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Claims for Patent: 9,938,273

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Summary for Patent: 9,938,273
Title:Compounds and methods for kinase modulation, and indications therefor
Abstract: Disclosed are compounds of Formula I: ##STR00001## or a pharmaceutically acceptable salt, a solvate, a tautomer, an isomer or a deuterated analog thereof, wherein Z.sup.2, Z.sup.3, and Z.sup.5 are as described herein, compositions thereof, and uses thereof.
Inventor(s): Wu; Guoxian (Foster City, CA), Wu; Jeffrey (Berkeley, CA), Chan; Katrina (Fremont, CA), Dong; Ken (Berkeley, CA), Ewing; Todd (Walnut Creek, CA), Ibrahim; Prabha N. (Mountain View, CA), Lin; Jack (Hercules, CA), Spevak; Wayne (Berkeley, CA), Zhang; Ying (Fremont, CA)
Assignee: Plexxikon Inc. (Berkeley, CA)
Application Number:15/370,631
Patent Claims:1. A compound having Formula I: ##STR00274## or a pharmaceutically acceptable salt or a solvate thereof, wherein: Z.sup.2 is alkynyl optionally substituted with R.sup.b, aryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, or heteroaryl, wherein each aryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, or heteroaryl is optionally substituted with 1-3 R.sup.1 groups; Z.sup.3 is hydrogen or halo; Z.sup.5 is -Cy-L; Cy is heterocycloalkylene, arylene, or heteroarylene, wherein Cy is optionally substituted with 1-2 R.sup.a groups; L is: --C(O)NR.sup.3R.sup.4, wherein: R.sup.3 is hydrogen or C.sub.1-6alkyl optionally substituted with 1-3 G groups, and R.sup.4 is alkoxy, hydroxyalkylene, cyano, cyanoalkylene, or aminocarbonylalkyl, wherein R.sup.4 is optionally substituted with 1-3 G groups; or R.sup.3 and R.sup.4, together with the N atom to which they are attached, join to form a heterocycloalkyl or heteroaryl moiety, wherein 1-2 carbon atoms of the heterocycloalkyl or heteroaryl moiety is substituted with 1-2 G groups; or --C.sub.1-3alkyl-heterocycloalkyl, --C(O)-heterocycloalkyl, --N(H)-heterocycloalkyl, --C(O)-cycloalkyl, or --O-heterocycloalkyl, each of which is optionally substituted with 1-3 G groups; or --C(O)--N(H)--O--R.sup.5 or --NH--C(O)--R.sup.c, wherein: R.sup.5 is hydrogen, C.sub.1-6alkyl, or cycloalkyl; and R.sup.c is C.sub.1-6alkyl, cycloalkyl, or heterocycloalkyl; or --SO.sub.2--NR.sup.6R.sup.7, --N(H)C(O)NR.sup.6R.sup.7, or --N(H)--SO.sub.2--NR.sup.6R.sup.7, wherein: R.sup.6 is hydrogen, C.sub.1-6alkyl, alkylcarbonyl, alkylsulfonyl, cycloalkylamino, or cycloalkyl, wherein each of the C.sub.1-6alkyl, alkylcarbonyl, alkylsulfonyl, cycloalkylamino, and cycloalkyl are optionally substituted with 1-3 G groups, R.sup.7 is hydrogen or C.sub.1-6alkyl optionally substituted with 1-3 G groups; or R.sup.6 and R.sup.7, together with the N atom to which they are attached, join to form a heterocycloalkyl or heteoraryl moiety, wherein 1-2 carbon atoms of the heterocycloalkyl or heteroaryl moiety is substituted with 1-2 G groups; or heterocycloalkyl substituted with 1-3 G groups; R.sup.1 is hydrogen, C.sub.1-6alkyl, cycloalkyl, --C(O)-cycloalkyl, --C(O)alkyl, cyano, cyanoalkyl, cyanocycloalkyl, cyanocycloalkylalkyl, hydroxy, alkoxy, alkoxyalkyl, hydroxyalkyl, halo, haloalkyl, oxo, aryl, arylalkyl, cycloalkylsulfonyl, alkylsulfonyl, alkylsulfonylalkyl, alkylcarbonylaminoalkyl, alkylsulfonylaminoalkyl, heterocycloalkyl optionally substituted with 1-2 R.sup.a, heterocycloalkylalkyl, --NR.sup.6R.sup.7, --C.sub.1-6alkylene-NR.sup.6R.sup.7, --C(O)O-alkyl, heterocycloalkyl optionally substituted with 1-2 R.sup.d groups, or heteroaryl optionally substituted with 1-2 R.sup.e groups; each G is independently C.sub.1-6alkyl, C.sub.1-6haloalkyl, halo, amino, alkylamino, dialkylamino, alkylaminoalkyl, --(C.sub.1-6alkylene)-amino, --CN, --C(O)--C.sub.1-6alkyl, --C(O)--O--C.sub.1-6alkyl, --CO.sub.2H, --C(O)--N(H)--C.sub.1-6alkyl, oxo, --N(H)--C(O)--C.sub.1-6alkyl, --C(.dbd.NH)--NH.sub.2, --OH, --N(H)--C(O)--O-- C.sub.1-6alkyl, --N(H)--C(O)--N(H)--C.sub.1-6alkyl, --N(H)--S(O).sub.2--C.sub.1-6alkyl, --S(O).sub.2--C.sub.1-6alkyl, hydroxyalkyl, cycloalkyl, cycloalkylamino, alkoxy, heterocycloalkyl, or heteroaryl, each R.sup.a is independently alkyl, oxo, halo, or hydroxy; R.sup.b is halo, C.sub.3-6cycloalkyl, aryl, heteroaryl, --NR.sup.6R.sup.7, or hydroxy; each R.sup.d is independently C.sub.1-6alkyl, halo, oxo, alkylaminosulfonyl, alkylsulfonyl, alkylcarbonyl, hydroxyalkyl, or hydroxy; and each R.sup.e is independently C.sub.1-6alkyl, halo, or hydroxy; provided that when G is cycloalkyl, Z.sup.2 is alkynyl optionally substituted with C.sub.3-C.sub.6cycloalkyl, --NR.sup.6R.sup.7, or hydroxy; and further provided that the compound is not ##STR00275##

