-{[3,5- 379 N NH bis(methoxy)phenyl]amino)quinoxalin-2 yl)amino]sulfonyl}phenyl)-L-prolinamide NXN H 380 'X bis(methoxy)phenyl]amino}quinoxalin-2 N NH H 2 yl)aninojsufonyl)phenyl)-D-serinamide HOH Nk N NH N-(3-{[(3-{[3,5 381 N H bis(methoxy)phenyl]aminoquinoxalin-2 107 yl)aminosulfonylphenyl)azetidine-3 O ,s carboxamide

HN

NH 107 Table 1 Cpd. No. Structure Name N-(3-{[(3-f[2-chloro-5 382 (methoxy)phenyl]amino)quinoxalin-2 yl)amino]sulfonyl}phenyl)-N-2-,2 dimethylalaninamide NHc"q

-

N-(3-{[(3-{[3,5 383 bis(methoxy)phenyl]amino}quinoxalin-2 yl)amino]sulfonyl}phenyl)-N-2-methyl-D 3N alaninamide ,eNH

HN

N NN-(3-{[(3-([2-bromo-5 384 (methoxy)phenyljamnino}quinoxalin-2 yl)aminolsulfonyl)phenyl)-N-2-,N-2 Or dimethylglycinamide N-(3-{[(3-{[3,5 385 bis(methoxy)phenyl]amino}quinoxalin-2 yl)amino]sulfonyl}phenyl)-N-2 propylglycinamide N NH oN-(3-{[(3-([2-chloro-5 386 (methoxy)phenyl]amino}quinoxalin-2 NXNH yl)aminojsulfonyl}phenyl)-N-2-methyl-L N NHalanmnamide 387 bis(methoxy)phenyl]amnino}quinoxalin-2 N H yI)aminojsulfony!)-2-methylphenyl)-beta alaninamide ______ ~ ~< NH 2 108 Table 1 Cpd. No. Structure Name

CH

3 cl N-(3-{[(3-{[2-chloro-5 388 N NH (methoxy)phenyl]amino) quinoxalin-2 IJ yl)amino]sulfonyljpheny)piperidine-3 N H -- NH carboxamide 0o _ N dlIN N-(3-{[(3-{[3,5--2 389 - 7--<N 9 bis(methoxy)phenyl]amino}quinoxalin-2 NH HN-N--Q yl)amino]sulfonyl}phenyl)-2-(4-methyl-1,4 -0 HN N diazepan-1 -yl)acetamide CH 2 NH (2S)-2-amino-N-(3-{[(3-{[3,5 390 bis(methoxy)phnyl]amino}quinoxalin-2 N NH yl)amino]sulfonyl}phenyl)butanamide 0110

NH

2

CH

3 N-(3-{[(3-{[3,5 391 N bis(methoxy)phenyl]amino)quinoxalin-2 yI)aminojsulfonyljphenyl)-N-2-(2 NH hydroxypropyl)glycinamide 0 N N-(3-{[(3-f[2-chloro-5 392" F (methoxy)phenyl]amino}quinoxalin-2 392 0NH yl)aminoJsulfonyl~phenyl)-N-2-(2 o f fluoroethyl)glycinamide N O0 3-amino-N-(2-([3,5 393 NH NH 2 bis(methoxy)phenyljamino}pyrido[2,3 bjpyrazin-3-yl)benzenesulfonamide 109 Table 1 Cpd. No. Structure Name N N - 0N-(3-{[(3-{[3,5 NH HN-- bis(methoxy)phenyl]amino}quinoxalin-2 /94 0N 0 yl)amino]sulfonyl}phenyl)-N-2-[(2 -0 HN NH methylpropyl)oxy]glycinamide N Cl 1-amino-N-(3-{[(3-{[2-chloro-5 395 (methoxy)phenyl]amino}quinoxalin-2 CX'.N'NH yl)amino]sulfonyt}phenyl)cyclopropanecarbo H~ xamide 0-S N NH2 NXN0 N-(3-{ [3,5 396 N NH HN'/ bis(methoxy)phenyl]amino}quinoxalin-2-y) H 3-(forinylamino)benzenesulfbnamide H" NH N-(3-{[(3-{[3,5 397 / \o [. / \ bis(methoxy)phenyl]amino)quinoxalin-2 N - yl)amino]sullbnyl}phenyl)-N-2 (cyclopropylmethyl)glycinamide N-(3-{ [(3-{ [3,5 398 NH bis(methoxy)phenyl]amino}quinoxalin-2 NINH yl)amino]sulfonyl}phenyl)-D-prolinamide N-(3-{[(3-{[2-chloro-5 399 (methoxy)phenylamino}quinoxalin-2 1'N H yl)amino]sulfonyl}phenyl)-2-[3 (dhnethylamino)azetidin-1 -yI]acetamide NH Cl N-(3-{[(3-{[2-chloro-5 400 --, N,(NH (methoxy)phenyl]amino}quinoxalin-2 yl)amino]sulfonyl} phenyl)-D-prolinamide 110 ________Table 1 Cpd. No. Structure Name NH3f(3{35 401 bis(methoxy)phenyljaminolquinoxalin-2 ' ' "NHyl)axninolsulfonyllphenyl)piperidine-2 cril carboxamide cl IN-(3-{[(3-{[2-chloro-5 402 N,,N H (methoxy)phenylaxninolquinoxalin-2 liii yl~aminolsulfonyIlphenyI)morpholine-4 C)(N carboxamide 0=§Q -! ,N-(3 -{ [(3-fEpclo5 404 0 ,NINH H- (methoxy)phenylaminoquinoxalin-2 NH ~ yI)amio]sulfonylphenyAT)-6-py6l- 10,dim laethy-Linad 404 bis NH(methoxy)phenyiaminoquinoxalin-2 a :-NH ~zyl)aminolsulfonyl} phenyl)-N-2-eth--2 0-1 my, rmethyllysinamide / , N-(3-{f(3-{E3,5 406 NJ~0 bis(niethoxy)phenyljamino~quinoxalin-2 405 NH- yl)arninojsulfonyl~phenyl)-]2-h-imdaa-2 -0 Hmylglet amide 406 b(mthoxy)phnylaminoquinoxalin-2 407 1 ~N" ~ 0 yl)anino]sulfonyl}phenyl)cyclopentianecarb " N- :NHxamide ("I NY 11H Table I Cpd. No. Structure Name ' 'N N-(3-{[(3-{[3,5 408 bis(mthoxy)phnyl]amino}quinoxalin-2 0 HH yl)amino]sulfonyl}pheny1)-N-2-(2 H NH methylpropyl)glycinamide N HN N-(3-{[(3-{[2-chloro-5 409 (methoxy)phenyl]amino}quinoxalin-2 yl)amino]sulfonyl}phenyl)-N-2-ethyl-N-2 methylglycinamide N NHNN(-[3{35 410 Ii X bis(methoxy)phenyl]amino~quinoxalin-2 1N H yl)amino]sulfonyl}phenyl)-l-(1H-imidazol-4 ylmethyl)azetidine-3-carboxamide ___ 0 cl N-(5-{[(3-{[2-chloro-5 411 (methoxy)phenyl]amino}quinoxalin-2 4 NH yl)amino]sulfonyl}-2-methylpheny)-N-2-,N 2-dimethylglycinamide N-(3-{j(3-{[3,5 412 bis(methoxy)phenyl]amino}quinoxalin-2 N NH yl)amino]sulfonyl}phenyl)-1-ethylazetidine-3 carboxamide -- HN-(3-{[(3-{[3,5 413 \ bis(methoxy)phenyl]anino} quinoxafln-2 413Q,& 4 -0 yl)amino]sulfonyl}phenyl)-N-2-methyl-N-2 (1-methylpyrrolidin-3-yl)glycinamide N-(3-{[(2-{[3,5 NH bis(methoxy)phenyl]amino}pyrido[2,3~ 414 b]pyrazin-3-yl)aminoJsulfonyl}phenyl)-N-2 NN NH [2-(dimethylamlno)ethyl]-N-2 0 methylglycinamide 112 Table 1 Cpd. No. Structure Name OH N N-(3-{[(3-{{3,5 415 / bis(methoxy)pheny]amino}quinoxalin-2 yl)amino]sulfbnyl)phenyl)-2-[(3S)-3 / \ Nhydroxypyrrolidin-1-yllacetamide 0 & I-amino-N-(3-{f(3-{f3,5 416 NH bis(methoxy)phenylamino}quinoxalin-2 yl)amino]sulfonyl}phenyl)cyclobutanecarbox amide 0 r~jN-(3-{{(3-{{3,5 417

-

bis(methoxy)phenyl]amino}quinoxalin-2 N0 yI)amino]sulfonyl}phenyl)-N-2 NH butylglycinanide N H N-(3-{[(3-{[2-chloro-5 418 ( 0 (methoxy)phenyl]amino}quinoxalin-2 N1 NH yl)amino]sulfonyl}phenyl)-2-(3-piperidin-l ylazetidin-1 -yl)acetamide A O NH 3-f(amninocarbonyl)amino]-N-(3-{[3,5 419 bis(methoxy)phenyl]amino}quinoxalin-2 N NH yl)benzenesulfonamide N NH2 N-(3-{[(3-{[3,5 420 NH bis(methoxy)phenyl]amino} quinoxalin-2 0 yl)amino]sulfonyl}phenyl)-l hydroxycyclopropanecarboxamide H 1 113 Table 1 Cpd. No. Structure Name N-(3-{[(3-{{3,5 421 bis(nethoxy)phenyljamino}quinoxalin-2 0 yl)amino]sulfonyl}phenyl)-2-(2,2 N.NH dimethylhydrazino)acetamide NV-(3-{[3,5 NH bis(methoxy)phenyllamino}quinoxalin-2-y) 422 3-[({[2 N H (dimethylamino)ethyljamino) carbonyl)aminol X Nl Nbenzenesulfonamide N H N-(3-{[(3-{[3-fluoro-5 423 (nethoxy)phenyl] amino)quinoxalin-2 N H yl)aminojsuffonyl}phenyl)-N-2 methylglycinamide 06F N-(3-{{(3-{[3,5 424 bis(methoxy)phenyl]amino) quinoxalin-2 NH N yl)amino]sulfonyl}phenyl)-2 -0 hydroxyacetamide N N-(3-{[(3-{[3,5 425 \ bis(methoxy)phenyl]amino) quinoxalin-2 yl)amino]sulfonyl}phenyl)pyridazine-4 -o H carboxamide NN-(3-{[(3-{[3,5 426 bis(methoxy)phenyl]amino}quinoxalin-2 4 o yl)amino]sulfonyl}phenyl)-N-2-(1 -o HNJ(.NH methylethyl)glycinamide S1-amino-N-(3-{[(3-{[3,5 427 N NH bis(methoxy)phenyl]amino}quinoxalin-2 42. yl)amino]sulfonyl}phenyl)cyclopentanecarbo N H xamide ONH2 114 Table 1 Cpd. No. Structure Name cei 3 ' 0

CH

8 I-k,~ NH I-amino-N-(3-{[(3-([3,5 428 bis(methoxy)phenyl]amino}quinoxalin-2 NH yl)amino]sulfonyl}phenyl)cyclopropanecarbo xamide N~ H5I' N NH N-(3-{[(3-{[3,5 429 bis(methoxy)phenyl]amino}quinoxalin-2 O 0 yl)amino]sulfonyl}phenyl)-2-[3 (dimethylamino)pyrrolidin-1-yl]acetamide N O' N NH N-(3-{[(3-{[3,5 430 bis(methoxy)phenyl] amino)quinoxalin-2 I NHyl)aminojsulfonyl}phenyl)-N-2-[2 Z, O (dimethylamino)ethyl]glycinamide O N N O 2-(dimethylamino)ethyl(3-{[(3-{[3,5 431 bis(methoxy)phenyl]amino)quinoxalin-2 NH yl)aminolsulfonyl}phenyl)carbamate O N N-(3-{[(3-{[3,5 432 bis(methoxy)phenyaminoquinoxn-2 432 a NIINH yl)amino]sulfonyI~phenyl)-I (cyclopropymethyl)azetidine-3-carboxamide N N N-(3-{[(3-{[3,5 433 Nbis(methoxy)phenyl]amino}quinoxalin-2 0 yl)amino]sulfonyl}phenyl)-N-2-(1,1

-

- NH dimethylethyl)glycinamide 115 Table 1 Cpd. No. Structure Name HN N-2-methyl-N-(3-{[(3-{[3 434 (mthoxy)phenyl]amino}quinoxalin-2 yl)amino]sulfonyl}phenyl)glycinmide yl)amino]sulfonyllphenyl)-1H-imidazoie-2 carboxamide NV-(3-{[(3-{[3,5 436 bis(methoxy)phenyl]amino}quinoxalin-2 yl)amino]sulfonyl}phenyl)isoxazole-5 0 I carboxamide HN _ N c~aN-(3-([(3-([2-chloro-5 437 \C (methoxy)phenyl]amino}quinoxalin-2 k';NXNH yl)amino]sulfonyl}phenyl)-N-2-(2,2,2 cl trifluoroethyl)glycinanide H N N-S8 0 3-amino-N-(3-{[2-methyl-5 438 N NH NH 2 (methoxy)phenyllamino}quinoxalin-2 yl)benzenesulfbnamide 0 N-(3-([(3-([3,5 439 Hbis(methoxy)phenyljaminolquinoxalin-2 N yl)amino]sulfonyl}phenyl)-3 oxocyclopentanecarboxamide N-(3-([(3-([3,5 44() bis(methoxy)phenyl]amino}quinoxalin-2 yl)amino]sulfonyl}phenyl)-6 H hydroXypyridine-2-carhoxamide OH S p N-(3-{[(3-{[3,5 441 bis(methoxy)phenyl]amino}quinoxalin-2 4 yl)aminolsufonylphnyl)-N-2-(3-fluoro-4 hydroxyphenyl)glycinamide 116 Table 1 Cpd. No. Structure Name 442 bis(methoxy)phenyllamino}quinoxalin-2 H yJ)amino]suJfonyI}pheny)-1 -(furan-2 ylmethyl)azetidine-3-carboxamide -,N N-(3-{ [(3-{[(3,5 443 bis(methoxy)pheny]amino}quinoxalin-2 o 0yl)amino]sulfonyl}phenyl)pyrimidine-5 carboxamide z N-(3-{[(3-{[3,5 444 H bis(methoxy)phenyl]amino}quinoxalin-2 Nl yl)amino]sulfonyl}phenyl)-1H-pyrrole-2 & W-f 1 0 carboxamide N N N-(3-{[(3-{[3,5 445 Hbis(methoxy)phenyl]amino}quinoxalin-2 yl)amino]sulfonyl}phenyl)-N-2-methyl-N-2 C/9 (1-methylethyl)glycinamide 0 HN N-(3-{[(3-{[3-fluoro-5 446 (methoxy)phenyl]amino}quinoxalin-2 NJNH yl)amino]sulfonyl}phenyl)-N-2-,N-2 dimethylglycinamide "a6F OV I HN-(3-{[(3-{[3,5 447 HH N bis(methoxy)phenyl]amino}quinoxalin-2 N yl)anino]sulfonyl}phenyl)-lH-imidazole-4 0 carboxamide bis(methoxy)phenyl]amino}quinoxalin-2 448 yi)aminolsulfonyl}phenyl)-N-2-,N-2 -- o diethylglycinamide 117 Table 1 Cpd. No. Structure Name I , H' N-(3-{[(3-{[3,5 4 / bis(methoxy)phenyllamino}quinoxalin-2 ) -NH HN-1 _ yl)amino]sulfonyl}phenyl)-2-(3 methylisoxazol-5-yl)acetamide -o N N-2-,N-2-dimethyl-N-(3-{[(3-{[2-methyl-5 450 N NH (methoxy)phenyljamino}quinoxalin-2 yl)amino]sulfonyl}phenyl)glycinamide 0 N-(3-{[(3-{[3,5 451 NH ~ bis(methoxy)phenyl]amino)quinoxalin-2 --o H H yl)amino]sulfonyl}phenyl)-N-2-[(3 4 LNH hydroxyphenyl)methyl]glycinamide _ HO~C N-(3-{[(3-{{3,5 452 bis(methoxy)pheny]]amino)quinoxalin-2 yl)amino]sulfonyl}phenyl)-l-methyl-IH _N pyrrole-2-carboxamide 4-amino-N-(3-{[(3-{[3,5 453 . N NH bis(methoxy)phenyl]amino}quinoxalin-2 yl)amino]sulfonyl}phenyl)tetrahydro-2H HNNH pyran-4-carboxamide

NH

2 Ifo NH N-(3-{[(3-{[3,5 454 | bis(methoxy)phenyl]amino)quinoxalin-2 N"NH H yl)amino]sulfonyl)phenyl)-2-[4 NK N (methylamino)piperidin-1-yljacetamide 0 N H N-(3-{[(3-{[3,5 455 N NH HN bis(methoxy)pheny]]amino)quinoxalin-2 N yl)amino]sulfonyl)phenyl)-2-piperidin-l ylacetamide 118 Table 1 Cpd. No. Structure Name -N N-(4-{[(3-[3,5 456 0 N bis(methoxy)phenyl]aminolquinoxalin-2 H- -H HN yl)amino]sulfonyl}phenyl)-N-2-,N-2 dimethylglycinamide 00 N-(3-{[(3-{[3,5 457 . NH H,, H bis(methoxy)phenyl]amino}quinoxalin-2 o yl)amino]sulfonyllphenyl)-1-methyl-L o o prolinamide N-(3-{[(3-{[3,5 4 NH H o bis(methoxy)phenyl]anino}quinoxalin-2 yl)anino]sulfonyl}phenyothiophene-3 N 0 carboxamide

NH

2 H 0 N N-S 0 3-amino-N-{3-[(2-chloro-5 459NH hydroxyphenyl)amino]quinoxalin-2 ClH yl}benzenesulfonamide HO 0= N N-(3-[(3-{[3,5 N, NH bis(methoxy)phenyljamino}quinoxalin-2 460 N'NH yl)amino]sulfonyl}phenyl)-l (cyclopropylcarbonyl)azetidine-3 carboxamide 0 N-(3-{[(3-{[3,5 461 bis(methoxy)phenyl]amino}quinoxalin-2 yl)anino]sulfonyl}phenyl)-2-(4 methylpiperazin-1-yl)acetamide N N N-(3-{[(3-{[3,5 462 bis(methoxy)phenyl]amino}quinoxalin-2 6N H yl)aminolsulfonyl}phenyl)-1 (phenylmethyl)azetidine-3-carboxamide 119 TabIe 1 Cpd. No. Structure Name C=3 N-(3-{[(3-{[3,5 463 N N NH bis(methoxy)phenyl]amino}quinoxalin-2 463 N0yl)amino]sulfonyl}phenyl)-2-chloropyridine NH N-& 3-carboxamide 0 N-(3-{[(3-{[3,.5 464 r 0 bis(methoxy)phenyl]amino}quinoxalin-2 -- /yI)aminoasulfonyl}phenyl)-2-pyridin-4 ylacetamide 0 d N-(3-{[(3-{[3,5 0 465NN-- bis(methoxy)phenyl]amino}quinoxalin-2 6 yl)amino]sulfonyl~phenyl)-N-2-methyl-N-2 -O H prop-2-en-I-ylglycinamide

CH

2 S0 N-(3-{[(3-{[3,5 466 ql'- bis(methoxy)phenyl]amino}quinoxalin-2 -6 0yl)amino]sulfonyl}phenyl)-N-2 -NH (phenylmethyl)glycinamide N-(3-{[(3-{[3,5 467 6-N NH bis(methoxy)phenyl]amino}quinoxalin-2 yl)aminojsulfonylphenyl)-2 N 0 c)(methoxy)acetamide o N ry NH H - N-(3-{[(3-{[3,5 468 bis(methoxy)phenyl]amino}quinoxalin-2 NH8 yl)amino]sulfonyljphenyl)-l propanoylazetidine-3-carboxamide H1 1 N-(3-{[(3-{[3,5 469 bis(methoxy)phenyl]amino}quinoxalin-2 yl)amino]sulfonylphenyl)pyridine-3 carboxamide _0 12 120 Table 1 Cpd. No. Structure Name N 0 N-(3-{[(3-{[3,5 470 NH bis(methoxy)phenyl]amino}quinoxalin-2 yl)amino]sulfonyl}phenyl)-N-2-[2 NH (methoxy)ethyl]glycinamide 0 0 N N- 1-acetyl-N-(3-{[(3-{[3,5 471 / HHN1& 0 bis(methoxy)phenyloamino}quinoxalin-2 -o H yl)amino]sulfonyllphenyl)piperidine-4 carboxamide 0-o N NH H N-(3-{[(3-{[3,5 472 bis(methoxy)phenyl]amino)quinoxalin-2 NH H yl)amino]sulfonyl}phenyl)-2-(2 - methylpyrrolidin-1-yl)acetamide N -0 N-(3-{1(3-{[3,5 473 Nbis(methoxy)phenyl]amino}quinoxalin-2 NH P- yl)anino]sulfonyllphenyl)furan-3 N 0 carboxamide N-2-,N-2-dimethyl-N-(3-{[(3-{[3 474 HN--- (methoxy)phenyljamino}quinoxalin-2 yl)aminolsulfonyl}phenyl)glycinamide N N C1 N-(3-{[(3-{[3,5 475 N N bis(methoxy)phenyl]amino}quinoxalin-2 5 H 0 yl)amino]sulfonyl}phenyl)-6-chloropyridine HN' NH 3-carboxamide 121 Table 1 Cpd. No. Structure Name - H cl 0 CSNH N-(3-{[(3-{[3,5 476 bis(methoxy)phenyl]amino}quinoxalin-2 / N\ H yl)amino]sulfonyl)phenyl)-2 chlorobenzamide -o N-(3-{[(3-{[3,5 477 >=o _ bis(methoxy)phenyl]amino)quinoxalin-2 NH HN-j--4/, yl)amino]sulfonyl}phenyl)-2-pyridin-2 -H ylacetamide NH N-(3-{[(3-{[3,5 478 NH bis(methoxy)phenyl]amino}quinoxalin-2 0 yl)amino]sulfonyl~phenyl)-2-[3 (dimethylamino)azetidin-1-yl]acetamide

N

N-(3-{[(3-{[3,5 479 N N bis(methoxy)phenyl]amino)quinoxalin-2 NH HHN- N yl)amino]sulfonyl)phenyl)-2-pyridin-3 O /HN ylacetamide -0 HN C-1 HN LN-(3-{[(3-{[3,5 480 cl bis(methoxy)phenyl]amino}quinoxalin-2 N yl)amino]sulfonyl)phenyl)-2-(2 N, chlorophenyl)acetamide N-(3-{[(3-{[3,5 SNH bis(methoxy)phenyl]amino)quinoxalin-2 481 yl)aminojsulfonyl)phenyl)-N-2-[3 -NH (dinethylamino)propyl]-N-2 o4Q \ 0 -- methylglycinamnide O N No N-(3-{[(3-{[3,5 482 NHHN- bis(methoxy)phenyl]amino)quinoxalin-2 8 o -H yl)amino]sulfonyl}phenyl)-N-2-ethyl-N-2-(2 HN- N 1 hydroxyethyl)glycinamide 122 Table 1 Cpd. No. Structure Name N-(3-{[(3-{[3,5 483 bis(methoxy)phenyl]anino~quinoxalin-2 q /yl)aminosulfonyl}phenyl)-2-[2 /\ NHHN+ (phenylmethyl)pyrrolidin-1-yllacetamide -- o 48 N NH N-(3-{{(3-{{3,5 484 N NH bis(methoxy)phenyllamino)quinoxalin-2 N yl)aminolsulfonyl)phenyl)propanamide N-(3-{{(3-{{3,5 485 0\ bis(methoxy)phenyl]amino}quinoxalin-2 yl)aminolsulfonyl)phenyl)furan-2 . 0 0 carboxamide 0 / N-(3-{[(3-{[3,5 486 H -N bis(methoxy)phenyl]amino} quinoxalin-2 yl)aminolsulfonyl}phenyl)-2-chloropyridine 0 I 4-carboxamide NH 91C N N-2-acetyl-N-(3-{[(3-{[3,5 487 N NH HN 0 bis(methoxy)phenyl]amino)quinoxalin-2 yl)amino]sulfonyl)phenyl)glycinamide N-(3-{{(3-{{3,5 488 . bis(methoxy)phenyl]amino}quinoxalin-2 yl)amino]sulfonyl}phenyl)butanamide N Cl N-(3-{[(3-{[3,5 ITc 489 o .-- -.. N bis(metboxy)phenyl]amino}quinoxalin-2 HN yl)amino]sulfonyl}phenyl)-4 NH chlorobenzamide 123 Table 1 Cpd. No. Structure Name N-(3-{{(3-{[3,5 490 HN- bis(methoxy)phenyl]amino}quinoxalin-2 yl)amino]sulfonyl}phenyl)-4 HN methylbenzamide 1,1-dimethylethyl{2-[(3-{[(3-{[3,5 491 N H HN bis(methoxy)phenyl]amino)quinoxalin-2 0 yl)amino]sulfonyl}phenyl)amino]-2 oxoethyl}carbamate N-(3-{[(3-{[3,5 492 NH bis(methoxy)phenyl]amino~quinoxalin-2 A4ef- 0 yl)amnino]sulfonyllphenyl)-1,3-benzodioxole 11 .N o 5-carboxamide N . H H N -N-(3-{{(3-{{3,5 493Q bis(methoxy)phenyl]amino)quinoxalin-2 -o HN-/§ yl)amino]sulfonyl}phenyl)-N-2-({[2 N*H (methoxy)phenyj]methyl}oxy)glyinamide Q/ \NN-(3-{[(3-{{3,5 494 NnmH-9 bis(methoxy)phenyljamino~quinoxalin-2 o/ 0 yl)aminojsulfonyl}phenyl)pyridine4 0 -- 0 carboxamide FI N-(3-{((3-{([4-fluoro-3 495 N HN"" (methoxy)phenylamino}quinoxalin-2 yl)amino]sulfonyl}phenyl)-N-2,N-2 dimethylglycinamide o12 124 Table 1 Cpd. No. Structure Name Cr ___N-(3-{[I(3-{[3,5 496 N Nbis(methoxy)phenyl]aminolquinoxalin-2 ,,L '6 0yl)amino~sulfonyl~phenyl)-2-[4-(3,4 N r N Idkhlorophenyl)piperazin-1 -yllacetamide 0 N-(3-{II(3-{13,5 497 \ / H NHN--J4 bis(methoxy)phenyllaino~quinoxalin-2 49 -- yl)amino~sulfonyllphenyl)-3-pyridin-3 H ylpropanwmide 498 N pbis(methoxy)phenyllamino~quinoxain-2 yloanino~sulfonyl~phenyl)tctrahydrofuran-3 & N Q' carboxamide NF % N-(3-{[(3-{[3,5 499 bis(methoxy)phenyllaminolquinoxalin-2 ~ / NHyl)wniino]sulfonyllphenyl)-N-2-[(2 -oH- CH. methylphenyl)niethyljglycinamide N N N(-[3j35 500 o~ bis(methoxy)phenyljamino~quinoxalin-2 SoH N -s yI)amino~sulfonyllphenyl)-2 00methylbutanamide /\NH HNf j 0V(-[3135 501 - - NJ1 H-' bls(methoxy)phenyl]amino~quinoxalin-2 Q fluorophonyl)acetaniide F 125 Table 1 Cpd. No. Structure Name A2N N N-(3-{ [(3-{[3,5 502 0' / bis(methoxy)phenyl]amino)quinoxalin-2 yl)amino]8ulfonyl)phenyl)-N-2-(1-methyl-1 -NH phenylethyl)glycinamide ql, N-(3-{[(3-{[3,5 503 NH bis(metboxy)phenyl]amino)quinoxalin-2 yl)amino]sulfonyl}phenyl)-2 methylcyclopropanecarboxamide N N N-(3-{[(3-{[3,5 504NH HN- bis(methoxy)phenyl]anino)quinoxalin-2 -4 yl)aminojsulfonyl}phenyl)-2-methyl-4 -o- (methoxy)benzamide N N ON-(3-{[(3-{[3,5 50 Nbis(methoxy)phenyl]amino)quinoxalin-2 505 OKiP yl)aminojsulfonyl}phenyl)-2-methylpyridine -o Hk- 3-carboxamide ) =(N N-(3-{[(3-{[3,5 506 NH H bis(methoxy)phenyl]amnino}quinoxalin-2 -0 yl)aminojsulfonyl)phenyl)-4 (methoxy)benzamide 0 507 - C bis(methoxy)phenyl]amino)quinoxalin-2 NHHYJ yl)amino]8ulfonylphenyl)-2-(4 - -O O0 HN N N ethylpiperazin-1-yl)acetamide 126 Table 1 Cpd. No. Structure Name N-(3-{[(3-{[3,5 50 Ob NH H 0 H bis(methoxy)phenyl]amino}quinoxalin-2 yl)amino]sulfonylphenylthiophene-2 N carboxamide 509 HN-< o H1- N-(3-{[(3-{[3,5 509 HN bis(methoxy)phenyl]amino}quinoxalin-2 yl)amino]sulfonyl)phenyl)-3-fluoro-2 N methylbenzamide 0~0 NN-(3-{[(3-{[3,5 510 N H bis(methoxy)phenyl]amino}quinoxalin-2 yl)aminolsulfonyl}phenyl)-2 bromothiophene-3-carboxamide 511 106 N -N p N-(3-{[(3-{[3,5 512 0 - bis(methoxy)phenyl]amino}quinoxalin-2 HN- NH yl)aminojsulfonyljphenyl)-4-fluorobenzamide N-(3-{[(3-{[3,5 512 - )-( 0 bis(methoxy)phenyl]amino}quinoxalin-2 \NH HNyi)amino]sulfonyl}phenyl)-2-(3 OHN- d methylpiperidin-l-ylacetamide - N N N-(3-[(3-{[3,5 513 bis(methoxy)phenyl]amino}quinoxalin-2 \/ NH HN--Q y])aminojsulfonyl~phenyl)-2 HN 0 methylpropanamnide 514 HNN-/r 0 N-(3-{[(3-{[3,5 514 NH HN_. bis(methoxy)phenyl]amn-do~quinoxalin-2 0 yl)amino]sulfonyllphenyl)pentanamide 127 Table 1 ____________________ Cpd. No. Structure Name 515 NH bis(methoxy)phenyljatmino~quinoxain-2 51J1 yl)aminojsulfonyl~phenyl)-2 (ethyloxy)acetamide Q NH HN-I J 51 C' is(methoxy)phenyljamino~quinoxalin-2 516N yl)aminojsulfonyl~phenyl)-N-2-(2 (J~i4' ~ fluoropheny~glycinamide 517 \/bis(methoxy)phenyl]amnino~quinoxalin-2 o yl)amino]sulfonyl~phenyt)-3 -HN- (dimethylamino)benzamide N-3-[3-[35 518 0bis(methoxy)phenyl]amino~quinoxalin-2 1, n. N-9g-.Qyloaminojsulfonyllphenyl)-2-(4 -0 HN-gc methylpiperidin-I -yl)acetainide N N N-(3-{t(3-{L3,5 519 \/ N bis(methoxy)phenyl]amino~quinoxalin-2 -oN- yl)amino]sulfonyl~phenyl)-N-2-(2 _NH propylphenyl)glycinamide 520 r NY NH~ bis(methoxy)phenyl]ajnno}quinoxalin-2 yl)amino]sulfonyljphenyl)benzamide 521 \ /bis(methoxy)phenyl]amino}quinoxali-2 N00NIQ yl)amino]sulfonyljphenyl)pyrazine-2 -0 HN-bcarboxamide 128 Table I Cpd. No. Structure Name 52 bis(methoxy)phenyl]amino}quinoxalin-2 yI)aminojsulfonyl~phenyl)-3-fluoro-4 -F 52 bis(metboxy)phenyl]amninolquinoxalin-2 523 Hyl)amino]sulfbnyl~phenyl)-2,2 8, dimethylbutanamide 52 . '.N bis(methoxy)phenyl) amino) quinoxalin-2 52 lb p yI)amino]sulfonyl~phenyl)-2-[(4 I-I~4~r Wf~Yfluorophenyl )oxy]acetamide o 1-acetyl-N-(3-{[(3-{[3,5. 525,, kHIIC bis(methoxy)phenyl]aminolquinoxalin-2 52 NXNH yl)aminojsulfonyl}phenyl)azetidine-3 carboxamide IN-(3-1[(3-{[3,5 526 bis(methoxy)phenyllamino~quinoxalin-2 -0 HN-A'_ yl)amnino]sulfonyl~phenyl)-N-2-(4 NH methylphonyl)glycinamide 527 \ / " bis(methioxy)phenyl] amino) quinoxalin-2 0 yl)amino]sulfonyljphenyl)-N-2 -HN-'(N phenyiglycinamide _/ 0V(-[3{35 528 0bis(methoxy)pheniyl~amino}quinoxalin-2 H-lN -Q-Nyl)amino]sulfonyl} phenyl)-2-(4-prop-2-en-1 -oNI/ - yipiperazin-1-yl)acetatnide 129 Table 1 Cpd. No. Structure Name - N N-(3-{[(3-{1[3,5 H- H bis(methoxy)phenyl]aminojquinoxalin-2 529 /NH HM- / yl)amino]sulfonyl}phenyl)-2 - HNmethylbenzamide Oo, / N-(3-{[(3-{13,5 530 ' NH bis(methoxy)phenyl]aminolquinoxalin-2 yl)amino]sulfonyl}phenyl)-3 N N' (methoxy)propanamide 6NH N-(3-{[(3-{[3,5 531 NH bis(methoxy)phenyl~amino}quinoxalin-2 531 __ yl)aminoJsulfonyl}phenyl)-3-methylfuran-2 ol o carboxamide N-(3-{[(3-{[3,5 532 NH bis(methoxy)phenyl]amino}quinoxalin-2 R o 0yl)amino]sulfonyl}phenyl)-2,2 N dimethylpropanamide 'NH N-(3-{[(3-{[3,5 HN-4 bis(methoxy)phenyljamino} quinoxalin-2 533 o o yl)aminolsulfonyl~phenyl)-NV-2 NIH [(phenylmethyl)oxylglycinamide . N-{3-[({3-{(2-chloro-5 534 \/hydroxyphenyl)amino]quinoxalin-2 yl}amino)sulfonylJphenyl}-N-2-,N-2 G H 6 Cdimethylglycinamide 130 Table I Cpd. No. Structure Name 00 I lNH HN 0 N-(3-{[(3-{[3,5 535 N q bis(methoxy)phenyl]amino} quinoxalin-2 NH yl)amino]sulfonyl}phenyl)-N-2-(3 o o/ chlorophenyl)glycinamide NH" .N-(3-{[(3-{E3,5 53 NH bis(methoxy)phenyl]amino}quinoxalin-2 yl)amino]sulfonyl}phenyl)cyclobutanecarbox NX amide N-(3-{[(3-{{3,5 537 bis(methoxy)phenyl]amino}quinoxalin-2 NH /N yl)aminojsulfonyl}phenyl)-2-[3 (methoxy)phenyllacetamide 0 538 N NH bis(methoxy)phenyl]amino}quinoxalin-2 01, 1,0 ryl)aminosulfonyl}phenyl)-1 methylcyclopropanecarboxamide NH_ Y§-H HNN-(3-{[(3-{[3,5 539 HN A bis(methoxy)phenyl]amino}quinoxalin-2 yl)amino]sulfonyl}phenyl)-3-fluorobenzamide 0 ~N-(3-{[(3-{[13,5 540 bis(methoxy)phenyljamino}quinoxalin-2 -o yl)amino]sulfonyl}phenyl)-4 (dimethylamino)benzamide N-(3-{[(3-{[3,5.. 541 HN bis(methoxy)phenyljamino}quinoxalin-2 HN yl)aminolsulfonyl}phenyl)-3,4 Hq iP dichlorobenzamide c3 ci131 Table 1 Cpd. No. Structure Name \/ NH O,\-,-NHHN-?N-(3-{[(3-{[3,5 542 0 bis(methoxy)phenyl]amino}quinoxalin-2 -o yl)amino]sulfonyl}phenyl)-N-2-{[2 NH (methylthio)phenylmethyl}glycinamide --S HN- N-(3-{[(3-{[3,5 543 0 F bis(methoxy)phenyl]amino}quinoxalin-2 75 00 yl)amino]sulfonyl}phenyl)-2-(2 N4 fluorophenyl)acetamide CH N N-(3-{[(3-([3,5 544 -NH HN-SC bis(mothoxy)phenyl]amino)quinoxalin-2 S/o yl)amino]sulfbnyl}phenyl)-N-2-ethyl-N-2-(1 CH HN.AL /-CH. methylethyl)glycinamide

CH

3 N-(3-{[(3-{[3,5 545 N NH bis(methoxy)phenyl]amino}quinoxalin-2 N Q yl)amino~sulfonyl)phenyl)-1,3-thiazole-4 ND $ carboxamide H/\ NHH