2. The compound according to claim 1, wherein: Z.sup.2 is ethynyl optionally substituted with C.sub.1-6alkyl, C.sub.1-6haloalkyl, C.sub.3-6cycloalkyl, aryl, --C.sub.1-C.sub.6alkylene-NR.sup.6R.sup.7, or hydroxyalkyl; or Z.sup.2 is phenyl, cyclohexyl, cyclohexenyl, pyrazolyl, pyrimidinyl, thiazolyl, pyridyl, pyridazinyl, pyrrolyl, dihydropyrrolyl, dihydropyranyl, dihydropyradinyl, tetrahydropyridyl, dihydrothiopyranyl, dihydrothiopyranyl oxide, or dihydrothiopyranyl dioxide, wherein each Z.sup.2 is optionally substituted with 1-2 R.sup.1 groups; Z.sup.3 is hydrogen or halo; Cy is phenyl, 1H-indazolyl, pyridyl, quinolinyl, isoindolinyl, or thiophenyl, wherein Cy is optionally substituted with 1-2 R.sup.a groups; L is --C(O)NR.sup.3R.sup.4, wherein: R.sup.3 is hydrogen or C.sub.1-6alkyl; R.sup.4 is cyano or cyano-C.sub.1-6alkylene optionally substituted with 1-3 G groups; or R.sup.3 and R.sup.4, together with the N atom to which they are attached, join to form a 4-6 membered heterocycloalkyl moiety substituted with 1-2 G groups; or --C(O)--N(H)--O--R.sup.5, wherein R.sup.5 is hydrogen or C.sub.1-6alkyl; or --SO.sub.2--NR.sup.6R.sup.7, --N(H)C(O)NR.sup.6R.sup.7, and --N(H)--SO.sub.2--NR.sup.6R.sup.7, wherein: R.sup.6 is hydrogen, C.sub.1-6alkyl, or C.sub.3-6cycloalkyl; R.sup.7 is hydrogen or C.sub.1-6alkyl; or R.sup.6 and R.sup.7, together with the N atom to which they are attached, join to form a heterocycloalkyl moiety substituted with 1-2 G groups; heterocycloalkyl substituted with 1-2 G groups, C.sub.1-3alkyl-heterocycloalkyl, --C(O)-heterocycloalkyl, --N(H)-heterocycloalkyl, or --O-heterocycloalkyl; R.sup.1 is hydrogen, cycloalkyl, --C(O)-cycloalkyl, C.sub.1-6alkyl, cyano, hydroxy, alkoxy, halo, haloalkyl, oxo, phenyl, heterocycloalkyl, heterocycloalkylalkyl, --C.sub.1-6alkylene-NR.sup.6R.sup.7, --C(O)O-- alkyl, or heteroaryl optionally substituted with 1-2 R.sup.e groups; each G is independently C.sub.1-6alkyl, halo, amino, --NH--C.sub.1-6alkyl, --N(C.sub.1-6alkyl).sub.2, --(C.sub.1-6alkylene)-N(H)--C.sub.1-6alkyl, --CN, --C(O)--C.sub.1-6alkyl, --C(O)--N(H)--C.sub.1-6alkyl, --N(H)--C(O)--C.sub.1-6alkyl, --C(.dbd.NH)--NH.sub.2, --N(H)--C(O)--O--C.sub.1-6alkyl, --N(H)--C(O)--N(H)--C.sub.1-6alkyl, --N(H)--S(O).sub.2--C.sub.1-6alkyl, --S(O).sub.2--C.sub.1-6alkyl, C.sub.3-6cycloalkyl, --N(H)--C.sub.3-6cycloalkyl, C.sub.1-C.sub.6alkoxy, 5-6 membered heterocycloalkyl or 5-6 membered heteroaryl, provided that when G is C.sub.3-6cycloalkyl, Z.sup.2 is alkynyl optionally substituted with C.sub.3-6cycloalkyl, --NR.sup.6R.sup.7, or hydroxy; and each R.sup.a is independently oxo, halo or hydroxy.

3. The compound according to claim 1, wherein L is --SO.sub.2--NR.sup.6R.sup.7, --C(O)NR.sup.3R.sup.4, --C(O)--N(H)--O--R.sup.5, --N(H)--SO.sub.2--NR.sup.6R.sup.7, or --N(H)C(O)NR.sup.6R.sup.7.