-

N \ - H HNi_ N-(3-{[(3-{[3,5 46 NH HN--bis(methoxy)phenyl]amino}quinoxalin-2 546 0 HN / yl)amino]sulfonyl)phenyl)-N-2-methyl-N-2 (phenylmethyl)glycinamide 132 Table 1 Cpd. No. Structure Name 00 HN N-(3-([(3-([3,5 547 Nbis(niethoxy)phenyl]amino~quinoxalin-2 HN- yl)aniinolsulfonyl}phenyl)-N-2-(2 thienylniethyl)glycinamide _____NHi0 548 bis(niethoxy)phenyl]amino) quinoxalin-2 -0 H yI)amino]sufonypheny)A-2-(pyridin-2 h-NH ylmethyl)glyeinamide '6N 549 0 bis(methoxy)phenyl]aniino} quinoxalin-2 54 / H "N+X / , Yl)aminojlsulfonyllphenyl)-3 -oHN-// (niethoxy)benzamide I I IQN N-3((3(35 550 -1NC 0 bis(niethoxy)phenyllaminolquinoxalin-2 NH H 0 Hr H yI)amnino]sulfcnyl~phenyl)-N-2-[(3-chloro-4 N miethylphenyl)rnethyl]glycinamide 0 /N AT-(3-([(3-{II3,5 55' \ /bis(methoxy)phenyljaminolquinoxalin.2 00 0 HIethylpentanamide ________Table I Cpd. No. Structure Name '-' / N-(3-{[(3-([3,5 552 HN NI bis(methoxy)phenyl]aminolquinoxalin-2 HN- r ylamino]sulfbnyljphenyl)-2-(4 N- chlorophenyl~acetamide /P 0 IN ( ~ N-(3-{[(3-([3,5 553 H N bis(methoxy)phenyl]aminolquinoxalin-2 HlM yl)aininojsulfonyllphetnyl)-3-fluoro-4 o - omethylbenzamide 0 NNi-(3-((3-{j3,5 554 N\ / H N ~- '--Q 0 bis(motboxy)phenyljamino~quinoxalin-2 8 //yI)amixiolsulfonu1}phenyl)-2-[(2 -0 jN-- methylphenyl)oxylacetamide 555 N -'N 0bis(methoxy)phenyl]amino~quinoxalin-2 O,-/NNH N0Q yI)amino]sulfonyllphenyl)-2 cyclohexylacetamide -00 556 -~ ~ t b( hx~hnylrioqunxln2 \/ N iM <>H \ /! yl)aminojsulfonyllphenyl) -oHN H phenylcyclopropanecarboxamide 0 I0 00 0 N / HN r 4 Nbis(methoxy)phenyljanmino)quinoxalin-2 570 /Pyl)amino]sulfonyl)phenyl)-3 - (\) chlorobonzaniide 134 Table 1 Cpd. No. Structure Name 0 N N N-3{/3(35 558 0/ bis(methoxy)phenyljamino~quinoxalin-2 -0 0 N (methoxy)phenyl]acetamide HN0 0 t 0 559 0 bis(methoxy)phenyl]amino~quinoxalin-2 -0 HY Yl)amnOlsulfonYl)phenYl)-3-[3 (methoxy)phenyl]propanamide -0 0 560 Hbis(methoxy)phenyl]amino~quinoxalin-2 yl)amino]sulfonyl}phenyl)-N-2-(2-fluoro-4 -N - ethlpenyl)glynand )==< 0'~ 0 N-(3-([(3-{[3,5 561 -oHN-' bis(methoxy)pheny]aniino~quinoxalin-2 HN yl)aminojsulfonyl~phenyl)-N-2-[(3 KI~ fluorophenyl)methyl]glycinamide 562 -bis(methoxy)phenyl]amnino~quinoxalin-2 562 N~HN~ / yl)amino]sulfonyllphenyl)-2-[4 -0 H - R (methoxy)phenyl]acetamide 0 563 -bis(methoxy)phenyl]amino)quinoxalin-2 \ -/NH HN---Q ~ yI)amino]sulfonyl)phenyl)-2-phenylacetamide -0 HN 0 135 Table 1 Cpd. No. Structure Name ClHN H NV-(3-{[(3-{[3,5 564 NH bis(methoxy)phenylamino}quinoxain-2 NH yl)aminoJsulfonyl}phenyl)-2,4 dichlorobenzanide -o 0 N -- > N-(3-{[(3-{[3,5 565 HH bis(methoxy)phenyl]amino}quinoxalin-2 yl)aminoJsulfonyl}phenyl)-3 -0 HN oxocyclohexanecarboxamide O0 0 0 -NH H P -0 H- -N-(3-{[(3-{[3,5 566 NH bis(methoxy)phenyl]anino}quinoxalin-2 NH yl)amino~sulfonylphenyl)-N-2-(3 <H fluorophenyl)glycinamide F 0 / NH HN~ N-(3-{[(3-{[3,5 567 bis(methoxy)phenyl]amino}quinoxalin-2 yI)amino]sulfonyl}phenyl)-2-(3 chlorophenyl)acetamide \9 N-(3-{[(3-([3,5 5H-bis(methoxy)phenyl]anino}quinoxalin-2 568 H / NH yl)aminosulfonyl}phenyl)-N-2-(2 8 Nphenylpropyl)glycinamide NN N-(3-{ [(3-{[3,5 569< N- bis(methoxy)phenyl]amino}quinoxalin-2 569 Nyl)amino]sulfonyl}phenyl)-N-2-[(2,4 {NH dimethylphenyl)methyl]glycinamide 136 Table 1 Cpd. No. Structure Name N N-3{(3{3N 570 0 bis(mothoxy)phenyllamino}quinoxalin-2 NH HN- yl)amino]sulfonyl}phenyl)-2-(2 -o H N methylpiperidin-1-yl)acetamide /oN q/ ?N-(3-{[(3-{[3,5 571 NH HN-& 7), bis(methoxy)phenyl]amino)quinoxalin-2 0 o yl)amino]sulfonyl}pheny)-N-2-[2 HMN H (methoxy)phenyl]glycinamide _ /~0-b __ N NN3 ( -9 - bis(mothoxy)phenyl]amino}quinoxalin-2 572 ~ / NH HN- \/ yl)aminojsulfonyl}phenyl)-2-(3,4 0 Hdihydroisoquinolin-2(1IH)-yl)acetamide N 0 N oN -(3 -{ [(3 -{ {3 ,5 573 N NH CH 2 bis(methoxy)phenyl]amino}quinoxalin-2 O yl)amino]sulfonyl}phenyl)pent-4-enamide NH 0 N N N-(3-{[(3-{{3,5 574 N H-bis(methoxy)phenyllamino}quinoxalin-2 o yl)amino]sulfonyl}phenyl)-N-2-(2 -- HN NH methylphonyl)glycinamide _ N N bis(mothoxy)phenylamino)quinoxalin-2 575 / NH HNyl)amino]sulfonyl}phenyl)-2-(4-oxopiperidin -- HN--No-- 1-yl)acetamide 137 Table I____________________ Cpd. No. Structure Name F NH N(-[3(35 576 Nbis(methoxy)phenyl]amino~quinoxalin-2 c5$ NH yl)ainiino]sulfonyllphenyl)-2-fluorobenzamide 577 0.N H 1J bis(methoxy)phenyl]amino~quinoxalin-2 -0 HyI)ainino]sulfonyllphenyl)-N-2-(1 -o HN-(phenylethyl)glyoinamide HN5 578 F -,NH bis(methoxy)phenyl]amino~quinoxalin-2 NH yJ)aminojsulfonyl~phenyl)-2-fluoro-6 (methox)benzamide 579 ~ ,- HHIN--- ) bis(methoxy)phenyl]ainino~quinoxalin-2 00 yI)amino]sulf'onyl}phenyl)-N-2-[2-(I -0 HNI mothylethyl)phonyl]glycinamide 0' N' N 580 N / H 1 bis(methoxy)phenyl]amino~quinoxalin-2 0S-Q 0yJ)ainino]sulfonyl~phenyl)-3-[2 -0oN4 (methoxy)phanyopropanainide 581 NH Hbis(methoxy)phenyl]amino)quinoxalin-2 NHH'N ~ oyI)aniino]sulfonyl~phenyj).4 HN-4 metbylpentanamide 138 Table 1 Cpd. No. Structure Name N-(3-{[(3-{[3,5 582 0 / bis(methoxy)phenyl]amino}quinoxalin-2 yl)amino]sulfonyljphenyl)-2-(2 -O H N\ phenylmorpholin-4-yl)acetamide N N--O N-(3-{[(3-{[3,5 583 o 0 bis(methoxy)phenyl]amino}quinoxalin-2 HN yl)amino]sulfonyl)pheny)-3-[4 (methoxy)phenyl]propanamide / N-(3-{[(3-{[3,5 584 bis(nethoxy)phenyl]amino}quinoxalin-2 yl)amino]sulfonyl}phenyl)-N-2-cyclopentyl HN 0 N-2-prop-2-en-1-ylglycinamide 6 0 N' 0N-(3-{[(3-{[3,5 585 NH bis(methoxy)phenyljamino}quinoxalin-2 o yl)amino]sulfonyl}phenyl)-N-2-methyl-N-2 -o HN [2-(methoxy)ethyl]glycinamide 0 NH N-(3-{[(3-{[3,5 586 0 bis(methoxy)phenyl]amino)quinoxalin-2 NH HN yl)amino]sulfonyllphenyl)-4-cyclopropyl-4 0 Noxobutanamide 139 Table 1 Cpd. No. Structure Name -NH HN N-(3-{{(3-{{3,5 587 Q bis(methoxy)phenyl]amino}quinoxalin-2 -- HN yl)amino]sulfonyl}phenyl)-N-2-[3-(1,1 NH dimethylethyl)phenyl]glycinamide Ni N N N-(3-{{(3-{[3,5 588 | H bis(methoxy)phenyl]amino}quinoxalin-2 588 I NH yl)amino]sulfonyl}phenyl)-N-2 (cyclopropylmethyl)-N-2-propylglycinamide i/HN N-(3-{{(3-{[3,5 589 0 bis(methoxy)phenyl]amino}quinoxalin-2 NH HN-- yl)amino]sulfonyl}phenyl)-2-(2 0 oxocyclopentyl)acetamide N T cl N-(3-{[(3-{[3,5 590 O N ')Jbis(methoxy)phenyllamino}quinoxalin-2 H H Nd H H Nyl)amino]sulfonyl}phenyl)-N-2-(4 N chlorophenyl)glycinamide NH 2-(1,4'-bipiperidin-l'-yl)-N-(3-{[(3-{[3,5 591 bis(methoxy)phenyl]aminojquinoxalin-2 k okN-NH yl)aminolsulfonyl}phenyl)acetamide N~fNH N-(3-{{(3-{[3,5 592 bis(methoxy)phenyl]amino}quinoxalin-2 o oyl)amino]sulfonyl}phenyl)-2-(4 0i-16N ~cyclopentylpiperazin-1-yl)acetamide 140 Table 1 Cpd. No. Structure Name N-(3-{[(3-{[3,5 593 bis(methoxy)phenyl]amino}quinoxalin-2 NH yl)amino]sulfonyl}phenyl)-2-(2 mthylphenyl)acetamide -0 HN4 0' / /\NH HN&-2J. -- o ~HN N-(3-{[(3-{[3,5 bis(methoxy)phenyl]amino}quinoxalin-2 594 yl)amino]sulfonyl}phenyl)-N-2-[(5-fluoro-2 mthylphenyl)methyl]glycinamide F N N N-(3-{{(3-{[,5 595bis(methoxy)phenyl]amino}quinoxalin-2 595 / HHN-9K"- yJ)amino]sulfonyl)phenyl)-3,3 S HN 0 dimethylbutananide 0 cl S."oN-(3-{[(3-{[3,5 NH bis(methyloxy)phenyl]amino}quinoxalin-2 596 N yl)amino]sulfonyl}phenyl)-N2-(2 NH chlorophenyl)glycinanide 0 0 \N--NH HN / -N N-(3-{[(3-{[3,5 HN N bis(methoxy)phenyl]amino)quinoxalin-2 597 / yl)amino]sulfonyl}phenyl)-5-fluoro-2 methylbenzamide F N F -(3-{{[(3-{[3,5 598 & F bis(methoxy)phenyl]amino}quinoxalin-2 598 HN yl)anino]sulfonyl}phenyl)-4-fluoro-3 N NH methylbenzamide 141 Table 1 Cpd. No. Structure Name CI 0 N-(3-{[(3-{[3,5 599 0-N NH bis(methoxy)phenyl]amino}quinoxalin-2 599 0 N -N NHyl)amino]sulfonyl}phenyl)-2,3 NH HN-0114-0 dichlorobenzamide 0 -0 0 jN-(3-{[(3-{[3,5 600 NH HN-&-Q bis(methoxy)phenyljanino}quinoxalin-2 -600 o yl)aminojsulfonyl}phenyl)-2 (phenyloxy)acetamide N 9N-(3-{[(3-{[3,5 601 0HN -\(/ 0 bis(methoxy)phenyl]amino}quinoxalin-2 -- yl)amino]sulfonyl}phenyl)-N-2-(2,3 "-NH dimethylphenyl)glycinamide \ / O 'N 3-amino-N-(3-{[3,5 602 N N NH NH 2 bis(methoxy)phenyllamino}pyrido[2,3 b]pyrazin-2-yl)benzenesulfonamide o 40 N-(3-{[(3-{[3,5 603 F NH bis(methoxy)phenyl]amino}quinoxalin-2 NH yl)aminojsulfonyl}phenyl)-2-fluoro-5 ( methylbenzmnide ZIN-§11 N-(3-{[(3-{[3,5 604 -0 0 bis(methoxy)phenyl]amino)quinoxalin-2 -o0 yl)anino]sulfonyl}phenyl)-N-2-{[(4 methylphenyl)methyl]oxy}glycinamide 142 Table I Cpd. No. Structure Name 0 N-(3-{f(3-{[3,5 o 14-2 605 ) o bis(mothoxy)phenyilaminolquinoxalin-2 HN--C methylethyl)piperazin-1-yllacetainide 0 N / HF bis(methoxy)phenyl~atmino~quinoxalin-2 606 HN Nyl)amino~sulfonyl~phenyt)-2-(4 fluorophenyt)acetamide 607 NH bis(methoxy)pheny1Jaminolquinoxalin-2 N ~1 %yo yl)aminolsulfonyl~phenyl)-3 mothylbutanamide / 0 N-(3-{[(3-{[3,5 608 \ / NH bis(methoxy)phenyl~aniino~quinoxalin-2 00 ,\/ yI)aminolsulfonyllphenyl)-4-methyl-2 -0HN 0- (methoxy)benzamide N N N-(3-{[(3-{E3,5 609 - HMJ - bis(methoxy)phenyl~amnino~quinoxalin-2 \/~ --N---- j yI)amino~sulfonyl~phenyl)-2-(4 -0HN7 propylpiperidin-1-yI)acetamide - 0 N-(3-([(3-(E3,5 61 HN-/ bis(methoxy)phenyllaminol quinoxalin-2 -0 HN-4 2 yI)amino~sulfonyl~phenyl)-2-[(3 _0 methylphenyl)oxy~acetainide 143 Table 1 Cpd. No. Structure Name 0 N-(3-{[(3-{[3,5 611NH H bis(methoxy)phenyljamino}quinoxalin-2 611 O 0 yl)amino]sulfonyl~phenyl)tetrahydrofuran-2 OI ) carboxanide 0O dl\ N-(3-{[(3--{[3,5 6 OH bis(methoxy)phenyl]amino}quinoxalin-2 612 NH HN &- / yl)amino]sulfonyl}phenyl)-2-[3 (hydroxymethyl)piperidin-1-yl]acetamide NH 1,1-dimethylethyl2-{[(3-{[(3-{[3,5 bis(methoxy)phenyl]amino}quinoxalin-2 613 N NH yl)aminolsulfonyllphenyl)amino]carbonyl}pi peridine-1-carboxylate / N N- (pridin-me tygycnmd N 0 N N NIHH IN-0N-(3-{[(3-{[3,5 615; - bis(methoxy)phenyl]amino}quinoxalin-2 614 ll-q yl)aminolsulfonyl}phenyl)-N-2-methyl-N-2 -o -phen-3-ylmethyl)glycinamide /oN\ 615 N HHN--- bis(methoxy)phenyl]amino} quinoxalin-2 0 yl)amino]sulfonyl}phenyl)-N-2-ethyl-N-2 -0 NI~ phenylglycinanide N0 bis(methoxy)phenyl]amino~quinoxalin-2 610 0 yl)amino]sulfonyllphenyl)-2-{[2 HN-A_ (methoxy)ethyl]oxy}acetamide 144 Table I Cpd. No. Structure Name NH-(3-{[(3-{[3,5 617 r / \ NH H, bis(methoxy)phenyllamino)quinoxalin-2 yl)aminolsulfonyl}phenyl)-3

N

6 / cyclopentylpropanamide c N-(3-{[(3-{[3,5 618 NH bis(methoxy)phenyljamino)quinoxalin-2 NH yl)aminojsulfonyl}phcnyl)-2,5 N --- dichlorobenzamide -0 2-(4-acetylpiperazin-1-yl)-N-(3-{[(3-{(3,5 619 -- -- bis(methoxy)phenyllamino}quinoxalin-2 O\ / N H yl)aminolsulfonyl}phenyl)acetamide N-(3-{[(3-f{3,5 620 H N a bis(methoxy)phenyllamino)quinoxalin-2 -- o yl)wnino]sulfonyl)phenyl)-5-fluoro-2 (methoxy)benzamide F ... o N-(3-{[(3-{[3,5 621H H bis(methoxy)phenyl]amino}quinoxalin-2 _0 O yl)amino]sulfonyl}phenyl)-N-2-cyclohexyl-N 2-ethylglycinamide 0 N.-(3-([(3-{[3,5 C H H bis(methoxy)phenyl]amino)quinoxalin-2 622 N N0 f y)aminolsulfonyl}phenyl)-5 N O methylisoxazole-3-carboxamide N/ N-(3-{[(3-{[3,5 S 11 bis(methoxy)phenyl)amino)quinoxalin-2 623 NH0 yl)amino]sulfonyl}phenyl)-3-methylpyridine 2-carboxamide 145 Table 1 Structure Name N N N-(3-{[(3-{[3,5 624 bis(methoxy)phenyllamino}quinoxalin-2 o yl)aminolsulfonyl}phenyl)-2 -Ho 0- (methoxy)pyridine-3-carboxamide

\N

N- N-(3-{{(3-([3,5 625/ bis(methoxy)phenyllamino) quinoxalin-2 H 0yl)amino]sulfonyl}phenyl)-3,5 C folo dichlorobenzamide NH j CI H N-(3-{{(3-{[3,5 626 C 0 bis(methoxy)phenyl]amino}quinoxain-2 NH HN- yl)amino]sulfonyl}phenyl)-2-(1,3-thiazolidin 0 3-yl)acetamide O N N N-(3-{[(3-([3,5 62- bis(methoxy)phenyl]amino}quinoxalin-2 627 NHHN --\ yl)amino]sulfonyl}phcnyl)-2-(4 0 H N \ N \ formylpiperazin-I -yl)acetamide 0 oN N-(3-{[(3-{[3,5 628 0 bis(methoxy)phenyl~amino}quinoxalin-2 /NH HN- yJ)aminojsulfonyl}pheiyl)-2-(2-pyridin-4 -- o ylpiperidin-1-yl)acetamide 0 N N N-(3-{[(3-{[3,5 bis(methoxy)phenyl]amino}quinoxalin-2 629 yl)amino)sulfonylphenyl)-2 (methoxy)benzamide 146 Table 1 Cpd. No. Structure Name \1 N-(3-{[(3-{[3,5 630 H HN- bis(methoxy)phenyl]amino}quinoxalin-2 63 o yl)aminocsulfonyl}phenyl)-N-2-methyl-N- 2 -O HN-'( (2-methylpropyl)glycinamide N-(3-{[(3-{{3,5 631 Nbis(methoxy)phenyl]amino}quinoxain-2 631HN-QN yl)amino]sulfonyl}phenyl)-2-(4-formyl-1,4 S HN N 0 diazepan-1-yl)acetamide HN-(V 0 N-(3-([(3-{[3,5 6 0- bis(methoxy)phenyl]amino}quinoxalin-2 633 N H N yl)amino]sulfonyl)phenyl)-2 mphenylolopropanecaboxamide HN\ N-(3-{{(3-{[3,5 633 bis(methoxy)phenyl]amino}quinoxalin-2 d yl)aminosulfonyl)phenyl)-2-(2,6 NH HN-e dim nylrpholin-4-y)acetamide NH N-(3-{{(3-[3r5 634 0 bis(inethoxy)phenyllaminolquinoxalin-2 ~yl)amio]sulfonyi)phenyl)-2-(2 l,,yN NH 3-1[(3-1[2-chloro-5 635NH (methoxy)phenyl]amino)quinoxalin-2 0=S=0 yl)amino]sulfonyl)-N-[2-(dimethylamino)-i 0 methylethyl]benzamide HN14 147 Table 1 Cpd. No. Structure Name NHC 3-{[(3-{[2-chloro-5 636 (methoxy)phenyl]amino}quinoxalin-2 N _3 yl)amino]sulfonyl}-N-[2 04, \ /H (dimethylamino)ethyl]benzamide 0 0 N I -Cl 5-{[(3-{{2-chloro-5 637 H (methoxy)phenyl]amino}quinoxalin-2 00 \ yl)amino]sulfonyl}-N-[2 NN /N N, (dimethylamino)ethyl]-2-fluorobenzamide H H F OCI N NH 3-{[(3-{[2-chloro-5 638 KNH (methoxy)phenyl]amino}quinoxalin-2 I= yl)aminosulfonyl}-N-pyrrolidin-3 H0ylbenzamide H 0 N ONH NH 3-{[(3-{[3,5 639 bis(methoxy)phenyljamino}quinoxalin-2 9N NH yl)amino]sulfonyl}-N-[2 (dimethylamino)ethyl]benzamide 0 NH HN 3-{[(3-{[2-chloro-5 640 N, (methoxy)phenyl]amino}quinoxalin-2 . INH yl)amino]sulfonyl}-N-(2-pyrrolidin-1 c, ylethyl)benzamide N-(2-aminoethyl)-3-{[(3-{[2-chloro-5 641 N H NH 2 (methoxy)phenyllamino}quinoxalin-2 cl yl)amino]sulfonyl}benzamide 148 Table I Cpd. No. Structure Name 642 (methoxy)phenyl]amino}quinoxafln-2 642 -lNHyI)aniino]sufbnyl}-N-j2 C~ \ H, (dimethylamino)ethyl]-N-methylbenzamide 0 0 c_ _ ___I_ _ ~N NH 3-{((3-{ (2-chloro-5 643 NXNH (methoxy)phenyl]amlno~quinoxain-2 O=A=0 yl)aminojsulfonyI}-N-(piperidin-2 ~N NH N NH3-UX(3-{[2-chloro-5 N-: NH(methoxy)phenyl~amino} quinoxalin-2 644 0-4 0yl)amnino]sulfony1}-N-(1-methylazetidin-3 yl)benzamide N 0D MHN '~~N~NH3-{[(3-{[2-rhloro-5 645 0 =O(methoxy)phenyllaminolquinoxalin-2 yI)amnino~sulfonyl}-N-(2-piperidin- -. 0 ylethyl)benzamide 149 Table 1 Cpd. No. Structure Name NNH N NH 3-([(3-{[2-chloro-5 646 0= -0 (metboxy)phenyl)amino}quinoxalin-2 yl)amino]sulfonyl}-N-[2 (diethylamino)ethyl]benzamide IN) NH 3-{[(3-{[3,5 647 bis(metboxy)phenyl]amino}quinoxalin-2 N N yl)amino]sulfonyl}-N-[2 (dimethylamino)ethyl]-N-mothylbenzmide NH. o 3-{[(3-{12-chloro-5 648 NH (methoxy)phenyllamino}quinoxalin-2 o S o yl)anino]sulfonyl}-N-(1-methylpiperidin-3 3 r yl)benzamide 0 "'Q '-X( H -3-{[(3-{[2-chloro-5 649 N NH (methoxy)phenyl]amino}quinoxalin-2 69s=o yl)aminolaulfonyl}-N-piperidin-3 ylbenzamide H ,O C) NH 3-{R3-{[2-chloro-5 650 N NH (nethoxy)pheny]amino}quinoxalin-2 yl)amino]sulfonyl}-N-[(1-methylpiperidin-2 yl)methyl]benzamide N__ N 150 Table 1 Cpd. No. Structure Name N NH N-{2-[bis(2-hydroxyethyl)aminolethyl)-3 651 K~ NXLNH r{[(3-f{[2-chloro-5 0= = o, -,_,O (methoxy)phenyl]amino~quinoxalin-2. 0 N y)amino~sulfonyl~benzamide ,^,.N NH 3-{R(3-{12-chloro-5 652 (metlioxy)phenyl]aminolquinoxalin-2 0o-s=O yI)amino]sulfonyl} -N-(1-ethylpiperidin-3 '.. ~ yI)benzarnide N, NHyIanosfoybnzmd 0

NH

2 ~N NH N e NH 3-[(3-amidnopyrrolidin-1-yl)carbonyl]-N-(3 654 0=8=0 {[2-chloro-5 (methoxy)phenyl] amino) quinoxalin-2 yl)benzenesulfonamido N0 dtNH 2 olp -C,5-{[(3-f{[2-chloro-5 65"k"N 0 \(methoxy)phenyl]amino~quinoxalin-2 (dimethylamino)etbyl]-2-(methoxy)benzamide 151 Table 1 Cpd . No. Structure Namie ~N NH N-(3-{[2-chloro-5 656 N xNH (methoxy)phenyl~amino}quinoxalin-2-yi)-3 {[3-(methylamino)pyrrolidin-1 O~O HN- yl~carbonyl~benzenesulfonatnide /0 o NH -[3f[-hoo5 657H (mthoxy)pheny1amino~quinoxalin-2 N '~ -yl)aminojsulfonyl~benzoicacid 0 3-([(3-{E2-chloro-5 658 _(niethoxy)pbenyl]amino}quinoxalin.2 659 A NH. 0 yl)aniino]sulfonyl}-N-(2-morhpolino-+- / Nyletyl~enzaiide '- 0 0 660 0 -([3-[2-chloro-5 659 1(methoxy)phenyljamino~quinoxalin-2 yl)melbenznslamide _ _ _ _ _ _ ~ ~ ~ ~ Zt 0 _ _ _ __ _ _ _ _ __ _ _ _ _ &f152 Table 1 __________________ Cpd. No. Structure Name N NH 3-{I(3-{12-chloro-5 661 11 (methoxy)phenyl~aminolquinoxalin-2 N N Hyl)aminojsulfonyl}-Nl-nethylbenzamide 0_ 0 NH_______________ I o=s=O 2-ylbenzonesulfonamide C NH 2 N-T N NH 3-{1(3-{[2-chloro-5 663 0=S=0 (methoxy)pheny!]aininojqinoxalin-2 yl)aminojsulfony]}-N-(pyridin-3 ylmotliyl)benzamide HN _ N6 00 N ' HN6 3-{[(3-{[2-chloro-5 664 (methoxy)pheny[]amino~quinoxalin-2 N X NH yl)amino~sulfonyl)-N-(pyridin-2 cl I ylmethyl)benzamide 00 N Htt HN 3-{[(3-{[2-chloro-5 665 iiNy(mcthoxy)phenyl]aniino~quinoxalin-2 yl)amino~suffonyl}-N-(2 '-"-' NH l OHhydroxyethylobenzamide 153 Table 1 Cpd, No. Structure Name 0 NH HN 3-{[(3-([2-chloro-5 666 r NH (methoxy)phenyl]amino}quinoxalin-2 NH NHy1)aminolsulfonyl)-N-(3-oxopyrazolidin-4 yI)benzamide NHN 3-{[(3-{[2-chloro-5 667 NH (methoxy)phenyl]amino}quinoxalin-2 N H yl)amino]sulfonyl}-N-[2-(If-imidazol-4 o F N H yl)ethyljbenzamide N N o IV-(3-{(2-chloro-5 668 0 (methoxy)phenyl]amino}quinoxalin-2-y)-3 H {[3-(dimethylamino)pyrrolidin-1 N HN C / ylcarbonyl}benzenesulfonamide '7N C1 N N 0 3-{[(3-{[2-chloro-5 669 / m CIO (methoxy)phenyl]amino}quinoxalin-2 S--NH HN yl)amino]sulfonyl}-N-(pyridin-4 HN ylmethyl)benzamide N 0 O N I N NH 3-{[(3-(2-chloro-5 670 N NH (methoxy)phenyljamino}quinoxalin-2 I / yl)amino]sulfonyl}-N-methyl-N-(I O S-0- methylpyrrolidin-3-yl)benzamide N 0 N NHN-(3-{2-chloro-5 671 N NH (methoxy)phenyljamino}quinoxalin-2-yi)-3 ---- = {[3-(diethylamino)pyrrolidin--l N-/ yl]carbonyl}benzenesulfonamide 154 Table 1 Cpd. No. Structure Name 672 N NH(methoxy)phenyl~amino~quinoxalin-2 672 X NHyJ)arnino]sulfonyl)-N-IH-pyrrol-1 I H 0 N NH HN3- 3-[-ho-5 673 if(methoxy)phenyljamino~quinoxalin-2 N : NHyl)amino]sulfonyl}-N-{3-pyffolidin-1 Nyipropyl)benzamide ' c' N N4 N~ NH .N 3-{[(3-{[2-chloro-5 674 (~ Y(methoxy)pheny3amino~quinoxain-2 C (NXNH N yl)amino]sulfony]}-N-(2-cyanoethyl)-N cl methylbenzamide N N 0 3-f{[(3-f{[2-chloro-5 675 /\- (methoxy)phenyl~amino~quinoxalin-2 - RNo yJ)aminolsulfonyl}-N-[2 HC 0 AS0 N NH N,3-{[(3-{[2-chloro-5. 676 (methoxy)phenyljamino~quinoxalin-2 Ix yl)atnino]sulfonyl) -N-(2-ryanoethyl)-N N NH clethylbenzaniide 155 Table 1 Cpd. No. Structure Name Cl N X NH 3-[(3-aminopipendin-1-yl)earbony]-N-(3-{{2 677 N NH chloro-5-(methoxy)phenyl]amino}quinoxalin o=s=o Ni( 2-yl)benzenesulfonamide 6, 678 ' N bis(methoxy)phenyl]ainoquinoxain-2 N NH yI)aminojsulfonyl~benzoicacid O OH N NH 3-{[(3-{{2-chloro-5 679 NNH (methoxy)phenyl]aminolquinoxalin-2 o=s=o yl)amino]sulfonyl}-N-[3 (diinethylamino)propyljbenzamide I l HN N N NH 3-{(W3-{[2-chloro-5 680 : (methoxy)phenyl]amino)quinoxalin-2 "^N NH -yl)amino]sulfonyl}-N-morpholin-4 : H / yibenzamide N O N-(3-{(2-chloro-5 0 (methoxy)phenyl]amino}quinoxalin-2-y)-3 681 / H - [(2,2 N H dimethylhydrazino)carbonyl]benzenesulfonam O -ide HN Cf -50 156 Table I Cpd. No. Structure Name 0 N N 3-{[(3-{[2-chloro-5 682 - S-NH HN (methoxy)phenyl]amino}quinoxalin-2 0 yl)amino]sulfonyl}-N-[3-(1H-imidazol-1 HN CI yl)propyl]benzamide KN 0 " N 0 H H 3-{[(3-{[2-chloro-5 683 (methoxy)phenyl]amino}quinoxalin-2 N NH yl)amino]sulfonyl}-N-[3 ~j~CI rN, (diethylamino)propyl]benzamnide N N N O 3-{[(3-{[2-chloro-5 684 O (methoxy)phenyl]amino}quinoxalin-2 68-N HN yl)amnino]sulfonyl)-N-(2 -NH \- / cyanoethyl)benzamide HN CI 0 / 1. methylN-[(3-{[(3-{[2-chloro-5 685 1-NH HN (metboxy)phenyl]amino}quinoxalin-2 o yl)amino]sulfonyl)phenyl)carbonyl]-beta HN C alaninate 0 0 N 3-{[(3-{[2-chloro-5 686 / -NH HN (methoxy)phenyl]amino}quinoxalin-2 I H HN / yl)amino]sulfonyl)-N-[2 N CI (methylthio)ethyl]benzamide 157 Table 1 Cpd. No. Structure Name 0' 1 0 SNNH HN 3-{[(3-{[2-chloro-5 687 | (mothoxy)phenyl]amino}quinoxain-2 N NH 8 yl)amino]sulfonyl}-N-[2 II cI K (othylthio)ethyl]benzamide NN Ob 3-{[(3-{[2-chloro-5 688 /- HN4 (methoxy)phenyl]amino}quinoxalin-2 \ 0 yl)amino]sulfotiyl}-N-[2 N cl (dimethylamino)ethyl]-N-ethylbenzamide -N\ NH 3-{[(3-([2-chloro-5 689 K N NH (methoxy)phenyllamino}quinoxalin-2 6== () yl)amino]sulfonyl}-N-[3-(2-oxopyrrolidin-1 s 0yl)propyl]bonzamide O~N N NH HN 3-{[(3-{[2-chloro-5 690 N X N(mothoxy)phenyl]amino)quinoxalin-2 NN H yl)amino]sulfonyl}-N-(2-pyridin-4 cl ylethyl)benzamide A 1NNH HN 3-{{(3-{{2-chloro-5 691 (nethoxy)phenyl]amino}quinoxalin-2 6N9NH yl)aminolsulfonyl}-N-[3 c o (othyloxy)propylqbenzamide N \ 3-{((3-{(2-chloro-5 6 N 0N (methoxy)phenyl]amino}quinoxalin-2 692-NH HN yl)aminolsulfonyl)-N-(3-morpholin-4 0 \ylpropyl)benzamide HN- CI 8 0 158 Table 1 Cpd. No. Structure Name N 3-{((3-{[2-chloro-5 693 -- :NH H (methoxy)phenyl]amino}quinoxalin-2 F 0 yl)amino]sulfonyl)-N-[3 O Ci (methoxy)propyl]benzamide H /O N- 3-{[(3-{[2-chloro-5 694 1 N N (methoxy)phenyl]amino}quinoxalin-2 S-NH HN y1)amino]sulfonyl}-N-[3 (dimethylamino)propy]-Nmethylbenzamide N - N ]ahojufoyl--3 N Cl NH 3-{[(3-{12-chloro-5 695 (methoxy)phenyl]amino}quinoxalin-2 695 INHyl)ainin]sufony)-A-(3 c o (propyloxy)propyl]benzamide N ethyJN-[(3-{[(3-{{2-chloro-5 696 0 (methoxy)phenyljamino}quinoxalin-2 0o -NH HN yl)ainino]sulfonyl}phenyl)carbonyl)-beta 0 alaninate HN- CI 0 N l 03-{{(3-{[2-chloro-5 697 0 1NH - 0(methoxy)phenyl]amino)quinoxalin-2 o - -- NH HN C yl)amino]sulfbnyl)-N-{3.-[(] 0 methylethyl)oxypropyl}benzamide 0 cl 3-{[(3-{[2-chloro-5 698 H (methoxy)pheny]amino}quinoxalin-2 l N I> yl)amino]sulfonyl}-N-(1,1-dimethyl-2 O i Jpiperidin-1-ylethyl)benzamide 159 Table 1I ___________________ Cpd. No. Structure Name N N 0 3-{[(3-{[2-chloro-5 69 0 & (methoxy)phenyljamino~quinoxalin-2 699-N \ / \ ' yl)amlno~sv1fonyl)-N-methyl-N / -HN\0 propylbenzamnide 0 o N NH NN 3-{[(3-{[2-chloro-5 700 HN.1' (methoxy)phenyl]amino~quinoxalin-2 N X NH yl)amino~sulfonyl) -N-piperidin-l cl ylbenzamide 0 0NR 3-{[(3-{[2-chloro-5 /4 \ methoxy~phenyllamino~quinoxalin-2 701 NH HIf yl)amino]sulfonyl}-N.{1-methyl-2 HN-P 0c (methoxy)ethygbenzaniide 0 NQ N 0 3-{[(3-{[2-chloro-5 700 y\ - (methoxy)phenyllamino~quinoxalin-2 K I \ aNH HN \ yl)aminolsulfonyl)-N-(1,1-dimethyl-2 N0 rnorpholin-4-yiethyl)benzamide 0-S N-(3-{[2-chloro-5 70 ~(mhoxy)phenylmio~qunoxain2yl)3 y1}catbony1)benzenesiaIfonamide 704 ; H(inethoxy)phenyl]amino~quinoxalin-2 0=6=0yl)aminolsulfonyl~benzamide 160 Table 1 Cpd. No. Structure Name N, -O3-{[(3-{f[2-chloro-5 705 N (methoxy)phenyl]amino) quinoxalin-2 QNK Hyl)amino]sulfonyl}-N-[4-(diethylamino)- Icl N-methylbutyl]benzamide N C 3-{f[(3-{1[2-chloro-5 706 r<N NH (methoxy)phenyl]amino)quinoxalin-2 ~N INH 0 .- yl)amino]sulfonyl}-N-(1,1-dimethyl-2-oxo-2 N O piperidin-1-ylethyl)benzamide 1__ H 0 0 0=8, N NH N N-(3-{[2-chloro-5 707 ~ (methoxy)phenyjjamino}quinoxalin-2-y)-3 N NH N [(4-methylpiperazin-1 Cl yl)carbonyl]benzenesulfbnamide N OH N-(3-{[2-chloro-5 708 KN (methoxy)phenyl]anino}quinoxalin-2-yl)-3 N~ NH([2-(piperidin-1-ylmethyl)piperidin-l cl yl]carbonyllbenzenesulfonamide O CN C, N NH N-(3-{[2-chloro-5 709 O (methoxy)phenyl]amino)quinoxalin-2-yl)-6 709 'X s oxo-1,6-dihydropyridine-3-sulfonamide N N N H Q- NH 0 O N N NH N-(3-{[3,5 710 i Obis(methoxy)phenyl]amino}quinoxalin-2-y) H k'o 6-oxo-1,6-dihydropyridine-3-sulfonamide NH 161 Table 1I __________________ Cpd. No. Structure Namie 0 NH 2 0 3-amino-N-(3-{[6-(methoxy)quinolin-8 711 yl]amino~quinoxalin-2 Nl NH yi)benzenesulfonamide N H 0 712 N' N H bis(methoxy)phenyl]amino) quinoxalin-2 yI)thiophene-2-sulfonamide N NH N-(3-([2-chloro-5 713 (methoxy)phenyl]amiriolquinoxalin-2-yI)-3 N1 NHyanobenzenesulfonamide ON NH 714 1: 0bis(methoxy)phenyl]amnino~quinoxalin-2-y) -N NH 3-(methylamino)benzenesulfonamide 00N 715 N O N 2 bis(methoxy)phenyl]amino)pyrido(2,3 b]pyrazin-3-yl)-3-nitrobenzenesulfonamide 0 0 N-(3-{112-chlora-5 I I (methoxy)pheny]]amino~quinoxalin-2-yl)-3 716 N HN-,N (1-{[2 0 H (dimethylamino)ethyl]amino)ethyl)benzenesu N N-S / Ifonaniide 162 Table 1 Cpd. No. Structure Name

NH

2 N .9" 0 / 3-amino-N-(3-{[3-(mcthoxy)-5 717 'N H nitrophenyl]amino}quinoxalin-2 yl)benzenesulfonamide O NO 2 Cl 3-acetyl-N-(3-{[2-chloro-5 718 N NH (methoxy)phenyl]amino}quinoxalin-2 / \, yl)benzenesulfonamide

NH

2 0 N N-S . 3-amino-N-(3-{[3-fluoro-5 719 NH (methoxy)phenyl]amino}quinoxalin-2 NX yl)benzenesulfonamide S01N-(3-{{2-chloro-5 720 eN NH (methoxy)phenyl]amino)quinoxalin-2-yl)- [2-(dimethylamino)ethyl]benzene-1,3 R disulfonamide c N-(3-{[2-chloro-5 721 N NH (methoxy)phenyl]amino}quinoxalin-2-y)-Y 72ANNH [3-(dimethylamino)propyl]benzene-1,3 0- s disulfonamide O 0 N NH N-(3-{[3,5 722 bis(methoxy)phenyl]amino}quinoxalin-2-yl) N 6-chloropyridine-3-sulfonamide H '3N Cl 163 Table I Cpd. No. Structure Name /0U NTN N-(3-ff2-chloro-5 72 (mL-thoxy)phenyljamino~quinoxalin-2-y)-3 73N NH -{5-1(diinethylamino)methyl]-1,3,4-oxadiazol 4\ / 2-yl~benzenesulfonamide 0 0 N 724 r N,,N8o bis(methoxy)phenyl]amino) quinoxalin-2-yl) CI""( x "Wo6-{[2-(dimethylamnino)ethyljamnino~pyridine N 3-sulfonamide

NH

2 0 3-amino-N-(3-([3-amino-5 72 N' N (mcthoxy)phenyl]amnino~quinoxalin-2 725 NX NHyl)beitzenesulfonamide Oj NH 2 _____________

N

N 726 8(III~ bis(methoxy)phenyljamino~quinoxalin-2-yi) NNH 3-(dimethylamino)benzenesulfonaniide N N8 bis(methoxy)phenyrjanino~quinoxalin-2-yl) 727 I 6-{[2-(dimethylamino)ethylloxylpyridine-3 NN sulfonamide ~N 728 m0bis(methoxy)phenyljarnino~quinoxalin-2-yI) C ( 6-(dimethylamino)pyridine-3 -sulfonamide N ~ QN 164 Table 1 Cpd. No. Structure Name -0, o 729 N ~NH I-3(35 729 ~ bis(methoxy)phenyl]aniino} quinoxalin-2-yI) N, Q 'o 4-cyanobenzenesulfonamide 730 N NH bis(methoxy)phenyljamino)quinoxalin-2-y) 4-fluorobenzenesulf'onamide HN .. A . H o I 731 0 N 0~N bis(methoxy)phenyl]aminolquinoxalin-2-y). N NH 4-fluoro-2-methylbenzenesulfonamide N NH N-3-[35 732 Ybis(methoxy)phenyl]amino}quinoxalin-2-y) , - N NH2-methylbenzenesuffonatnide N NH -3f35 733 bis(methoxy)phenyllamino}quinoxalin-2-y) '' N X NH 3-cyanobenzenesulfonamide 0 165 Table I Cpd. No. Structure Name A O N NH N-(3-f[3,5 734 bis(methoxy)phenyl]amino}quinoxalin-2-yl) N C F 3,5-difluorobenzenesulfonamide H N N H N-(3-{ [3,5 735 bis(methoxy)phenyl]amino}quinoxalin-2-yl) NH 2-chlorobenzenesulfonamide CI H H N N N 0 N-(4-{[(3-{[3,5 736 bis(metboxy)phenyl]amino}quinoxalin-2 N NH yl)amino]sulfonyl}phenyl)acetamide