4. The compound according to claim 1, wherein: L is --C(O)NR.sup.3R.sup.4.

5. The compound according to claim 1, wherein Z.sup.5 is ##STR00276##

6. The compound according to claim 1, wherein Z.sup.5 is: ##STR00277##

7. The compound according to claim 1, wherein Z.sup.5 is: ##STR00278##

8. The compound according to claim 1, wherein Z.sup.5 is: ##STR00279## wherein B is a bond, methylene, or ethylene.

9. The compound according to claim 1, wherein Z.sup.2 is: ##STR00280## ##STR00281## ##STR00282## wherein: m is 0-2; n is 0-3; R.sup.8 is hydrogen, C.sub.1-6alkyl, --C(O)O--C.sub.1-6alkyl, C.sub.3-6cycloalkyl, --C(O)C.sub.3-6cycloalkyl, aryl-C.sub.1-6alkyl, 5-6 membered heterocycloalkyl-C.sub.1-6alkyl, or C.sub.1-6haloalkyl; and R.sup.9 is C.sub.1-6alkyl, C.sub.1-6haloalkyl, C.sub.3-6cycloalkyl, aryl, --C.sub.1-6alkylene-NR.sup.6R.sup.7, hydroxy-C.sub.1-6alkylene, or hydroxy.

10. The compound according to claim 1 having one of the following Formulae: ##STR00283## ##STR00284## wherein: Q is N or CH; R.sup.9 is C.sub.1-6alkyl, C.sub.1-6haloalkyl, C.sub.3-6cycloalkyl, aryl, --C.sub.1-6alkylene-NR.sup.6R.sup.7, hydroxy-C.sub.1-6alkylene, or hydroxy; and n is 0-2.

11. The compound according claim 1 having one of the following Formulae: ##STR00285## ##STR00286## wherein: n is 0-2; L is --C(O)NR.sup.3R.sup.4; R.sup.3 is hydrogen or C.sub.1-6alkyl; R.sup.4 is cyano or cyano-C.sub.1-6alkylene optionally substituted with halo or --OH; or R.sup.3 and R.sup.4, together with the N atom to which they are attached, join to form a 4-6 membered heterocycloalkyl moiety substituted with 1-2 G groups.

12. The compound according to claim 1, wherein L is one of the following moieties: ##STR00287##

13. The compound according to claim 1, wherein R.sup.1 is C.sub.1-3alkyl, C.sub.1-3haloalkyl, C.sub.3-6cycloalkyl, --C.sub.1-3alkylene-CN, cyano, --(C.sub.1-3alkylene)-C.sub.1-3alkoxy, heterocycloalkyl, or --C(O)--C.sub.3-6cycloalkyl.

14. The compound according to claim 1, wherein R.sup.1 is --CH.sub.3, --CHF.sub.2, --CH.sub.2F, --CF.sub.3, cyclopropyl, --C.sub.1-3alkylene-CN, cyano, methoxy-(C.sub.1-3alkylene)-, piperidinyl, morpholinyl, tetrahydrofuranyl, or --C(O)-cyclopropyl.

15. The compound according to claim 1 having one of the following Formulae: ##STR00288## ##STR00289## wherein R.sup.9 is C.sub.1-6alkyl, C.sub.1-6haloalkyl, C.sub.3-6cycloalkyl, phenyl, --(C.sub.1-6alkylene)-NR.sup.6R.sup.7, or hydroxy-C.sub.1-4alkylene.

16. The compound according to claim 1 having one of the following Formulae: ##STR00290## ##STR00291## ##STR00292## ##STR00293## ##STR00294## ##STR00295## ##STR00296## ##STR00297## ##STR00298## ##STR00299## wherein each of R.sup.1a, R.sup.1b, R.sup.1c, R.sup.1d, R.sup.1e, and R.sup.1f are as defined as R.sup.1; and R.sup.8 is hydrogen, --CH(CH.sub.3).sub.2, --C(O)OC(CH.sub.3).sub.3, cyclopropyl, --C(O)cyclopropyl, --(CH.sub.2).sub.0-2-phenyl, --(CH.sub.2).sub.0-2-morpholinyl, --(CH.sub.2).sub.0-2-tetrahydrofuranyl, --(CH.sub.2).sub.0-2-piperidinyl, --CH.sub.3, --CF.sub.3 or --CHF.sub.2.

17. The compound according to claim 16 having one of Formulae V(a), V(b), V(c), V(d), V(e), V(f), V(g), V(h), V(aa), V(bb), V(cc), V(dd), V(ee), V(ff), V(gg), or V(hh).

18. The compound according to claim 16 having one of Formulae VI(a), VI(b), VI(c), VI(d), VI(e), VI(f), VI(g), VI(h), VII(a), VII(b), VII(c), VII(d), VII(e), VII(f), VII(g), VII(h), VIII(a), VIII(b), VIII(c), VIII(d), VIII(e), VIII(f), VIII(g), or VIII(h).

19. The compound according to claim 16, wherein: R.sup.1a is hydrogen, cyclopropyl, --OC(H)(CH.sub.3).sub.2, morpholinyl, --CF.sub.3, --CHF.sub.2, or F; R.sup.1b is hydrogen, F, cyano, cyclopropyl, or cyanocyclopropyl; R.sup.1c is hydrogen, cyclopropyl, methoxy, --OC(H)(CH.sub.3).sub.2, pyrrolidinyl, ethoxy, --CH.sub.3, --CF.sub.3 or --CHF.sub.2; R.sup.1d is hydrogen or --CH.sub.3; R.sup.1e is hydrogen, methoxy, cyclopropyl, morpholinyl, --CF.sub.3, --CHF.sub.2, --CH.sub.3, pyrrolidinyl, or F; and R.sup.1f is hydrogen or cyclopropyl.

20. The compound according to claim 1, wherein G is amino, --N(H)C(O)--C.sub.1-6alkyl, --C(O)--N(H)--C.sub.1-6alkyl, --N(H)--C(O)--N(H)--C.sub.1-6alkyl, --N(H)--S(O).sub.2--C.sub.1-6alkyl, --N(H)--C.sub.1-6alkyl, --N(C.sub.1-6alkyl).sub.2, --C(.dbd.NH)--NH.sub.2, --OH, C.sub.1-6alkyl, C.sub.1-6haloalkyl, halo, --N(H)--C.sub.3-6cycloalkyl, C.sub.1-6alkoxy, C.sub.4-6heterocycloalkyl, C.sub.5-6heteroaryl, --CN, --C(O)--C.sub.1-6alkyl, or --C.sub.1-3alkylene-N(H)--C.sub.1-3alkyl.

21. The compound according to claim 1, wherein G is amino, --N(H)C(O)--C.sub.1-4alkyl, --C(O)--N(H)--C.sub.1-4alkyl, --N(H)--C(O)--N(H)--C.sub.1-4alkyl, --N(H)--S(O).sub.2--C.sub.1-3alkyl, --N(H)--CH.sub.3, --N(CH.sub.3).sub.2, --C(.dbd.NH)--NH.sub.2, --OH, --C.sub.1-3alkyl, --CF.sub.3, fluoro, --N(H)--C.sub.3-6cycloalkyl, C.sub.1-3alkoxy, morpholinyl, imidazolyl, --CN, --C(O)--C.sub.1-3alkyl, or --C.sub.1-2alkylene-N(H)--CH.sub.3.