NO

2 N 0 N-(3-([6-(methoxy)quinolin-8 737 N NH yl]amino}quinoxalin-2-yl)-3 nitrobenzenesulfonamide o O NH N-(3-{[3,5 738 N NH -bis(methoxy)phenyl]anino}quinoxalin-2-yl) 3 / 3-(2H-tetral-5-yl)benzenesulfonamide O N N, O N N NH N-(3-{[3,5 739 bis(methoxy)phenyl]aminolquinoxalin-2 - yl)naphthalene-1-sulfonamide 166 Table I Cpd. No. Structure Name IO ci N-{[(3-{[(3-{[2-chloro-5 NNH (methoxy)phenyl]amino)quinoxalin-2 740 yl)amino]sulfonyl}-4 N NH methylphenyl)amino](dimethylamino)methyli o_ N dene}-N-methylmethanaminium F IZ N, ' N-(3-{[3,5 741 IIII kIO bis(methoxy)phenyl]amino)quinoxalin-2-yl) N NH 3-fluorobenzenesulfonamide 0 0

NO

2 N-(3-{[2-bromo-5 742 N NH (methoxy)phenyl]amino}quinoxalin-2-yl)-3 Br nitrobenzenesulfonamide 0 F N NH N-(3-{ [3,5 743 bis(methoxy)phenyl]amino}quinoxalin-2-y) N NH 4-[(difluoromethyl)oxy]benzenesulfonamide OO& FF N ,hN-(3-{[3,5 744 0 bis(methoxy)phenyl]amino)quinoxalin-2-yl) N NH 2-(trifluoromethyl)benzenesulfonamide OI N NH N-(3-{[3,5 745 bis(methoxy)phenyl]amnino}quinoxalin-2-yl) N NH 3-chloro-4-fluorobenzenesulfonamide 167 Table 1 Cpd. No. Structure Name FF H F N ;N-(3-{f3,5 746 !0.11, bis(methoxy)phenyl]amino}quinoxalin-2-yl) N NH 4-(trifluoromethyl)benzenesulfonamide I o N H OiN-(3-([3,5 747 bis(methoxy)phenyl]amino}quinoxalin-2-y) NX NH 3-(methylsulfonyl)benzenesulfonamide O O N_, N P6 N_3-([3,5 748 N CI bis(methoxy)phenyl]amino}quinoxalin-2-y) 2,5-dichlorothiophene-3-sulfonamide NH N NH N-(3-{[3,5 749 1NH bis(methoxy)phenyl]amino}quinoxalin-2-yl) 3,5-dichlorobenzenesulfonamide Cll/ C' SN N-S NX N-3-{ [2-mnethyl-5 750 N NH NO 2 (methoxy)phenyljamino}quinoxalin-2-yl)-3 nitrobenzenesulfonamide N F + x N-(3-([3,5 751 N NH bis(methoxy)phenyllamino}quinoxalin-2-yl) 4-[(trifluoromethyl)oxy]benzenesulfonanide 168 Table 1 Cpd. No. Structure Name oq os N-(3-{[(3-{[3,5 752 bis(methoxy)phenyljaminojquinoxalin-2 N I NH yl)aminojsulfonyl)phenyl)-2-[4 , N , ~ (dimethylamino)piperidin-1-yl]acetamide o o N NH N-(3-{[3,5 753 O 0 0 bis(methoxy)phenyl]amino}quinoxain-2-yl) CX 5-chloro-2-(methoxy)benzenesulfonamide H 0 F N N-(3-{[3,5 54 bis(methoxy)phenyl]amino}quinoxalin-2-yl) NH 3-(trifluoromethyl)benznesulfonamide o o N NH N-(3-{{3,5 755 N NH bis(methoxy)phenyl]amino}quinoxalin-2-yl) N 2,5-bis(methioxy)benzenesulfonamide H N NH " O~ q o "N -(3-{{3,5 756 N NH bis(methoxy)phenyl]aminojquinoxalin-2-y) %t/ 3,5-dimethylisoxazole-4-sulfonamide N'CNH N-(3-{[3,5 757 tto b Iis(maethoxy)pheny]]amino~quinoxalin-2-yl) N-- 5-bromo-2-(methoxy)benzenesulfonamide H Br 169 Table 1 Cpd. No. Structure Name NH N-(3-{[3,5 758 9,0 bis(methoxy)phenyl]anino}quinoxalin-2-yl) N ' N 4-fluoro-3 N (trifluoromethyl)benzenesulfonamide F F F 0 NO 2 Hn NyN-O N-(3-{[3-fluoro-5 759H (methoxy)phenyl]amino}quinoxalin-2-yl)-3 nitrobenzenesulfonamide 0 F O O N NH N-(3-{[3,5 760 bis(methoxy)phenyl]amino}quinoxalin-2-yl) N NH 3-fluoro-4-methylbenzenesulfonamide Oi F X NH N-(3-{[3,5 761 1 bis(methoxy)phenyl]amino}quinoxalin-2-yl) N NH 3-chloro-4-mothylbenzenesulfonamide N N N-(3-[,5 762 bis(methoxy)phenyl]amino}quinoxalin-2-y) s H H\N 2,5-dimethylthiophene-3-sulfonamide N 02 763O N-(3-{[3-(methoxy)phenyl]amino}quinoxalin N NH 2-yl)-3-nitrobenzenesulfonamide 170 ________Table 1 Cqpd. No. Structure Name N0 2 0 N-{3-[(2-chloro-5 764 (N NH hydroxyphenyl)amino]quinoxalin-2-yl}-3 'Cl nitrobenzenesulfonamide NH N-(3-([(3-([3,5 76~ o bis(niethoxy)phenyl]aniinolquinoxalin-2 s 0 yl)amino~sulfonyl}phenyl)-4-methyl-3 N ,, , ,u,(methoxy)benzamide O 0 766 N N bis(methoxy)phenyl]amino~quinoxalin-2-yl) [ 'kI I-phenylmethanesulfonamide N, NH ,O

NO

2 N 0 - N-G3-{[3-(methoxy)-5 767 N X NH nitrophenyl]amino~quinoxalin-2-yl)-3 ' 'O& NO2nitrobenzenesulfonamide 768 0~) ~ bis(methoxy)phenyl]amninolquinoxalin-2-yI) S-NH H N / 1-(3-chlorophenyl)methanesulfonamide CI 0P N N 769 -l bis(niethoxy)phenyljamino~quinoxalin-2-yl) S.I.,- N HH N -4,5-dichlorothiohene-2-sulfonamide 171 Table 1 Cpd. No. Structure Name N-(3-{[3,5 770 N NH bis(methoxy)phenyl]amino}quinoxalin-2-yl) 0 5-chloro-1,3-dimethyl-IH-pyrazole-4 N j%- 8 sulfonamide Cl N C N' 'O O N NH 771 N N ,, 0 F bis(methoxy)phenyl]amino}quinoxalin-2-yl) NN H F 3,5-bis(trifluoromethyl)benzenesulfonamide F F F General Administration [00145] In one aspect, the invention provides pharmaceutical compositions comprising an inhibitor of P13K according to the invention and a pharmaceutically acceptable carrier, excipient, or diluent. In certain other specific embodiments, administration may specifically be by the oral route. Administration of the compounds of the invention, or their pharmaceutically acceptable salts, in pure form or in an appropriate pharmaceutical composition, can be carried out via any of the accepted modes of administration or agents for serving similar utilities. Thus, administration can be, for example, orally, nasally, parenterally (intravenous, intramuscular, or subcutaneous), topically, transdermally, intravaginally, intravesically, intracistemally, or rectally, in the form of solid, semi-solid, lyophilized powder, or liquid dosage forms, such as for example, tablets, suppositories, pills, soft elastic and hard gelatin capsules, powders, solutions, suspensions, or aerosols, or the like, specifically in unit dosage forms suitable for simple administration of precise dosages. [00146] The compositions will include a conventional pharmaceutical carrier or excipient and a compound of the invention as the/an active agent, and, in addition, may include carriers and adjuvants, etc. [001471 Adjuvants include preserving, wetting, suspending, sweetening, flavoring, perfuming, emulsifying, and dispensing agents. Prevention of the action of microorganisms can be ensured by various antibacterial and antifungal agents, for example, parabens, 172 chlorobutanol, phenol, sorbic acid, and the like. It may also be desirable to include isotonic agents, for example sugars, sodium chloride, and the like. Prolonged absorption of the injectable pharmaceutical form can be brought about by the use of agents delaying absorption, for example, aluminum monostearate and gelatin. [001481 If desired, a pharmaceutical composition of the invention may also contain minor amounts of auxiliary substances such as wetting or emulsifying agents, pH buffering agents, antioxidants, and the like, such as, for example, citric acid, sorbitan monolaurate, triethanolamine oleate, butylalted hydroxytoluene, etc. [001491 The choice of formulation depends on various factors such as the mode of drug administration (e.g., for oral administration, formulations in the form of tablets, pills or capsules) and the bioavailability of the drug substance. Recently, pharmaceutical formulations have been developed especially for drugs that show poor bioavailability based upon the principle that bioavailability can be increased by increasing the surface area i.e., decreasing particle size. For example, U.S. Pat. No. 4,107,288 describes a pharmaceutical formulation having particles in the size range from 10 to 1,000 nm in which the active material is supported on a crosslinked matrix of macromolecules. U.S. Pat. No. 5,145,684 describes the production of a pharmaceutical formulation in which the drug substance is pulverized to nanoparticles (average particle size of 400 nm) in the presence of a surface modifier and then dispersed in a liquid medium to give a pharmaceutical formulation that exhibits remarkably high bioavailability. [00150] Compositions suitable for parenteral injection may comprise physiologically acceptable sterile aqueous or nonaqueous solutions, dispersions, suspensions or emulsions, and sterile powders for reconstitution into sterile injectable solutions or dispersions. Examples of suitable aqueous and nonaqueous carriers, diluents, solvents or vehicles include water, ethanol, polyols (propyleneglycol, polyethyleneglycol, glycerol, and the like), suitable mixtures thereof, vegetable oils (such as olive oil) and injectable organic esters such as ethyl oleate. Proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersions and by the use of surfactants. [00151] One specific route of administration is oral, using a convenient daily dosage regimen that can be adjusted according to the degree of severity of the disease-state to be treated. [001521 Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active compound is admixed with at 173 least one inert customary excipient (or carrier) such as sodium citrate or dicalcium phosphate or (a) fillers or extenders, as for example, starches, lactose, sucrose, glucose, mannitol, and silicic acid, (b) binders, as for example, cellulose derivatives, starch, alignates, gelatin, polyvinylpyrrolidone, sucrose, and gum acacia, (c) humectants, as for example, glycerol, (d) disintegrating agents, as for example, agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, croscarmellose sodium, complex silicates, and sodium carbonate, (e) solution retarders, as for example paraffin, (f) absorption accelerators, as for example, quaternary ammonium compounds, (g) wetting agents, as for example, cetyl alcohol, and glycerol monostearate, magnesium stearate and the like (h) adsorbents, as for example, kaolin and bentonite, and (i) lubricants, as for example, tale, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, or mixtures thereof In the case of capsules, tablets, and pills, the dosage forms may also comprise buffering agents. [00153] Solid dosage forms as described above can be prepared with coatings and shells, such as enteric coatings and others well known in the art. They may contain pacifying agents, and can also be of such composition that they release the active compound or compounds in a certain part of the intestinal tract in a delayed manner. Examples of embedded compositions that can be used are polymeric substances and waxes. The active compounds can also be in microencapsulated form, if appropriate, with one or more of the above-mentioned excipients. [00154] Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, and elixirs. Such dosage forms are prepared, for example, by dissolving, dispersing, etc., a compound(s) of the invention, or a pharmaceutically acceptable salt or solvate thereof, and optional pharmaceutical adjuvants in a carrier, such as, for example, water, saline, aqueous dextrose, glycerol, ethanol and the like; solubilizing agents and emulsifiers, as for example, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propyleneglycol, 1,3 butyleneglycol, dimethylformamide; oils, in particular, cottonseed oil, groundnut oil, corn germ oil, olive oil, castor oil and sesame oil, glycerol, tetrahydrofurfuryl alcohol, polyethyleneglycols and fatty acid esters of sorbitan; or mixtures ofthese substances, and the like, to thereby form a solution or suspension. 100155] Suspensions, in addition to the active compounds, may contain suspending agents, as for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and 174 sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth, or mixtures of these substances, and the like. [00156] Compositions for rectal administrations are, for example, suppositories that can be prepared by mixing the compounds of the present invention with for example suitable non-irritating excipients or carriers such as cocoa butter, polyethyleneglycol or a suppository wax, which are solid at ordinary temperatures but liquid at body temperature and therefore, melt while in a suitable body cavity and release the active component therein. [001571 Dosage forms for topical administration of a compound of this invention include ointments, powders, sprays, and inhalants. The, active component is admixed under sterile conditions with a physiologically acceptable carrier and any preservatives, buffers, or propellants as may be required. Ophthalmic formulations, eye ointments, powders, and solutions are also contemplated as being within the scope of this invention. [001581 Compressed gases may be used to disperse a compound of this invention in aerosol form. Inert gases suitable for this purpose are nitrogen, carbon dioxide, etc. [00159] Generally, depending on the intended mode of administration, the pharmaceutically acceptable compositions will contain about 1% to about 99% by weight of a compound(s) of the invention, or a pharmaceutically acceptable salt or solvate thereof, and 99% to 1% by weight of a suitable pharmaceutical excipient. In one example, the composition will be between about 5% and about 75% by weight of a compound(s) of the invention, or a pharmaceutically acceptable salt or solvate thereof, with the rest being suitable pharmaceutical excipients. [001601 Actual methods of preparing such dosage forms are known, or will be apparent, to those skilled in this art; for example, see Remington's Pharmaceutical Sciences, 18th Ed., (Mack Publishing Company, Easton, Pa., 1990). The composition to be administered will, in any event, contain a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt or solvate thereof, for treatment of a disease-state in accordance with the teachings of this invention. [00161] The compounds of the invention, or their pharmaceutically acceptable salts, are administered in a therapeutically effective amount which will vary depending upon a variety of factors including the activity of the specific compound employed, the metabolic stability and length of action of the compound, the age, body weight, general health, sex, diet, mode and time of administration, rate of excretion, drug combination, the severity of the particular disease-states, and the host undergoing therapy. The compounds of the present invention can be administered to a patient at dosage levels in the range of about 0.1 to about 1,000 mg 175 per day. For a normal human adult having a body weight of about 70 kilograms, a dosage in the range of about 0.01 to about 100 mg per kilogram of body weight per day is an example. The specific dosage used, however, can vary. For example, the dosage can depend on a number of factors including the requirements of the patient, the severity of the condition being treated, and the pharmacological activity of the compound being used. The determination of optimum dosages for a particular patient is well known to one of ordinary skill in the art. [001621 Representative pharmaceutical formulations containing a compound of Formula I are described below in the Pharmaceutical Composition Examples. UTILITY [00163] Certain compounds of this invention have been tested using the assay described in Biological Example I and have been determined to be PI3K inhibitors. As such compounds of Formula I are useful for treating diseases, particularly cancer in which PI3Kactivity contributes to the pathology and/or symptomatology of the disease. For example, cancer in which P13K activity contributes to its pathology and/or symptomatology include breast cancer, colorectal cancer, endometrial cancer, gastric carcinoma, glioblastoma, hepatocellular carcinoma, small cell lung cancer, non-small cell lung cancer, melanoma, ovarian cancer, pancreatic cancer, prostate carcinoma, and thyroid carcinoma, and the like. [00164] Suitable in vitro assays for measuring P13K activity and the inhibition thereof by compounds are known. Typically, the assay will measure P13K-induced ATP consumption. For further details of an in vitro assay for measuring P13K activity see Biological Examples, Example 1 infra. Cellular activity can be determined using assays as described in Biological Examples 2, 3, and 4 infra. Suitable in vivo models of cancer are known to those of ordinary skill in the art. For further details of in vivo assays see Biological Examples 5-10, infra.Following the examples disclosed herein, as well as that disclosed in the art, a person of ordinary skill in the art can determine the inhibitory activity of a compound of this invention. PREPARATIONS OF THE INTERMEDIATES AND COMPOUNDS OF THE INVENTION [00165] Compounds of this invention can be made by the synthetic procedures described below. The starting materials and reagents used in preparing these compounds are either available from commercial suppliers such as Aldrich Chemical Co. (Milwaukee, Wis.), or 176 Bachem (Torrance, Calif.), or are prepared by methods known to those skilled in the art following procedures set forth in references such as Fieser and Fieser's Reagents for Organic Synthesis, Volumes 1-17 (John Wiley and Sons, 1991); Rodd's Chemistry of Carbon Compounds, Volumes 1-5 and Supplementals (Elsevier Science Publishers, 1989); Organic Reactions, Volumes 1-40 (John Wiley and Sons, 1991), March's Advanced Organic Chemistry, (John Wiley and Sons, 4 a Edition) and Larock's Comprehensive Organic Transformations (VCH Publishers Inc., 1989). These schemes are merely illustrative of some methods by which the compounds of this invention can be synthesized, and various modifications to these schemes can be made and will be suggested to one skilled in the art having referred to this disclosure. The starting materials and the intermediates of the reaction may be isolated and purified if desired using conventional techniques, including but not limited to filtration, distillation, crystallization, chromatography and the like. Such materials may be characterized using conventional means, including physical constants and spectral data. [001661 Unless specified to the contrary, the reactions described herein take place at atmospheric pressure and over a temperature range from about -78 *C to about 150*C, more specifically from about 0 *C. to about 125 "C and most specifically at about room (or ambient) temperature, e.g., about 20 *C. Unless otherwise stated (as in the case of an hydrogenation), all reactions are performed under an atmosphere of nitrogen. [001671 Prodrugs can be prepared by techniques known to one skilled in the art. These techniques generally modify appropriate functional groups in a given compound. These modified functional groups regenerate original functional groups by routine manipulation or in vivo. Aides and esters of the compounds of the present invention may be prepared according to conventional methods. A thorough discussion of prodrugs is provided in T. Higuchi and V. Stella, "Pro-drugs as Novel Delivery Systems," Vol 14 of the A.C.S. Symposium Series, and in Bioreversible Carriers in Drug Design, ed. Edward B. Roche, American Pharmaceutical Association and Pergamon Press, 1987, both of which are incorporated herein by reference for all'purposes. [001681 The compounds of the invention, or their pharmaceutically acceptable salts, may have asymmetric carbon atoms or quaternized nitrogen atoms in their structure. Compounds of Formula I that may be prepared through the syntheses described herein may exist as single stereoisomers, racemates, and as mixtures of enantiomers and diastereomers. The compounds may also exist as geometric isomers. All such single stereoisomers, racemates and mixtures thereof, and geometric isomers are intended to be within the scope of this 177 invention. Some of the compounds of the invention may exist as tautomers. For example, where a ketone or aldehyde is present, the molecule may exist in the enol form; where an amide is present, the molecule may exist as the imidic acid; and where an enamine is present, the molecule may exist as an imine. All such tautomers are within the scope of the invention. [00169] In particular, in this application B can be 2-hydroxy-pyridinyl, also described as its structure: N OH 14. Both 2-hydroxy-pyridinyl and the above structure 14 include, and are equivalent to, pyridin 2(1H)-one and its structure 15: (RW)0-2 NO, H 15. Regardless of which structure or which terminology is used, each tautomer is included within the scope of the Invention. [001701 The present invention also includes N-oxide derivatives and protected derivatives of compounds of Formula I. For example, when compounds of Formula I contain an oxidizable nitrogen atom, the nitrogen atom can be converted to an N-oxide by methods well known in the art. When compounds of Formula I contain groups such as hydroxy, carboxy, thiol or any group containing a nitrogen atom(s), these groups can be protected with a suitable "protecting group" or "protective group". A comprehensive list of suitable protective groups can be found in T.W. Greene, Protective Groups in Organic Synthesis, John Wiley & Sons, Inc. 1991, the disclosure of which is incorporated herein by reference in its entirety. The protected derivatives of compounds of Formula I can be prepared by methods well known in the art. [00171] Methods for the preparation and/or separation and isolation of single stereoisomers from racemic mixtures or non-racemic mixtures of stereoisomers are well known in the art. For example, optically active (R)- and (S)- isomers may be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques. Enantiomers 178 (R- and S-isomers) may be resolved by methods known to one of ordinary skill in the art, for example by: formation of diastereoisomeric salts or complexes which may be separated, for example, by crystallization; via formation of diastereoisomeric derivatives which may be separated, for example, by crystallization, selective reaction of one enantiomer with an enantiomer-specific reagent, for example enzymatic oxidation or reduction, followed by separation of the modified and unmodified enantiomers; or gas-liquid or liquid chromatography in a chiral environment, for example on a chiral support, such as silica with a bound chiral ligand or in the presence of a chiral solvent. It will be appreciated that where a desired enantiomer is converted into another chemical entity by one of the separation procedures described above, a further step may be required to liberate the desired enantiomeric form. Alternatively, specific enantiomer may be synthesized by asymmetric synthesis using optically active reagents, substrates, catalysts or solvents or by converting on enantiomer to the other by asymmetric transformation. For a mixture of enantiomers, enriched in a particular enantiomer, the major component enantiomer may be further enriched (with concomitant loss in yield) by recrystallization. [00172] In addition, the compounds of the present invention can exist in unsolvated as well as solvated forms with pharmaceutically acceptable solvents such as water, ethanol, and the like. In general, the solvated forms are considered equivalent to the unsolvated forms for the purposes of the present invention. [00173] In Compounds of Formula I RS2

R

53

OR

51 W' N N H O 0 NN-S-C) wH N1 0 the hydrogen on the -NHS(O) 2 - group is highly acidic. Thus, intermediates leading to Compounds of Formula I, as well as Compounds of Formula I themselves, can be recovered as uncharged or zwitterionic molecules, or cationic salts such a sodium or potassium, depending on the substitutions on the B ring and on reaction conditions. In the examples that follow, unless otherwise specified, the final form of the compound was assumed to be 179 the uncharged molecule in the absence of analytical techniques that would have determined otherwise. [001741 Compounds of Formula I can be prepared using methods known to one of ordinary skill in the art. Specifically, fusion of appropriate reagents at 180 *C in the presence of a base such as K 2 C0 3 and metallic copper is known to provide intermediates of formula 1 (see S. H. Dandegaonker and C. K. Mesta, J Med. Chem. 1965, 8, 884). [00175] Alternatively, the intermediate of formula 3 can be prepared according to the scheme below where each LG 1 is a leaving group (specifically, halo, more specifically, chloro) and all other groups are as defined in the Detailed Description of the Invention. Scheme 1

R

62 s 52

R

5 ) OR" 1 OiW W N LG W N LG RM R50 R ROD

B-S(O)

2

NH

2 (2)

NH

2 N NH 1w~ N LG 1 base, solvent, reflux solvent, reflu N~~ NB- ovnrfu I3 0 [001761 In scheme 1, an intermediate of formula 3 can be prepared by briefly heating commercially available 2,3-dichloroquinoxaline and an intermediate of formula 2 (which are commercially available or can be prepared by one of ordinary skill in the art), a base such as K 2 C0 3 , in a solvent, such as DMF or DMSO. Upon completion (about 2 hours), the reaction mixture is then poured into water and followed by 2 N HCL. The product is then extracted into a solvent such as ethyl acetate and washed with water and brine. The organic layers are combined and dried over a drying agent such as sodium sulfate, filtered, and concentrated under vacuum. [00177] The intermediate of formula 3 is then treated with an intermediate of formula 4 in a solvent such as DMF or p-xylene at reflux temperature. Upon completion of the reaction (about 16 hours or less), the reaction is allowed to cool, extracted into DCM, washed with 2 N HCl and brine, dried over a drying agent such as sodium sulfate or magnesium sulfate, filtered, and concentrated to give a compound of Formula I. [001781 Alternatively, other methods to prepare quinoxaline derivatives are known to one skilled in the art and include, but are not limited to S. V. Litvinenko, V. I. Savich, D. D. Bobrovnik, Chem. Heterocycl. Compd. (Engl. Transl), 1994, 30, 340 and W. C. Lumma, R. D. Hartman, J Med. Chem. 1981, 24, 93. 180 100179] The following compounds were prepared in a manner similar to that described above. Example 1: N-(3-{[2,5-bis(methoxy)phenyl]amino}quinoxalin-2-yl)-3 nitrobenzenesulfonamide. Example 2: N-(3-{[2,5-bis(methoxy)phenyl]amino}quinoxalin-2-yl)-4 chlorobenzenesulfonanide. Example 3: N-(3-chloroquinoxalin-2-yl)-3-nitrobenzenesulfonamide. Example 4: 4-chloro-N-(3-chloroquinoxalin-2-yl)benzenesulfonamide. Example 5: 4-chloro-N-(3-(2,5-dimethoxy-phenylamino)quinoxalin-2 yI)benzenesulfonamide.11H NMR (400 MHz, DMSO-d 6 ) 8 9.18 (s, 11), 8.78 (s, 111), 8.40 8.60 (m, 3H), 7.98 (t, 2H), 7.62 (d, 111), 7.41 (m, 2H), 6.98 (d, 1H), 6.59 (d, 1H), 3.78 (s, 3H), 3.76 (s, 3H); MS (EI) m/z for C 22 HIN50 6 S: 482.1 (MH). Example 6: N-(3-(2,5-diinethoxyphenylamino)quinoxalin-2-yl)-3 nitrobenzenesulfonamide. 1H NMR (400 MHz, CDC1 3 ) 8 12.68 (br s, 1H), 9.18 (s, 1H), 8.55 (s, 1H), 8.08 (d, 2H), 7.98 (d, 1H), 7.78 (d, 2H), 7.62 (dd, 111), 7.40 (m, 2H), 7.00 (d, 1H), 6.60 (dd, 1H), 3.78 (s, 6H) ; MS (EI) m/z for C2 2

H

1 9 C1N40 4 S: 471.1 (MIW). Example 7: N-(3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sufamoyl)-4 methylphenyl)-2-(dimethylamino)acetamide. 'H NMR (400 MHz, DMSO-d 6 ) 5 12.0 (br s, 1 H), 10.6 (s, 1 H), 10.0 (br s, 1 H), 9.52 (s, 1 H), 8.91 (d, 1 H), 8.25 (d, 1 H), 7.69 (dd, 1H), 7.47 (m, 1 H), 7.39 (d, 1 H), 7.16 (m, 3 H), 6.01 (dd, I H); MS (EI) m/z for C26H 27

CW

6 0 4 8: 555 (MH). [00180] Compounds of Formula I where B is phenyl substituted with R 3 a where R 3 a is alkylamino or dialkylamino or B is heteroaryl substituted with R 3 where R 3 is amino, alkylamino, or dialkylamino, and all other groups are as defined in the Summary of the Invention can be prepared according to Scheme 2. 181 Scheme 2

R

53

OR

5 ' R 53

OR

1 e R R6 0 RM R6o C N NH N NH H" B LG - - NRSRb 0 0 5 (c) LO is a leaving group such as chloro. 5 is reacted with NHRaRe or HO-C1.-C 6 -alkylene NHRaRe where Ra and R are independentlyhydrogen or alkyl. The reaction is carried out in the presence of a base, such as KHCO 3 , in a solvent such as DMjF. [00181] Compounds of Formula I where B is phenyl substituted with R 3 a where R 3 a is aminoalkyloxy, alkylaminoalkyloxy, or dialkylaminoalkyloxy or B is heteroaryl substituted with R 3 where R 3 is aminoalkyloxy, alkylaminoalkyloxy, or dialkylaminoalkyloxy, and all other groups are as defined in the Summary of the Invention can be prepared according to Scheme 3. Scheme 3 RM

R

53 OR" R. R50 6Y Ny NH O-CN-Sr O Ce-alkylene-NRaRb H 0 1(c) The reaction is carried out in the presence of a base such as NaH in a solvent such as DMF. [001821 Compounds of Formula I where B is phenyl substituted with R 3 a or B is heteroaryl substituted with R 3 where R 3 ' and R 3 are i. -N(R)C(O)-C-C6-alkylene-N(Ra)(R') Where R 7 , R 7 a, and Rib are as defined in the Summary of the Invention; ii. -NR 9

C(O)R

9 a where R 9 is as defined in the Summary of the Invention; iii. -NRllC(O)NRu1aRI1b where Riua, Rua, and R1 b are as defined in the Summary of the Invention; iv. -NReC(O)ORua where R" and R' 3 a are as defined in the Summary of the Invention; 182 v. -N(R")C(O)-Cl-C6-alkylene-N(Rub)C(0)Rlsa where R1 8 , R8a, and R 8 b are as defined in the Summary of the Invention; vi. -N(R2)C(O)-CrCw-alkylene-C(0)Ra Where R 20 and Ra as defined in the Summary of the Invention; vii. -NReS(O) 2 R-C.C-alkylene-N(R21b)R 2 a where R 2 1 , R 2 Ia, and R 2 1b are as defined in the Summary of the Invention; viii. -N(Rw)C(O)-CO-Cbalkylene-N(R2)-N(R2"(a), Where R 22 , R 22 a and R2b are as defined in the Summary of the Invention; ix. -NReC(O)-C.C-alkylene-OR 24 a where R 4 and R 2 4 a are as defined in the Summary of the Invention; and where the alkylene in R 3 and R 3 a are independently optionally substituted as described in the Summary of the Invention can be prepared according to Scheme 4 by reacting with an intermediate of formula 9(a), 9(b), 9(c), 9(d), 9(e), 9(f), or 9(g): 9(a) HOC(O)-Ci-C 6 -alkylene-N(R 7 a)(R7) where R ais Rya or a N-protecting group, such as Boc or Fmoc; 9(b) HOC(O)R 9 a; 9(c) HOC(O)NR' uaR i; 9(d) HOC(O)OR'la; 9(e) HOC(O)-CrC 6 -alkylene-N(R"Sb)C(O)R8a; 9(t) HOC(O)-Cr-C 6 -alky1ene-C(O)R 2 oa; 9(g) LG-S(O) 2 R-C1.C 6 -alkylene-N(R 2 b1)Ra where R is R 21 a or a N-protecting group, such as Boc or Fmoc. Scheme 4

R

52

R

52 R5 OR 51

R

53

OR

51 R65 R60 9()9gR54 R N NH N NH KNIN B3 NHRa B NHR 1 00 H 0& Ni 0 8 1(e)

R

1 00 in Scheme 4 is -C(O)R 9 a, -C(O)NRlaRllb, -C(O)ORua, -C(O)-CC6-alkylene N(R"b)C(O)R'1a, -C(O)-CrCo-alkylene-C(O)ROa Or -S(O) 2 R-C.C-alkylene-N(R 2 b1)Ra. The reaction is carried out under standard amide coupling conditions known to one of 183 ordinary skill in the art. In particular, the reaction is carried out in the presence of a coupling agent such as HATU, a base such as DIEA, and in a solvent such as DMF. Where applicable, the N-protecting group is then removed using procedures known to one of ordinary skill in the art, such as treating with acid where PG is Boc. [001831 Proceeding as described for Scheme 4, compounds of the invention where B is phenyl substituted with R 3 a or B is heteroaryl substituted with R 3 where R 3 a and R? are a) -C(O)NRRaa; b) -C(O)N(R'")-Ci-C6alkylene-N(Ri ")RIG; c) -C(O)R 12 where R' 2 is an N-substituted heterocycloalkyl; d) -C(O)N(R14)N(Ra4a)(R111); e) -C(O)N(R 6 )_-C1C 6 ealkylene-C(O)OR1 6 a; or f) -C(O)N(R 19 )-C1-C 6 -alkylene-C(O)R a; or can be prepared by exchanging the starting materials as necessary. In particular, the intermediate of formula 11:

R

2

R

63 OR R,54 RSO N NH N N-S- C(O)OH 11 is used instead of 8. [00184] Compounds of Formula I where B is phenyl substituted with R 3 a or B is heteroaryl substituted with R 3 where R 3 a and R 3 are -NHC(O)CH 2

NR

7 aRIb where R 7 a and

R

7 b are as defined in the Summary of the Invention can be prepared according to Scheme 5. 184 Scheme 5

R

53 OR6 R 5 ORr

R

54

R

6 " NHRTaR 7 b R54 RO N NH 0 LG N NH 0 NR 7 8R7b "NH ' N-Os NH 12 I(f) LG is a leaving group such as bromo or chloro. 12 is reacted with NH(RR 7 a in the presence of a base, such as DIEA, in a solvent such as ACN. [001851 Compounds of Formula I can be prepared according to Scheme 6. Scheme 6 LG RR 52 OR 51

R

52

R

6 ORB' AN ~N LG R0 R 50 R 4' 5 N A-- O NH 2 N N 13 H (h) LG in Scheme 6 is a leaving group such as chloro. The reaction can be carried out by irradiating in a solvent such as DMA. Alternatively, the reaction can be carried out in the presence of acetic acid in a solvent such as DMA and by heating. 185 Example 8 6-chloro-N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)pyridine-3-sulfonamide Ci N CI N CN NN CI KCO _ -N

CI'OH

2 N- DMSO, hea CI SO DIEA xylene, heat N H N j9 \/CI 0 1001861 6-chloropyridine-3-sulfonamide. 6-chloropyridine-3-sulfonyl chloride (4.1 g, 19.3 mmol) was stirred in ammonium hydroxide (30 mL) at room temperature for 2 hr. The reaction mixture was diluted with EtOAc (150 mL) and any insoluble material filtered. The filtrate was transferred to a separatory funnel and the phases were separated. The aqueous phase was further extracted with EtOAc (1 x 15 mL). The combined EtOAc extractions were washed with H 2 0 (1 x 50 mL) and saturated NaCl (1 x 50 mL), dried over Na 2

SO

4 , and concentrated in vacuo to give 6-chl1orpyridine-3-sulfonamide (2.58 g, 69%). MS (EI) m/z for C 5

H

5 Cl 2

N

2 0 2 S: 190.9 (MH'). 100187] 6-chloro-N-(3-chloroquinoxalin-2-yl)pyridine-3-sulfonamide. 2,3-dichloroquinoxaline (1.09 g, 5.48 mmol), 6-chloropyridine-3-sulfonamide (1.05 g, 5.45 mmol), K 2 C0 3 (753 mg, 5.45 mmol) and dry DMSO (30 mL) were combined and heated to 150 "C with vigorous stirring for 3-4 hr. The reaction mixture was allowed to cool to room temperature, then poured into 1% AcOH in ice water (300 mL) with vigorous stirring. The resulting solids were filtered, washed with H20 and dried under high vacuum to give 6 chloro-N-(3-chloroquinoxalin-2-yl)pyridine-3-sulfonamide (1.87g, 96%). MS (EI) m/z for C1 3 HsC1 2

N

4 0 2 S: 354.99 (MR). [001881 6-chloro-N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)pyridine-3 sulfonamide. 6 -Chloro-N-(3-chloroquinoxalin-2-yl)pyridine-3-sulfonamide (775 mg, 2.2 mmol), 3,5-dimethoxyaniline (355 mg, 2.3 mmol) and toluene (12 inL) were combined and heated to 125 "C with stirring overnight. The reaction was allowed to cool to room temperature and diluted with Et 2 O with vigorous stirring. The resulting solids were filtered, washed with Et 2 O and dried to give 6-chloro-N-(3-(3,5-dimethoxy 186 phenylamino)quinoxalin-2-yl)pyridine-3-sulfonamide (920 mg, 89%). 'H NMR (400 MHz, DMSO-d 6 ) 8 12.20 (br s, 1H), 9.12 (d, 1H), 9.01 (br s, 1H), 8.53 (dd, IH), 7.91 (br d, lH), 7.77 (d, 1H), 7.60 (dd, 1H), 7.40 (m, 4H), 6.26 (m, 1H), 3.78 (s, 6H). MS (E) m/z for

C

21 HisClNSO 4 S: 472.0 (MH. Example 9 N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-y)-6-(2-(dimethylamino) ethylamino)pyridine-3-sulfonamide oNNN KHCO 3 , DMF, heat 1 N N -- CI N NH 00 [00189] 6-chloro-N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-pyridine-3 sulfonamide (100 mg, 0.21 mmol), prepared using procedures similar to those used in Example 8, KHCO 3 (40 mg, 0.40 mmol), N,N-dimethylethane-1,2-diamine (225 pL, 2.0 mmol) and dry DMF (1.0 mL) were combined and heated to 130 "C with stirring overnight. The reaction mixture was concentrated in vacuo and purified by preparative HPLC to give N-(3-(3,5-dimethoxy-phenylamino)-quinoxalin-2-yl)-6-(2 (dimethylamino)ethylamino)pyridine-3-sulfonamide (21.0 mg, 19%). 'H NMR (400 MHz, DMSO-d 6 ) 8 8.76 (br s, 1H), 8.63 (d, 1H), 8.07 (dd, 1H), 7.40 (m, 1H), 7.34 (m, 1H), 7.28 (d, 2H), 7.14 (m, 4H), 6.47 (d, 1H), 6.12 (m, 1H), 3.75 (s, 6H), 3.35 (m, 2H), 3.14 (m, 2H), 2.74 (s, 6H). MS (EI) MI/z for C 25 11 29

N

7 0 4 S: 524.1 (MH*). [00190] Example 10: N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-y)-6 (dimethylamino)pyridine-3-sulfonamide was prepared using procedures similar to those used in Example 9. 'H- NMR (400 MHz, DMSO-ds) 8 12.00 (br s, 1H), 8.92 (br s, 1H), 8.74 (d, 1H), 8.10 (dd, 1H), 7.38 (br s, 1H), 7.54 (m, 1H), 7.33 (m, 4H), 6.70 (d, 111), 6.22 (s, IH), 3.77 (s, 6H), 3.08 (s, 6H). MS (EL) m/z for C 2 3

H

2 4

N

6 0 4 S: 481.1 (MH). 187 Example 11 N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-6-(2-(diimethylamino) ethoxy)pyridine-3-sulfonamide /0~ 0- /0- 0" 60% NaH, DMF ~NNI N N HON " NN H HO H O [001911 N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)pyridine-3-sulfonamide (100 mg, 0.21 mmol), prepared using procedures similar to those described above in Example 1, 2-(dimethylamino)ethanol (50 iL, 0.50 mmol) and dry DMF were combined and 60% NaH in oil (80 mg, 2.0 mmol) was added. The mixture was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo and purified by preparative HPLC to give N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-6-(2 (dimethylamino)ethoxy)pyridine-3-sulfonamide (23 mg, 21%). 'H NMR (400 MHz, DMSO-d 6 ) 8 8.78 (d, 111), 8.73 (s, 1H), 8.38 (dd, 1H), 7.40 (dd, 1H), 7.31 (m, 3H), 7.14 (m, 211), 6.85 (d, 1H), 6.12 (m, 1H), 4.56 (m, 2H), 3.76 (s, 6H), 3.43 (m, 2H), 2.77 (s, 6H). MS (EI) m/z for C 25

H

2 sN 6 0 5 S: 525.1 (MH). Example 12 N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-6-oxo-1,6-dihydropyridine 3-sulfonamide / H0 /0 O N NI, ~ N 3N NaOH, DMSO, heat ,NH N IN NN H [00192] N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-y)pyridine-3-sulfonamide (220 mg, 0.47 mmol), prepared using procedures similar to those described above in Example 8, DMSO (5 mL), and 3N NaOH (5 mL) are combined and heated to 100 *C overnight with stirring. Upon cooling to room temperature, the reaction mixture was diluted with H 2 0 and the pH was adjusted to 7.0 with iN HC. The resulting solid was filtered, washed with 1120, 188 and air-dried. The solid was then sonicated in EtOAc, filtered, washed with EtOAc, and dried under high vacuum to give N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-6-oxo 1,6-dihydropyridine-3-sulfonamide (190 mg, 90%). 1H NMR (400 MHz, DMSO-d 6 ) 8 12.23 (br s, 111), 12.10 (br s, 1H), 8.97 (s, 1H), 8.23 (s, 1H), 7.95 (m, 2H), 7.59 (m, 111), 7.37 (m, 4H), 6.43 (d, 1H), 6.25 (s, 1H), 3.77 (s, 6H). MS (E) m/z for C 21

H

19

N

5 0 5 S: 454.0 (M). [0185] Example 13: N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-y)-6 oxo-1,6-dihydropyridine-3-sulfonamide. The title compound was prepared according to the above Example 12. 'H NMR (400 MHz, DMSO-d 6 ) 6 12.22 (br s, 1H), 12.10 (br s, 1H), 9.16 (s, 1H), 8.60 (s, 1H), 8.14 (d, 1H), 7.94 (m, 111), 7.85 (dd, 1H1), 7.62 (m, 1H), 7.40 (m, 3H) 6.69 (dd, 1H), 6.43 (d, 1H), 3.81 (s, 3H). MS (EI) m/z for C 20

H

1 6 C1Ns0 4 S: 456.0 (MH-). Example 14 3-amino-N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)benzenesulfonamide. 01 NO2 NO2 ro,,N NH NO OH N CX Xylene N NH MeO N OMe [00193] N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-y)-3 nitrobenzenesulfonamide. A flask was charged with N-(3-chloroquinoxalin-2-yl)-3 nitrobenzenesulfonamide (5 g, 13.7 mmol), prepared using procedures similar to those in Example 1, 3,5-dimethoxyaniline (4.2 g, 27.4 mmol), and 80 mL of xylene. The reaction mixture was stirred under an N 2 atmosphere at 150 *C for 3 hours, after which time, solvent was removed on a rotary evaporator, and 10 mL of Dichloromethane and 50 mL of methanol were added. The slurry was heated to reflux and filtered while hot, resulting in 4.6 g (69.7 %) of N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-3 nitrobenzenesulfonamide MS (EI) m/z for C 2 2

HN

5 0 6 S: 482.2(MH+) 189 Example 1 53-amino-N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2 yl)benzenesulfonamide

NO

2 NH 2 OM S=O 0::S=O I I NH N NH MeOH Meo OMe MeO OMe {001941 A flask was charged with N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-3 nitro-benzenesulfonanide (3.4g, 7.06 mmol), prepared using procedures similar to those in Example 14, tin chloride solvate (6.4 g, 28.2 mmol), and 30 mL of DMA. A few drops of water were added and the reaction mixture was stirred at 80 "C for 3 hours, after which time, solvent was removed on a rotary evaporator, and 50 mL of water and 10 mL of Methanol were added. The slurry was filtered, and the filtrate was washed with MeOH, water, and diethyl ether (20 mL of each), resulting in 3.25 g 3-amino-N-(3-(3,5-dimethoxy phenylamino)quinoxalin-2-yl)benzenesulfonamide. 1 H NvR (400 MHz, DMSO) 6 12.2 (br s, 111), 8.85 (s, 111), 7.90 (br s, 111), 7,50-7.60 (m, 1H), 7.3-7.4 (m, 4H), 7.2 (m, 31), 6.74 (m, 1H), 6.24 (m, 1H), 5.56 (br s, 2H), 3.76 (s, 614). MS (EJ) m/z for C22H21NsO4S: 452.0 (MH ). [001951 The following compounds were made using procedures similar to those used in Example 15. Example 16: Proceeding as above, 3-amino-N-(3-(2,5-dimethoxy phenylamino)quinoxalin-2-yl)benzenesulfonamide was prepared. 11 NMR (400 MHz, DMSO) 6 12.4 (br s, 1H), 9.20 (s, 1H), 8.56 (d, 1H), 7.95 (d, 1H), 7.62 (m, 1H), 7.38 (m, 2H), 7.24 (q, 2H), 7.14 (d, 1H), 6.98 (d, 1H), 6.8 (m, 111), 6.60 (m, 1H), 5.6 (br s, 2H), 3.78 (d, 6H). MS (E) m/z for C 2 2

H

21 NsO 4 S: 452.3 (MHW). Example 17: Proceeding as above, 3-amino-N-(3-(2-chloro-5-hydroxy phenylamino)quinoxalin-2-yl)benzenesulfonamide was prepared. MS (EI) m/z for

C

20 H1 6 ClNsO 3 S 1.0 x C 2

H

1 0 2

F

3 : 442.2, 444.2 (MH*). 190 Example 18: Proceeding as above, 3-amino- -(3-(6-methoxyquinolin-8 ylamino)quinoxalin-2-yl)benzenesulfonamide was prepared. MS (E) m/z for

C

24

H

20

N

6 0 3 S: 473.0 (M0. Example 19: 3-amino-N-(3-(3-fluoro-5-methoxy-phenylamino)quinoxalin-2 yl)benzenesulfonamide. MS (EI) m/z for C 21

H

18

FN

5 0 3 S: 439.99 (MH*). Example 20: 3-amino-N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2 yl)benzenesulfonamide. MS (EI) m/z for C 21 HiSCIN 5 0 3 S: 457.02 (MH). Example 21: 3-amino-N-(3-(5-methoxy-2-methyl-phenylamino)quinoxalin-2 yl)benzenesulfonamide. MS (11) m/z for C 22

H

2 1N 5 03S: 436.32 (MH*). Example 22a and Example 22b 3-amino-N-(3-(3-methoxy-5-nitro-phenylamino)quinoxalin-2-yl)benzenesulfonamide and 3-amino-N-(3-(3-amino-5-methoxy-phenylamino)quinoxalin-2 yl)benzenesulfonamide No HO HKo H NH2 S NH 2 02N i 0 - Pd(C, THF/EtOH jbj., 0 2 N o oaN~ O/ H 2 N o [00196] To a mixture of N-(3-{[3-(methyloxy)-5-nitropheny1]amino}quinoxalin-2-y)-3 nitrobenzenesulfonamide (400 mg), THF (2 mL) and EtOH (2 mL) was added formic acid (938 VL), potassium formate (203 mg). After the mixture was Rushed with N 2 , 10%wt Pd/C (50 mg) was added. The resulting mixture was heated at 60 "C with stirring. LC/MS analysis indicated that the reaction mixture contained the complete reduced di-amino compound as the major product and the partially reduced mono-amino compound as a minor product. A portion of the crude mixture was purified by FPLC to give the two products. Product A: 3-amino-N-(3-(3-methoxy-5-nitro-phenylamino)quinoxalin-2 yl)benzenesulfonamide. 'H NMR (400 MHz, DMSO) 8 12.2 (br s, 1H), 9.51 (s, 11), 8.77 (s, 11), 8.21 (s, 1H), 7.92 (s, IH), 7.48 (m, IH), 7.43-7.38 (m, 311), 7.24-7.16 (m, 3H), 6.75 (d, 1H), 5.57 (br s, 2H), 3.90 (s, 3H). MS (BI) for C 2 1HisN 6 0 5 S: 467.00 (MH4+). Product B: 3-amino-N-(3-(3-amino-5-methoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide. 'H NMR (400 MHz, DMSO) 8 12.0 (br. s, 1H), 8.53 (s, 1H), 7.84 (s, 1H4), 7.56 (d, 1H), 191 7.37-7.30 (m, 2H), 7.21-7.17 (m, 311), 6.87 (s, 111), 6.81 (s, 1H), 6.74 (br s, 2H), 5.91 (s, 1H), 5.56 (br s, 3H), 3.69 (s, 3H). MS (EI) for C 2 1

H

2 0

N

6 0 3 S: 437.2 (MH+). Example 23a and Example 23b N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-3-(hydroxyamino) benzenesulfonamide and 3-amino-N-(3-{[3,5-(dimethoxy)phenyllamiuo}quinoxalin-2 yl)benzenesulfonamide N PdC O NH2 MeOHfrHF O [001971 To a solution N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl) 3-nitrobenzenesulfonamide (1.3g) in 20 mL of THF and 10 mL of MeOH was added 1O%wt Pd/C (100 mg). The mixture was stirred under a H2 balloon ovemight. A portion of the reaction mixture was taken out and filtered, then purified by HPLC to afford two products. Product A: N-(3-{ [3,5-bis(methyloxy)phenyl]amino}quinoxalin-2-y)-3 (hydroxyamino)benzenesulfonamide. MS (EI) for C22H 2 1NsOsS: 468.1 (MH*). Product B: 3-amino-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide. 'H NMR (400 MHz, DMSO) 5 12.2 (br s, 1H), 8.85 (s, 1H), 7.90 (br s, 11), 7.50-7.60 (m, 111), 7.3 7.4 (m, 4H), 7.2 (m, 3H), 6.74 (m, 1H), 6.24 (m, 111), 5.56 (br s, 2H), 3.76 (s, 611). MS (EI) for C 22

H

2 1

N

5 0 4 S: 452.0 (MH). 192 Example 24 (S)-2-amino-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)propanamide hydrochloride. N NH HA NH~ O O NH + HO Boc HATU/DIEA NOO__NO + . B o SN Step A H NHN

NH

2 NH 1-0, 0-1 Boo HC 4N HCll0oxane

-

I I Step B (" N~ NH 0 0 H N

-

N H (00198] (S)-tert-butyl 1-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2 yl)sulfamoyl)phenylamino)-1-oxopropan-2-ylearbamate. 3-amino-N-(3-(3,5-dimethoxy phenylamino)quinoxalin-2-yl)benzenesulfonamide (1.1 mmol, 500 mg), prepared using procedures similar to those described above in Example 15, (L)-Boc-Ala-OH (1.5 mmol, 284 mg), dichloromethane (15 mL), DMF (10 mL), DIEA (2 mmol, 330 pL), and HATU (2 mmol, 760 mg) stirred at room temperature over night. The crude mixture was column purified using 1/1 ethyl acetate/hexanes on silica to gave 160 mg. [001991 (S)-2-amino-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2 yl)sulfamoy)phenyl)propanamide hydrochloride. 4 N HCI is dioxane (10 mL) was added to a solution of (S)-tert-butyl 1-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin 2-yl)sulfamoyl)phenylamino)-1-oxopropan-2-ylcarbamate (160 mg) and DCM (15 mL). The mixture was stirred at room temperature for 3 hours. The solvent decanted and ether added to the solid, ether decanted to gave 80 mg product as HCl salt. 'H NMR (400 MHz,

CD

3 0D) S 8.50-8.49 (t, 1H), 7.89-7.87 (m, 1H), 7,74-7.72 (m, 1H), 7.61-7.5 (m, 3H), 7.40 7.36 (i, 211), 7.21-7.20 (d, 2H), 6.23-6.21 (t, 1M), 4.09-4.03 (q, If), 3.78 (s, 6H), 1.60-1.58 (d, 311); MS (BI) m/z for C 25

H

2 NOsO58-HCl: 523.1 (MIW). 193 [002001 The following compounds were prepared as the free amine and/or HCI salt using procedures similar to those in Example 24. Where the deprotection step is not necessary, Step B in the above scheme was not preformed. Example25: N-(2-chloro-5-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(methylamino)acetamide. The title compound was prepared according to the Examples above. 'H NMR (400 MHz, DMSO-d 6 ) 5 10.50 (s, 1H), 9.14 (s, 1H), 9.03 (m, 2H), 8.63 (d, 1H), 8.44 (d, 111), 7.98 (m, 1H), 7.91 (dd, 1H), 7.80 (d, 1H), 7.67 (m, 1H), 7.44 (m, 3H), 6.71 (dd, 1H), 4.06 (m, 2H), 3.83 (s, 3H), 2.64 (t, 3H). MS (EI) m/z for C24HnCl 2

N

6

O

4 S: 561.0 (MH. Example 26: (S)-2-amino-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)propanamide hydrochloride. 'H NMR (400 MiHz, CD 3 0D) a 8.72 8.71 (d, IH), 8.48-8.46 (t, IH), 7.86-7.84 (m, 1H), 7.80-7.78 (m, 1H), 7.63-7.59 (m, 2H), 7.58-7.55 (t, 1H), 7.41-7.38 (m, 2H), 7.24-7.22 (d, 1H), 6.60-6.58 (dd, 1H), 4.10-4.04 (q, 1H), 3.83 (s, 3H), 1.61-1.60 (d, 3H); MS (El) m/z for C 24

H

23 ClN 6 0 4 S-HC: 527.2 (MH*). Example 27: (S)-2-amino-N-(3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)butanamide hydrochloride, 1H NMR (400 MHz, CD 3 0D) 8 8.74 8.73 (d, 1H), 8.80-8.47 (t, 1H), 7.87-7.85 (m, 1H), 7.80-7.78 (m, 1H), 7.67-7.61 (m, 2H), 7.59-7.55 (t, 1H), 7.42-7.39 (m, 2H), 7.26-7.24 (d, 1H), 6.62-6.59 (dd, 1H), 3.96-3.93 (t, 1H), 3.84 (s, 3H), 2.02-1.94 (m, 2H, 1.09-1.06 (t, 3H); MS (EI) m/z for

C

25 H2 5 C1N 6 0 4 S-HC1: 541.3 (MH). Example 28: (S)-N-(3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2 yl)sulfamoyl)pheny)pyrrolidine-2-carboxamide hydrochloride. 'H NMR (400 MHz,

CD

3 0D) 8 8.78-8.77 (d, 1H), 8.47-8.46 (t, 1H), 7.87-7.85 (m, 1H), 7.80-7.75 (m, I), 7.69-7.65 (m, 2H), 7.59-7.55 (t, 1H1), 7.45-7.41 (m, 2H), 7.31-7.28 (d, 1H), 6.65-6.63 (dd, 1H), 4.42-4.38 (m, 1H), 3.86 (s, 3H), 3.48-3.42 (m, 2H), 2.55-2.49 (m, 1H1), 2.18-2.08 (m, 3H); MS (EI) m/z for C 26

H

2 sC1N 6

O

4 S-HC1: 553.3 (MH). Exmaple 29: (S)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)pyrrolidine-2-carboxamide hydrochloride. 'H NMR (400 MHz,

CD

3 0D) 8 10.62 (br s, 1H), 8.50-8.49 (t, 1H), 7.90-7.87 (m, 1H), 7.76-7.73 (m, 1H), 7.63 7.58 (m, 3H), 7.43-7.35 (m, 2H), 7.14 (s, 2H), 6.27-6.26 (t, 1H), 4.43-4.38 (m, 1H), 3.78 (s, 6H), 3.48-3.41 (m, 1H), 3.40-3.36 (m, 1H(, 2.54-2.48 (m, 1H), 2.19-2.05 (m, 3H); MS (EI) m/z for C 27

H

28

N

6 0 5 S-HC: 549.3 (MH*) 194 Example 30: (R)-2-amino-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-3-hydroxypropanamide hydrochloride. 'H NMR (400 MHz,

CD

3 0D) 6 8.49-8.48 (t, 111), 7.89-7.87 (m, 1H), 7.75-7.72 (m, 1H), 7.65-7.62 (m, 2H), 7.62-7.5 5 (t, 1H), 7.44-7.38 (m, 2H), 7.23-7.22 (d, 2H), 6.27-6.26 (t, 1H), 4.07-4.05 (m, 1H), 3.99-3.93 (m, 2H), 3.80 (s, 6H); MS (EI) m/z for C 25

H

2 6

N

6 0 6 S-HCI: 539.1 (MH*). Example 31: N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxain-2 yl)sulfamoyl)phenyl)piperidine-3-carboxamide hydrochloride. 'H NMR (400 MHz,

CD

3 0D) 8 8.79-8.78 (d, 1H), 8.45 (m, 1H), 7.83-7.81 (d, 1H), 7.76-7.74 (i, 1H), 7.636 (m, 211), 7.54-7.50 (t, 1H), 7.41 (m, 2H), 7.30-7.28 (d, 1H), 6.65-6.62 (dd, 1H), 3.86 (s, 3H), 3.40-3.32 (m, 2H), 3.20-3.13 (m, 3H), 2.93 (m, 1H), 2.15-2.11 (m, 1H, 1.98-1.93 (m, 2H), 1.83 (m, 1H); MS (El) mi/z for C 27

H

2 7 C1N 6 0 4 S-HCI: 567.3 (MH*). Example32: (S)-2-amino-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)butanamide hydrochloride. MS (EI) m/z for C 26

H

2 sN 6 0 5 S-HCI: 537.1 (MH*). Example 33: (R)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)pyrrolidine-2-carboxamide hydrochloride. MS (El) m/z for C27H28N60sS-HCl: 549.1 (MH0. Example 34: (R)-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)pyrrolidine-2-carboxamide hydrochloride. MS (El) m/z for

C

26

H

25

CIN

6 0 4 S-HC: 553 (MH*). Example 35: (R)-2-amino-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)propanamide. 'H NMR (400 MHz, DMSO-d 6 ) 8 10.2 (br s, 1 H), 8.82 (s, I H), 8.27 (m, 1 H), 7.75 (m, 2 H), 7.33 (m, 5 11), 7.13 (m, 2 H), 6.14 (t, 1 H), 3.77 (s, 6 H), 1.39 (d, 3 H); MS (EI) m/z for C 25

H

2 6

NV

6 0 5 S: 523 (MHW). Example 36:N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(methylamino)acetamide. 'H NMR (400 MHz, DMSO-d 6 ) 8 10.6 (s, 1 H), 9.48 (s, 1 H), 8.95 (br s, 1 11), 8.75 (br s, 1 H), 8.19 (br s, 1 H), 7.77 (dd, 1 H), 7.69 (dd, I H), 7.41 (m, 4 H), 7.17 (m, 2 H), 6.60 (dd, 1 H), 3.91 (s, 2 H), 3.82 (s, 6 H), 2.62 (s, 3 H); MS (EI) m/z for C24H 2 3 C1N 6 0 4 S: 527 (H*). Example 37: (R)-2-amino-N(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)propanamide. 'H NMR (400 MHz, DMSO-d) 6 10.5 (s, 1 H), 9.47 (s, 1 H), 8.95 (d, 1 H), 8.22 (d, 2 H), 8.14 (br s, 2 H), 7.76 (m, 2 1), 7.40 (i, 4 H), 7.17 (m, 195 2 H), 6.60 (m, 1 H), 3.97 (q, 1 H), 3.96 (s, 3 H), 1.45 (d, 3 H); MS (EI) m/z for

C

2 4H 23 ClN 6 0 4 S: 527 (MHU). Example 38: 2-amino-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxain-2 yl)sulfamoyl)phenyl)-2-methylpropanamide. 1H NMR (400 MHz, DMSO-d 6 ) 8 10.1 (s, 1 H), 9.46 (s, 1 11), 8.95 (d, 1 H), 8.50 (br s, 1 H), 8.27 (m, 1 H), 7.81 (m, 2 H), 7.47 (m, I H), 7.37 (m, 3 H), 7.17 (m, 2 H), 6.61 (dd, 1 H), 3.83 (s, 3 H), 1.60 (s, 6 H); MS (El) m/z for

C

25

H

2 5 C1N 6 0 4 S: 541 (M+). Example 39: 2-amino-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-methylpropanamide. 'H NMR (400 MHz, DMSO-d6) 8 10.33 (s, 1 1), 8.89 (s, 1 M), 8.32 (br s, 4 H), 7.92 (m, 3 H), 7.59 (m, 21'), 7.37 (m, 41H), 6.24 (s, 1 H), 3.76 (s, 6 H), 1.61 (s, 6 H); MS (EI) n/z for C 26 H2sNOsS: 537 (MH"). Example 40: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-4 methylphenyl)-2-(dimethylamino)acetamide. 1H NMR (400 MHz, DMSO-d) 8 10.58 (s, I H), 9.80 (br s, 1 H), 8.85 (s, 1 H), 8.25 (s, 1 H), 7.67 (dd, 1 H), 7.30 (m, 7 H), 6.16 (m, I H), 4.02 (br s, 2 H), 3.77 (s, 6 H), 2.81 (s, 6 H), 2.54 (s, 3 H); MS (EI) m/z for

C

2 7

H

3 oN 6 0 5 S: 551 (MIH*). Example 41: N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-((2-(dimethylamino)ethyl)(methyl)amino)acetamide. 'H NMR (400 MHz, DMSO-d6) 5 10.0 (s, 1 H), 9.48 (s, 1 H), 8.96 (d, 1 H), 8.16 (m, 1 H), 7.76 (m, 2 H), 7.39 (m, 4 H), 7.17 (m, 2 H), 6.61 (dd, I H), 3,82 (s, 3 H), 3.40 (br s, 2 H), 2.94 (br s, 2 H), 2.71 (br t, 2 H), 2.60 (s, 6 H), 2.33 (s, 3 H); MS (EI) M/z for C 28

H

32 C1N 7 0 4 S: 598 (MH*). Example 42: 2-amino-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)acetamide. 'H NMR (400 MHz, DMSO-d 6 ) 8 10.5 (s, 1 H), 9.48 (s, 1 H), 8.94 (s, 1 H), 8.15 (s, 1 H), 8.06 (br s, 3 H), 7.74 (m, 2 H), 7.39 (m, 4 H), 7.18 (m, 21H), 6.61 (dd, 1 H), 3.83 (s, 3 H), 3.77 (s, 2 H); MS (EI) m/z for C 23

H

21 ClN 6 0 4 S: 513 (MHf). Example 43: N-(3-(N-(3-(2-acetyl-5-methoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(dimethylamino)acetamide. 'H NMR (400 MHz, DMSO-d) 8 12.4 (s, 1 H), 10.5 (s, 1 H), 9.27 (s, 1 H), 8.25 (s, 1 H), 8.01 (d, 1 H), 7.82 (d, 1 H), 7.71 (d, 1 H), 7.42 (m, 3 H), 7.21 (m, 2 H), 6.63 (dd, 1H),3.91 (m, 5 H), 2.75 (s, 6 H), 2.61 (s, 3 H); MS (EI) m/z for C 27

H

2 sN 6 0 5 8: 549 (MH). Example 44: N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)formamide. 'H NMR (400 MHz, DMSO-d 6 ) 8 12.6 (s, 1 H), 10.5 (s, 196 1 H), 9.16 (s, 1 H), 8.53 (br s, I H), 8.35 (in, 2 H), 8.02 (s, 1 H), 7.56 (m, 7 H), 6.70 (dd, 1 H), 3.83 (s, 3 H); MS (EI) m/z for C22HiC1NsO 4 S: 484 (MH*). Example 45: 2-amino-N-(5-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)-2-methylphenyl)acetamide. 'H NMR (400 MHz, DMSO-d 6 ) 8 12.4 (s, 1 H), 10.1 (br s, 1 H), 8.82 (s, I H), 8.20 (m, 3 H), 7.82 (mn, I H), 7.30 (m, 6 H), 6.20 (s, 1 H), 3.85 (s, 2 H), 3.77 (s, 6 H), 2.26 (s, 3 H); MS (EI) m/z for C 2 5

H

2 6

N

6 0 5 S: 523 (MH*). Example 46: N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-methyl-2-(methylamino)propanamide. 'H NMR (400 MHz, DMSO-d 6 ) 8 10.09 (s, 1 H), 9.46 (s, I H), 8.95 (m, 3 H), 8.28 (s, I H), 7.81 (m, 2 H), 7.41 (m, 4 H), 7.17 (m, 2 H), 6.60 (dd, 1 H), 3.82 (s, 3 H), 2.53 (s, 3 H), 1.60 (s, 6 H); MS (EI) m/z for C 26

H

27 ClN 6 0 4 S: 555 (MH). Example 47: (S)-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(methylamino)propanamide 'H NMR (400 MHz, DMSO-d 6 ) 8 10.61 (s, I H), 9.47 (s, I H), 8.95 (s, I H), 8.82 (br s, 2 H), 8.27 (m, I H), 7.74 (m, 2 H), 7.42 (m, 4 H), 7.17 (m, 2 H), 6.60 (dd, I H), 3.90 (m, 1 H), 3.82 (s, 3 H), 2.59 (s, 3 H), 1.49 (d, 3 H); MS (E) m/z for C 25

H

25

CN

6 0 4 S: 541 (MH). Example 48: 3-amino-N-(5-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2 yl)sulfamoyl)-2-methylphenyl)propanamide. 'H NMR (400 MHz, DMSO-d) & 12.25 (s, 1 H), 9.77 (s, I H), 8.82 (s, I H), 7.84 (m, 5 H), 7.50 (d, I H), 7.37 (m, 5 H), 6.22 (m, I H), 3.74 (s, 6 H), 3.08 (m, 2 H), 2.77 (m, 2 H), 2.27 (s, 3 H); MS (EI) m/z for C 2 6

H

2 8N 6 0 5 S: 537 (MH). Example 49: 1-amino-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)cyclopropanecarboxamide. 1H NMR (400 MHz, DMSO-d 6 ) 8 9.54 (br s, I H), 9.42 (s, I H), 8.91 (s, 1 H), 8.21 (s, 1 H), 8.20 (br s, 2 H), 7.81 (m, 2 H), 7.48 (m, 4 H), 7.22 (m, 2 H), 6.61 (dd, I H), 3.82 (s, 3 H), 1.63 (in, 2 H), 1.26 (m, 2 H); MS (EI) m/z for C 2

SH

23 C1N 6 0 4 8: 539 (MH). Example 50: (S)-2-amino-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxain-2 yl)sulfamoyl)phenyl)-6-(dimethylamino)hexanamide. 'H NMR (400 MHz, DMSO-d 6 ) 8 9.47 (br s, 1 H), 8.95 (d, 1 H), 8.26 (m, I H), 7.73 (m, 2 H), 7.30 (m, 4 H), 7.26 (m, 4 H), 7.16 (in, 2 H), 6.59 (dd, I H), 3.82 (s, 3 H), 3.34 (m, I H), 2.20 (i, 2 H), 2.09 (s, 6 H), 1.50 (m, 6 H); MS (EI) m/z for C 2 9 H3 4 ClN 7 0 4 S: 610 (MH*). Example 51: 1-amino-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)cyclopentanecarboxamide. 'H NMR (400 MHz, DMSO-d 6 ) 8 10.12 197 (br s, I H), 9.46 (s, I H), 8.95 (d, 1 H), 8.26 (m, 1 H), 8.16 (m, 3 H), 7.84 (m, 2 H), 7.35 (m, 6 H), 6.60 (dd, 1 H), 3.82 (s, 3 H), 2.34 (m, 2 H), 1.91 (m, 6 H); MS (EI) m/z for

C

27

H

27 C1N 6 0 4 S: 567 (MH). Example 52: N-(5-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl) 2-methylphenyl)-2-(dimethylamino)acetamide. 'H NMR (400 MHz, DMSO-d) 5 12.0 (br s, 1 H), 9.98 (s, 1 H), 9.43 (s, 1 H), 8.91 (m,1 H), 8.08 (s, 1 H), 7.84 (dd, 1 H), 7.32 (m, 6 H), 6.61 (dd, 1 H), 4.07 (s, 2 H), 3.82 (s, 3 H), 2.82 (s, 6 H), 2.21 (s, 3 H); MS (EI) m/z for C 26

H

27

CIN

6 0 4 S: 555 (MH*). Example 53: 1-amino-N-(3-(N-(3-(3,5-dimethoxy-phenylaminD)quinoxalin-2 yl)sulfamoyl)phenyl)cyclobutanecarboxamide. 'H NMR (400 MHz, DMSO-d 6 ) 8 10.34 (br s, 1 H), 8.81 (s, 1 H), 8.49 (br s, 3 H), 8.34 (s, 1 H), 7.83 (m, 2 H), 7.43 (m, 3 H), 7.31 (m, 2 H), 7.16 (m, 2 H), 6.16 (s, I H), 3.77 (s, 6 H), 2.83 (m, 2 H), 2.25 (m, 3 H), 2.05 (m, 1 H); MS (EI) i/z for C 2 7

H

2 gN 6

O

5 S: 549 (MH*). Example 54: N-(3-(3,5-dimethoxyphenylamino)quinoxain-2-yl)-3-(3-(2 (dimethylamino)ethyl)ureido)benzenesulfonamide. 'H NMR (400 MHz, DMSO-d 6 ) 8 8.91 (br s, 1 H), 8.81 (s, I H), 8.08 (s, I H), 7.60 (s, 1 H), 7.38 (m, 9 H), 6.28 (m, I H), 6.15 (s, 1 H), 3.78 (s, 6 H), 3.40 (m, 2 H), 3.08 (m, 2 H), 2.74 (s, 6 H); MS (EI) m/z for

C

27

H

3

N

7 0 5 S: 566 (MHi). Example 55: 1-amino-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)cyclopentanecarboxamide. 'H NMR (400 MHz, DMSO-d 6 ) 6 12.40 (br s, I H), 10.58 (s, 1 H), 8.46 (m, 4 H), 7.80 (m, 3 H), 7.59 (m, 2 H), 7.34 (m, 4 H), 6.25 (m, I H), 3.76 (s, 6 H), 2.35 (i, 2 H), 1.90 (m, 8 H); MS (EI) m/z for

C

2 H3ON 6 0 5 S: 563 (MH). Example 56: 1-amino-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)cyclopropanecarboxamide. 'H NMR (400 MHz, DMSO-d) 8 9.54 (br s, I H), 8.84 (s, 1 H), 8.29 (s, I H), 7.75 (m, 2 H), 7.39 (m, 6 H), 7.17 (m, 2 H), 6.16 (m, I H), 3.78 (s, 6 H), 1.52 (m, 2 H), 1.17 (m, 2 H); MS (El) m/z for C 2

JH

2 6

N

6 0 5 S: 535 (MH*). Example 57: 2-(dimethylamino)ethyl 3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin 2-yl)sulfamoyl)phenylcarbamate. 'H NMR (400 MHz, DMSO-d 6 ) 8 9.78 (br s, I H), 8.79 (s, 1 H), 8.19 (s, 1 H), 7.66 (d, 1 H), 7.31 (m, 9 H), 6.14 (m, 1 H), 4.17 (t, 2 H), 3.78 (s, 6 H), 2.54 (t, 2 H), 2.21 (s, 6 H): MS (EI) m/z for C 2 7

H

30

N

6 0 6 S: 567 (MH). Example 58: 4-amino-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)tetrahydro-2H-pyran-4-carboxamide. 'H NMR (400 MHz, 198 DMSO-d 6 ) 8 12.2 (br s, 1 H), 10.6 (s, 1 H), 8.74 (m, 5 H), 7.93 (m, 2 H), 7.47 (m, 6 H), 6.24 (M, 1 H), 3.77 (m, 10 H), 2.45 (m, 2 H), 1.81 (m, 2 H); MS (EI) m/z for C 28 11 3 oN 6 0,S: 579 (VH). Example 59: N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)-N3-(2 (dimethylamino)ethyl)benzene-1,3-disulfonamide. 'H NMR (400 MHz, DMSO-d 6 ) 8 9.35 (m, 2 H), 8.92 (m, 1 H), 8.64 (s, 1 H), 8.30 (m, 1 H), 8.11 (s, 1 H), 7.86 (m, 1 H), 7.68 (m, 1 H), 7.49 (s, 1 H), 7.42 (m, 2 H), 7.21 (m, 2 H), 6.61 (b, 1 H), 3.82 (s, 3 H), 3.05 (m, 4 H), 2.74 (s, 6 H); MS (El) m/z for C 25

H

27 C1N 6 0 5

S

2 : 591 (MH*). Example 60: N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-y)-N3-(3 (dimethylamino)propyl)benzene-1,3-disulfonamide. 'H NMR (400 MHz, DMSO-d 6 ) 8 9.38 (m, 2 H), 8.90 (b, 1 H), 8.60 (s, 1 H), 8.32 (m, 1 H), 8.12 (s, 1 H), 7.88 (m, 1 H), 7.72 (m, 1 H), 7.59 (s, 1 H), 7.40 (m, 2 H), 7.20 (m, 2 H), 6.67 (m, 1 H), 3.82 (s, 3 H), 2.97 (m, 2 H), 2.78 (m, 2 H), 2.71 (s, 6 H), 1.70 (m, 2 H); MS (El) m/z for C 26

H

2 9 C1N 6 0 5

S

2 : 605 (MH*). Example 61: N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sufamoyl) 4-methylphenyl)-2-(methylamino)acetamide. MS (EI) m/z for C 25

H

2 5

CIN

6

O

4 S: 541.0 Example 62: (S)-2-amino-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)-4-methylphenyl)propanamide. MS (EI) M/z for C 25

H

2 5 ClN 6

O

4 S: 541.2 (MH*). Example 63: (R)-2-amino-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)-4-methylphenyl)propanamide. MS (EI) m/z for C 25 112s CIN 6

O

4 S: 541.0 (MH*). Example 64: (S)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(methylamino)propanamide. MS (EI) m/z for C 26

H

2 8 N 6 OsS: 537.1 (MH*). Example 65: (R)-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(methylamino)propanamide. MS (E) m/z for C 2 5

H

2 5 C1N 6 0 4 S: 541.1(MH*). Example 66: (R)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(methylamino)propanamide. MS (EI) m/z for C 2 JH2 8

N

6 0 5 S: 537.3 (MH*). 199 Example 67: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)piperidine-2-carboxamide. MS (EI) m/z for C 28

H

3 0

N

6 0 5 S: 563.1 QvH). Example 68: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(2-(dimethylamino)ethylamino)acetamide. MS (EI) m/z for C2 8

H

33

N

7 0 5 S: 580.1 (MH4). Example 69: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(4-(methylamino)piperidin-1-yl)acetamide. MS (EI) m/z for

C

30

H

3 5

N

7 0 6 S: 606.1 (MH). Example 70: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(4-(dimethylamino)piperidin-1-yl)acetamide. MS (E) m/z for

C

31

H

37

N

7 0 5 S: 620.1 (MH). Example 71: N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2 yl)sufamoyl)phenyl)-2-(dimethylamino)acetamide. 'H NMR (400 MHz, DMSO) 8 12.4 (br s, 1H), 10.9 (s, 1H1), 9.8 (s, 1H), 8.9 (s, 1H), 8.3 (br s, 1H), 7.9 (d, 21), 7.8 (d, 1H), 7.6 (t, 211), 7.4 (q, 2H), 7.3 (s, 1H), 6.25 (s, 1H), 4.15 (s, 2H), 3.8 (s, 6H), 2.9 (s, 611). MS (EI) m/z for C 26

H

2 sN 6 0 5 S 2.0 x C 2 HiO 2

F

3 : 537.1 (MH*). Example 72: N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(ethylamino)acetamide. 'H NMR (400 MHz, DMSO) 6 10.8 (s, 111), 9.20 (s, 1H), 8.84 (br s, 2H), 8.64 (br s, 1H), 8.30 (s, 1H), 7.9-8.0 (br s, 1H), 7.80 (t, 2H), 7.55-7.68 (m, 2H), 7.4 (d, 3H), 6.70 (m, 1H), 3.97 (br s, 2H), 3.83 (s, 3H), 3.04 (br s, 2H), 1.3 (t, 311). MS (EL) m/z for C 2 5 H25CIN 6

O

4 S 2.0 x C 2 HlO 2

F

3 : 541.3, 543.2 (MHt). Example 73: 2-(azetidin-1-yl)-N-(3-(N-(3-(2-chloro-5 methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. 'H NMR (400 MHz, DMSO) S 10.8 (s, 1H), 10.2 (s, 111), 9.2 (s, 111), 8.7 (s, 1H), 8.3 (s, 111), 7.9-8.0 (br s, IH), 7.80 (d, 1H), 7.72 (d, 1H), 7.65 (br s, 1H), 7.56 (t, IH), 7.40 (d, 3H), 6.70 (m, 1H), 4.28 (s, 2H), 4.15 (m, 4H), 3.82 (s, 311), 2.32 (br s, 1H). MS (EI) m/z for C 2 6

H

25 C1N 6 0 4 S 2.0 x C 2

H

1 0 2

F

3 : 553.3, 555.2 (MU 4 ). Example 74: N-(3-(N-(3-(2-bromo-5-methoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(methylamino)acetamide. The title compound was prepared according to the Examples above. 'H NMR (400 MHz, DMSO) 5 10.6 (s, 1H), 9.5 (s, 1H), 8.95 (d, 111), 8.18 (t, 1H), 7.78 (m, 1H), 7.70 (m, 111), 7.54 (d, 1H), 7.46 (m, 1H), 7.38 (t, 1H), 7.32 (d, 1H), 7.12-7.22 (m, 2H), 6.56 (m, 1H), 3.90 (s, 2H), 3.82 (s, 311), 2.62 (s, 3H). MS (EL) m/z for C 24

H

23 BrN 6

O

4 S: 572.77, 570.90 (M). 200 Example 75: 2-(dimethylamino)-N-(3-(N-(3-(6-methoxy-quinolin-8 ylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. The title compound was prepared according to the Examples above. '11 NMR (400 MRz, DMSO) 8 10.9 (s, 1H), 10.6 (s, 1H), 9.13 (s, 111), 8.80 (d, 1H), 8.26-8.30 (m, 211), 7.85 (d, 1H), 7.70 (d, 1H), 7.60 (q, 111), 7.54 (m, IH), 7.44 (t, 2H), 7.20 (t, 2H), 6.80 (d, 1H), 4.00 (s, 2H), 3.94 (s, 3H), 2.78 (s, 6H). MS (EI) m/z for C 28

H

27

N

7 0 4 S: 558.3 (MH*). Example 76: N-(3-(N-(3-(2-bromo-5-methoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(dimethylamino)acetamide. 'H NMR (400 MHz, DMSO) 8 10.6 (s, 1H), 9.4 (s, 111), 8.9 (s, 1H), 8.25 (s, 1H), 7.78 (d, 111), 7.70 (d, 1H), 7.54 (d, 111), 7.48 (d, 1H), 7.40 (t, 2H), 6.56 (d, 1H), 4.02 (s, 211), 3.82 (s, 311), 2.80 (s, 6H). MS (EI) m/z for

C

25

H

25 BrN 6 0 4 S: 586.79, 584.91 (MH'). Example 77: N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(2-fluoroethylamino)acetamide. 1H NMR (400 MHz, DMSO) 8 10.6 (s, 1H), 9.4 (s, 1H), 8.9 (d, 1H), 8.20 (s, 1H), 7.78 (d, 1H), 7.70 (d, 1H), 7.48 (m, 111), 7.36-7.44 (m, 3H), 7.20 (q, 3H), 6.6 (m, 111), 4.78 (t, 1H), 4.66 (t, 1H), 3.94 (s, 2H), 3.82 (s, 31), 3.4 (t, 11H), 3.3 (t, 1H). MS (EI) m/z for C 2 5

H

24

CFN

6 0 4 S: 559.2, 561.2 (MH). Example 78: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoy)phenyl)formamide. 'H NMR (400 MHz, DMSO) S 12.4 (br s, 1H), 10.5 (s, 1H1), 8.90 (s, 111), 8.3 (s, 1H), 7.9 (br s, 111), 7.85 (d, 111), 7.75 (d, 1H), 7.5-7.6 (m, 2H), 7.3-7.4 (m, 4H), 6.2 (s, 1H), 3.8 (s, 311). MS (EI) m/z for C 23

H

21

N

5 0 5 S: 480.1 (MH*). Example 79: N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(3-(dimethylamino)azetidin-1-yl)acetamide. 1H NMR (400 MHz, DMSO) 5 10.2 (br s, 111), 9.5 (s, 11), 8.95 (d, 111), 8.2 (s, 111), 7.75 (d, 1H1), 7.65 (d, 1H), 7.45 (d, 111), 7.40 (d, 1H), 7.30-7.35 (t, 111), 7.1-7.2 (q, 211), 6.60 (m, 1H), 3.82 (s, 3H). MS (E) m/z for C 2 sH 30

CN

7 0 4 S: 480.1 (lH). Example 80: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(pyrrolidin-1-yl)acetamide. MS (EI) m/z for C 28

H

30

N

6 0SS: 563.18 (MH*). Example 81: N-(3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(ethyl(methyl)amino)acetamide. 'H NMR (400 MHz, DMSO) 5 12.0 (s, 1H), 10.6 (s, 1H), 9.65 (s, 111), 9.5 (s, 1H), 8.95 (s, 1H), 8.25 (s, 1H), 7.8 (d, 1H), 7.70 (d, 1H), 7.45-7.50 (d, 111), 7.3-7.4 (m, 311), 7.2 (t, 2H), 6.60 (d, 111), 4.02 (br s, 2H), 3.82 (s, 3H), 3.14 (br s, 2H), 2.80 (s, 3H) 1.2 (t, 3H). MS (EI) m/z for C 2 6H 27 C1N 6 0 4 S: 555.2, 557.3 (MH). 201 Example 82: N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(3-(piperidin-1-yl)azetidin-1-yl)acetamide. MS (El) m/z for