22. The compound according to claim 1, wherein R.sup.a is oxo, fluoro, chloro, or hydroxy.

23. A compound selected from: TABLE-US-00010 N-[1-[3-[2-(4-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]benzoyl]-4-piper- idyl]acetamide; P-0001 N-methoxy-N-methyl-3-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide; P-- 0002 N-methoxy-3-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide; P-0003 N-cyclopropyl-3-(2-ethynyl-1H-pyrrolo[2,3-b]pyridin-5-yl)benzenesulfonamid- e; P-0004 [4-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl]urea; P-0005 1-methyl-3-[4-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl]urea; P-0006 5-[3-(dimethylsulfamoylamino)phenyl]-2-phenyl-1H-pyrrolo[2,3-b]pyridine; P- -0007 N-cyclopropyl-3-[2-(3-hydroxyprop-1-ynyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]be- nzenesulfonamide; P-0008 N-cyclopropyl-3-[2-[3-(dimethylamino)prop-1-ynyl]-1H-pyrrolo[2,3-b[pyridin- -5-yl]benzenesulfonamide; P-0009 3-[2-(2-cyclohexylethynyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N-cyclopropyl-be- nzenesulfonamide; P-0010 tert-butyl N-[1-[5-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-indazole-3-- carbonyl]-4-piperidyl]carbamate; P-0011 (4-amino-1-piperidyl)-[5-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-indaz- ol-3-yl]methanone; P-0012 (4-amino-1-piperidyl)-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-pyridy- l]methanone; P-0013 N-cyclopropyl-3-2-(2-phenylethynyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]benzenes- ulfonamide; P-0014 [(3S)-3-aminopyrrolidin-1-yl]-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-- 2-pyridyl]methanone; P-0015 [(3S)-3-aminopyrrolidin-1-yl]-[5-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-- 1H-indazol-3-yl]methanone; P-0016 tert-butyl N-[1-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridine-2-carb- onyl]-4-piperidyl]carbamate; P-0017 N-[1-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridine-2-carbonyl]-4-pip- eridyl]acetamide; P-0020 N-[1-[5-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-indazole-3-carbonyl]-4- -piperidyl]acetamide; P-0021 [4-(hydroxymethyl)-1-piperidyl]-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl- )-2-pyridyl]methanone; P-0023 1-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridine-2-carbonyl]piperidin- e-4-carboxylic acid; P-0024 ethyl 1-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridine-2-carbonyl]pip- eridine-4-carboxylate; P-0025 [4-(aminomethyl)-1-piperidyl]-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-- 2-pyridyl]methanone; P-0026 (4-methyl-1-piperidyl)-[5-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-inda- zol-3-yl]methanone; P-0027 [3-(methylamino)pyrrolidin-1-yl]-[5-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-y- l)-1H-indazol-3-yl]methanone; P-0028 (3-aminoazetidin-1-yl)-5-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-indaz- ol-3-yl]methanone; P-0029 N-methyl-1-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridine-2-carbonyl]- piperidine-4-carboxamide; P-0030 1-ethyl-3-[1-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridine-2-carbony- l]-4-piperidyl]urea; P-0031 N-[1-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridine-2-carbonyl]-4-pip- eridyl]methanesulfonamide; P-0032 (4-amino-1-piperidyl)-[3-methyl-6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)- -2-pyridyl]methanone; P-0033 1-[2-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-8-quinolyl]piperidin-4-amine- ; P-0034 (4-amino-1-piperidyl)-2-methyl-5-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)p- henyl]methanone; P-0035 [(3S)-3-aminopyrrolidin-1-yl]-[3-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)p- henyl]methanone; P-0036 (4-amino-1-piperidyl)-[3-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl]me- thanone; P-0037 (4-amino-1-piperidyl)-[4-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-pyridy- l]methanone; P-0038 [3-(methylamino)pyrrolidin-1-yl]-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-y- l)-2-pyridyl]methanone; P-0040 [4-(methylamino)-1-piperidyl]-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-- 2-pyridyl]methanone; P-0041 (4-amino-1-piperidyl)-5-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-indol-- 3-yl]methanone; P-0042 [6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-pyridyl]-(4-piperidyl)methan- one P-0043 [4-(methylamino)-1-piperidyl]-[5-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-- 1H-indazol-3-yl]methanone; P-0044 [(3S)-3-aminopyrrolidin-1-yl]-[4-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-- 2-pyridyl]methanone; P-0046 2-(3-aminocyclopentanecarbonyl)-4-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)- isoindolin-1-one; P-0047 [(3S)-3-aminopyrrolidin-1-yl]-[2-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)t- hiazol-4-yl]methanone; P-0048 [6-[2-[1,3-dimethylpyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-2-pyridyl]- -[3- P-0049 (methylamino)pyrrolidin-1-yl]methanone; 2-phenyl-5-[6-(4-piperidyloxy)-2-pyridyl]-1H-pyrrolo[2,3-b]pyridine; P-005- 0 [(3S)-3-(methylamino)pyrrolidin-1-yl]-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridi- n-5-yl)-2-pyridyl]methanone; P-0051 [3-(methylamino)azetidin-1-yl]-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)- -2-pyridyl]methanone; P-0052 [(3S)-3-aminopyrrolidin-1-yl]-[5-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)t- hiazol-2-yl]methanone; P-0054 [6-[2-(4-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-2-pyridyl]-[3-(methy- lamino)pyrrolidin-1-yl]methanone; P-0055 5-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-N-(4-piperidyl)-1H-indazol-3-am- ine; P-0056 4-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridine-2-carbonyl]piperazin- e-1-carboxamidine; P-0057 [(3R)-3-(methylamino)pyrrolidin-1-yl]-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridi- n-5-yl)-2-pyridyl]methanone; P-0058 5-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-N-pyrrolidin-3-yl-1H-indazol-3-- amine; P-0059 [6-[2-(2-methoxy-4-pyridyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-2-pyridyl]3- P-- 0060 (methylamino)pyrrolidin-1-yl]methanone; [3-(methylamino)pyrrolidin-1-yl]-[6-[2-[1-(2,2,2-trifluoroethyl)pyrazol-4-- yl]-1H-pyrrolo[2,3-b]pyridin-5- P-0061 yl]-2-pyridyl]methanone; 3-[5-[6-[3-(methylamino)pyrrolidine-1-carbonyl]-2-pyridyl]-1H-pyrrolo[2,3-- b]pyridin-2-yl]benzonitrile; P-0062 N-methyl-1-[[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-pyridyl]sulfonyl- ]pyrrolidin-3-amine; P-0063 (3-amino-1-piperidyl)-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-pyridy- l]methanone; P-0067 (3-hydroxypyrrolidin-1-yl)-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-p- yridyl]methanone; P-0068 (3-hydroxy-1-piperidyl)-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-pyri- dyl]methanone; P-0069 [6-[2-(4,4-dimethylcyclohexen-1-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-2-pyrid- yl]3- P-0070 (methylamino)pyrrolidin-1-yl]methanone; N-(azetidin-3-yl)-6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridine-2-sul- fonamide; P-0071 