C

3 1

H

3 4 C1N 7 0 4 S 2.0 x C 2

H

1 0 2

F

3 : 636.3, 638.3 (MH). Example 83: N-(3-(N-(3-(3-fluoro-5-methoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(methylamino)acetamide. MS (EI) m/z for C 2 4

H

2 3

FN

6 0 4 S: 511.04 (M ). Example 84: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-1-methylpiperidine-4-carboxamide. MS (EI) m/z for

C

29

H

32

N

6 0 5 S 1.0 x C 2

H

4 0 2 : 577.2 (MHW). Example 85: N-(3-(N-(3-(3-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl) 2-(methylamino)acetamide. 'H NMR (400 MHz, DMSO) S 10.6 (s, 1H), 8.82 (s, 1H), 8.22 (t, 1H), 7.86 (t, 1H), 7.76 (m, 111), 7.66 (m, 1H), 7.46 (m, 1N), 7.41 (m, 1H), 7.38 (t, 111), 7.28 (m 1H), 7.24 (t, 1H), 7.12 (m, 2H), 6.56 (d, 1$), 3.88 (s, 2H), 3.80 (s, 3H), 2.60 (s, 3H). MS (EI) m/z for C 2 4

H

24

N

6 0 4 S: 492.99 (MH*). Example 86: N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)pbenyl)-2-(2,2,2-trifluoroethylamino)acetamide. 'H NMR (400 MHz, DMSO) 6 10.4 (s, 1H), 9.2 (s, 1H), 8.65 (s, IH), 8.4 (s, IH), 8.00 (m, lH), 7.80 (d, 1H), 7.75 (d, 1H), 7.65 (q, 1H), 7.55 (t, 1H), 7.40-7.5 (m, 3H), 6.7 (n, 1H), 3.82 (s, 3H), 3.62 (br s, 2H), 3.55 (br d, 2H). MS (EI) m/z for C 2 sH 22 C1F 3

N

6 0 4 S 1.0 x C 2 11 1 0 2

F

3 : 595.0, 597.0 (MH*). Example 87; N-(3-(N-(3-(3,5-dimethoxy-pheuiylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-3-(piperidin-1-yl)propanamide. MS (E) m/z for C 3 0

H

34

N

6 0 5 S: 591.2 (MH). Example 88: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yI)sulfamoyl)phenyl)-4-(dimethylamino)butanamide. MS (E1) m/z for C 2 sHs 2

N

6 sS 1.0 x C 2

H

4 0 2 : 565.2 (MH). Example 89: 2-(dimethylamino)-N-(3-(N-(3-(3-fluoro-5-methoxy phenylamino)quinoxalin-2-yi)sulfamoyl)phentyl)acetamide. 'I1 NMR (400 MHz, DMSO) 8 10.9 (s, 1H), 9.8 (br s, 1M), 9.1 (s, 1H), 8.34 (s, 1H), 7.90 (d, 111), 7.76 (d, 111), 7,52-7.68 (m, 4H), 7.40 (m, 2H), 6.54 (m, 1H), 4.16 (s, 2H), 3.82 (s, 311), 2.86 (s, 6H). MS (EI) m/z for C 25

H

25

FN

6 0 4 S: 525.05 (MH*). Example 90: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yI)sulfamoyl)phenyl)-2-(piperidin-1-yl)acetamide. MS (El) m/z for C 29

H

3 2

N

6 0 5 S: 577.37 (MH*). 202 Example 91: 2-(dimethylamino)-N-(3-(N-(3-(3-methoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)acetamide. 'H NMR (400 MHz, DMSO) 8 10.5 (s, 1H), 8.8 (s, 1H), 8.25 (s, 1H), 7.83 (t, 1H), 7.76 (d, 1H), 7.64 (d, 111), 7.3-7.48 (m, 4H), 7.22 (t, 1H), 7.12 (t, 2H), 6.56 (m, 1H), 3.96 (s, 211), 3.78 (s, 3H), 2.76 (s, 6H). MS (EI) m/z for C25H 2 6N 6

O

4 S: 507.1 (MH). Example 92: N-(3-(N-(3-(2-chloro-5-hydroxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(dimethylamino)acetamide. 'H NMR (400 MHz, DMSO) 8 10.8 (s, 1H), 9.9 (s, 1H), 9.8 (s, 1H), 9.1 (s, 1H), 8.55 (s, 1H), 8.34 (s, 1H), 7.9-8.0 (br s, 1H), 7.82 (d, 1H), 7.76 (d, 1H), 7.52-7.66 (m, 211), 7.42 (t, 111), 7.26 (d, 1H), 6.50 (m, 1H), 4.16 (s, 211), 2.86 (s, 6H). MS (E1) m/z for C 2 4H 23

CIN

6

O

4 8: 527.1, 529.0 (MH*). Example 93: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-morpholinoacetamide. MS (EI) m/z for C 2 sH 30

N

6 0 6 S: 579.1 (MHW). Example 94: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z for C 24

H

23

N

5 0 5 S: 494.0 (MH*). Example 97: 2-amino-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)-4-methylphenyl)-2-methylpropanamide. MS (EI) m/z for

C

26

H

27 ClN 6 0 4 S: 556.12 (MH). Example 98: N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(dimethylamino)acetamide. MS (El) m/z for C 25

H

25 ClN 6 0 4 S: 542.05 (MH*). Example 99: 2-amino-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z for C 2 4H 24

N

6 0 5 S: 509.59 (MH). 203 Example 100 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sufamoyl)benzoe acid C1 Cl N NH 6N NaoHlheat N NH H CN H CO 2 H [00201] To a solution ofN-(3-{[2-chloro-5-(methoxy)-phenyl]amino}quinoxalin-2-yl)-3 cyanobenzenesulfonamide (6.02 g, 12.95 mmol), prepared using procedures similar to those in Example 115 or Example 423, in methanol (20 mL) and 1,4-dioxane (20 mL) was added 6.0 N aqueous sodium hydroxide (40 mL) at room temperature. The solution was stirred at 90 0 C for 3.5 h. The reaction was cooled to room temperature and neutralized slowly by adding 2.0 Nhydrochloric acid until the pH of the solution became in the 2-3 range at 0* C. The solution was diluted with ethyl acetate (300 mL). The organic layer was washed with saturated aqueous sodium chloride (50 mL) and dried over magnesium sulfate. Filtration and concentration at reduced pressure afforded 3-{[(3-{[2-chloro-5-(methoxy) phenyl]amino}quinoxalin-2-yl)amino]sulfonyl}benzoic acid (5.921 g, 94%). MS (EI) m/z for C 2 2

H

1 7 C1N 4 0 5 S: 485.0 (MH). [00202J The following compounds were preapred using procedures ismilar to those used in Example 100. Example 101: Proceeding as above, 3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2 yl)sulfamoyl)benzoic acid was prepared. MS (El) m/z for C23120 N 4 0 6 S: 481.0 (MH). Example 102: 3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-y)sulfamoyl) N-(2-methyl-1-(piperidin-1-yl)propan-2-yl)benzamide. MS (EI) m/z for C 3

H

3 5 ClN 6 0 4 S: 623.06 (MH). Example 103: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl) N-(2-methyl-1-oxo-1-(piperidin-1-yl)propan-2-yl)benzamide. MS (EI) m/z for

C

3 1

H

33

CIN

6 0 5 S: 637.65 (MPH). 204 Example 104 3-{[(3-{[2-chloro-5-(methoxy)phenyllamino}quinoxain-2-yl)aminosulfonyl}-N-[2 (dimethylamino)ethyllbenzamide O C1 HATU/DIEA C1 C N H 2 NNH N N N H )\ CO 2 H HN-\ ' [00203] To a solution of 3-{[(3-{[2-chloro-5-(methoxy)phenyl]amino}quinoxalin-2 yl)amino]sulfonyl}benzoic acid (0.20 g, 0.42 mmol), prepared using procedures similar to Example 100, in dimethylformamide (4 mL) were added 2-(7-aza-1H-benzotriazole-1-yl) 1,1,3,3-tetramethyluronium hexafluorophosphate ( HATU, 0.32 g, 0.83 mmol) and N-ethyldiisopropylamine (DIEA, 0.13 g, 1.04 mmol) at room temperature. The reaction was stirred for 15 min before N, N-dimethylethane-1,2-diamine (73 mg, 0.83 mmol) was added. The reaction mixture was allowed to stir overnight. The reaction was diluted with ethyl acetate (200 mL) and washed with water (50 mL), saturated aqueous sodium bicarbonate (40 mL), 1.0 N aqueous hydrochloric acid (30 mL), and saturated aqueous sodium chloride (25 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated at reduced pressure to afford 3-{[(3-{[2-chloro-5 (methoxy)phenyl]amino}quinoxalin-2-yl)amino]sulfonyl}-N-[2 (dimethylamino)ethyl]benzamide (0.20 g, 87%) as yellow solid. MS (E) m/z for C 26

H

27 CIN6O 4 S: 555.1 (MIi-). [002041 The following compounds were prepared using procedures similar to those in Example 104. Example 105: 5-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl) N-(2-(dimethylamino)ethyl)-2-methoxybenzamide 'H NMR (400 MHz, DMSO-d 6 ) 8 9.45 (s, 1H), 8.95 (d, 1H), 8.57 (d, 1H), 8.28 (t, 1H-), 8.14 (dd, IH), 7.46 (dd, IH), 7.39 (m, 2H), 7.17 (m, 4H), 6.60 (dd, IH), 3.89 (s, 3H), 3.82 (s, 3H), 3.38 (m, 211), 2.43 (m, 211), 2.21 (s, 6H). MS (El) m/z for C 2 7

H

2 9

C]N

6 0 5 S: 585.3 (MI). Example 106: 5-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxain-2-yl)sulfamoyl) N-(2-(dimethylamino)ethyl)-2-fluorobenzamide. 1 H NMR (400 MHz, DMSO-d) 3 9.40 205 (br s, 1H), 9.16 (s, 111), 8.73 (in, 111), 8.67 (d, 1H), 8.36 (dd, 1W), 8.26 (mn, 111), 7.94 (br s, 1W), 7.66 (mn, 1H1), 7.59 (t, 1H1), 7.43 (in, 3H), 6.71 (dd, 1H), 3.83 (s, 311), 3.62 (mn, 2H), 3.27 (mn, 21W), 2.85 (d, 6H). MS (EI) in/z for C 26 H42C1FN6Q 4 S: 573.1 WMf). Example 107: 3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2 (dimethylamino)ethyl)benzamide. MS (El)mn/zfor C 27

H

30

N

6 0 5 S: 551.1 (ME1). Example 108: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quiuoxaln-2-yl)sulfamoy) N-(2-(dimethylamino)ethyl)-N-methylbenzamide. MS (El) ni/z for C 27

H

29

CIN

6

O

4 S: Example 109: 3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2 (dlmethylamino)ethyl)-N-methylbenzamide. MS (El) m/z for C 2 sH32N 6 QsS: 565.1 Uv1RH). Example 110: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxain-2 yl)sulfamoyl~benzamide. MS (El) m/z for C 22

HI

8 C1N 5

O

4 S: 484.0 (W). Example 111: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalii-2-yl)sulfamoyl) N-(2-morpholinoethyl)benzamide. MS (El) mlz for C 28

H

29

CIN

6 OsS: 597.0 (W). Example 112: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxaln-2-yl)sulfamoyl) N-methylbenzamide. MS (El) m/z for C 23

H

20 C1N 5

O

4 S: 498.0 (MW). Example 113: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl) N-morpholimobenzamide. MS (El) nI/z for C 26 11 25 C1N 6

Q

5 S: 569.0 (MW'). Example 114 N-(3-{[2-chloro-5-(methoxy)phenyllamino~quinoxalin-2-yl)-3-{5 [(dimethylamino)methylj-1,3,4-oxadiazol-2-yl)benzenesulfonamide 1. HATU/DIEA0 N HH -'N\/-z NH 0'2. POC1 3 ~ JN'N N H /\ C0 2 H- H y \ 'N [002051 To a solution of 3-{ [(3-{[2-chloro-5-(inethoxy)phenyl]araino} quinoxalin 2-yl)ainino]sulfonyl~benzoic acid (0.25 g, 0.52 minol), prepared as described above in Example 100, in diinethylforinamide (2.6 mL) were added 2-(7-aza-1IH-benzotriazole-1I-yI) 1,1 ,3,3-tetrainethyluronium hexafluorophosphate (HATU, 0.25 g, 0.67 inmol) and N 206 ethyldiisopropylamine (DIEA, 0.11 g, 0.88 mmol) at room temperature. The reaction was stirred for 15 min before 2-(dimethylamino)acetohydrazide (78 mg, 0.67 mmol) was added. The reaction mixture was allowed to stir overnight. The reaction was diluted with ethyl acetate (200 mL) and washed with water (30 mL), saturated aqueous sodium bicarbonate (30 mL), 1.0 N aqueous hydrochloric acid (20 mL), and saturated aqueous sodium chloride (25 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated at reduced pressure to afford 180 mg of a coupled intermediate which was then heated in phosphorus oxychloride (5 mL) at 100 OC for 4h. The reaction was cooled to room temperature and treated with ice water (50 mL) and extracted with dichloromethane (3 X 50 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated at reduced pressure to afford a crude product which was subjected to reverse phase HPLC to afford N-(3-{[2-chloro-5-(methoxy)-phenyl]amino}quinoxalin-2-yl)-3-{5 [(dimethylamino)methyl]-1,3,4-oxadiazol-2-yl)-benzenesulfonamide (16 mg, 5 %) as yellow solid. MS (EI) m/z for C 26

H

24 ClN 7

O

4 S: 566.0 (MH). Example 115 N-(3-(3-methoxy-5-nitro-phenylamino)-quinoxalin-2-yl)-3-nitrobenzenesulfonamide

NO

2

NO

2 N0 2

NH

2 0HO '

H

2 N-O -2 / O N O - N Cl K 2 C0,, DMSO N C0N-NH 0 2 N 0 [002061 N-(3-chloroquinoxalin-2-yl)-3-nitrobenzenesulfonamide. 2,3-Dichloroquinoxaline (26.1 g, 131.1 mmol), m-Nitrobenzene sulfonamide (26.5 g, 131.1 mmol) and potassium carbonate (18.1 g, 131.1) were dissolved in anhydrous DMSO (500 mL). The reaction was heated to 150 *C for 2 h. The reaction mixture was poured into water (400 mL), followed by addition of 2M HCI (60 mL). The product was extracted with EtOAc (3 x 500 mL). The organic layers were combined and washed water (2 x 500 mL) and brine (2 x 500 mL). The product was then dried with sodium sulfate to give N-(3 chloroquinoxalin-2-y)-3-nitrobenzenesulfonamide. MS (EI) m/z for C 1 41 9 C1N 4 0 4 S: 364.94, 366.97 (MW) 207 100207] N-(3-(3-methoxy-5-nitrophenylamino)quinoxalin-2-yl)-3-nitro benzenesulfonamide. N-(3-chloroquinoxalin-2-yl)-3-nitrobenzenesulfonamide (700 mg, 1.92 mmol), 3-methoxy-5-nitroaniline (645 mg, 3.84 mmol) and p-xylene (7 mL) were combined and heated to 140*C, then stirred for 16 hours at 130 *C. The reaction was allowed to cool, placed in a sep. funnel, diluted with DCM, and washed with 2M HCl and brine and concentrated in vacuo. The resulting solid was washed with Et 2 O to give N-(3-(3 methoxy-5-nitro-phenylamino)quinoxalin-2-y)-3-nitrobenzenesulfonamide (400 mg, 42%). MS (EI) m/z for C 2 1 Hi 6

N

6 0 7 S: 496.94 (MH*). 100208] The following compounds were prepared using procedures similar to those in Example 115. Example 116: N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)-3 cyanobenzenesulfonamide. MS (EI) m/z for C 22

H

16 CN503S: 465.9 (MH*). Example 117: 3-cyano-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)benzenesulfonamide. MS (EI) m/z for C 23 HiqN 5 0 4 S: 462.3 (MH*). Example 118: N-(3-(2,5-dimethoxy-phenylamino)quinoxalin-2-yl)-3 fluorobenzenesulfonamide. MS (El) M/z for C22H 1 9

FN

4 0 4 S: 456.0 (MH). Example 119: 3-bromo-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)benzenesulfonamide. MS (EI) m/z for C 2 2 HigBrN 4 0 4 S: 516.9 (MH). Example 120: 3-bromo-N-(3-(2,5-dimethoxy-phenylamino)quinoxalin-2 yl)benzenesulfonamide. MS (El) m/z for C 22

H

19 BrN 4 0 4 S: 516.9 (MH). Example 121: N-(3-(3-methoxyphenylamino)quinoxalin-2-yl)benzenesulfonamide. MS (EI) m/z for C 21 His N 4 0 3 S: 407.0 ("0. Example 122: N-(3-(4-fluoro-3-methoxyphenylamino)quinoxalin-2 yl)benzenesulfonamide. MS (EI) m/z for C 21

H

1 7

FN

4 0 3 S: 425.0 (MH*). Example 123: N-(3-(2,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4 methoxybenzenesulfonamide. MS (EI) m/z for C 23

H

22

N

4 0sS: 467.0 (MH). Example 124: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4 methoxybenzenesulfonamide. MS (EI) m/z for C 23

H

22

N

4 0sS: 467.0 (M+). Example 125: N-(3-(4-chloro-3-methoxy-phenylamino)quinoxalin-2 yl)benzenesulfonamide. MS (EI) M/z for C 21

H

17 C1N 4 0 3 8: 440.9 (M+). Example 126: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)thiophene-2 sulfonamide. MS (EI) m/z for C 20 Hi 8

N

4 0 4

S

2 : 443.0 (MH). Example 127: N-(3-(6-methoxyquinolin-8-ylamino)quinoxalin-2-yl)-3 nitrobenzenesulfonamide. MS (EI) m/z for C 24

H

1 sN 6 0 5 S: 502.95 (MH). 208 Example 128: 3-nitro-N-(3-(pyridin-4-ylamino)quinoxalin-2-yl)benzenesulfonamide. MS (El) m/z for C 19

H

14

N

6 0 4 S: 423.2 (MH 4 ). Example 129: N-(3-(2-chloropyridin-4-ylamino)quinoxalin-2-yl)-3 nitrobenzenesulfonamide. MS (E) m/z for C 19

H

1 3

CIN

6 0 4 S: 456.93, 458.90 (MH). Example 130: N-(3-(4,6-dimethoxypyrimidin-2-ylamino)quinoxalin-2-yl)-3 nitrobenzenesulfonamide. MS (EI) M/z for C 20

H

17

N

7 0 6 S: 484.03 (MH). Example 131: N-(3-(4-hydroxy-6-methoxypyrimidin-2-ylamino)quinoxain-2-yl)-3 nitrobenzenesufonamide. MS (E) m/z for C 1 9 Hi 5

N

7 0 6 S: 469.97 (MH). Example 132: N-(3-(3,5-dimethoxy-phenylamino)quinoxain-2-y)-2 finorobenzenesulfonamide. MS (EI) m/z for C 22

H

19

FN

4 0 4 S: 455.3 (MH*). Example 133: N-(3-(2-bromo-5-methoxy-phenylamino)quinoxain-2-yl)-3 nitrobenzenesulfonamide. MS (El) m/z for C 2 1

H

16 BrN 5 5 S: 531.82, 532.84 (MH*). Example 134: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4 methylbenzenesulfonamide. MS (EI) m/z for C 23 HnN 4 0 4 S: 451.0 (MR). Example 136: N-(3-(2,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4 methylbenzenesulfonamide. MS (EI) m/z for C 23 H2N 4 04S: 451.0 (MH). Example 137: N-(3-(3-fluoro-5-methoxy-phenylamino)quinoxalin-2-yl)-3 nitrobenzenesulfonamide. MS (EI) m/z for C 21

H

1 6 FNsOsS: 470.0 (MH*). Example 138: 4-bromo-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)benzenesulfonamide. MS (El) m/z for C 22 1H 1 gBrN 4 04S: 516.9, 514.9 (MH*). Example 139: N-(3-(3-methoxyphenylamino)quinoxalin-2-y)-3-nitro benzenesulfonamide. MS (EI) m/z for C 21

H

1 7

N

5 0 5 S: 451.93 (MI). Example 140: N-(3-(2-chloro-5-hydroxy-phenylamino)quinoxalin-2-yl)-3 nitrobenzenesulfonamide. MS (EI) m/z for C 20

H

1 4 ClNsO 5 S: 472.15,474.13 (MH*). Example 141: 3-acetyl-N-(3-(2-chloro-5-methoxy-phenylamino)quinoxain-2 yl)benzenesulfonamide. MS (EI) M/z for C 23 HIgClN 4 0 4 S: 483.08 (MH). Example 142: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide. MS (EI) m/z for CnH 2

ON

4 04S: 437.49 (MH*). Example 143: N-(3-(5-methoxy-2-methyl-phenylamino)quinoxalin-2 yl)benzenesulfonamide. MS (EI) m/z for C 22

H

20

N

4 0 3 S: 421.46 (MH*). Example 144: N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2 yf)benzenesulfonamide. MS (El) m/z for C 21

H

1 7 ClN 4 0 3 S: 440.59 (MH*). Example 145: N-(3-(2,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide. MS (EI) m/z for C 22

H

20

N

4 0 4 S: 437.53 (MH*). 209 Example 146: 4-chloro-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)benzenesulfonamide. MS (EI) M/z for C 22

H

19 ClN 4 0 4 S: 470.54 (MH). Example 147: N-(3-(5-methoxy-2-methyl-phenylamino)quinoxalin-2-yl)-3 nitrobenzenesulfonamide. MS (EI) m/z for C 22

H

19

N

5 OsS: 466.32 (MH*). Example 148: N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-y)-3 nitrobenzenesulfonamide. MS (El) m/z for C 21

H

1 6 ClN 5 0 5 S: 485.86 (MH*). Example 149: N-(3-(4-chloro-2,5-dimethoxy-phenylamino)quinoxalin-2 yl)benzenesulfonamide. MS (EI) m/z for C 22

H

19 ClN 4 0 4 S: 470.99 (MI). Example 150 N-(3-{[3,5-bis(methoxy)phenyl]amino)quinoxalin-2-yl)-3-(2H-tetrazol-5 yl)benzenesulfonamide N NH NaN 3

/NH

4 CI N NH N -SO i | N N 0 N--N H , \ N H "NH [00209] To a stirred solution of 3-cyano-N-(3-(3,5-dimethoxyphenylamino)quinoxalin 2-yl)benzenesulfonamide (0.20 g, 0.44 mmol), prepared using procedures similar to those described in Example 115, in dimethylformamide (1.2 mL) at 50 *C were added sodium azide (0.11 g, 1.76 mmol) and ammonium chloride (94 mg, 1.76 mmol). The crude mixture was heated at 100 *C overnight. The reaction was cooled to room temperature treated with ice water (20 mL) followed by concentrated hydrochloric acid (10 mL). The solid obtained was filtered under reduced pressure and washed with hexane (20 mL), diethyl ether (20 mL), and ethyl acetate (5 mL) to afford N-(3-{[3,5-bis(methoxy)phenyljamino}quinoxalin 2-yl)-3-(2H-tetrazol-5-yl)benzenesulfonamide (55 mg, 25%) as light yellow solid. MS (EI) m/z for C 23

H

2 0 NsO 4 S: 505.0 (MH*). 210 Example 151 N-(3-(2,6-dichloropyridin-4-ylamino)quinoxain-2-yl)-3-nitrobenzenesulfonamide. [002101 A mixture of N-(3-chloroquinoxalin-2-yl)-3-nitrobenzenesulfonamide (1 g), 2,6 dichloropyridin-4-amine (760 mg) and p-xylene (10 mL) was heated at 135 "C with stirring overnight. Upon cooling to room temperature, the mixture was dissolved in dichloromethane, washed with 2 N HCl (2 x) and brine, concentrated in vacuo to give a crude product of N-{3-{(2,6-dichloropyridin-4-yl)amino]quinoxalin-2-yl}-3 nitrobenzenesulfonamide. A small portion of this crude product was purified by HPLC to give N-{3-[(2,6-dichloropyridin-4-yl)amino]quinoxalin-2-yl}-3-nitro-benzenesulfonamide. 'H NMR (400 MHz, DMSO) 8 9.71 (s, 111), 8.90 (s, 111), 8.50 (d, 2H), 8.8.41 (d, 1H), 8.30 (s, 2H), 7.88-7.78 (m, 27.65 (d, 1H), 7.47-7.37 (m, 2H); MS (EI) m/z for C 19

H

12 C1 2

N

6 0 4 S: 491.1, 493.1 (MHW). Example 152 N-(3-(2-chloro-6-methoxypyridin-4-ylamino)quinoxalin-2-yl)-3 nitrobenzenesulfonamide [002111 To a crude product of N-{3-[(2,6-dichloropyridin-4-yl)amino]quinoxalin-2-yl} 3-nitrobenzenesulfonamide (1.24 g) prepared using procedures similar to those for Example 151, was added anhydrous DMSO (10 mL), followed by sodium methoxide (273 mg). The resulting mixture was heated at 100 *C for 3 days. The mixture was diluted with EtOAc and water, and the pH was adjusted to about 4 by adding acetic acid. The product was extracted with EtOAc (3 x). The combined extracts were washed with brine to give the crude product. A portion of the crude product was purified by prep HPLC to give N-(3-{[2 chloro-6-(methyloxy)pyridin-4-yl]amino}quinoxalin-2-yl)-3-nitrobenzenesulfonamide. 1HI NNMR (400 MHz, DMSO) 8 9.44 (s, 1H), 8.90 (s, 1H), 8.50 (d, 1H), 8.42 (d, 1H), 7.88-7.84 (m, 2H), 7.77 (s, 1H), 7.74 (s, 1H), 7.64 (d, 1H), 7.45-7.38 (m, 211), 3.82 (s, 3H); MS (El) m/z for C 20 H2 5

CN

6 0 5 S: 496.94 (MH). 211 Example 153 2-(dimethylamino)-N-(3-(N-(3-(3-(2-(dimethylamino)acetamido)-5-methoxy phenylamino)quinoxain-2-yl)sulfamoyl)phenyl)acetamide 02 0 H 2 HN Pd/C, THF/EtoH HN) 9N NIJHATU U N H DIEA, DMF 02N'6 01 H 2

N

1 01.I ,6 0 [00212) 3-amino-N-(3-(3-amino-5-methoxyphenylamino)quinoxalin, 2-yl)benzenesulfonamide. N-(3-(3-Methoxy-5-nitrophenylamino)quinoxalin-2-yl)-3 nitrobenzenesulfonamide (400 mg, 0.81 mmol), prepared as described above in Example 115, was dissolved in 1:1 THF:EtOH (4 mL), to which was added formic acid (938 pl, 2.42 mmol) and potassium formate (203 mg, 2.42 mmol). The system was flushed with nitrogen, and then 10%wt Pd/C (50 mg) was added. The reaction was then heated to 60*C. Once the reaction was determined complete by LC-MS, it was allowed to cool, and DMF was added for solubility. The solution was then filtered through a nylon frit to remove the catalyst. The filtrate was diluted water and the pH adjusted to 7 and extracted with DCM (2x) and EtOAc (2x). All organic layers were combined and evaporated to dryness to give 3-amino-N-(3-(3 amino-5-methoxyphenylamino)quinoxalin-2-yl)benzenesulfonamide (330 mg, 93%). MS (EI) m/z for C 2 1

H

20

N

6 0 3 S: 437.06 (M1) [002131 2-(dimethylamino)-N-(3-(N-(3-(3-(2-(dimethylamino)-acetamido)-5 methoxyphenylamino)quinoxalin-2-yl)-sulfamoyl)pheny~acetamide. 3-Amino-N-(3-(3 amino-5-methoxyphenylamino)quinoxalin-2-yl)benzenesulfonamide (330 mg, 0.76 mmol), DMF (4 mL), N,N,-Dimethylglycine (312 mg, 3.02 mmol), HATU (1.15 g, 3.02 mmol), and 1.29(mL) (7.56 mmol) DIEA (1.29 mL, 7,56 mmol) were combined and heated to 90*C, followed by heating at 50*C for over 16 hours. The reaction was allowed to cool, placed into a sep. funnel diluted with water and aqueous LiCI and extracted with EtOAc. The final compound was then purified by prep. HPLC to give 2-(dimethylamino)-N-(3-(N-(3-(3-(2 (dimethylamino)acetamido)-5-methoxy-phenylamino)-quinoxalin-2 yl)sulfamoyl)phenyl)acetamide. '1H NMR (400 MHz, CD 3 0D) 8 8.45 (t, 1H), 7.93 (t, IH), 7.85-7.88 (in, 1H), 7.70-7.74 (m, 1H), 7.65-7.68 (in, 1H), 7.58-7.62 (m, 1H), 7.58 (t, 111), 212 7.34-7.42 (m, 3H), 7.0 (t, 1H), 4.05 (d, 2H), 3.8 (s, 3H), 2.9-3.0 (d, 12H). MS (El) m/z for

C

2 9H 34

N

8

O

5 S: 607.2 (MH). [00214] The following title compounds were prepared using procedures similar to those in Example 153. Example 154: N-(3-(2,5-dimethoxyphenylamino)-7-methylquinoxalin-2 yl)benzenesulfonamide. MS (El) M/z for C 23 H22N 4 04S: 451.0 (MH*). Example 155a and Example 155b N-(3-(3,5-dimetboxy-phenylamino)quinoxalin-2-yl)-3 (methylamino)benzenesilfonamide and N-(3-(3,5-dimethoxy-phenylamino)quinoxalin 2-yl)-3-(dimethylamino)benzenesulfonamide. 2 Mel 0 NHDMF OMO '-N NHC M N N - N NO [002151 To a solution of 3-amino-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)benzenesulfonamide (414 mg) in DMF (4.5 mL) was added iodomethane (114 pL). The reaction mixture was heated at 35-50 "C until the formation of both mono-methylated and di-methylated products was detected by LC/MS. The mixture was diluted with EtOAc, washed with water, 10% LiCI (2 x) and brine. After removal of solvent in vacuo, the crude mixture was purified by flash silica column chromatography eluting with 15% EtOAc in hexanes, affording the mono-methylated and di-methylated products. Product A: N-(3-(3,5 dimethoxyphenylamino)quinoxalin-2-y)-3-(methylamino)-benzenesulfonamide (35 mg). 'H NMR (400 MHz, DMSO) 8 12.2 (s, 1H), 8.93 (s, 1H), 7.85 (d, 1H), 7.58 (d, 111), 7.40 7.20 (m, 7H), 6.76 (m, 111), 6.24 (m, 111), 6.16 (br s, 1H), 3.77 (s, 6H1), 2.71 (s, 311). MS (El) for C 2 3

H

2 3

N

5 0 4 S: 466.05 (MH+). Product B: N-(3-(3,5 dimethoxyphenylamino)quinoxalin-2-yl)-3-(dimethylamino)benzenesulfonamide (33 mg). 2H NMR (400 MHz, DMSO) 8 1220 (s, 1H), 8.98 (s, 1H), 7.98 (d, 1H), 7.56 (d, 1H), 7.42 7.32 (m, 7H), 6.74 (ma, 1H), 6.24 (m, 111), 3.77 (s, 6H), 2.97 (s, 6H). MS (EI) for

C

2 425N 5 04S: 480.04 (MH+). 213 Example 156 N-(3-{([(2-{1[3,5-bis(methoxy)phenyl]amino}pyrido2,3-b]pyrazin 3-yI)aminojsulfonyl}phenyl)-N-2-[2-(dimethylamino)ethy]-N-2-methylglycinamide - 1. C H H C1 H H NHo NO [002161 To a THF suspension (1.3 mL) of 3-amino-N-(3-{[3,5-(dimethoxy) phenyllamino}-quinoxalin-2-yl)benzenesulfonamide (126 mg, 0.28 mmol), prepared using procedures similar to those described for Example 15, was added 0.143 mL of 2M aqeuos Na 2

CO

3 . To this yellow suspension is added dropwise 33 pL (0.42 mmol) of chlororacetyl chloride. The reaction mixture turns clear after a few minutes and is allowed to stir at 23*C for lh. To the reaction is added a DMSO (1 mL) solution containing 180 pL (1.4 mmol) of N,N',N' trimethylethelyenediamine. The reaction is then warmed to 60"C and stirred for 18h. The product is isolated by preparative RP-HPLC (NH 4 OAc/ACN) gradient, the appropriate fractions were pooled and lyophilize to give a solid yellow as the acetic acid salt: 59 mg (51%). 'H-NMR (400 MHz, CDCL 3 ): 8 10.1 (br s, 1H), 8.37 (br s, 2H), 8.18 (d, 1H), 7.97 (d, 1H), 7.60 (br d, 1H), 7.27 (s, 2H), 7.20 (br s, 3H), 6.15 (s, 1H), 3.82 (m, 21H), 3.65 (s, 6H), 3.20 (br m, 2H), 2.82 (br s, 8H), 2.42 (s, 3H), 2.02 (s, 3H). MS (EI) m/z for

C

28

H

3 4

N

8

O

5 S: 595.84 (MH*). [00217] The following title compounds were prepared using similar procedures to those in Example 156. Example 157: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-((3-(dimethylamino)propyl)(methyl)amino)acetamide. MS (El) m/z for C 30

H

3 7

N

7 0 5 S: 608.1 (MH*). Example 158: 2-(1,4'-bipiperidin-1'-yl)-N-(3-(N-(3-(3,5-dimethoxy phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z for

C

3 4H 41

N

7 0 5 S: 660.1 (MH*). Example 159: tert-butyl 2-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)suifamoyl)phenylcarbamoyl)piperidine-1-carboxylate. MS (EI) m/z for C 3 3

H

38

N

6 0 7 S: 663.1 (MH+). 214 Example 160: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-ylsulfamoyl) N-(1-(dimethylamino)propan-2-yl)benzamide. MS (EI) m/z for C 27

H

2 9

CIN

6 0 4 S: 569.0 (M4-3). Example 161: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-3 ureidobenzenesulfonamide. MS (El) m/z for C 23

H

22

N

6 0 5 S: 495.40 (MH). Example 162: 2-(dimethylamino)-N-(3-(N-(3-(5-methoxy 2-methylphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z for

C

26

H

28

N

6 0 4 S: 521.69 (MH*). Example 163: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(4-methylpiperazin-1-yl)acetamide. MS (EI) m/z for

C

29

H

33

N

7 0 5 S: 592.61 (MH*) Example 164: 2-acetamido-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2 yI)sulfamoyl)phenyl)acetamide. MS (El) m/z for C 26

H

2 6

N

6 068: 550.59 (M 4 ). Example 165: tert-butyl 2-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenylamino)-2-oxoethylearbamate. MS (El) m/z for C 29

H

32

N

6 0 7 S: 609.32 (MH 4 ). Example 166 N-(2-(3,5-dimethoxy-phenylamino)pyrido[2,3-b]pyrazin-3-yl)-3 nitrobenzenesulfonamide ~N CI"10-11110" I H N NH N N NH H 2 N 0 oN N NH [002181 To a xylene suspension (15 mL) of N-(2-chloropyrido[2,3-b]pyrazin-3-yl) 3-nitrobenzenesulfonamide (1 g, 2.7 mmol) (prepared using procedures similar to those in Asier, et al J Org Chem 2005, 70(7), 2878 and Leeson, et al J. Med. Chem 1991, 34, 1243) was added 420 mg (2.7 mmol) of 3,5 dimethoxyaniline. After refluxing the reaction for lh, the reaction is cooled , the precipitate is collected by filtration and dried under vacumn to give 830 mg of the product as a -6:1 mixture of isomers with the major being N-(2-(3,5 dimethoxy-phenylamino)pyrido[2,3-b]pyrazin-3-yl)-3-nitrobenzenesulfonamide which was assigned by known chemical reactivity. Analytical HPLC, ret. time = 3.3 min (14%), 3.05 215 min (86%), (conditions: Phenomenex Gemini C18 50x4.6 column, gradient 5% to 95% MeCN/H 2 0, in the presence of 0.1% TFA, 5 min run at 3.5 ml/min flow rate, k =254 nm). 'H-NMR (400 MHz, DMSO-d6): major isomer S 9.14 (br s, 1H), 8.69 (dd, 1H), 8.60 (dd, 1H), 8.33 (dt, 2H), 7.77 (t, 1H), 7.49 (dd, 1H), 7.37 d, 2H), 7.05 (s, 1H), 6.26 (t, IH), 3.77 (s, 6H); MS (El) m/z for C 21 HisN 6 0 6 S: 483.08 (MIT'). Example 167 3-amino-N-(2-(3,5-dimethoxy-phenylamino)pyrido[2,3-b]pyrazin-3 yl)benzenesulfonamide. [00219] To a 1:1 THF/EtOH suspension (1 mL) of N-(3-(3,5-dimethoxyphenylamino) pyrido[3,2-b]pyrazin-2-y)-3-nitrobenzenesulfonamide (190 mg, 0.21 mmol) (prepared using procedures similar to those in Examples 166) was added 47 ptL (1.26 mmol) of formic acid plus 99 mg (1.17 mmol) of potassium formate and 50 mg of 10% palladium on charcoal. After refluxing the reaction for lh, hot filtration through celite (washing with a small portion of DMF), dilution with 30 mL of water, the pH was adjusted to 5.5 with 5% NaHC0 3 , the product is isolated as a precipitate 140 mg (80%) of white powder. Analytical HPLC, ret. time = 2.6 min (90%), 3.05 min (10%), 100% pure (conditions: YMC C18 5x4.6 column, gradient 10% to 90% MeCN/H 2 0, in the presence of 0.1% TFA, 9 min run at 1 ml/min flow rate, k =254 nm). 'H-NMR (400 MHz, CDCL 3 ): 8 8.48 (br s, 1H), 8.34 (dd, 1H), 7.92 (dd, 1H), 7.41 (dd, I), 7.15 (m, 3H), 7.13 (d, 211), 6.86 (dd, 1H), 6. 28 (t, 1H), 3.83 (s, 6H); MS (EI) m/z for C 2 1

H

20

N

6 0 4 S: 453.03 (MIH'). Example 168 3-amino-N-(3-{[3,5-bis(methoxy)phenylamino}pyrido[2,3-bpyrazin 2-yl)benzenesulfonamide 00 +cx 0' ~0 0 /O O H) OH H OK Pd/C, THFIEtOH NINH N"'NHO NX Q NO 2 NH2 [00220] To a 1:1 THF/EtOH suspension (1 mL) of 3-nitro-N-(3-{[3,5-bis(methoxy) phenyl]amino}pyrido[2,3-b]pyrazin-2-yl)benzenesulfonamide (100 mg, 0.21 mmol) (prepared using procedures similar to those used in Example 166) was added 46 gL (0.63 216 mmol) of formic acid plus 100mg (0.63 mmol) of potassium formate and 100 mg of 10% palladium on charcoal. After refluxing the reaction for lh, hot filtration through celite, and concentration, the product is isolated by preparative RP-BPLC (NH 4 OAc/ACN) gradient. The appropriate fractions were pooled and lyophilize to give solid yellow product: 3.2 mg (4%). 'H-NMR (400 MHz, CDC1 3 ): & 8.62 (d, 1H), 8.52 (s, 1H), 7.62 (d, 1H), 7.3 (m, 4H), 7.18 (d, 2H), 6.88 (d, 1H), 6.27 (t, 1H), 3.96 (br s, 2H), 3.83 (s, 6H). MS (El) m/z for

C

21

H

2 0

N

6 0 4 S: 453.22 (MH*). Example 169 N-(3-{[2-chloro-5-(methoxy)phenyljaminoquinoxalin-2-yl)-3-(1-{[2-(dimethylamino) ethyl] amino)ethyl)benzenesulfonamide trifluoracetic acid salt ol I ~H2N -- '" NaBH 3 CN AcOH , N H N H6 [00221] To a dichloroethane solution (0.6 mL) of 3-acetyl-N-(3-{[2-chloro-5-(methoxy) phenyl]amino)quinoxalin-2-yl)benzenesulfonamide (150 mg, 0.31 mmol), prepared using procedures similar to those in Example 115, and 51 sL (0.37 mmol) of N,N-dimethylethylenediamine was added 19 pL of acetic acid followed by 132 mg (0.62 mmol) of sodium cyanoborohydride. The reaction mixture was refluxed for 18h under a nitrogen atmosphere. After concentration (in vacuo), the product is isolated by preparative RP-HPLC (0.1 % TFA/ACN) gradient, followed by lyophilization of appropriate fractions to give solid yellow solid: 189 mg (90%). 'H-NMR (400 MHz, d 3 -MeOD): 6 8.74 (s, 1H), 8.18 (s, 1H), 8.12 (d, 1H), 7.71 (m, 3H), 7.48 (m, 411), 7.28 (d, 1H), 6.63 (d, 111), 4.38 (q, 1H), 3.80 (s, 311), 3.30 (m, 3H), 3.12 (m, 1H1), 2.84 (s, 3H1), 1.60 (d, 3H). MS (El) m/z for

C

27

H

3 C1N 6 0 3 S: 555.56 (MH). 217 Example 170 N,N-{[(3-{[(3-{{2-chloro-5-(methoxy)phenyllamino}quinoxalin-2-yl)amino]sulfonyl}-4 methylphenyl)amino](dimethylamino)methylidene}-N-methylmethanaminium CI Oc CI DIEA as NH2 HATU - N [00222] To a dimethylformamide solution (1 mL) of 3-amino-N-(3-{[2-chloro-5 (methoxy)-phenyl]amino}quinoxalin-2-yl)2-methylbenzenesulfonamide (200 mg, 0.40 mmol), prepared using procedures similar to those described in Example 115, is added 312 pL (1.8 mmol) of DIEA and 122 mg (0.6 mmol) of HATU. After stirring for 18h at 60 *C, the product was precipitated from a 1:1 mixture of hexane/ethyl acetate, filtered and dried to afford 60 mg (26%). 1 H NMR (400 MHz, DMSO-d 6 ): 8 9.26 (b rs, 1H), 8.96 (br s, 1H), 7.80 (s, 1H), 7.51 (br s, 1H), 7.45 (d, 111), 7.18 (brm, 4H), 6.91 (br s, 111), 6.60 (br d, 1H), 3.82 (s, 3H), 3.36 (s, 3H), 2.85 (s, 6H), 2.58 (s, 3H). MS (EI) m/z for C 27

H

31

CIN

7 0 3 S*: 569.32 (MH*). Example 171 2-Bromo-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)acetamide IqI ),.,Br HO Br N CNH S NH2 DICI DCM Br N N N'C N N < Br [00223] In a 50 mL round-bottom flask was added 2-bromoacetic acid (1.87 g, 13.5 mmol), NN-diisopropylcarbodiimide (860 mg, 6.8 mmol) and 10 mL DCM. To this mixture was added 3-amino-N-(3-(3,5-dimethoxyphenylamino) quinoxalin-2-yl) benzenesulfonamide (2.03 g, 4.5 mmol), prepared using procedures similar to those in Example 168. The reaction was stirred overnight at room temperature. Complete consumption of the starting aniline was confirmed by LCMS. The solvent was evaporated off to yield the crude product (2-bromo-N-(3-(N-(3-(3,5-dimethoxyphenylamino) 218 quinoxalin-2-yl)sulfamoyl) phenyl) acetamide). This was used directly in the next step without purther purification. General Alkylation Procedure 1 amine, aniline, I hydrazine, C)II~NXNH alkoxylamines N NH 0 B A/ Acetonitrile 0 R [00224] Into a 2-dram vial was placed 2-bromo-N-(3-(N-(3-(3,5-dimethoxy phenylamino)quinoxalin-2-yl) sulfamoyl) phenyl) acetamide (86 mg, 0.15 mmol), prepared using procedures similar to those in Example 171,along with 2 mL of acetonitrile. Eight equivalents (1.2 mmol) of the desired amine, aniline, hydrazine or alkoxyamine were added followed by the addition of Hunig's Base (41 pL, 0.25 mmol). The reaction then was stirred at 50 *C for one hour (overnight for aniline reagents). Preparative reverse-phase HPLC was used to isolate the desired product directly from the crude reaction mixture. A Waters Fractionlynx preparative reverse-phase HPLC - equipped with a Waters SunFire Prep Cl 8, OCD 5 pM, 30 X 70 mim column and running a 5-100 % gradient with a binary solvent system of 25 mM ammonium acetate in water/acetonitrile - was used to carry out the purification. [01861 The following title compounds were prepared according to General Library Alkylation Procedure 1. Example 172: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(methylamino)acetamide. 'H-NMR (400MHz, d 6 -DMSO): 8.81 (s, 11), 8.23 (t, 1H), 7.75 (d, 1H), 7.66 (d, 1H), 7.41-7.38 (in, 1H), 7.35 (in, 1H), 7.32 (d, 2H), 7.29-7.27 (m, 1H), 7.14-7.11 (in, 2H), 6.14 (t, IH), 3.80 (s, 1H), 3.78 (s, 6H), 2.58 (s, 3H), 1.91 (s, 2H); MS (El) m/z C 25

H

2 6

N

6 s0 5 S: 523.6 (MH*). Example 173: 2-(cyclopropylmethylamino)-N-(3-(N-(3-(3,5 dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. IH-NMR (400MHz, d 6 -DMSO): 10.58 (s, 1H), 8.81 (s, IH), 8.20 (t, 1H), 7.76 (d, 1H), 7.67 (d, I), 7.42-7.36 (m, 2H), 7.32 (d, 2H), 7.27 (s, 1H), 7.14-7.12 (m, 2H), 6.15 (t, IH), 3.93 (s, 2H), 219 3.78 (s, 611), 2.89 (s, IH), 2.88 (s, 1H), 1.05-1.00 (m, 1H), 0.59 (d, 1H), 0.57 (d, 111), 0.35 (d, 1H), 0.34 (d, 1H); MS (EI) m/z C 28

H

30

N

6 0 5 S: 563.6 (IvH*. Example 174: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(2-hydroxy-propylamino)acetamide. 'H-NMR (400MHz, d 6 DMSO): 10.49 ppm (s, 1H), 8.81 ppm (s, 1H), 8.23 ppm (t, 1H), 8.13 ppm (s, 1H), 7.76 ppm (d, 1H), 7.765-7.763 (dd, 111), 7.41-7.37 ppm (m, 2H), 7.33-7.32 ppm (d, 1H), 7.30 7.28 ppm (m, 1H), 7.16-7.09 ppm (m, 211), 6.55 ppm (s, 1H), 6.14 ppm (t, 1H), 5.49 ppm (d, 211), 5.25 ppm (s, 1H), 3.85 ppm (s, 1H), 3.78 ppm (s, 6H) 3.67-3.59 ppm (m, 111), 3.00 2.89 ppm (dd, 1H), 2.79-2.76 ppm (im, 1H), 1.10 ppm (d, 1H), 1.01-0.99 ppm (d, 1H); MS (EI) m/z C 27

H

30

N

6 0 6 S: 566.6 (MH). Example 175: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(3-fluorobenzylamino)acetamide. 'H-NMR (400MHz, d 6 DMSO): 10.42 ppm (s, 1H), 8.82 ppm (s, 1H), 8.23 ppm (s, 1H), 8.14 ppm (s, IH), 7.75 ppm (d, 111), 7.65 ppm (d, 111), 7.49-7.32 ppm (m, 6H), 7.25-7.20 ppm (m, 1H), 7.14-7.12 ppm (m, 211), 6.55 ppm (s, 1H), 6.15 ppm (t, 111), 4.14 ppm (s, 2H), 3.78 ppm (s, 6H), 3.74 ppm (s, 211); MS (E1) m/z C 3 1

H

2 9

FN

6 0 5 S: 616.7 (MW). Example 176: 2-(benzylamino)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C 3 1

H

30

N

6 0 5 S: 599 (M+). Example 177: 2-(diethylamino)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C 28

H

32

N

6 0 5 S: 565 (MH*). Example 178: 2-(4-(3,4-dichlorophenyl)piperazin-1-yl)-N-(3-(N-(3-(3,5 dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z

C

3 4H 33 Cl 2

N

7 0 5 S: 722 (M1H). Example 179: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(2,2-dimethylhydrazinyl)acetamide. MS (El) m/z C 2 6H 2 9

N

7 0sS: 552 (MH*). Example 180: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(p-tolylamino)acetamide. MS (EI) m/z C 31

H

30

N

6 0 5 S: 599 (MH*). Example 181: 2-(benzyloxyamino)-N-(3-(N-(3-(3,5-dimethoxy phenylamino)quinoxalin-2-yl)sulfamoyl)pheny)acetamide. MS (EI) m/z C 31

H

30

N

6 0 6 S: 615 (MH*). 220 Example 182: 2-(2-chlorophenylamino)-N-(3-(N-(3-(3,5 dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (El) m/z

C

3 oH 27 C1N 6

O

5 S: 619 (MU'). Example 183: N-(3-(N-(3-(3,5-dimethoxyphenylamino)quiuoxalin-2 yl)sulfamoyl)phenyl)-2-(isopropylamino)acetamide. MS (EI) m/z C 27

H

3 0

N

6 0 5 S: 551 MI-). Example 184: 2-(4-cyclopentylpiperazin-1-yl)-N-(3-(N-(3-(3,5 dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z

C

33

H

3 9

N

7 0 5 S: 646 (MH'). Example 185: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(4-propylpiperidin-1-yl)acetamide. MS (El) m/z C 32

H

3 gN 6 0 5 S: 619 (MH). Example 186: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(isobutoxyamino)acetamide. MS (EI) n/z C 2 gH 3 2

N

6 0 6 S: 581 (MI1). Example 187: 2-(3-tert-butylphenylamino)-N-(3-(N-(3-(3,5 dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (El) m/z

C

3 4H 36

N

6 0 5 S: 641 (MHi). Example 188: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)snlfamoyl)phenyl)-2-(2-phenylpropan-2-yamino)acetamide. MS (EI) ni/z

C

33

H

34

N

6 0 5 S: 627 (MH). Example 189: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(3-fluoro-4-hydroxyphenylamhino)acetamide. MS (EI) m/z

C

3 oH 27

FN

6 0 6 S: 619 (MH*). Example 190: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(2-(methylthio)benzylamino)acetamide. MS (El) m/z

C

32

H

32

N

6 0 5

S

2 : 645 (MIf). Example 191: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(5-fluoro-2-methylbezylamino)acetamide. MS (EI) m/z

C

32

H

3 tFNS 6 0 5 : 631 (MH*). Example192: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(2-phenylpyrroidin-1-yl)acetamide. MS (E) m/z C 34

H

34

N

6 0 5 S: 639 (MH*). 221 Example 193: 2-(2-benzylpyrrolidin-1-yl)-N-(3-(N-(3-(3,5-dimethoxy phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C 35

H

36

N

6 0 5 S: 653 (MI). Example 194: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(2-phenylmorpholino)acetamide. MS (EI) m/z C 3 4

H

34

N

6 0 6 S: 655 (MI-f). Example 195: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(2-(pyridin-4-yl)piperidin-1-yl)acetamide. MS (EI) m/z

C

34

H

35

N

7 0 5 S: 654 (MH*). Example 196: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(o-tolylamino)acetamide. MS (EI) m/z C 31

H

30

N

6 0 5 S: 599 QH*). Example 197: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(2,4-dimethylbenzylamino)acetamide. MS (E) m/z

C

33

H

34

N

6 0 5 S: 627 (Mu'). Example 198: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(methyl(pyridin-3-ylmethyl)amino)acetamide. MS (EI) m/z

C

31

H

3 iN 7 0 5 S: 614 (ME). Example 199: 2-(3-chloro-4-methylbenzylamino)N-(3-(N-(3-(3,5 dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (El) m/z

C

32

H

31

CIN

6 0 5 S: 647 (MH*). Example 200: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-((2-(dimethylamino)-ethyl)(methy)amino)acetamide. MS (EI) MIz C 29

H

3 sN 7 0sS: 594 (MII). Example 201: 2-(4-acetylpiperazin-1-yl)-N-(3-(N-(3-(3,5 dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (El) m/z

C

3 oH33N7O6S: 620 (MH*). Example 202: N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(methyl(1-methylpyrrolidin-3-yl)amino)acetamide. MS (EI) m/z C 30

H

35

N

7 0 5 S: 606 (MWH). Example 203: N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(4-methyl-1,4-diazepan-1-yl)acetamide. MS (EI) m/z C3oH35N7OsS: 606 (MH*). 222 Example 204: 2-(4-allylpiperazin-1-yl)-N-(3-(N-(3-(3,5 dimethoxyphienylamino)quinoxalin-2-yl)sufamoyl)phenyl)acetamide. MS (El) m/z

C

31

H

35

N

7 0 5 S: 618 (MH*). Example 205: N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(4-isopropylpiperazin-1-yl)acetamide MS (EI) m/z

C

3

H

37

N

7 0sS: 620 (MH). Example 206: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(3-(dimethylamino)pyrrolidin-1-yl)acetamide. MS (EI) m/z

C

30

H

35

N

7 0 5 S: 606 (MHW . Example 207: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)pheny)-2-(3-(dimethylamino)azetidin-1-yl)acetamide. MS (E) m/z

C

2 9H 3 3N 7 0sS: 592 (MH). Example 208: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(4-oxopiperidiu-1-yl)acetamide. MS (EI) m/z C 2 pH 30

N

6

O

6 S: 591 (MH*). Example 209: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-((2-methoxyethyl)(methyl)amino)acetamide. MS (El) m/z

C

2

SH

32

N

6 0 6 S: 581 (MH). Example 210: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(4-methylbenzyloxyamino)acetamide. MS (EI) m/z

C

32

H

32

N

6 0 6 S: 629 (MH*). Example 211: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(2-methoxybenzyloxyamino)acetamide. MS (E) m/z

C

32

H

32

N

6 0 7 S: 645 (MH). Example 212: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(propylamino)acetamide. MS (El) m/z C 27 H3oN 6 0 5 S: 551 (MH). Example 213: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(ethyl(methyl)amino)acetamide. MS (EI) m/z C 27

H

30

N

6 0 5 S: 551 (MH). Example 214: 2-(allyl(methyl)amino)-N-(3-(N-(3-(3,5-dimethoxy phenylamino)quinoxalin-2-yl)sulfamoyI)phenyl)acetamide. MS (El) m/z C 28

H

3 0

N

6 0 5 S: 563 (MH*). 223 Example 215: 2-(tert-butylamino)-N-(3-(N(3-(3,5-dimethoxy phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C 2 sH 3 2

N

6 0 5 S: 565 (MH*). Example 216: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(isobutylamino)acetamide. MS (EI) m/z C 2 sH 32

N

6 OsS: 565 (MH). Example 217: 2-(butylamino)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)pheuyl)acetamide. MS (EI) m/z C 28

H

3 2

N

6 0sS: 565 (MRf). Example 218: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(isopropyl(methyl)amino)acetamide. MS (EI) m/z C 2 sH 32

N

6 OsS: 565 (MH* 4 ), Example 219: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(4-formylpiperazin-1-yl)acetamide. MS (EI) m/z C 29 11 3

N

7 0 6 S: 606 (M+). Example 220: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(4-ethylpiperazin-1-yl)acetamide. MS (El) m/z C 3 oH 35

N

7 0 5 S: 606 (MHE). Example 221: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxain-2 yl)sulfamoyl)phenyl)-2-(4-formyl-1,4-diazepan-1-yl)acetamide. MS (EI) m/z

C

30

H

33

N

7 0 6 S: 620 (MH*). Example 222: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(ethyl(2-hydroxyethyl)amino)acetamide. MS (EI) m/z

C

2 sH 32

N

6 0 6 S: 581 (MH). Example 223: (S)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(3-hydroxypyrrolidin-1-yl)acetamide. MS (EI) m/z

C

2 8

H

3 oN 6 OsS: 579 (MH*). Example 224: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(2,6-dimethylmorpholino)aeetamide. MS (EI) m/z

C

3 oH 34

N

6 0 6 S: 607 (MH*). Example 225: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(2-methylbenzylamino)acetamide. MS (EI) m/z C 32

H

32

N

6 0 5 S: 613 (MH). 224 Example 226: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyf)-2-(2-methoxy-ethylamino)acetamide. MS (EI) m/z C 27

H

30

N

6 0 6 S: 567 (MH). Example 227: N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2 yl)sulfamoyl)phenyf)-2-(thiazolidin-3-y)acetamide. MS (El) m/z C 27 11 2

BN

6 0 5

S

2 : 581 WMl). Example 228: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yI)sulfamoyl)phenyf)-2-(3-(hydroxymethyl)piperidin-1-y)acetamide. MS (BI) m/z

C

30

H

3 4N 6

O

6 S: 607 (MH). Example 229: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyf)-2-(2-phenylpropylamino)acetamide. MS (EI) m/z C 3 3

H

3 4

N

6 0 5 S: 627 (MH*). Example 230: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(isobutyl(methyl)amino)acetamide. MS (El) m/z C 29

H

34

N

6 0 5 S: 579 (MH). Example 231: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(phenylamino)acetamide. MS (EI) m/z C 30

H

28

N

6 0 5 8: 585 (MH*). Example 232: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yf)sulfamoyl)phenyf)-2-(2-propylphenylamino)acetamide. MS (EI) m/z C 33

H

34

N

6 0 5 S: 627 (MHW). Example 233: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(2-isopropylphenylamino)acetamide. MS (EI) m/z

C

33

H

34

N

6 0 5 S: 627 (MH. Example 234: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(2-fluoro-4-methylphenylamino)acetamide. MS (El) m/z

C

31 H2qFN 6 0 5 S: 617 (MH*). Example 235: 2-(4-chlorophenylamino)-N-(3-(N-(3-(3,5-dimethoxy phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z

C

30

H

27 C1N 6 0 5 S: 619 (MH. Example 236: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(2-methoxyphenylamino)acetamide. MS (El) m/z C 31

H

3 0

N

6 0 6 S: 615 (MH). 225 Example 237: 2-(3-chlorophenylamino)-N-(3-(N-(3-(3,5-dimethoxy phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C3oH 27

CIN

6

O

5 S: 619 (MIH). Example 238: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(2,3-dimethylphenylamino)acetamide. MS (El) m/z

C

3 2

H

3 2

N

6 0SS: 613 (MH). Example 239: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(2-fluorophenylamino)acetamide. MS (El) m/z C 3 oH 2 7

FN

6

O

5 S: 603 (MH*). Example 240: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(3-fluorophenylamino)acetamide. MS (EI) m/z C 3 0

H

27

FN

6 0sS: 603 (MIH). Example 241: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(thiophen-2-ylmethylamino)acetamide. MS (EI) m/z

C

2 9

H

2 8

N

6 0SS 2 : 605 (Mi). Example 242: 2-(cyclohexyl(ethyl)amino)-N-(3-(N-(3-(3,5 dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z

C

32

H

38

N

6 0 5 S: 619 (MH). Example 243: 2-((cyclopropylmethyl)(propyl)amino)-N-(3-(N-(3-(3,5 dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z

C

31

H

36

N

6 0 5 S: 605 (MHT). Example 244: 2-(allyI(cyclopentyl)amino)-N-(3-(N-(3-(3,5 dimethoxyphenylamino)quinoxain-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z

C

3 2

H

36

N

6 0 5 S: 617 (MH). Example 245: N-(3-(N-(3-(3,5-dimetoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(ethyl(isopropyl)amino)acetamide. MS (EI) mhz C 29

H

34

N

6 sS: 579 (QM). Example 246: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)pheiyl)-2-(ethyl(phenyl)amino)acetamide. MS (EI) m/z C 32

H

32

N

6 0 5 S: 613 (MI-0. Example 247: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(2-methylpyrrolidin-1-yl)acetamide. MS (EI) m/z C 29

H

32

N

6 0 5 S: 577 (MIT'). 226 Example 248: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxain-2 yl)sulfamoyl)phenyl)-2-(2-methylpiperidin-1-yl)acetamide. MS (EI) m/z C 3 oH 3 4

N

6 OSS: 591 (MH). Example 249: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(pyridin-2-ylmethylamino)acetamide. MS (EI) m/z

C

3 oH 29

N

7 0 5 S: 600 (NMH). Example 250: 2-(benzyl(methyl)amino)-N-(3-(N-(3-(3,5-dimethoxy phenylamino)quinoxain-2-yl)sulfamoyl)pheny)acetamide. MS (EI) m/z C 3 2

H

3 2

N

6 0S: 613 (MH). Example 251: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)qninoxalin-2 yl)sulfamoyl)phenyl)-2-(1-phenylethylamino)acetamide. MS (EI) m/z C 3 2

H

3 2

N

6 0 5 S: 613 (MF). Example 252: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(3-miethylpiperidin-1-yl)acetamide. MS (EI) m/z C 30

H

3 4

N

6 0 5 S: 591 (MH). Example 253: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(4-methylpiperidin-1-yl)acetamide. MS (EL) m/z C 30

H

3 4

N

6 0 5 8: 591 (MH*). Example 254: 2-(3,4-dihydroisoquinolin-2(H)-yl)-N-(3-(N-(3-(3,5 dimethoxyphenylamino)quinoxalin-2-yl)sufamoyl)phenyl)acetamide. MS (EI) m/z

C

33

H

32

N

6 0 5 S: 625 (MH). Example 255: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(2,6-dimethylpiperidin-1-yl)acetamide. MS (EI),m/z

C

31

H

36

N

6 0 5 S: 605 (MH). Example 256: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yf)sulfamoyl)phenyl)-2-(3-hydroxybenzylamino)acetamide. MS (El) m/z C 31

H

30

N

6 0 6 S: 615 (MH). 227 General Library Acylation Procedure 1 0 R OH 0,N e O HATU 4/0 H N 1 S NH2 s NYR H H 1 0 [00225] Into a 2-dram vial were added 3-amino-N-(3-(3,5-dimethoxy phenylamino)quinoxalin-2-yl)benzenesulfonamide (54 mg, 0.12 mmol), prepared using procedures similar to those described in Example 15, DMA (2 mL) and the desired carboxylic acid (0.17 mmol). DIEA (70 pL, 0.4 mmol) followed by HATU (53 mg,0.14 mmol) were added to the vial and the reaction mixture stirred at 50 "C overnight. Preparative reverse-phase HPLC was used to isolate the desired product directly from the crude reaction mixture. A Waters Fractionlynx preparative reverse-phase HPLC; equipped with a Waters SunFire Prep C18, OCD 5 pM, 30 X 70 mm column and running a 5-100 % gradient with a binary solvent system of 25 mM ammonium acetate in water/acetonitrile; was used to carry out the purification. 1002261 The following title compounds were prepared according to General Library Acylation Procedure 1. Example 257: N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)morpholine-4-carboxamide: MS (EI) m/z for C 26

H

25 ClN 6 0 5 S: 567 (MH~). Example 258: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(dimethylamino)acetamide. MS (El) m/z for C 2 rH 28

N

6 0 5 S: 535.1 (MW). Example 259: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)propionamide. 'H-NMR (400Mz, d 6 -DMSO): 12.37 (s, 1H), 10.20 (s, 1H), 8.88 (s, 11), 8.37 (s, 1H), 7.93 (s, 1H), 7.77 (t, 2H), 7.59 (t, 1H), 7.51 (t, 1H), 7.41 7.34 (m, 4H), 6.24 (t, 1H), 3.76 (s, 6H), 2.36-2.31 (dd, 2H), 1.10 (s, 1H), 1.08 (s, IH), 1.06 (s, IH); MS (E) m/z C 2 sH 2 5

N

5 0 5 S: 508.6 (MH*). Example 260: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)pyridazine-4-carboxamide. 'H-NMR (400MHz, d 6 -DMSO): 11.01 (s, 1H), 9.66 (dd, 1H), 9.52 (dd, 1H), 8.90 (s, 1H), 8.55 (s, IH), 8.13 (dd, 1H), 7.99 (d, 1H), 228 7.93 (d, 111), 7.65-7.58 (M, 211), 7.42-7.35 (m, 4H), 6.24 (t, 1H), 3.75 (s, 6H); MS (EI) m/z

C

27

H

23

N

7 0 5 S: 558.6 (MH*). Example 261: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2~ yl)sulfamoyl)phenyl)-2-methylnicotinamide. 'H-NMR (400MHz, d 6 -DMSO): 10.78 ppm (s, 1H), 8.90 ppm (s, 1H), 8.58-8.57 ppm (dd, 2H), 7.90-7.86 (m, 4H1), 7.60-7.56 ppm (m, 2H), 7.42-7.34 (m, 5H), 6.23 ppm (t, 11), 3.74 ppm (s, 6H), 2.57 ppm (s, 3H); MS (EI) m/z

C

29 H2 6 NsOsS: 570.6 (MH*). Example 262: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(o-tolyloxy)acetamide. 'H-NMR (400MHz, d 6 -DMSO): 12.37 ppm (s, 1H), 10.41 ppm (s, IH), 8.90 ppm (s, 1H), 8.41 ppm (s, IH), 7.93 ppm (s, 1H), 7.90-7.8 (m, 2H), 7.59-7.53 ppm (m, 2H), 7.42-7.33 ppm (m, 4H), 7.17-7.12 ppm (m, 2H), 6.89-6.85 ppm (m, 2H), 6.24 ppm (t, 1H), 4.74 ppm (s, 2H), 3.76 ppm (s, 6H), 2.33 ppm (s, 2H); MS (EI) m/z C 3 lH 29

N

5 6 S: 599.7 (MH). Example 263: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxain-2 yl)sulfamoyl)phenyl)-3-methoxy-4-methylbenzamide. MS (El) M/z C 31

H

29

N

5 0 6 S: 600 (MH). Example 264: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)pheny)-3-methoxy-4-methylbenzamide. MS (El) m/z C 28

H

2 4

N

6 0 5 S: 557 (MH*). Example 265: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)thiazole-4-carboxamide. MS (EI) m/z C 26

H

22

N

6 0 5

S

2 : 563 (MH*). Example 266: 2-bromo-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yI)sulfamoyl)phenyl)thiophene-3-carboxamide. MS (EI) m/z C 2 7

H

2 2 BrN 5

O

5

S

2 640 (MW). Example 267: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)pivalamide. MS (EI) m/z C 27

H

2 9

N

5 0 5 S: 536 (MH*). Example 268: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)pent-4-enamide. MS (EI) m/z C 27

H

27 NsSS: 534 (MH*). Example 269: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)benzamide. MS (EI) m/z C 2 9

H

2 sN 5 0S: 556 (MH*), Example 270: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)butyramide. MS (EI) m/z C 2 6

H

2 7

N

5 0 5 S: 522 (MH*). Example 271: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-methoxyacetamide. MS (EI) m/z C 25

H

25

N

5 0 6 S: 524 (MH). 229 Example 272: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxaliu-2 yl)sulfamoyl)phenyl)cyclobutanecarboxamide. MS (EI) m/z C 27

H

27

N

5 0 5 S: 534 (MHI). Example 273: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-methyleyelopropanecarboxamide. MS (EI) m/z C 27 H2N 5 05S: 534 (MH*). Example 274: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxain-2 yl)sulfamoyl)phenyl)-1-methyleyelopropanecarboxamide. MS (EI) m/z C 27

H

27

N

5 0 5 S: 534 (MH*). Example 275: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-3-methylbutanamide. MS (EI) m/z C 27

H

29

N

5 0 5 S: 536 (MH). Example 276: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-ethoxyacetamide. MS (EL) m/z C 26

H

27

N

5 0 6 s: 538 (MH'). Example 277: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-3-methoxypropanamide. MS (El) m/z C 26

H

2 7 Ns0 6 S: 538 (MHT). Example 278: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-hydroxyacetamide. MS (El) m/z C 24 H2 3

N

5 0 6 S: 510 (MH*). Example279: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)isobutyramide. MS (EI) m/z C 26

H

27

N

5 0 5 S: 522 (MH*). Example 280: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-1-hydroxycyclopropanecarboxamide. MS (EI) m/z C 26

H

25

N

5 0 6 S: 536 (MH*'). Example 281: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)furan-3-carboxamide. MS (EI) m/z C 27

H

23

N

5 0 6 S: 546 (MW). Example 282: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)tetrahydrofuran-3-carboxamide. MS (El) m/z C 27

H

27

N

5 0 6 S: 550 (MH'). Example 283: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)pkenyl)tetrahydrofuran-2-carboxamide. MS (E) m/z C 27

H

27

N

5 0 6 S: 550 (MH). Example 284: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)furan-2-carboxamide. MS (E) m/z C 27 H2 3

N

5 0 6 S: 546 (MH*). Example 285: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)isonicotinamide. MS (EI) m/z C 2 sH 2 4

N

6 0 5 S: 557 (MH+ 230 Example 286: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yt)sulfamoyl)phenyl)-1H-pyrrole-2-carboxamide. MS (EI) M/z C 27

H

24

N

6 0 5 S: 545 (MIH). Example 287: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)pyrazine-2-carboxamide. MS (EI) m/z Cz 7

H

23

N

7 0sS: 558 (MH). Example 288: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-1-methyl-lH-pyrrole-2-carboxamide. MS (EI) m/z C 28

H

26

N

6 0 5 S: 559 (MH*). Example 289: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-5-methylisoxazole-3-carboxamide. MS (EI) m/z C 27

H

24

N

6 0 6 S: 561 (MHR). Example 290: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)thiophene-2-carboxamide. MS (EI) m/z C 27 H23NsO 5

S

2 : 562 (MH). Example 291: (S)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-1-methylpyrrolidine-2-carboxamide. MS (EI) m/z C 2 sH 30

N

6 0 5 S: 563 (MH). Example 292: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-methylbenzamide. MS (EI) m/z C 3 oH27NsOSS: 570 (MH*). Example 293: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-phenylacetamide. MS (EI) m/z C 3

H

27

N

5 0sS: 570 (MHi). Example 294: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-3-methylpicoliUnamide. MS (EI) m/z C 2 9

H

26

N

6 0 5 S: 571 (MH), Example 295: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(pyridin-3-yI)acetamide. MS (El) m/z C 29

H

26

N

6 0 5 S: 571 (MH*) Example 296: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-6-hydroxypicolinamide. MS (EI) m/z C 2 8

H

2 4

N

6 0 6 S: 573 (MH*). Example 297: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-fluorobenzamide MS (EI) m/z C 29 H2 4 FNsOsS: 574 (MH). Example 298: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-4-fluorobenzamide. MS (El) m/z C 29

H

2 4

FN

5 0 5 S: 574 (MH*). Example 299: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-3-fluorobenzamide. MS (EI) m/z C 29

H

2 4

F

5 0 5 S: 574 (MH). Example 300: 2-cyclohexyl-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C 3

OH

3 3

N

5 OsS: 576 (MH*). 231 Example 301: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(2-oxocyclopentyl)acetamide. MS (El) m/z C 29

H

29

N

5 0 6 S: 576 (MH). Example 302: 4-cyclopropyl-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-4-oxobutanamide. MS (EI) m/z C 2 9Hz9NsO 6 S: 576 (MH*). Example 303: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-3-oxocyclohexanecarboxamide. MS (EI) m/z C 2 9

H

2 9

N

5 0 6 S: 576 (MH). Example 304: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-3-(pyridin-3-yl)propanamide. MS (EI) m/z C 30 H2&N0sS: 585 (MHW). Example 305: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-methoxybenzamide. MS (EI) m/z C 3 oH2 7 NsO 6 S: 586 (MH+' Example 306: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yI)sulfamoyl)pheny)-3-methoxybenzamide. MS (EI) ni/z C 3 oH 27

N

5 0 6 S: 586 (MW). Example 307: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-phenoxyacetamide. MS (EI) m/z C 30

H

27

N

5 0 6 S: 586 (MH'). Example 308: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-4-methoxybenzamide. MS (EI) M/z C 30

H

27

N

5 0 6 S: 586 (MH). Example 309: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(4-fluorophenyl)acetamide. MS (EI) M/z C 30

H

26

FN

5 0 5 S: 588 (MH). Example 310: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(2-fluorophenyl)acetamide. MS (EI) m/z C 30 H2 6

FN

5 0 5 S: 588 (MW). Example 311: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(3-fluorophenyl)acetamide. MS (EI) m/z C 30

H

2 6

FN

5 0 5 S: 588 (MH'). Example 312: 2-chloro-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)benzamIde. MS (EI) m/z Cz9Hz 4 CINsOsS: 590 (MH*). Example 313: 4-chloro-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)benzamide. MS (EI) m/z C 2 9

H

24 C1NsO 5 S: 590 (MH). Example 314: 3-chloro-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)benzamide. MS (EI) m/z C 2 9

H

24 CNsOs 5 S: 590 (MH*). 232 Example 315: (1R,2R)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-phenyleyelopropanecarboxamide. MS (E) m/z C 3 2

H

29 NSOsS: 596 (MH*). Example 316: N-(3-(N-(3-(3,5-dimethoxy-phenylaminuo)quinosalin-2 yl)sulfamoyl)phenyl)-1-phenyleyelopropanecarboxamide. MS (EI) m/z C 32

H

29 NsOsS: 596 (MH). Example 317: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(I1H-imidazol-4-yl)acetamide. MS (EI) m/z C 27

H

2 sN70 5 S: 560 (MH). Example 318: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-4-methoxy-2-methylbenzamide. MS (EI) m/z C 31

H

29

N

5 06S: 600 (MH). Example 319: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxain-2 yl)sulfamoyl)phenyl)-2-(4-fluorophenoxy)acetamide. MS (EI) m/z C 3 0 H2 6 FNsO 6 S: 604 (MH*), Example 320: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-5-fluoro-2-methoxybenzamide. MS (EI) m/z C 30

H

26 FN30 6 S: 604 Example 321: 2-(4-chlorophenyl)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin 2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C 3 0

H

26 ClN 5 0 5 S: 604 (MH*). Example 322: 2-(2-chlorophenyl)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin 2-yl)sulfamoyl)phenyl)acetamide. MS (El) m/z C 3 oH 2 6 ClNSO 5 S: 604 (MH). Example 323: 2-(3-chlorophenyl)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin 2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C 3 0

H

2 rClNsO 5 S: 604 (MH). Example 324: 1-acetyl-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)piperidine-4-carboxamide. MS (EI) m/z C 30

H

3 2

N

6 0 6 S: 605 (MH). Example 325: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(pyridin-4-yl)acetamide. MS (El) m/z C 2 9H 2

N

6

O

5 S: 571 (MHW). Example 326: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(pyridin-2-yl)acetamide. MS (EI) m/z C 29

H

26

N

6 0 5 S: 571 (MH). Example 327: 2,4-dichloro-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)benzamide. MS (EI) m/z C 29

H

2 3 Cl 2

N

5 OsS: 624 (MHE). Example 328: 3,4-dichloro-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)benzamide. MS (EI) m/z C 2 9

H

2 3 Cl 2 N3OS: 624 (MH*). 233 Example 329: 2,5-dichloro-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)benzamide. MS (EI) m/z C 2 9 H23Cl 2 NsO 5 S: 624 (MH). Example 330: 3,5-dichloro-N-(3-(N-(3-(3,5-dimethoxy-phenyamino)quinoxalin-2 yl)sulfamoyl)phenyl)benzamide. MS (EI) m/z C 29

H

23

C

2

N

5 0 5 S: 624 (MH*). Example 331: 2,3-dichloro-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 y])sulfamoyl)phenyl)benzamide. MS (EI) m/z C 29

H

23 Cl 2 NsO 5 S: 624 (MH*). Example 332: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)pentanamide. MS (EI) m/z C 2 7

H

2 9 NsO 5 S: 536 (MH*). Example 333: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yI)sulfamoyl)phenyl)-2-methylbutanamide. MS (E) m/z C 27

H

29

N

5 0 5 S: 536 (MH). Example 334: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-1H-imidazole-2-carboxamide. MS (EI) m/z C 26

H

2 3

N

7 0sS: 546 (MH*). Example 335: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-1H-imidazole-4-carboxamide. MS (EI) m/z C 2 6 H23N 7 0 5 S: 546 (MH*). Example 336: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)isoxazole-5-carboxamide. MS (EI) m/z C 2 6

H

2 2

N

6 0 6 S: 547 (MH). Example 337: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yI)sulfamoyl)phenyl)-3,3-dimethylbutanamide. MS (EI) m/z C 2 gH3N 5 OsS: 550 (MH). Example 338: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-methylpentanamide. MS (EI) m/z C 2 sH 3 1 NsOsS: 550 (MH+. Example 339: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2,2-dimethylbutanamide. MS (El) m/z C 28

H

31

N

5 0 5 S: 550 (MH*). Example 340: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yI)sulfamoyl)phenyl)-4-methylpentanamide. MS (EI) m/z C 2 8

H

31

N

5

O

5 S: 550 (MHI). Example 341: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)pyrimidine-5-carboxamide. MS (EI) m/z C 2 7

H

23

N

7 0 5 S: 558 (MH*). Example 342: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-3-methylfuran-2-carboxamide. MS (EI) m/z C 2 sH 25

N

5 0 6 S: 560 (MH*). Example 343: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)thiophene-3-carboxamide. MS (EI) m/z C 27

H

23

N

5

O

5

S

2 : 562 (MHE). 234 Example 344: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-3-oxocyclopentanecarboxamide. MS (E) m/z C 28

H

27 N50 6 S: 562

(MH

4 ). Example 345: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(2-methoxyethoxy)acetamide. MS (EI) m/z C 27

H

29

N

5 O7S: 568 (MIf). Example 346: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-4-methylbenzamide. MS (EI) m/z C 3 oH 27 N5O 5 S: 570 (MH*). Example 347: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(3-methylisoxazol-4-yl)acetamide. MS (EI) m/z C 28

H

26

N

6 0 6 S: 575 (MH*). Example 348: 3-cyclopentyl-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)propanamide. MS (EI) m/z C 30

H

33

N

5 0 5 S: 576 (MH*). Example 349: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-o-tolylacetamide. MS (El) m/z C 31

H

2 9 NSOsS: 584 (MH*). Example 350: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-methoxynicotinamide. MS (EI) m/i C 29

H

26

N

6 0 6 S: 587 (MH). Example 351: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-4-fluoro-3-methylbenzamide. MS (EI) m/z C 30

H

2 6 FN5O 5 S: 588 (MHlf). Example 352: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-3-fluoro-2-methylbenzamide. MS (El) m/z C 3 oH 26

FN

5 0 5 S: 588 (MI). Example 353: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-3-fluoro-4-methylbenzamide. MS (El) m/z C 3 0

H

2 6

FN

5 0 5 S: 588 Example 354: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-fluoro-5-methylbenzamide. MS (EI) m/z C 3 0H 26 FN5OSS: 588 (MH*). Example 355: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-5-fluoro-2-methylbenzamide. MS (El) m/z C 30

H

26

FN

5 0 5 S: 588 (MH*). Example 356: 6-chloro-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)nicotinanide. MS (El) mn/z C 2 sH 23

CN

6 0 5 S: 591 (MH*). 235 Example 357: 2-chloro-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)nicotinamide. MS (EI) m/z C 2 sH 2 3 C1N 6 0 5 S: 591 (MH*). Example 358: 2-chloro-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)isonicotinamide. MS (EI) m/z C 28

H

23 ClN 6 0sS: 591 (MH*). Example 359: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)suifamoyl)phenyl)-4-(dimethylamino)benzamide. MS (E) M/z C 31

H

3

DN

6 0 5 S: 599 (MH*). Example 360: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yI)sulfamoyl)phenyl)-3-(dimethylamino)benzamide. MS (EI) m/z C 31

H

3 0

N

6 0 5 S: 599 (MH*). Example 361: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)benzo[d][1,3]dioxole-5-carboxamide. MS (EI) m/z C 30