6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-N-pyrrolidin-3-yl-pyridine-2-su- lfonamide; P-0072 1-[[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-pyridyl]sulfonyl]piperidi- n-4-amine; P-0073 (4-amino-1-piperidyl)-[5-[2-[1-(cyclopropanecarbonyl)-2,5-dihydropyrrol-3-- yl]-1H-pyrrolo[2,3-b]pyridin-5- P-0074 yl]-1H-indazol-3-yl]methanone; [3-amino-3-(trifluoromethyl)pyrrolidin-1-yl]-[6-(2-phenyl-1H-pyrrolo[2,3-b- ]pyridin-5-yl)-2-pyridyl]methanone; P-0077 (3-amino-3-methyl-pyrrolidin-1-yl)-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5- -yl)-2-pyridyl]methanone; P-0078 [3-(methylaminomethyl)pyrrolidin-1-yl]-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyrid- in-5-yl)-2-pyridyl]methanone; P-0079 [3-(methylamino)-1-piperidyl]-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-- 2-pyridyl]methanone; P-0080 (4-amino-4-methyl-1-piperidyl)-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)- -2-pyridyl]methanone; P-0081 (3-amino-3-methyl-1-piperidyl)-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)- -2-pyridyl]methanone; P-0082 [(7S)-7-amino-5-azaspiro[2.4]heptan-5-yl]-[6-(2-phenyl-1H-pyrrolo[2,3-b]py- ridin-5-yl)-2-pyridyl]methanone; P-0083 N-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-pyridyl]azetidine-3-carbox- amide; P-0084 [3-(cyclopropylamino)pyrrolidin-1-yl]-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridi- n-5-yl)-2-pyridyl]methanone; P-0085 6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-N-(4-piperidyl)pyridine-2-sulfo- namide; P-0086 N-methyl-1-[[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-pyridyl]methyl]p- yrrolidin-3-amine; P-0087 N-(4-aminocyclohexyl)-6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridine-2- -sulfonamide; P-0088 (4,4-difluoro-1-piperidyl)-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-p- yridyl]methanone; P-0089 (3,3-difluoroazetidin-1-yl)-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-- pyridyl]methanone; P-0090 (3-methoxyazetidin-1-yl)-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-pyr- idyl]methanone; P-0091 methyl 4-methyl-1-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridine-2-ca- rbonyl]piperidine-4-carboxylate; P-0092 (3,3-difluoropyrrolidin-1-yl)-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-- 2-pyridyl]methanone; P-0093 4-methyl-1-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridine-2-carbonyl]- piperidine-4-carbonitrile; P-0094 (3-methoxypyrrolidin-1-yl)-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-p- yridyl]methanone P-0095 N-methyl-1-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridine-2-carbonyl]- pyrrolidine-3-carboxamide; P-0096 (3-imidazol-1-ylpyrrolidin-1-yl)-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-y- l)-2-pyridyl]methanone; P-0097 (4-methoxy-1-piperidyl)-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-pyri- dyl]methanone; P-0098 N-(2-cyanoethyl)-6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridine-2-carb- oxamide; P-0099 N-(2-cyano-2-methyl-propyl)-6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyri- dine-2-carboxamide; P-0100 N-[1-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridine-2-carbonyl]pyrrol- idin-3-yl]methanesulfonamide; P-0101 (3-morpholinopyrrolidin-1-yl)-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-- 2-pyridyl]methanone; P-0102 [6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-pyridyl]-[3-(trifluoromethyl- )pyrrolidin-1-yl]methanone; P-0103 [3-(dimethylamino)pyrrolidin-1-yl]-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5- -yl)-2-pyridyl]methanone; P-0104 1-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridine-2-carbonyl]pyrrolidi- ne-3-carbonitrile; P-0105 [(3R)-3-(methylamino)pyrrolidin-1-yl]-[5-(2-phenyl-1H-pyrrolo[2,3-b]pyridi- n-5-yl)-2-thienyl]methanone; P-0106 N-(1-methylsulfonylpyrrolidin-3-yl)-6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5- -yl)pyridine-2-sulfonamide; P-0107 N-(2-cyano-2-methyl-propyl)-6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyri- dine-2-sulfonamide; P-0108 N-cyclopropyl-6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridine-2-sulfona- mide; P-0109 (3,3-difluoropyrrolidin-1-yl)-[6-[2-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]- -1H-pyrrolo[2,3-b]pyridin-5-yl]- P-0112 2-pyridyl]methanone; N-(2-cyano-2-methyl-propyl)-6-[2-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]-1H- -pyrrolo[2,3-b]pyridin-5-yl]pyridine- P-0113 2-carboxamide; 3-fluoro-1-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridine-2-carbonyl]- pyrrolidine-3-carbonitrile; P-0115 1-[6-[2-(4-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]pyridine-2-carbonyl- ]pyrrolidine-3-carbonitrile; P-0116 (3S)-1-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridine-carbonyl]pyrrol- idine-3-carbonitrile; P-0117 N-(1-cyano-1-methyl-ethyl)-6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrid- ine-2-carboxamide; P-0118 N-(2-cyanoethyl)-N-methyl-6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridi- ne-2-carboxamide; P-0119 1-[6-[2-(cyclohexen-1-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl]pyridine-2-carbony- l]pyrrolidine-3-carbonitrile; P-0120 1-[[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-pyridyl]sulfonyl]pyrrolid- ine-3-carbonitrile; P-0121 (3R)-1-[6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridine-2-carbonyl]pyrr- olidine-3-carbonitrile; P-0122 N-(2-cyano-2-methyl-propyl)-6-[2-(cyclohexen-1-yl)-1H-pyrrolo[2,3-b]pyridi- n-5-yl]pyridine-2-carboxamide; P-0123 1-[6-(2-phenyl-3H-imidazo[4,5-b]pyridin-6-yl)pyridine-2-carbonyl]pyrrolidi- ne-3-carbonitrile; P-0124 6-(3-chloro-2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-N-(2-cyanoethyl)pyridi- ne-2-carboxamide; P-0125 6-(3-bromo-2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-N-(2-cyano-2-methyl-pro- pyl)pyridine-2-carboxamide; P-0126 N-(2-cyano-2-methyl-propyl)-6-(3-iodo-2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-- yl)pyridine-2-carboxamide; P-0127 N-(3-cyanopropyl)-6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridine-2-car- boxamide; P-0128 1-[6-[2-(4-cyano-2-methyl-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]pyridine-2- -carbonyl]pyrrolidine-3-carbonitrile; P-0130 1-[6-[2-(4,4-dimethylcyclohexen-1-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl]pyridi- ne-2-carbonyl]pyrrolidine-3-carbonitrile; P-0131 1-[6-[2-(3,6-dihydro-2H-pyran-4-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl]pyridine- -2-carbonyl]pyrrolidine-3-carbonitrile; P-0132 1-[6-[2-(3-cyanophenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]pyridine-2-carbonyl]- pyrrolidine-3-carbonitrile; P-0133 1-[6-[2-[1-(difluoromethyl)pyrazol-4-yl]-1H-pyrrolo[2,3-b]pyridin-5-yl]pyr- idine-2- P-0134 carbonyl]pyrrolidine-3-carbonitrile; tert-butyl 3-[5-[6-[3-cyanopyrrolidine-1-carbonyl)-2-pyridyl]-1H-pyrrolo[2- ,3-b]pyridin-2-yl]- P-0135 2,5-dihydropyrrole-1-carboxylate; 1-[6-[2-[1-(cyclopropanecarbonyl)-2,5-dihydropyrrol-3-yl]-1H-pyrrolo[2,3-b- ]pyridin-5-yl]pyridine- P-0136 2-carbonyl]pyrrolidine-3-carbonitrile;