H

25

N

5 0 7 S: 600 (MIHt). Example 362: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(m-tolyloxy)acetamide. MS (El) m/z C 31

H

29

N

5 0 6 S: 600 (MH). Example 363: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(4-methoxyphenyl)acetamide. MS (E) m/z C 31

H

29

N

5 0 6 S: 600 (MO. Example 364: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(2-methoxyphenyl)acetamide. MS (EI) m/z C 31

H

2 9

N

5 0 6 S: 600 (MH*). Example 365: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-(3-methoxyphenyl)acetamide. MS (El) m/z C 31

H

29

N

5 0 6 S: 600 (MH). Example 366: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-methoxy-4-methylbenzamide. MS (El)m/z C3 nH 29 NS0 6 S: 600 (MHT). Example 367: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-3-fluoro-4-methoxybenzamide. MS (E) m/z C 30

H

26

FN

5 0 6 S: 604 (MH. Example 368: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-2-fluoro-6-methoxybenzamide. MS (EI) m/z C 3 oH 26 FNsO 6 S: 604 NMH2). 236 Example 369: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yr)sulfamoyl)phenyl)-3-(4-methoxyphenyl)propanamide. MS (EI) M/z C 32 1 3

N

5 0 6 S: 614 (MH). Example 370: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-3-(2-methoxyphenyl)propanamide. MS (El) m/z C 3 2

H

31 NsO 6 S: 614 (MH+. Example 371: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-3-(3-methoxyphenyl)propanamide. MS (EI) m/z C 32

H

3 INsO 6 S: 614 (MH+ Example 372 N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)azetidine-3 earboxamide. 0 0 HO 0 N INH 1) HATU, DIEA,/DMA NJI O X NH N'H /O

NH

2 2) HCV dioxane, EtOAc NH 1002271 Into a 20 mL vial was added 3-amino-N-(3-(3,5-dimethoxy phenylamino)quinoxalin-2-yl)benzenesulfonamide (0.24 mmol, 1 equiv), prepared using procedures similar to those described in Example 15, DMA ( 5 mL) and I -(tert butoxycarbonyl)azetidine-3-carboxylic acid (0.336 mmol, 1.4 equiv). Hunig's Base (0.792 mmol, 3.3 equiv) and HATU (0.288 mmol, 1.2 equiv) were added to the vial and the reaction mixture was then stirred at room temperature, overnight. Completion of the reaction was indicated by LCMS. The solvent was removed by rotary evaporation. The crude mixture was carried forward without further purification. The residue was suspended in 5 mL ethyl acetate and chilled in an ice bath. A solution of 4 N HCI in dioxane ( 3 mL, 5 equiv) was added with stirring. The reaction mixture was then stirred at room temperature overnight. The solid materials were collected by filtration, washed with ethylacetate then purified further by preparative reverse-phase HPLC (ammonium acetate/ACN). A Waters Fractionlynx preparative reverse-phase HPLC; equipped with a Waters SunFire Prep C18, 237 OCD 5 pM, 30 X 70 mm column and running a 5-100 % gradient with a binary solvent system of 25 mM ammonium acetate in water/acetonitrile; was used to carry out the purification. N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)azetidine-3-carboxamide was obtained (26 mg, 20%). 'H-NMR (400MHz, d 6 -DMSO): 10.26 (s, 111), 8.81 (s, 1H), 8.25 (t, IH), 8.14 (s, 1H), 7.74 (d, 111), 7.69 (d, 1H), 7.41-7.39 (m, 1H), 7.36 (d, 1H), 7.32 (d, 2H), 7.30-7.28 (dd, 1H), 7.14-7.11 (m, 2H), 6.14 (t, 1H), 4.09 (d, 4H), 3.78 (s, 611); MS (El) m/z C 26

H

26

N

6 0sS: 535.6 (MH*). Example 373 N-(3-(4-fluorophenylamino)quinoxalin-2-yl)benzenesulfonamide 0F

H

2 N, e/ ;k N C I DM S N C I H 2 N - N - F DMSO 0 1 y~i~ji M ~~~ CI Cc003 N 120 C, Microwave 160 C NXI H 0 [00228] A flask was charged with 2,3-dichloroquinoxaline (3.5 g, 18 mmol), 85 mL of dimethylsulfoxide, benzene sulfonamide (2.8 g, 18 mmol), and cesium carbonate (5.8 g, 18 mmol). The reaction mixture was stirred under an N 2 atmosphere for 15 h at 150 *C, after which time, it was transferred to a separatory funnel and 100 mL of water were added. Concentrated HCl was then added in order to acidify the reaction mixture to pH<2. The aqueous layer was subsequently washed three times with 90 mL ethyl acetate. The ethyl acetate layers were then washed two times with 150 mL water, three times with 100 mL brine and then dried over sodium sulfate. The ethyl acetate was removed on a rotary evaporator. A slurry was formed by adding ethyl acetate and dichloromethane to the dried crude product, filtration yielded N-(3-chloroquinoxalin-2-y)-benzenesulfonamide which was used without further purification. MS (El) m/z C14HioCIN 3 0 2 S: 319.9 (MH*). [00229] A CEM microwave reaction vessel was charged with N-(3-chloroquinoxalin-2 yl)benzenesulfonamide (52 mg, 0.16 mmol), prepared using procedures similar to those described in the above step, 4-fluoroaniline (36 mg, 0.32 mmol), and 0.8 mL of dimethylacetamide. The vessel was sealed and the reaction mixture was heated under microwave radiation for 25 m at 120 "C in a CEM Discover microwave instrument. Methanol (1 mL) was added to the reaction mixture and after 20 minutes the product 238 precipitated out of the solution. Filtration yielded N-(3-(4-fluorophenylamino)quinoxalin-2 yl)benzenesulfonamide (39 mg, 62 %). 'H-NMR (400MHz, d 6 -DMSO): 8 12.30 (s, 1H), 9.11 (s, 1H), 8.16-8.10 (d, 211), 8.02-7.90 (m, 3H), 7.68-7.58 (m, 311), 7.55-7.51 (m, 111), 7.41-7.32 (m, 2H), 7.25-7.16 (m, 2H); MS (EI) m/z C 2 oHisFN 4 0 2 S: 395.0 (MH*). Example 374 N-(3-(N-(3-chloroquinoxalin-2-yl)sulfamoyl)phenyl)-2-(dimethylamino)acetamide Scheme A 0 0 i0

H

2 N, O N

H

2 N, SAcetone,:H 2 0 0~ NaHCO 3 Scheme B

H

2 N H S N N CI DMA N HN Q IN>Xci DMA YNXCI ~ CsCO 3 0 140C NCN' Scheme A [002301 A flask was charged with 3-aminobenzene sulfonamide (3.3 g, 19 mmol), and 20 mL of 1:1 acetone:H 2 0. The solution was stirred at room temperature until the aminobenzene sulfonamide had dissolved. The flask was then cooled in an ice bath and dimethylamino-acetyl chloride HCI (4.6 g, 29 mmol) was added. To the resulting slurry sodium bicarbonate (4.8 g, 57 mmol) was added over a 15 m period, After 30 min the reaction was removed from the ice bath and allowed to stir at room temperature for 15 h. The reaction mixture was then filtered and washed with methanol and acetonitrile. The filtrate was dried on a rotary evaporator to yield 2-(dimethylamino)-N-(3-sulfamoyl phenyl)acetamide, which was submitted to the next step without further purification. MS (E) m/z CioHi 5

N

3 0 3 8: 258.0 (MH*). Scheme B 1002311 A flask was charged with dichloroquinozaline (1.0 g, 5.8 mmol), 10 iL of dimethylacetamide, 2-(dimetyhlamino)-N-(3-sulfamoylphenyl)acetamide (0.70 g, 2.7 mmol), and cesium carbonate (1.8 g, 5.5 mmol). The reaction mixture was stirred for 3 h at 239 140 "C and then filtered. The solvent was evaporated from the filtrate on a rotary evaporator to yield (N-(3-(N-(3-chloroquinoxalin-2-yl)sulfamoyl)phenyl) 2-(dimethylamino)acetamide) which was submitted to the next step without further purification. MS (El) m/z C 8 His 8 CNsO3S: 420.0 (MHE). General Amination Procedure la

NH

2

(R

2 e)1 5 H-N 0 28"HN O -~N H O ~ -- (RN)H N O coc;Mo- co;Y ~ I Microwave

H

0 irradiation N ~fb [00232] A CEM microwave reaction vessel was charged with N-(3-(N-(3 chloroquinoxalin-2-yl)sulfamoyl)phenyl)-2-(dimethylamino)acetamide (30 mg, 0.071 mmol), prepared using procedures similar to those described in Example 374, the desired aniline (16 mg, 0.14 mmol, 2 eq), and 0.5 mL of dimethylacetamide. The vessel was sealed and the reaction mixture was heated under microwave radiation for 70 min at 140 *C in a CEM Discover microwave instrument. The solvent was then removed by rotary evaporation. Purification of the final product was accomplished by preparatory reverse phase HPLC with the eluents 25 mM aqueous NH4OAc/ACN to the desired product. [002331 The following compounds were prepared according to the above General Amination Procedure la. Example 375: 2-(dimethylamino)-N-(3-(N-(3-(3-fluorophenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)acetamide. 'H-NMR (400MHz, CDC1 3 ): 9.40 ppm (s, 1H), 8.43 ppm (s, 1H), 8.22 ppm (s, 111), 8.07-8.02 ppm (d, 1H), 7.97-7.93 ppm (d, 1H), 7.76-7.71 (m, 2H), 7.53-7.48 ppm (t, 1H), 7.45-7.36 ppm (m, 411), 7.35-7.28 ppm (m, 2H), 6.84-6.77 ppm (t, 1H), 3.10 ppm (s, 2H), 2.38 ppm (s, 611); MS (EI) m/z C 2 4H 2 3

FN

6 0 3 S: 495 (MH). Example 376: 2-(dimethylamino)-N-(3-(N-(3-(4-fluorophenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C24H 2 3

FN

6 03S: 495 (MH). Example 377: N-(3-(N-(3-(4-chloro-phenylamino)quinoxalin-2-yl)sufamoyl)phenyl)-2 (dimethylamino)acetamide. MS (EI) m/z C 2 4H 2 3

CN

6 03S: 511 (MHA). 240 General Amination Procedure lb I NH 2 (R2e).

5 N 0* HN O -(R HNI O N CI :INHcog IDMA N N

H

0 ~irradiation N r 1002341 A CEM microwave reaction vessel was charged with N-(3-(N-(3 chloroquinoxalin-2-yl)sulfamoyl)phenyl)-2-(dimethylamino)acetamide (62 mg, 0.147 mmol), prepared using procedures similar to those in Example 374, the desired aniline (0.567 mmol, 4 eq), and 1.0 mL of toluene. The vessel was sealed and the reaction mixture was heated under microwave radiation for 60 min at 180 *C in a CEM Discover microwave instrument. The solvent was removed on a rotary-evaporator. Purification of the final product was done by preparatory HPLC with NH 4 0Ac/ACN as eluent to yield the desired product. [00235] The following compounds were prepared according to the above General Amination Procedure 1b. Example 378N-(3-(N-(3-(3-chloro-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2 (dimethylamino)acetamide. MS (ElI) m/z C 24

H

23 C1N 6 0 3 S: 511 (MH*). Example 379: 2-(dimethylamino)-N-(3-(N-(3-(4-fluoro-3 methoxyphenylamino)quinoxalin-2-y)sulfamoyl)phenyl)acetamide. 2 (dimethylamino)-N-(3-(N-(3-(4-fluoro-3-methoxyphenylamino)quinoxalin-2 yl)sulfamoyl)phenyl). 'H-NMR (400MHz, CDCl 3 ): 8 9.47 (s, 1H), 8.36 (s, 1H), 8.29 (s, 1H), 7.91-7.87 (d, 1H), 7.80-7.73 (in, 2H), 7.66-7.63 (d, 1H), 7.53-7.47 (t, 1H), 7.43-7.30 (m, 4H), 7.10-7.04 (t, 1H), 6.55-5.95 (br s, 1H), 3.96 (s, 3H), 3.12 (s, 2H), 2.39 (s, 6H), 2.08 (s,3H(AcOH); MS (EI) m/z C 25

H

25

FN

6 0 4 S: 525 (MH*). Example 380 N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4-isopropoxybenzenesulfonamide N CI H2N N O H2N N N N C[ K2C3 NNlH DMA IJ DMA 126 *C 125 C 241 [002361 N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4-isopropoxy benzenesulfonamide. A solution of 2,3-dichloroquinoxaline (2.0 mL, 0.38 M) was combined with K 2 C0 3 (105 mg, 0.76 inmol) in a glass vial. A solution of 4-isopropoxybenzene sulfonamide (1.75 mL, 0.43 M) was added and the solution was stirred overnight at 125 *C. After cooling, acetic acid (45 mL, 0.79 mmol) and 3,5-dimethoxyaniline (230 mg, 1.5 mmol) were added. The reaction mixture was stir-red again at 125 *C overnight. Upon cooling, the reaction mixture was diluted with 8 mL of methanol and then 8 mL of water. The precipitate was collected by filtration and recrystallized from NN-dimethylacetamide/water to give N-(3-(3,5-dimethoxy phenylamino)quinoxalin-2-yl)-4-isopropoxy-benzenesulfonamide (45 mg, 12%). IH-NMR (400MHz, d 6 -DMSO): 12.16 (bs, IH), 8.93 (s, 1H1), 8.03 (d, 2H), 7.92 (bs, IH), 7.56 (d, 1H), 7.36 (m, 4H), 7.07 (d, 2H), 6.24 (s, I1H), 4.72 (m, IH), 3.76 (s, 6H), 1.27 (d, 6H); MS (El) m/z C25H12N40sS: 495 (MIf). [01871 Examples 381-411 were synthesized proceeding as above in Example 423. In the cases where the product did not precipitate, the mixture was purified by reverse phase HPLC. Example 381: 3-chloro-N-(3-(3,5-dimethoxy-phenylamino)quinoxain-2-yl)-4 methylbenzenesulfonamide. 'H-NMR (400MT*z, d 6 -DMSO): 12.31 (bs, 1H), 8.96 (s, 1H), 8.18 (s, 1H), 7.98 (d, 1H), 7.92 (bs, 1H1), 7.58 (d, 2H), 7.43-7.33 (m, 4H), 6.24 (t, 111), 3.76 (s, 6H), 2.39 (s, 3H); MS (EI) m/z C 23

H

21 C1N 4 0 4 S: 485 (M1). Example 382: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)naphthalene-1 sulfonamaide. MS (El) m/z C 26

H

22

N

4 0 4 S: 487 (MH*). Example 383: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4 fluorobenzenesulfonamide. MS (EI) m/z C 22

H

19

FN

4 0 4 S: 455 (MH*). Example 384: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-3 fluorobenzenesulfonamide. MS (EI) m/z C 22 H1FN 4 0 4 8: 455 (MH*), Example 385: N-(3-(3,5-dimethoxy-phenylamino)quinoxali-2-yl)-3 (trifluoromethyl)benzenesulfonamide. MS (EI) m/z C 23 HwqF3N 4 04S: 505 (MH*). Example 386: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4 (trifluoromethyl)benzenesulfonamide. MS (EI) m/z C 2 3

H

1 9

F

3

N

4 0 4 S: 505 (MH). Example 387: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4 (trifluoromethoxy)benzenesulfonamide. MS (EI) m/z C 2 3 Ht 9

F

3

N

4 0sS: 521 (MH*). 242 Example 388: N-( 4 -(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C 24

H

23

N

5 0 5 S: 494 (MH). Example 389: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4-fluoro-2 methylbenzenesulfonamide. MS (EI) m/z C 2 3

H

2 1

FN

4 0 4 S: 469 (MW'). Example 390: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-2 methylbenzenesulfonamide. MS (EI) m/z C 23

H

22

N

4 0 4 S: 451 (MH*). Example 391: 2-chloro-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)benzenesulfonamide. MS (El) m/z C 2 2

H

1 9 C1N 4 0 4 S: 471 (MH). Example 392: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-3,5 difluorobenzenesulfonamide. MS (EI) m/z C 2 2 Hi 8

F

2

N

4 0 4 S: 473 (MH). Example 393: 3,5-dichloro-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 y])benzenesulfonamide. MS (EI) M/z C 22

H

8

C

2

N

4 0 4 S: 505 (Mi). Example 394: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-3-fluoro-4 methylbenzenesulfonamide. MS (EI) m/z C 23

H

2 1

FN

4 0 4 S: 469 (MH'). Example 395: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-2 (trifluoromethyl)benzenesulfonamide. MS (EI) m/z C 23

H

19

F

3

N

4 0 4 S: 505 (MH). Example 396: 4-cyano-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 y])benzenesulfonamide. MS (EI) m/z C 23 Hi 9

N

5 0 4 S: 462 (MH). Example 397: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-1 phenylmethanesulfonamide. MS (EI) m/z C 23

H

22

N

4 0 4 S: 451 (MH). Example 398: 4,5-dichloro-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)thiophene-2-sulfonamide. MS (EI) m/z C 20 Hi 6 Cl 2

N

4 0 4

S

2 : 511 (MH*). Example 399: 1-(3-chlorophenyl)-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)methanesulfonamide. MS (EI) m/z C 23

H

21

CIN

4 0 4 S: 485 (MH*). Example 400: N-(3-(3,5-dimethoxy-phenylamino)quinoxain-2-y)-2,5 dimethylthiophene-3-sulfonamide. MS (EI) m/z C 22

H

2 2

N

4 0 4 8 2 : 471 (MH). Example 401; N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-y)-3,5 bis(trifluoromethyl)benzenesulfonamide. MS (El) m/z C 2 4 Hi 8

F

6

N

4 0 4 S: 573 (MH'). Example 402: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4-fluoro-3 (trifluoromethyl)benzenesulfonamide. MS (EI) m/z C 23 Hi 8 F4N 4 0 4 S: 523 (MH*). Example 403: 5-chloro-N-(3-(3,5-dimethoxy-phenylamino)quinoxain-2-yl)-1,3 dimethyl-1H-pyrazole-4-sulfonamide. MS (EI) m/z C 2 1H 21 C1N 6 04S: 489 (MH*). Example 404: 5-chloro-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-2 methoxybenzenesulfonamide. MS (EI) m/z C 23

H

2 1 C1N 4 0sS: 501 (Mi'). 243 Example 405: 5-bromo-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-2 methoxybenzenesulfonamide. MS (EI) M/z C 23

H

2 1BrN 4 0 5 S: 545 (MH). Example 406: 2,5-dichloro-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)thiophene-3-sulfonamide. MS (El) m/z C 2 0i1 1 6

C

2

N

4 0 4

S

2 : 511 (MH*). Example 407: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-3,5 dimethylisoxazole-4-sulfonamide. MS (EI) m/z C 21

H

21

N

5 0 5 S: 456 (MH*). Example 408: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-2,5 dimethoxybenzenesulfonamide. MS (EI) m/z C 24

H

24

N

4 0 6 S: 497 (MH*). Example 409: 3-chloro-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4 fluorobenzenesulfonamide. MS (EI) m/z C 22 HisC1FN 4 0 4 S: 489 (MH'). Example 410: 4-(difluoromethoxy)-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)benzenesulfonamide MS (EI) m/z C 23

H

20

F

2

N

4 0 5 S: 503 (MH'). Example 411: N-(3-(3,5-dimethoxy-phenylamino)quinoxain-2-yl)-3 (methylsulfonyl)benzenesulfonamide. MS (E) M/z C 23

H

22

N

4 0 6

S

2 : 515 (MH*'). General Acylation Procedure 2 - 0 o I oil N NH CI R NN O N NH DIPEA N NH DCE MeO OMe MeO OMe [00237] N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl) sulfamoyl)phenyl)azetidine-3-carboxamide (125 mg, 0.23 mmol), prepared using procedures similar to those described in Example 372, was dissolved into 5 mL DCE in a 10 mL round-bottom flask. DIEA (1.17 mmol, 5.0 equiv.) was then added with stirring followed by acid chloride (0.47 mmol, 2.0 equiv.). The reaction was then stirred at room temperature for 1 hour or until complete as indicated by LCMS. The solvent was subsequently removed under reduced pressure on a rotary evaporator. The crude material was then redissolved in methanol. Purification of the final product was accomplished by preparatory reverse-phase HPLC with the eluents 25 mM aqueous NH 4 0Ac/CAN. A Waters Fractionlynx preparative reverse-phase HPLC; equipped with a Waters SunFire Prep C18, OCD 5 pM, 30 X 70 mm column and running a 5-100 % gradient with a binary 244 solvent system of 25 mM ammonium acetate in water/acetonitrile; was used to carry out the purification. [00238] The following compounds were prepared according to General Acylation Procedure 2. Example 412: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-1-propionylazetidine-3-carboxamide. 'H-NMR (400MHz, d 6 DMSO): 12.40 (s, 1H), 10,45 (s, 1H), 8.88 (s, 1H), 8.40 (s, 1H), 7.93 (s, 1H), 7.82 (d, 1H), 7.77 (d, 1H), 7.60-7.45 (m, 2H), 7.41-7.30 (m, 411), 6.24 (s, 1H), 4.26 (t, 1H), 4.22-4.17 (m, 1H), 3.99 (t, 1H), 3.95-3.89 (m, 1H), 3.76 (s, 611), 3.59-3.45 (m, 111), 2.05 (dd, 211), 0.95 (t, 3H); MS (El) M/z C 29

H

3 0

N

6 0 6 S: 591 (M ). Example 413: 1-acetyl-N-(3-{[(3-{[3,5-bis(methoxy)-phenyl]amino}quinoxalin-2 yl)amino]sulfonyl}phenyl)azetidine-3-carboxamide. MS (EI) m/z C 28

H

28

N

6 0 6 S: 577

(MH*).

Example 414: 1-(cyclopropanecarbonyl)-N-(3-(N-(3-(3,5-dimethoxy phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)azetidine-3-carboxamide. MS (BI) m/z

C

30

H

30

N

6 0 6 S: 603 (MH). General Reductive Amination Procedure I 0a0 0 N 0 0 =S N O S N NH NH O'R NH NR Tetramethyl ammonia triacetoxyborohydride MeO OMe DCM/DMF MeO OMe [00239] To a solution of N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)azetidine-3-carboxamide (110 mg, 0.19 mmol), prepared using procedures similar to those described in Example 372, in 3 mL of DCE and 200 gL of DMF, aldehyde (0.77 mmol, 4.0 eq.)was added slowly followed by tetramethylammonium triacetoxyborohydride (1.16 mmol, 6.0 eq). The reaction was stirred at room temperature overnight. LC/MS indicated the reaction was completed. The solvent was subsequently removed under reduced pressure on a rotary evaporator. The crude material was then redissolved in methanol. Purification of the final product was accomplished by preparatory reverse-phase HPLC with the eluents 25 mM aqueous NH40Ac/CAN. A Waters Fractionlynx preparative reverse-phase HPLC; equipped with a Waters SunFire Prep C18, 245 OCD 5 gM, 30 X 70 mm column and running a 5-100 % gradient with a binary solvent system of 25 mM ammonium acetate in water/acetonitrile; was used to carry out the purification. [002401 The following title compounds were prepared according to General Reductive Amination Procedure 1. Example 415: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-1-ethylazetidine-3-carboxamide. 'H-NMR (400MHz, d 6 -DMSO): 10.29 (s, 1H), 8.82 (s, 1H), 8.25 (t, 111), 7.75-7.68 (m, 2H), 7.43-7.38 (m, 1H), 7.375-7.340 (m, 111), 7.338-7.310 (d, 2H), 7.305-7.262 (m, 1H), 7.15-7.08 (m, 2H), 6.56 (s, 1H), 6.15 (t, 1H), 4.15-4.08 (m, 2H), 4.06-3.95 (m, 2H), 3.78 (s, 6H), 3.65-3.56 (m, 1H), 3.12-3.04 (m, 2H), 1.03 (t, 3H); MS (EI) m/z C 28

H

30

N

6 0 5 S: 563 (MHf). Example 416: 1-(cyclopropylmethyl)-N-(3-(N-(3-(3,5-dimethoxy phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)azetidine-3-carboxamide. MS (EI) m/z

C

30

H

32

N

6 OsS: 589 (MH). Example 417: 1-benzyl-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxain-2 yl)sulfamoyl)phenyl)azetidine-3-carboxamide. MS (EI) m/z C 33

H

32

N

6 0 5 S: 625 (MH. Example 418: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)phenyl)-1-(furan-2-ylmethyl)azetidine-3-carboxamide. MS (EI) m/z

C

31 H30N 6

O

6 S: 615 (MWH). Example 419: 1-((1H-imidazol-5-yl)methyl)-N-(3-(N-(3-(3,5-dimethoxy phenylamino)quinoxalin-2-y)sulfamoyl)phenyl)azetidine3-carboxamide. MS (El) m/z

C

3 oH 3 oN8O 5 S: 615 (MH*). General Amide Formation Procedure la O I go-pCI N NH NHR'R", HATU, DIEA N NH 0 O o o DMA N OH N N" NR'R" H H 4 [002411 Into a small 1 dram vial was added 3-(N-(3-(2-chloro-5-methoxy-phenylamino) quinoxalin-2-yl)sulfamoyl)benzoic acid (61 mg, 0.13 mmol, 1.1 equiv), prepared using procedures described for Example 100. The acid was dissolved in DMA (1 mL) and DIEA (42 pL, 0.24 mmol, 2 equiv) was added then added to the solution. The amine reagent (1 246 mL of 0.12 M solution in DMA) was added to solution with stirring followed by HATU (64 mg, 0.17 mMol, 1.4 equiv). The reaction was stirred overnight at room temperature. Upon completion as indicated by LCMS analysis, 2 mL of methanol was added to the solution. Preparative reverse-phase HPLC was used to isolate the desired product. A Waters Fractionlynx preparative reverse-phase HPLC - equipped with a Waters SunFire Prep C18, OCD 5 pM, 30 X 70 mm column and running a 5-100 % gradient with a binary solvent system of 25 mM ammonium acetate in water/acetonitrile - was used to carry out the purification. [00242] The following compounds were prepared according to General Amide Formation Procedure 1. Example 420: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl) N-(3-(dimethylamino)propyl)benzamide. 3-(N-(3-(2-chloro-5 methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-N-(3-(dimethylamino)propyl)benzamide: 'H NMR (400 MHz, d 6 -DMSO): 9.44 (s, 1H), 8.94 (s, 1H4), 8.79 (t, 1H), 8.54 (s, 1H), 8.24 (d, 1H), 7.87 (d, 1H), 7.48 (m, 3H), 7.33 (d, IH), 7.18 (m, 2H), 6.60 (dd, 1H), 3.82 (1H), 3.04 (m, 3H), 2.51 (m, 5H), 1.91 (s, IH), 1.86 (m, 3H); MS (EI) m/z for C 2 7

H

29

CIN

6

O

4 S: 569 (M H. Example 421: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl) N-(1-methylazetidin-3-yl)benzamide. 3-(N-(3-(2-chloro-5 methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-N-(-methylazetidin-3-yl)benzamide: 'H NMR (400 MHz, d 6 -DMSO): 9.43 (s, 1H), 9.23 (d, IH), 8.94 (d, 1H), 8.58 (s, 1H), 8.29 (d, 1H), 7.89 (d, 1H), 7.56 (t, 1H), 7.47 (d, 1H), 7.44 (d, 1H), 7.33 (d, 1H), 7.18 (m, 21), 6.60 (dd, 1H4), 4.81 (m, 1H), 4.33 (m, 211), 4.19 (m, 2H), 3.82 (s, 1H), 2.51 (s, 3H); MS (El) m/z for C 26

H

2 sC1N 6 0 4 S: 553 (MH*). Example 422: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoy) N-(pyridin-4-ylmethyl)benzamide. MS (EI) m/z C 28 1 2 3 C1N 6 0 4 S: 575 (NH*). Example 423: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoy) N-(3-(dimethylamino)propyl)benzamide. MS (EI) m/z C 28 11 26 C1N 7 0 4 S: 592 (MH). Example 424: N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)-3-(2,2 dimethylhydrazinecarbonyl)benzenesulfonamide. MS (EI) m/z C 2 41 23 C1N 6 0 4 S: 527 (MH). Example 425: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoy) N-(2-methoxyethyl)benzamide. MS (El) m/z C 2 sH 24 C1N 5 0 5 S: 542 (MH). 247 Example 426: N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)-3-(4 methylpiperazine-1-carbonyl)benzenesulfonamide. MS (EI) m/z C 27

H

27 C1N 6 0 4 S: 567 (MIW). Example 427: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxain-2-yl)sulfamoyl) N-(2-(pyrrolidin-1-yl)ethyl)benzamide. MS (EI) m/z C 2 8

H

29 C1N 6 0 4 S: 581 (MH'). Example 428: 3 -(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl) N-(2-(pyridin-4-yl)ethyl)benzamide. MS (EI) m/z C 2 9H 2 5C1N 6

O

4 S: 589 (MH*). Example 429: N-(2-(1H-imidazol-4-yl)ethyl)-3-(N-(3-(2-chloro-5 methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)benzamide. MS (EI) m/z

C

27

H

24 C1N 7 0 4 S: 578 (M+. Example 430: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl) N-(piperidin-1-yl)benzamide. MS (El) m/z C 2 7

H

27 C1N 6 0 4 S: 567 (MH*). Example 431: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl) N-(2-hydroxyethyl)benzamide. MS (El) m/z C 2 4H 22 C1N 5 0 5 S: 528 (MH*). Example 432: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl) N-(3-ethoxypropyl)benzamide. MS (EI) m/z C 27

H

28 ClN 5 0 5 S: 570 (MH. Example 433: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl) N-(3-(pyrrolidin-1-yl)propyl)benzamide. MS (EI) m/z C 29

H

31 C1N 6 0 4 S: 595 (MH'). Example 434: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxain-2-yl)sulfamoyl) N-(3-(diethylamino)propyl)benzamide. MS (EI) m/z C 2 9

H

3 3 C1N 6 0 4 S: 597 (MH*). Example 435: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxain-2-yl)sulfamoyl) N-(3-(2-oxopyrrolidin-1-yl)propyl)benzamide. MS (EI) m/z C 29

H

2 9

CN

6 0 5 S: 609 (MW). Example 436: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoy) N-(pyridin-2-ylmethyl)benzamide. MS (EI) m/z C 28

H

23 C1N 6 0 4 S: 575 (MH*). Example 437: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxain-2-yl)sulfamoyl) N-(2-cyanoethyl)-N-methylbenzamide MS (EI) m/z C 2 6

H

23

CN

6 04S: 551 (MH). Example 438: 3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl) N-(2-cyanoethyl)-N-ethylbenzamide. MS (EI) m/z C 27

H

2 sClN 6 04S: 565 (MH. Example 439: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl) N-(2-(ethylthio)ethyl)benzamide. MS (EI) m/z C 26

H

26 C1N 5 0 4

S

2 : 572 (MH). Example 440: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl) N-(3-propoxypropyl)benzamide. MS (EI) m/z C 2 8H 3 0C1N 5 0sS: 584 (MH*). Example 441: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl) N-(5-(diethylamino)pentan-2-yl)benzamide. MS (EI) I/z C31H 3 7 C1N60 4 S: 625 (MH). 248 Example 442: 3

-(N-(

3 -(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl) N-(3-methoxypropyl)benzamide. MS (EI) m/z C 2 6

H

26 C1N 5 0 5 S: 556 (MH~). Example 443: 3 -(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl) N-(3-morpholinopropyl)benzamide MS (E) m/z C 2 9

H

31 C1N 6 0 5 S: 611 (MH*). Example 444: 3 -(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl) N-(pyridin-3-ylmethyl)benzamide MS (EI) m/z C 2 8

H

2 3

CJN

6 0 4 S: 575 (MH*). Example 445: 3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl) N-(2-cyanoethyl)benzamide. MS (EL) m/z C 25

H

21

CN

6 0 4 8: 537 (MH). Example 446: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl) N-(1-methoxypropan-2-yl)benzamide. MS (E) mi/z C 26

H

2 6 C1N 5 0 5 S: 556 (MH*). Example 447: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl) N-(2-(methylthio)ethyl)benzamide. MS (EI) m/z C 25

H

24 C1N 5 0 4

S

2 : 558 (MH'). Example 448: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-y)sulfamoyl) N-(3-(dimethylamino)propyl)-N-methylbenzamide. MS (EI) m/z C 28

H

31

CIN

6 0 4 S: 583 (MH*). Example 449: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)snfamoyl) N-(3-isopropoxypropyl)benzamide. MS (EI) m/z C 2 8

H

3 0 ClN 5 0 5 S: 584 (MW). Example 450: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl) N-(2-(dimethylamino)ethyl)-N-ethylbenzamide. MS (El) m/z C 2 sH 31 ClN 6 0 4 8: 583 (MW). Example 451: N-(3-butoxypropyl)-3-(N-(3-(2-chloro-5-methoxy phenylamino)quinoxalin-2-yl)sulfamoyl)benzamide. MS (EI) m/z C 29

H

32 C1N 5 0 5 S: 598 (MH*). Example 452: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxain-2-yl)sulfamoyl) N-(2-(diethylamino)ethyl)benzamide. MS (EI) m/z C 28

H

31 C1N 6 0 4 S: 583 (ME'). Example 453: methyl 3-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)benzamido)propanoate. MS (EI) m/z C 26 H24C1N50 6 S: 570 (MH). Example 454: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxain-2-yl)snlfamoyl) N-methyl-N-propylbenzamide. MS (EI) m/z C26H 26 C1NsO 4 S: 540 (MH). Example 455: ethyl 3-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2 yl)sulfamoyl)benzamido)propanoate. MS (EI) m/z C 27

H

26 C1N 5 0 6 S: 584 (MH). Example 456: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-y)sulfamoyl) N-(2-(piperidin-1-yl)ethyl)benzamide. MS (EI) m/z C 29

H

31 C1N 6 0 4 S: 595 (MI). 249 Example 457: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl) N-((1-ethylpyrrolidin-2-yl)methyl)benzamide. MS (EI) m/z C 29

H

31 ClN 6 0 4 S: 595 (MH*). Example 458: N-(2-(bis(2-hydroxyethyl)amino)ethyl)-3-(N-(3-(2-chloro-5 methoxyphenylamino)quinoxain-2-yl)sulfamoyl)benzamide. MS (EI) m/z

C

28

H

31

CN

6 0 6 S: 615 (MH*). Example 459: N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)-3-(3 (diethylamino)pyrrolidine-l-carbonyl)benzenesulfonamide. MS (EI) m/z

C

30

H

33 C1N 6 0 4 S: 609 (MH). Example 460: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl) N-methyl-N-(1-methylpyrrolidin-3-yl)benzamide. MS (EI) m/z C 28 11 29

CIN

6 0 4 S: 581 Example 461: N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)-3-(3 (dimethylamino)pyrrolidine-l-carbonyl)benzenesulfonamide. MS (EI) m/z

C

28

H

29

CIN

6 0 4 S: 581 (MH*). Example 462: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl) N-(2-methyl-l-morpholinopropan-2-yl)benzamide. MS (EI) m/z C 30

H

33

CN

6 0 5 S: 625 (MH*I). Example 463: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl) N-(1H-pyrrol-1-y)benzamide. MS (El) m/z C 2 6

H

2 1 ClNsO 4 S: 549 (MH+' Example 464: 3-(N-(3-(2-chloro-5-methoxy-phenylaino)quinoxalin-2-yl)sulfamoy) N-(3-oxopyrazolidin-4-yl)benzamide. MS (El) m/z C 25

H

22 C1N 7 0 5 S: 568 (MH). Example 465: N-(3-(2-chloro-5-methoxy-phenylamino)quinoxain-2-yl)-3-(2 ((dimethylamino)methyl)piperidine-1-carbonyl)benzenesulfonamide. MS (EI) m/z

C

30

H

33 ClN 6 0 4 S: 609 (MH). Example 466: N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)-3-(2 (piperidin-1-ylmethyl)piperidine-l-carbonyl)benzenesulfonamide. MS (EI) m/z

C

33

H

37 C1N 6 0 4 S: 649 (MHE). Example 467: 3-(N-(3-(2-chloro-5-methoxy-pheinylamino)quinoxalin-2-yl)sulfamoyl) N-(l-ethylpiperidin-3-yl)benzamide MS (El) m/z C 29 H3CIN 6

O

4 S: 595 (MH). General Amide Formation Procedure lb [002431 The procedure outlined in General Amide Formation Procedure la was used to incorporate a number of amines that contained a second amine group protected as the tert-butylcarbamate (i.e. where R', within NHR'R", contained a Boc-protected amine 250 group). The deprotection was carried out after HPLC purification of the Boc-protected precursor. [002441 Into a small 1 dram vial was added 3-(N-(3-(2-chloro-5-methoxy phenylamino)quinoxalin-2-yl)sulfamoyl)benzoic acid (61 mg, 0.13 mmol, 1.1 equiv). The acid was dissolved in I mL of DMA and DIEA (42 pL, 0.24 mmol, 2 equiv) was added then added to the solution. The mono-Boc-protected diamine reagent (1 mL of 0.12 M solution in DMA, 1 equiv) was added to solution with stirring followed by HATU (64 mg, 0.17 mmol, 1.4 equiv). The reaction was stirred overnight at room temperature. Upon completion as indicated by LCMS analysis, 2 mL of methanol was added to the solution. Preparative reverse-phase HPLC was used to isolate the desired product directly from this crude reaction solution. A Waters Fractionlynx preparative reverse-phase HPLC; equipped with a Waters SunFire Prep C18, OCD 5 pM, 30 X 70 mm column and running a 5-100 % gradient with a binary solvent system of 25 mM ammonium acetate in water/acetonitrile; was used to carry out the purification. The product fractions were combined and concentrated to dryness under reduced pressure by rotary evaporation. A solution of 4 N HC1 in dioxane (2 mL) was added, The solution was then stirred at room temperature until no starting material was detected. The deprotected product precipitated out of solution as an HCL salt and was collected by filtration, washed with ether and dried under vacuum. 100245 The following compounds were prepared according to the above General Amide Formation Procedure 1b. Example 468: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sufamoyl) N-(piperidin-3-yl)benzamide. 3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2 yl)sulfamoyl)-N-(piperidin-3-yl)benzamide: 'H NMR (400 Mz, d 6 -DMSO): 12.82 (s, 1H), 9.12 (s, 1H), 9.04 (s, 11), 8.85 (d, 111), 8.65 (s, H), 8.55 (s, 1H), 8.18 (m1, 1H), 7.98 (s, 111), 7.69 (in, 2H), 7.43 (in, 2H), 6.69 (dd, 1H), 4.21 (s, 1H), 3.83 (s, 311), 3.69 (m, 111), 3.48 (m, 1H), 3.18 (s, 1H), 2.84 (q, 2H), 1.91 (s, 211); MS (EI) m/z for C 2 7

H

2 7 C1N 6 0 4 S: 567 Example 469: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl) N-(piperidin-2-ylmethyl)benzamide. 3-(N-(3-(2-chloro-5 methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-N-(piperidin-2-ylmethyl)benzamide: NMR (400 MHz, d6-DMSO): 12.78 (s, 1H), 9.16 (s, 1H), 9.09 (s, 111), 8.79 (s, 1H), 8.59 (d, 2H), 8.22 (t, 2H), 7.99 (s, 1H), 7.74 (t, 111), 7.66 (s, 1H), 7.42 (m, 2H), 6.69 (dd, 1H), 3.82 251 (s, 3H), 3.69 (dd, 1H), 3.57 (m, 1H), 3.50 (m, 3H), 3.22 (s, 2H), 2.82 (d, 1H), 1.68 (m, 5H); MS (EI) M/z for C 2 8H 2 9ClN 6

O

4 S: 581 (MH+. Example 470: 3-(3-aminopyrrolidine-1-carbonyl)-N-(3-(2-chloro-5-methoxy phenylamino)quinoxalin-2-yl)benzenesulfonamide. MS (EI) m/z C 2 6