6-(3-chloro-2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-N-(2-cyano-2-methyl-pr- opyl)pyridine-2-carboxamide; P-0138 N-(2-cyano-2-methyl-propyl)-6-[2-[1-(cyclopropanecarbonyl)-2,5-dihydropyrr- ol-3- P-0141 yl]-1H-pyrrolo[2,3-b]pyridin-5-yl]pyridine-2-carboxamide; 1-[6-[3-chloro-2-(3,6-dihydro-2H-pyran-4-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl- ]pyridine- P-0142 2-carbonyl]pyrrolidine-3-carbonitrile; N-(2-cyanoethyl)-6-(3-iodo-2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridine- -2-carboxamide; P-0143 N-(2-cyano-2-methyl-propyl)-6-[2-(4-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin- -5-yl]pyridine-2-carboxamide; P-0144 N-(1-cyano-1-methyl-ethyl)-6-[2-(4-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-- 5-yl]pyridine-2-carboxamide; P-0145 6-(3-bromo-2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-N-(2-cyanoethyl)pyridin- e-2-carboxamide; P-0147 N-(2-hydroxy-2-methyl-propyl)-6-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)py- ridine-2-carboxamide; P-0150 N-(2-cyano-2-methyl-propyl)-6-[2-(2-cyclopropyl-4-pyridyl)-1H-pyrrolo[2,3-- P-0152 b]pyridin-5-yl]pyridine-2-carboxamide; N-(2-cyano-2-methyl-propyl)-6-[2-[1-(difluoromethyl)pyrazol-4-yl]-1H-pyrro- lo[2,3- P-0153 b]pyridin-5-yl]pyridine-2-carboxamide; N-(2-cyano-2-methyl-propyl)-6-[2-(2-methoxy-4-pyridyl)-1H-pyrrolo[2,3-b]py- ridin-5-yl]pyridine-2-carboxamide; P-0154 N-(2-cyano-2-methyl-propyl)-6-[2-(1-methyl-6-oxo-3-pyridyl)-1H-pyrrolo[2,3- - P-0155 b]pyridin-5-yl]pyridine-2-carboxamide; N-(2-cyano-2-methyl-propyl)-6-[2-(4,4-difluorocyclohexen-1-yl)-1H-pyrrolo[- 2,3-b]pyridin-5- P-0157 yl]pyridine-2-carboxamide; 3-[3-chloro-2-(2-cyclopropyl-4-pyridyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N-(- 2-cyano-2-methyl-propyl)benzamide; P-0158 N-(2-cyano-2-methyl-propyl)-6-[2-(3,6-dihydro-2H-thiopyran-4-yl)-1H-pyrrol- o[2,3-b]pyridin-5- P-0159 yl]pyridine-2-carboxamide; N-(2-cyano-2-methyl-propyl)-6-[2-(1,1-dioxo-3,6-dihydro-2H-thiopyran-4-yl)- -1H-pyrrolo[2,3-b]pyridin-5- P-0160 yl]pyridine-2-carboxamide; N-(2-cyano-2-methyl-propyl)-6-[2-(1-oxo-3,6-dihydro-2H-thiopyran-4-yl)-1H-- pyrrolo[2,3-b]pyridin-5- P-0161 yl]pyridine-2-carboxamide; N-(2-cyano-2-methyl-propyl)-6-[2-[1-(cyclopropanecarbonyl)-3,6-dihydro-2H-- pyridin-4-yl]-1H-pyrrolo[2,3- P-0162 b]pyridin-5-yl]pyridine-2-carboxamide; N-(1-cyano-1-methyl-ethyl)-6-[2-(6-methylpyridazin-4-yl)-1H-pyrrolo[2,3-b]- pyridin- P-0163 5-yl]pyridine-2-carboxamide; N-(1-cyano-1-methyl-ethyl)-6-[2-[1-(difluoromethyl)pyrazol-4-yl]-1H-pyrrol- o[2,3- P-0164 b]pyridin-5-yl]pyridine-2-carboxamide; N-(1-cyano-1-methyl-ethyl)-6-[2-(1-cyclopropylpyrazol-4-yl)-1H-pyrrolo[2,3- - P-0165 b]pyridin-5-yl]pyridine-2-carboxamide; N-(1-cyano-1-methyl-ethyl)-6-[2-(2-cyclopropylpyrimidin-5-yl)-1H-pyrrolo[2- ,3- P-0166 b]pyridin-5-yl]pyridine-2-carboxamide; N-(1-cyano-1-methyl-ethyl)-6-(2-thiazol-4-yl-1H-pyrrolo[2,3-b]pyridin-5- P- -0167 yl)pyridine-2-carboxamide; N-(1-cyano-1-methyl-ethyl)-6-[2-(6-cyclopropyl-3-pyridyl)-1H-pyrrolo[2,3- - P-0168 