H

25 ClN 6 0 4 S: 553 (MH). Example 471: 3-(3-aminoazetidine-1-carbonyl)-N-(3-(2-chloro-5-methoxy phenylamino)quinoxalin-2-yl)benzenesulfonamide. MS (El) m/z C 2 5

H

2 3 C1N 6 0 4 S: 539 (MH'). Example 472: 3-(3-aminopiperidine-1-carbonyl)-N-(3-(2-chloro-5-methoxy phenylamino)quinoxalin-2-yl)benzenesulfonamide. MS (EI) m/z C 27

H

2 7 C1N 6 0 4 S: 567 (MH*). Example 473: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl) N-(pyrrolidin-3-yl)benzamide. MS (EI) m/z C 2 6

H

2 5 C1N 6 0 4 S: 553 (MH*). Example 474: N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-y)-3-(3 (methylamino)pyrrolidine-1-carbonyl)benzenesulfonamide. MS (EI) m/z C27H 2 7ClN6O 4 S: 567 (MH). Example 475: N-(2-aminoethyl)-3-(N-(3-(2-chloro-5-methoxy phenylamino)quinoxalin-2-y)sulfamoyl)benzamide. MS (El) m/z C 2 4

H

23 C1N 6 0 4 S: 527 Example 476: 3-(4-amino-3-oxopyrazolidine-1-carbonyl)-N-(3-(2-chloro-5 methoxyphenylamino)quinoxalin-2-yl)benzenesufonamide. MS (EI) m/z

C

25

H

22 C1N 7 0 5 S: 568 (MH*). Example 477 3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl) N-((1-methylpiperidin-2-yl)methyl)benzamide [002461 3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxain-2-yl)sulfamoyl)-N (piperidin-2-ylmethyl)benzainide (299 mg, 0.51 mmol, I equiv), prepared using procedures similar to those described for Example 514, was dissolved in 2.3 mL of DMA. Formic acid (388 pLL, 10.28 mmol, 20 equiv) was added to solution with stirring followed by the addition of formaldehyde (508 jiL of 37% aq. solution). The reaction was then stirred at room temperature overnight. Analysis of an aliquot of the reaction mixture by LCMS indicated the complete consumption of starting material. The reaction was diluted with methanol (2 mL). Preparative reverse-phase HPLC was used to isolate the desired product 252 directly from the crude reaction mixture. A Waters Fractionlynx preparative reverse-phase HPLC; equipped with a Waters SunFire Prep C18, OCD 5 pM, 30 X 70 mm column and running a 5-100 % gradient with a binary solvent system of 25 mM ammonium acetate in water/acetonitrile; was used to carry out the purification.'H NMR (400 MHz, d 6 -DMSO): 9.44 (s, 1H), 8.94 (s, IH), 8.79 (t, 111), 8.57 (s, 111), 8.27 (d, 1H), 7.90 (d, 1H) 7.54 (t, 11), 7.46 (d, I), 7.39 (d, 111), 7.33 (d, 111), 7.18 (m, 2H), 6.60 (dd, 1H), 3.82 (s, 3H), 3.59 (m, 211), 3.00 (s, 111), 2.90 (s, 311), 1.62 (m, 711); MS (EI) m/z for C 2 9H 3 C1N 6 04S: 595 (MH). Example 478 3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl) N-(1-methylpiperidin-3-y)benzamide [00247] The title compound was prepared using similar procedures to those used in Example 522. 'H NMR (400 MHz, d 6 -DMSO): 9.43 (s, 1H), 8.93 (s, 1H), 8.59 (s, 111), 8.24 (d, 1H), 7.87 (d, 111), 7.47 (m, 2H), 7.40 (d, 11), 7.33 (d, IH), 7.19 (m, 2H), 6.60 (dd, 1H), 4.21 (s, 1H), 3.82 (s, 1H), 2.76 (s, 1H), 2.50 (m, 711), 1.91 (m, 211), 1.63 (m, 2H); MS (EI) m/z for C 2 aH 2 ClN 6 0 4 S: 581 (MR). Biological Examples Biological Example 1 PI3Kalpha Luciferase-Coupled Chemiluminescence Assay Protocol [002481 PI3Ka activity is measured as the percent of ATP consumed following the kinase reaction using luciferase-luciferin-coupled chemiluminescence. Reactions were conducted in 384-well white, medium binding microtiter plates (Greiner). Kinase reactions were initiated by combining test compounds, ATP, substrate (PIP2), and kinase in a 20 pL volume in a buffer solution. The standard PI3Kalpha assay buffer is composed 50 mM Tris, pH 7.5, 1 mM EGTA, 10 mM MgCl 2 , I mM DTT and 0.03% CHAPS. The standard assay concentrations for enzyme, ATP, and substrate are 0.5-1.1 nM, 1tM, and 7.5 RM, respectively. The reaction mixture was incubated at ambient temperature for approximately 2 h. Following the kinase reaction, a 10 pL aliquot of luciferase-luciferin mix (Promega Kinase-Glo) was added and the chemiluminescence signal measured using a Victor2 plate reader (Perkin Elmer). Total ATP consumption was limited to 40-60% and IC50 values of control compounds correlate well with literature references. [002491 Certain compounds of the invention demonstrated the ability to bind to P13K when tested in this assay. The following embodiments are directed to the compounds themselves as well as their use in a method of treating. For example, in one embodiment of 253 the invention, the P13K inhibitor is selected from the compounds in Table 1 having a P13K binding affinity of about 8 pM or less. In another embodiment, the P13K inhibitor is selected from the compounds in Table 1 having a P13K-binding affinity of about 4 VM or less. In another embodiment, the P13K inhibitor is selected from the compounds in Table 1 having a P13K-binding affinity of about 3 [M or less. In another embodiment, the P13K inhibitor is selected from the compounds in Table 1 having a PI3K-binding affinity of about 2 pM or less. In another embodiment, the P13K inhibitor is selected from the compounds in Table 1 having a P13K-binding affinity of about 1.5 PM or less. In another embodiment, the P13K inhibitor is selected from the compounds in Table 1 having a P13K-binding affinity of about I pM or less. In another embodiment, the PI3K inhibitor is selected from the compounds in Table 1 having a P13K-binding affinity of about 0.750 JIM or less. In another embodiment, the P13K inhibitor is selected from the compounds in Table I having a P13K-binding affinity of about 0.5 [tM or less. In another embodiment, the P13K inhibitor is selected from the compounds in Table 1 having a P13K-binding affinity of about 0.3 pAM or less. In another embodiment, the P13K inhibitor is selected from the compounds in Table I having a P13K-binding affinity of about 0.2 1 M or less. In another embodiment, the P13K inhibitor is selected from the compounds in Table I having a P13K-binding affinity of about 0.1 pM or less. In another embodiment, the P13K inhibitor is selected from the compounds in Table 1 having a P13K-binding affinity of about 0.075 pM or less. In another embodiment, the PI3K inhibitor is selected from the compounds in Table 1 having a PI3K-binding affinity of about 0.050 pM or less. Biological Example 2 Phospho AKT assay [00250] PC3 cells were seeded on 6-well plates at 150,000 cells/well. Cells were cultured for 3 days, then treated with compounds in serum-free medium for 3 hr. EGF (100 ng/ml) was added for the last 10 min. Cells were lysed in TENN buffer. Phospho T308 Akt and total Akt were quantfied by ELISA performed according to the Biosource assay protocol. The readings of phospho Akt were normalized to total Akt readings. Biological Example 3 Phospho S6 assay [00251] PC3 cells were seeded on 96-well plates at 8,000 cells/well. For each experiment, cells were seeded and treated in duplicated plates: one plate for phospho S6 CellELISA, and one plate for total S6 CeIIELISA. Cells were cultured on the plates for 3 254 days, then treated with compounds in serum-free medium for 3 hr in triplicate. Cells were fixed with 4% formaldehyde, quenched with 0.6% H202, blocked with 5% BSA, incubated with either phospho S6 antibody or total S6 antibody overnight, incubated with goat-anti rabbit-IgG-IRP for 1 hr, and developed in chemiluminescent substrate. Biological Example 4

PIP

3 assay 100252 MCF-7 cells grown in 10-cm dishes were starved for 3 hours in DMEM, and then treated with compounds for 20 minutes. In the last 2 minutes of the incubation with the compounds, EGF (100 ng/ml) was added to stimulate the production of PIP3. The medium was aspirated and the cells were scraped with 10% trichloroacetic acid. The lipids were extracted from the pellet after the cell lysates were centrifuged. PIP3 in the cellular lipid extraction was quantified with the AlphaScreen [Registered TM of PerkinElmer] assay in which Grpl-PH is used as the PIP3 specific probe. The amount of cellular PIP3 was calculated from the standard curve of diCs PI(3,4,5) P3. Biological Example 5-10 In vivo models [002531 Female and male athymic nude mice (NCr) 5-8 weeks of age and weighing approximately 20 g were used in the following model. Prior to initiation of a study, the animals were allowed to acclimate for a minimum of 48 h. During these studies, animals were provided food and water ad libitum and housed in a room conditioned at 70-75*F and 60% relative humidity. A 12 h light and 12 h dark cycle was maintained with automatic timers. All animals were examined daily for compound-induced or tumor-related deaths. [002541 PC-3 human prostate adenocarcinoma cells were cultured in vitro in DMEM (Mediatech) supplemented with 20%' Fetal Bovine Serum (Hyclone), Penicillin-Streptomycin and non-essential amino acids at 37*C in a humidified 5% CO 2 atmosphere. On day 0, cells were harvested by trypsinization and 3x106 cells (passage 13, 99% viability) in 0.1 mL of ice-cold Hank's balanced salt solution were implanted subcutaneously into the hindflank of 5-8 week old male nude mice. A transponder was implanted in each mouse for identification, and animals were monitored daily for clinical symptoms and survival. Body weights were recorded daily. 1002551 U-87 MG human glioblastoma cells were cultured in vitro in DMEM (Mediatech) supplemented with 10% Fetal Bovine Serum (Hyclone), Penicillin-Streptomycin and non-essential amino acids at 37*C in a humidified 5% CO 2 atmosphere. On day 0, cells were harvested by trypsinization and 2x10 6 cells (passage 5, 255 96% viability) in 0.1 mL of ice-cold Hank's balanced salt solution were implanted intradermally into the hindflank of 5-8 week old female nude mice. A transponder was implanted in each mouse for identification, and animals were monitored daily for clinical symptoms and survival. Body weights were recorded daily. [00256] A549 human lung carcinoma cells were cultured in vitro in DMEM (Mediatech) supplemented with 10% Fetal Bovine Serum (Hyclone), Penicillin-Streptomycin and non-essential amino acids at 37*C in a humidified 5% CO 2 atmosphere. On day 0, cells were harvested by trypsinization and 10x10 6 cells (passage 12, 99% viability) in 0.1 mL of ice-cold Hank's balanced salt solution were implanted intradermally into the hindflank of 5-8 week old female nude mice. A transponder was implanted in each mouse for identification, and animals were monitored daily for clinical symptoms and survival. Body weights were recorded daily. [00257] A2058 human melanoma cells were cultured in vitro in DMEM (Mediatech) supplemented with 10% Fetal Bovine Serum (Hyclone), Penicillin-Streptomycin and non-essential amino acids at 37*C in a humidified, 5% CO 2 atmosphere. On day 0, cells were harvested by trypsinization and 3x106 cells (passage 3, 95% viability) in 0.1 ml ice-cold Hank's balanced salt solution were implanted intradermally in the hind-flank of 5-8 week old female athymic nude mice. A transponder was implanted in each mouse for identification, and animals were monitored daily for clinical symptoms and survival. Body weights were recorded daily. [00258] WM-266-4 human melanoma cells were cultured in vitro in DMEM (Mediatech) supplemented with 10% Fetal Bovine Serum (Hyclone), Penicillin-Streptomycin and non-essential amino acids at 37*C in a humidified, 5% CO 2 atmosphere. On day 0, cells were harvested by trypsinization and 3x1 06 cells (passage 5, 99% viability) in 0.1 ml ice-cold Hank's balanced salt solution were implanted intradermally in the hind-flank of 5-8 week old female athymic nude mice. A transponder was implanted in each mouse for identification, and animals were monitored daily for clinical symptoms and survival. Body weights were recorded daily. [002591 For subcutaneous or intradermal tumors, the mean tumor weight of each animal in the respective control and treatment groups was determined twice weekly during the study. Tumor weight (TW) was determined by measuring perpendicular diameters with a caliper, using the following formula: tumor weight (mg)= [tumor volume - length (mm) x width 2 (mm 2 )]/2 256 1002601 These data were recorded and plotted on a tumor weight vs. days post-implantation line graph and presented graphically as an indication of tumor growth rates. Percent inhibition of tumor growth (TGI) is determined with the following formula: LI- '~(X -]X]) *100 (Yr-XO ) where Xo = average TW of all tumors on group day Xr= TW of treated group on Day f Yf= TW of vehicle control group on Day f If tumors regress below their starting sizes, then the percent tumor regression is determined with the following formula: (Xo-Xf) * 100 Xo Tumor size is calculated individually for each tumor to obtain a mean 4: SEM value for each experimental group. Statistical significance is determined using the 2-tailed Student's t-test (significance defined as P<0.05). Pharmaceutical Composition Examples [002611 The following are representative pharmaceutical formulations containing a compound of Formula I. Tablet Formulation The following ingredients are mixed intimately and pressed into single scored tablets. Ingredient Quantity per tablet, mg compound of this invention 400 Cornstarch 50 croscarmellose sodium 25 Lactose 120 magnesium stearate 5 Capsule Formulation The following ingredients are mixed intimately and loaded into a hard-shell gelatin capsule. 257 Ingredient Quantity per tablet, mg compound of this invention 200 lactose, spray-dried 148 magnesium stearate 2 Suspension Formulation The following ingredients are mixed to form a suspension for oral administration. Ingredient Amount compound of this invention 1.0 g fumaric acid 0.5 g sodium chloride 2.0 g methyl paraben 0.15 g propyl paraben 0.05 g granulated sugar 25.5 g sorbitol (70% solution) 12.85 g Veegum K (Vanderbilt Co.) 1.0 g Flavoring 0.035 mL Colorings 0.5 mg distilled water q.s. to 100 mL Injectable Formulation The following ingredients are mixed to form an injectable formulation. Ingredient Amount compound of this invention 1.2 g sodium acetate buffer solution 0.4 M 2.0 mL HO (I N) or NaOH (1 M) q.s. to suitable pH water (distilled, sterile) g.s.to 20 mL [002621 All of the above ingredients, except water, are combined and heated to 60 70.degree. C. with stirring. A sufficient quantity of water at 60.degree. C. is then added with vigorous stirring to emulsify the ingredients, and water then added q.s. to 100 g. Suppository Formulation A suppository of total weight 2.5 g is prepared by mixing the compound of the invention with Witepsol.RTM. H-15 (triglycerides of saturated vegetable fatty acid; Riches Nelson, Inc., New York), and has the following composition: 258 - 259 Ingredient Quantity per tablet, mg compound of this invention 500 Witepsol*l- 15 balance 100263] The foregoing invention has been described in some detail by way of illustration and example, for purposes of clarity and understanding. It will be obvious to 5 one of skill in the art that changes and modifications may be practiced within the scope of the appended claims. Therefore, it is to be understood that the above description is intended to be illustrative and not restrictive. The scope of the invention should, therefore, be determined not with reference to the above description, but should instead be determined with reference to the following appended claims, along with the full scope of 10 equivalents to which such claims are entitled. All patents, patent applications and publications cited in this application are hereby incorporated by reference in their entirety for all purposes to the same extent as if each individual patent, patent application or publication were so individually denoted. 15 100264] The reference in this specification to any prior publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgment or admission or any form of suggestion that that prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavour to which this specification relates. 20 100265] Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", and variations such as "comprises" and "comprising", will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or 25 steps.

Claims (12)

1. A process for preparing a compound of Formula I: R 52 R 53 OR 51 R5,4 R50 V 1 N NH W' NH W 4 N N-S H 11 0 or a single stereoisomer, mixture of stereoisomers, or tautomer thereof, and optionally as a pharmaceutically acceptable salt or solvate thereof, wherein: W', W 2 , W 3 , and W 4 are -C(R')=; or one or two of W', W 2 , W 3 , and W 4 are independently -N= and the remaining are -C(R')=; and where each R1 is independently hydrogen, alkyl, haloalkyl, nitro, alkoxy, haloalkoxy, halo, hydroxy, cyano, amino, alkylamino, or dialkylamino; R 5 1 is hydrogen or alkyl; R 52 is hydrogen or halo; R 5 ', R 5 3 , and R 54 are independently hydrogen, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, hydroxy, alkoxy, alkenyloxy, haloalkoxy, nitro, amino, alkylamino, dialkylamino, -N(R 5)C(O)-Ci-C 6 -alkylene-N(Rsa )R5", alkylcarbonyl, alkenylcarbonyl, carboxy, alkoxycarbonyl, cyano, alkylthio, -S(0) 2 NR"Ra, or alkylcarbonylamino and where R 55 and R55b are independently hydrogen, alkyl, or alkenyl and R 55 a is hydrogen, alkyl, alkenyl, hydroxy, or alkoxy; or R 53 and R 5 4 together with the carbons to which they are attached form a 5- or 6-membered heteroaryl or 5- or 6 membered heterocycloalkyl; wherein (i) B is phenyl substituted with R3a at the meta position and optionally further substituted with one, two, or three R 3 ; where R 3 a is hydroxyamino; alkylamino; dialkylamino; haloalkoxy; aminoalkyloxy; alkylaminoalkyloxy; dialkylaminoalkyloxy; or - 260 - a) -N(R')C(O)-CrC6-alkylene-N(R a)(R") where R 7 is hydrogen, alkyl, or alkenyl and R 7 a and R 7 b are independently hydrogen, alkyl, alkenyl, hydroxyalkyl, haloalkyl, alkoxy, alkoxyalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl, aryl, arylalkyl, or arylalkyloxy and where the aryl, cycloalkyl, heterocycloalkyl and heteroaryl rings in R 7 a and R 7 b (either alone or as part of arylalkyl, cycloalkylalkyl, heterocycloalkylalkyl and heteroarylalkyl) are independently optionally substituted with 1, 2, or 3 groups independently selected from alkyl, amino, alkylamino, dialkylamino, hydroxy, halo, alkoxy, alkylthio, and oxo); b) -C(O)NRRsa where R8 is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, haloalkyl, or haloalkoxy and RSa is hydrogen, alkyl, alkenyl, hydroxyalkyl, cyanoalkyl, alkoxyalkyl, alkylthioalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, aryl, or arylalkyl and where the aryl, cycloalkyl, heteroaryl, and heterocycloalkyl rings in RSa (either alone or as part of arylalkyl, cycloalkylalkyl, heterocycloalkylalkyl and heteroarylalkyl) are independently optionally substituted with 1, 2, or 3 groups independently selected from alkyl, alkenyl, alkoxy, halo, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, oxo, amino, alkylamino, dialkylamino, alkylcarbonyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, alkoxycarbonyl, and -C(O)H; c) -NR 9 C(O)R 9 a where R9 is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, haloalkyl, or haloalkoxy and R 9 a is hydrogen, C 2 - 6 -alkyl, alkenyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl, aryl, or arylalkyl; where the aryl, cycloalkyl, heteroaryl, and heterocycloalkyl rings in R 9 a (either alone or as part of arylalkyl, cycloalkylalkyl, heterocycloalkylalkyl and heteroarylalkyl) are independently optionally substituted with 1, 2, or 3 groups independently selected from alkyl, alkenyl, alkoxy, hydroxy, hydroxyalkyl, halo, haloalkyl, haloalkoxy, oxo, amino, alkylamino, -261 - dialkylamino, alkylcarbonyl, alkoxycarbonyl, -C(O)H, aryl (optionally substituted with one or two halo), arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkyl, cycloalkylalkyl, and cycloalkylcarbonyl; d) -C(O)N(R' )-Ci-C 6 -alkylene-N(Rioa)ROb where RiOa is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, haloalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, or hydroxyalkyl and R1 0 and ROb are independently hydrogen, alkyl, alkenyl, haloalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, or hydroxyalkyl; e) -NR"C(O)NR'laRi lb where R'ua is hydrogen, alkyl, alkenyl, hydroxy, or alkoxy and R" and R' Ilb are independently hydrogen, alkyl, alkenyl, aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; f) -C(O)R1 2 where R1 2 is heterocycloalkyl optionally substituted with 1, 2, or 3 groups selected from alkyl, oxo, amino, alkylamino, and heterocycloalkylalkyl; g) -NRI 3 C(O)OR1 3 a where R1 3 is hydrogen, alkyl, or alkenyl and RI 3 a is aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, aryl, or arylalkyl; h) -C(O)N(R" 4 )N(R 4 a)(R' 4 1) where R 4 , R 1 4a, and R 1 4 b are independently hydrogen, alkyl, or alkenyl; i) -S(0) 2 N(R")-Ci-C 6 -alkylene-N(R 5 a)R1 5 b where R 5 , R 5 ", and R1 5 b are independently hydrogen, alkyl, or alkenyl; j) -C(O)N(Ri 6 )-C 1 -C 6 -alkylene-C(O)ORi1a where Ri 6 is hydrogen, alkyl, or alkenyl and Ri 6 a is alkyl or alkenyl; k) heteroaryl optionally substituted with one or two aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; 1) -N(R")-C(=N(R' 7 b)(R 7 a))(NR17cR17d) where R1 7 , R1 7 a, R 1 7 b, R 1 7 c, and R1 7 d are independently hydrogen, alkyl, or alkenyl; m) -N(R')C(O)-CI-C 6 -alkylene-N(R' Ib)C(O)R 8a where R' 8a is hydrogen, alkyl, alkenyl, or alkoxy and R1 8 and R1 8 b are independently hydrogen, alkyl, or alkenyl; - 262 - n) .- C(O)N(RI9)-C-C6-alkylene-C(O)Riga where R1 9 is hydrogen, alkyl, or alkenyl and R19a is amino, alkylamino, dialkylamino, or heterocycloalkyl; o) -N(R20)C(O)-Ci-C6-alkylene-C(O)R20a where R 20 is hydrogen, alkyl, or alkenyl and R 2 oa is cycloalkyl or heterocycloalkyl; p) -NR21S(O)2-C1.C6-alkylene-N(R 21)R21a where R21 is hydrogen, alkyl, or alkenyl and R 2 a and R 2 Ib are independently hydrogen, alkyl, or alkenyl; q) -N(R )C(O)-C1..C6-alkylene-N(R22b)-N(Rm)(R2a) where R 22 , R 22 a and R 22 b are independently hydrogen, alkyl, or alkenyl; r) -CO.C 6 -alkylene-N(R 2 3 )-CI..C 6 -alkylene-N(R 2 3 b)R 2 3 a where R 2 3 , R 2 3 a and R 2 3 b are independently hydrogen, alkyl, or alkenyl; or s) -NR 2 4 C(O)-CI.C 6 -alkylene-OR 2 4 a where R 2 4 is hydrogen, alkyl, or alkenyl and R 2 4 a is alkoxyalkyl or aryl optionally substituted with one or two halo or alkyl; and where each of the alkylene in R 3 a is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, amino, alkylamino, and dialkylamino; and each R 3 (when R 3 is present) is independently alkyl; alkenyl; alkynyl; halo; hydroxy; oxo; alkoxy; cyano; hydroxyamino; carboxy; alkoxycarbonyl; amino; alkylamino; dialkylamino; alkylcarbonyl; haloalkoxy; alkylsulfonyl; aminoalkyloxy; alkylaminoalkyloxy; dialkylaminoalkyloxy; or a) -N(R')C(O)-CI-C6-alkylene-N(R7a)(R 7) where R 7 is hydrogen, alkyl, or alkenyl and R 7 a and R 7 b are independently hydrogen, alkyl, alkenyl, hydroxyalkyl, haloalkyl, alkoxy, alkoxyalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl, aryl, arylalkyl, or arylalkyloxy and where the aryl, cycloalkyl, heterocycloalkyl and heteroaryl rings in R 7 a and R 7 b (either alone or as part of arylalkyl, cycloalkylalkyl, heterocycloalkylalkyl and heteroarylalkyl) are independently optionally substituted with 1, 2, or 3 groups independently selected from alkyl, amino, alkylamino, dialkylamino, hydroxy, halo, alkoxy, alkylthio, and oxo); - 263 - b) -C(O)NRRla where R 8 is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, haloalkyl, or haloalkoxy and R 8 a is hydrogen, alkyl, alkenyl, hydroxyalkyl, cyanoalkyl, alkoxyalkyl, alkylthioalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, aryl, or arylalkyl and where the aryl, cycloalkyl, heteroaryl, and heterocycloalkyl rings in R8a (either alone or as part of arylalkyl, cycloalkylalkyl, heterocycloalkylalkyl and heteroarylalkyl) are independently optionally substituted with 1, 2, or 3 groups independently selected from alkyl, alkenyl, alkoxy, halo, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, oxo, amino, alkylamino, dialkylamino, alkylcarbonyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, alkoxycarbonyl, and -C(O)H; c) -NR 9 C(O)R 9 a where R 9 is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, haloalkyl, or haloalkoxy and R 9 a is hydrogen, C 2 - 6 -alkyl, alkenyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl, aryl, or arylalkyl; where the aryl, cycloalkyl, heteroaryl, and heterocycloalkyl rings in R 9 a (either alone or as part of arylalkyl, cycloalkylalkyl, heterocycloalkylalkyl and heteroarylalkyl) are independently optionally substituted with 1, 2, or 3 groups independently selected from alkyl, alkenyl, alkoxy, hydroxy, hydroxyalkyl, halo, haloalkyl, haloalkoxy, oxo, amino, alkylamino, dialkylamino, alkylcarbonyl, alkoxycarbonyl, -C(O)H, aryl (optionally substituted with one or two halo), arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl, cyloalkyl, cyloalkylalkyl, and cycloalkylcarbonyl; d) -C(O)N(R' 0 )-C-C 6 -alkylene-N(Rioa)R'Ib where R'oa is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, haloalkyl, or hydroxyalkyl and Rio and R1Ob are independently hydrogen, alkyl, alkenyl, haloalkyl, or hydroxyalkyl; e) -NR"C(O)NR' laRilb where RuIa is hydrogen, alkyl, alkenyl, hydroxy, or alkoxy and R" and R' lb are independently hydrogen, alkyl, alkenyl, aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; - 264 - f) -C(O)R1 2 where R1 2 is heterocycloalkyl optionally substituted with 1, 2, or 3 groups selected from alkyl, oxo, amino, alkylamino, and heterocycloalkylalkyl; g) -NR"C(O)ORua where R 3 is hydrogen, alkyl, or alkenyl and R' 3 a is aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, aryl, or arylalkyl); h) -C(O)N(R" 4 )N(R 4 a)(R" 4 b) where R' 4 , R' 4 a, and R 4 b are independently hydrogen, alkyl, or alkenyl; i) -S(O) 2 N(R 5 )-Cl.C 6 -alkylene-N(Raa)R' 5 b where R", R'5a, and RI 5 b are independently hydrogen, alkyl, or alkenyl; j) -C(O)N(R1 6 )-Ci.C 6 -alkylene-C(O)OR 6 a where R16 is hydrogen, alkyl, or alkenyl and Ri 6 a is alkyl or alkenyl; k) heteroaryl optionally substituted with one or two aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; 1) -N(R' )-C(=N(Rl 7 b)(R 7 a))(NR4 7 cR1 7 d) where R 7 , Ra, R 17 b, R 17C, and R1 7 d are independently hydrogen, alkyl, or alkenyl; m) -N(R" )C(O)-Ci-C 6 -alkylene-N(R' 8 b)C(O)Ra where R' 8a is hydrogen, alkyl, alkenyl, or alkoxy and R1 8 and RIab are independently hydrogen, alkyl, or alkenyl; n) -C(0)N(R")-Ci-C6-alkylene-C(O)R19a where R1 9 is hydrogen, alkyl, or alkenyl and R' 9a is amino, alkylamino, dialkylamino, or heterocycloalkyl; o) -N(R20)C(O)-C -C6-alkylene-C(O)R20a where R 20 is hydrogen, alkyl, or alkenyl and R20a is cycloalkyl or heterocycloalkyl; p) -NR 2 S(O) 2 -C1.C 6 -alkylene-N(R 2 1b)R 2 1a where R 2 1 is hydrogen, alkyl, or alkenyl and R 2 1a and R 2 Ib are independently hydrogen, alkyl, or alkenyl; q) -N(R )C(O)-C I.C6-alkylene-N(R 22)-N(R34)(R2a), where R 22 , Ra 22 and R 22 b are independently hydrogen, alkyl, or alkenyl; r) -CO.C6-alkylene-N(R2)-Ci.C6-alkylene-N(R23b)R2a where R 23 , R 23 a and R 23 b are independently hydrogen, alkyl, or alkenyl; or s) -NR 24 C(O)-Ci.C 6 -alkylene-OR 24 a where R 2 4 is hydrogen, alkyl, or alkenyl and R 24 a is alkoxyalkyl or aryl optionally substituted with one or two halo or alkyl; -265- wherein each of the alkylene in R 3 is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, amino, alkylamino, and dialkylamino; or (ii) B is heteroaryl substituted with one R 3 , and optionally substituted with a second or third R 3 ; each R 3 is independently hydroxyamino; haloalkoxy; aminoalkyloxy; alkylaminoalkyloxy; dialkylaminoalkyloxy; or a) -N(R')C(O)-Ci-C6-alkylene-N(R7a)(R7b) where R 7 is hydrogen, alkyl, or alkenyl and R 7 a and R 7 b are independently hydrogen, alkyl, alkenyl, hydroxyalkyl, haloalkyl, alkoxy, alkoxyalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl, aryl, arylalkyl, or arylalkyloxy and where the aryl, cycloalkyl, heterocycloalkyl and heteroaryl rings in R 7 a and R 7 b (either alone or as part of arylalkyl, cycloalkylalkyl, heterocycloalkylalkyl and heteroarylalkyl) are independently optionally substituted with 1, 2, or 3 groups independently selected from alkyl, amino, alkylamino, dialkylamino, hydroxy, halo, alkoxy, alkylthio, and oxo); b) -C(O)NR 8 R 8 a where R 8 is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, haloalkyl, or haloalkoxy and R 8 a is alkenyl, hydroxyalkyl, cyanoalkyl, alkoxyalkyl, alkylthioalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, aryl, or arylalkyl and where the aryl, cycloalkyl, heteroaryl, and heterocycloalkyl rings in R 8 a (either alone or as part of arylalkyl, cycloalkylalkyl, heterocycloalkylalkyl and heteroarylalkyl) are independently substituted with 1, 2, or 3 groups independently selected from alkyl, alkenyl, alkoxy, halo, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, oxo, amino, alkylamino, dialkylamino, alkylcarbonyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, alkoxycarbonyl, and -C(O)H; c) -NR 9 C(O)R 9 a where R 9 is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, haloalkyl, or haloalkoxy and R 9 a is hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, - 266 - heteroarylalkyl, aryl, or arylalkyl; where the aryl, cycloalkyl, heteroaryl, and heterocycloalkyl rings in R 9 a (either alone or as part of arylalkyl, cycloalkylalkyl, heterocycloalkylalkyl and heteroarylalkyl) are independently substituted with 1, 2, or 3 groups independently selected from alkyl, alkenyl, alkoxy, hydroxy, hydroxyalkyl, halo, haloalkyl, haloalkoxy, oxo, amino, alkylamino, dialkylamino, alkylcarbonyl, alkoxycarbonyl, -C(O)H, aryl (optionally substituted with one or two halo), arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl, cyloalkyl, cyloalkylalkyl, and cycloalkylcarbonyl; d) -C(0)N(R")-Ci-C6-alkylene-N(Roa )R IN where R Oa is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, haloalkyl, or hydroxyalkyl and Rio and R Ob are independently hydrogen, alkyl, alkenyl, haloalkyl, or hydroxyalkyl; e) -NR"1C(O)NR1laRlIb where Rila is hydrogen, alkyl, alkenyl, hydroxy, or alkoxy and R" and R' lb are independently hydrogen, alkyl, alkenyl, aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; wherein where RIa is hydrogen, alkyl, alkenyl, at least one of R" and R' lb is aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl f) -C(O)R1 2 where R1 2 is heterocycloalkyl substituted with at least 1 group selected from oxo, alkyl, amino, alkylamino, and heterocycloalkylalkyl groups and optionally substituted with one or two further groups selected from alkyl, oxo, amino, alkylamino, and heterocycloalkylalkyl; g) -NR" 3 C(O)OR 3 a where R1 3 is hydrogen, alkyl, or alkenyl and Ria is aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, or arylalkyl); h) -C(O)N(R" 4 )N(R 1 4 a)(R 14b) where R 14, R'a, and R 14b are independently hydrogen, alkyl, or alkenyl; i) -S(0) 2 N(R 5 )-C1.C 6 -alkylene-N(Rsa)Rsb where R 15 , RIsa, and R 5 are independently hydrogen, alkyl, or alkenyl; j) -C(O)N(Ri 6 )-C1.C 6 -alkylene-C(O)OR 6 a where Ri 6 is hydrogen, alkyl, or alkenyl and R 16 a is alkyl or alkenyl; k) heteroaryl substituted with one or two aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; - 267 - 1) -N(R1 7 )-C(=N(R17b)(R1 7 a))(NR17R 1 7 ) where R17, R1 7 a, R17b, R 17 c , and RId are independently hydrogen, alkyl, or alkenyl; m) -N(R'")C(O)-CI-C 6 -alkylene-N(R1 B)C(O)RIsa where R' 8a is hydrogen, alkyl, alkenyl, or alkoxy and R' 8 and R' 8b are independently hydrogen, alkyl, or alkenyl; n) -C(O)N(R'9)-C,-C6-alkylene-C(O)R19a where R1 9 is hydrogen, alkyl, or alkenyl and Ri 9 a is amino, alkylamino, dialkylamino, or heterocycloalkyl; o) -N(R2)C(O)-CI-C6-alkylene-C(O)R20a where R 20 is hydrogen, alkyl, or alkenyl and R 20 ' is cycloalkyl or heterocycloalkyl; p) -NR 2 IS(0) 2 -Ci.C 6 -alkylene-N(R 2 Ib)R 2 1a where R 2 1 is hydrogen, alkyl, or alkenyl and R 2 1 a and R 2 lb are independently hydrogen, alkyl, or alkenyl; q) -N(R 2 )C(O)-C 1 C 6 -alkylene-N(R 2 2 b)-N(R 22 c)(R 22 a), where R 2 , R 2 a and R 22 b are independently hydrogen, alkyl, or alkenyl; r) -Co.C6-alkylene-N(R2)-C-alkylene-N(R3 )R23 where R 3 , R 3 ' and R 23 are independently hydrogen, alkyl, or alkenyl; or s) -NR 24 C(O)-Ci.C 6 -alkylene-OR 2 4 a where R 24 is hydrogen, alkyl, or alkenyl and R 24 , is alkoxyalkyl or aryl optionally substituted with one or two halo or alkyl; wherein each of the alkylene in R 3 is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, amino, alkylamino, and dialkylamino; and provided that when R 50 and R 52 are hydrogen, R 5 1 is hydrogen or methyl, R 53 is hydrogen or methoxy, and R 54 is hydrogen or methoxy, then B is not 2,3 dihydro-1,4-benzodioxinyl, thien-2-yl, or thien-2-yl substituted with one R 3 where R 3 is halo; said process comprising: (a) reacting an intermediate of: -268- R52 R 53 ORS 1 R64 R60 S B LG H 50 5 wherein LG is a leaving group and R 0 , R 5 , R , R 3 , and B are as defined in claim 1, with an intermediate of formula NHRaRb or HO-Ci-C 6 -alkylene-NHRaR, wherein Ra and Rb are independently hydrogen or alkyl to yield, respectively, R 52 R 5 s OR"' R:]4 R"0 N B NRaR 0 I(c) or R62 R6 3 OR 5 1 R641 R50 CN NH CB N ,0-& -C1-C6-alkylene-NRaRb 0 I(d); or (b) reacting an intermediate of formula 8 Rs2 R 53 OR6 1 Ri 41 R50 N NH N N-8- B NHRa H 1 0 8 - 269 - where Ra is R 7 , R 9 , R", R , R 7 , R", R 20 , R 2 ', R", or R 24 , with an intermediate of formula 9(a), 9(b), 9(c), 9(d), 9(e), 9(f), or 9(g); wherein: 9(a) is HOC(0)-CI-C 6 -alkylene-N(R 7 a)(R 7 b), wherein Ra is R 7 a or a N-protecting group that is Boc or Fmoc; 9(b) is HOC(O)R 9 a; 9(c) is HOC(0)NRu1aRb; 9(d) is HOC(O)OR 13a; 9(e) is HOC(0)-Ci-C 6 -alkylene-N(R' 8 b)C(O)Risa 9(f) is HOC(0)-Ci-C 6 -alkylene-C(0)R20a; 9(g) is LG-S(0)2R-Cl-C6-alkylene-N(R21b)R, wherein Ra is R 2 la or a N-protecting group that is Boc or Fmoc; to yield RR2 R 53 OR"i N NH -- NHR 1 00 I(e) wherein R1 00 is -C(0)R 9 a, -C(O)NR aR 1b, C(O)OR1 3 a, -C(O)-C 1 -C 6 -alkylene N(R' 8 b)C(O)R 8a, -C(0)-Ci-C 6 -alkylene-C(0)R 2 a, or -S(0) 2 R-C-C 6 -alkylene N(R 2 Ib)Ra; or (c) reacting an intermediate of formula 11 R 52 R 53 OR 51 R64 R50 NH 11 - 270 - with an intermediate selected from the group consisting of: NHR 8 R 8 a, NH(R 0 )-Ci C 6 -alkylene-N(Roa)R0b, a cyclic amine, NH(R 14)N(R1 4a)(R 14), NHR 16-C C 6 -alkylene-C(O)OR 16a, and NH(R' 9 )-Ci-C 6 -alkylene-C(O)R' 9a, to yield a Compound of Formula I; or (d) reacting an intermediate of formula 12: R 52 R 53 OR 51 R§' R"0 N NH 0 LG 0 11 &NH 12 with an intermediate of formula NH(R 7 b )R 7 a to yield a Compound of Formula I(f): R 5 2 R6 3 OR" R.5 R50 N NH 0 NR 7 "R 7 b H"N-S - NH I(f); or (e) reacting an intermediate of formula 13 wherein LG is a leaving group: N LG 13 with an intermediate of formula: R52 R 53 OR 51 R04 R50 NH 2 to yield a Compound of Formula I(h): -271 - R52 R 53 OR" 1 R 54 /R5 N NH I(h); and (f) optionally further resolving individual isomers.

2. A process for preparing: CI N NH ~N ' N-- N C' NH 2 H 7O Example 38 comprising coupling: 0 C CI N NH N NH 2 with: CINH 2 0

3. A process according to claim 2, wherein the reaction is carried out in DMF in the presence of HATU and DIEA.

4. A process according to claim 2, further comprising the step of reducing: -272- O' C CI N NH 0 '9 NO 2 N N-S - H 0 to provide. O' C CI N NH N N-S NH 2 H6 I/,

5. A process according to claim 4, wherein the reaction is carried out in the presence of formic acid, potassium formate, and 10% palladium on charcoal.

6. A process according to claim 4, further comprising the step of reacting: NN CI (N>NS NO 2 H6/ with: 0 CI NH 2 to provide: 0 CI N NH N NNO 2 - 273 -

7. A process according to claim 6, wherein the reaction is carried out at reflux in a solvent that is DMF or p-xylene.

8. A process according to claim 6, further comprising the step of reacting: C N CI with: 0 NO 2 H 2 N-S to prepare: N CI N N-S Hd'K

9. A process according to claim 8, wherein the reaction is carried out in DMF or DMSO in the presence of K 2 C0 3 .

10. A compound which is: C1 CI N NH N NH N NO2rN X NH 2 N d N-Hd'- _z or

11. A process as defined in any one of claims 1 to 9 substantially as herein described with reference to any example thereof. -274-

12. A compound as claimed in claim 10 substantially as herein described with reference to any example thereof. -275-