b]pyridin-5-yl]pyridine-2-carboxamide; N-(1-cyano-1-methyl-ethyl)-6-[2-(2-isopropyl-4-methyl-thiazol-5-yl)-1H-pyr- rolo[2,3-b]pyridin-5-yl]pyridine- P-0169 2-carboxamide; 6-[2-[1-(2-cyanoethyl)pyrazol-4-yl]-1H-pyrrolo[2,3-b]pyridin-5-yl]-N-(1-cy- ano-1- P-0170 methyl-ethyl)pyridine-2-carboxamide; 6-[2-(1-benzylpyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N-(1-cyano-1-me- thyl-ethyl)pyridine-2-carboxamide; P-0171 N-(1-cyano-1-methyl-ethyl)-6-[2-[1-(2-methoxyethyl)pyrazol-4-yl]-1H-pyrrol- o[2,3- P-0172 b]pyridin-5-yl]pyridine-2-carboxamide; N-(1-cyano-1-methyl-ethyl)-6-[2-(1-tetrahydrofuran-3-ylpyrazol-4-yl)-1H-py- rrolo[2,3-b]pyridin-5-yl]pyridine-2- P-0173 carboxamide; N-(1-cyano-1-methyl-ethyl)-6-[2-[1-(2-morpholinoethyl)pyrazol-4-yl]-1H-pyr- rolo[2,3-b]pyridin-5-yl]pyridine-2- P-0174 carboxamide; N-(1-cyano-1-methyl-ethyl)-6-(2-ethynyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyri- dine-2-carboxamide; P-0175 N-(1-cyano-1-methyl-ethyl)-6-[2-(2-phenylethynyl)-1H-pyrrolo[2,3-b]pyridin- -5-yl]pyridine-2-carboxamide; P-0176 N-(1-cyano-1-methyl-ethyl)-6-[2-[2-(3-methylimidazol-4-yl)ethynyl]-1H-pyrr- olo[2,3-b]pyridin-5- P-0177 yl]pyridine-2-carboxamide; N-(1-cyano-l-methyl-ethyl)-6-[2-(1-isopropyl-3-methyl-pyrazol-4-yl)-1H-pyr- rolo[2,3-b]pyridin-5- P-0178 yl]pyridine-2-carboxamide; N-(2-amino-1,1-dimethyl-2-oxo-ethyl)-6-[2-[1-(cyclopropanecarbonyl)-2,5-di- hydropyrrol-3-yl]-1H-pyrrolo[2,3- P-0179 b]pyridin-5-yl]pyridine-2-carboxamide; N-(1-cyano-1-methyl-ethyl)-6-[2-(3,6-dihydro-2H-thiopyran-4-yl)-1H-pyrrolo- [2,3-b]pyridin-5-yl]pyridine-2- P-0180 carboxamide; N-(1-cyano-1-methyl-ethyl)-6-[2-[1-(cyclopropanecarbonyl)-3,6-dihydro-2H-p- yridin-4-yl]-1H-pyrrolo[2,3-b]pyridin- P-0181 5-yl]pyridine-2-carboxamide; N-(1-cyano-1-methyl-ethyl)-6-[2-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrol- o[2,3-b]pyridin-5-yl]pyridine- P-0182 2-carboxamide; N-(1-cyano-1-methyl-ethyl)-6-[2-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin- -5-yl]pyridine-2-carboxamide; P-0183 N-(1-cyano-1-methyl-ethyl)-6-[2-[1-(cyclopropanecarbonyl)pyrazol-4-yl]-1H-- pyrrolo[2,3-b]pyridin- P-0184 5-yl]pyridine-2-carboxamide; 6-[3-chloro-2-[1-(difluoromethyl)pyrazol-4-yl]-1H-pyrrolo[2,3-b]pyridin-5-- yl]-N-(1-cyano-1-methyl- P-0185 ethyl)pyridine-2-carboxamide; N-(1-cyano-l-methyl-ethyl)-6-[2-(1,1-dioxo-3,6-dihydro-2H-thiopyran-4-yl)-- 1H-pyrrolo[2,3-b]pyridin- P-0186 5-yl]pyridine-2-carboxamide; N-(1-cyano-1-methyl-ethyl)-6-[2-[1-(4-piperidyl)pyrazol-4-yl]-1H-pyrrolo[2- ,3-b]pyridin- P-0187 5-yl]pyridine-2-carboxamide; N-(1-cyano-1-methyl-ethyl)-6-[2-(1-cyclopropylsulfonyl-3,6-dihydro-2H-pyri- din-4-yl)-1H-pyrrolo[2,3- P-0188 b]pyridin-5-yl]pyridine-2-carboxamide; N-(1-cyano-1-methyl-ethyl)-6-[2-(4-cyclopropylphenyl)-1H-pyrrolo[2,3-b]pyr- idin-5-yl]pyridine- P-0189 2-carboxamide; N-(1-cyano-1-methyl-ethyl)-6-[2-(6-isopropoxy-3-pyridyl)-1H-pyrrolo[2,3-b]- pyridin-5-yl]pyridine- P-0190 2-carboxamide; N-(1-cyano-1-methyl-ethyl)-6-[2-(2-isopropoxypyrimidin-5-yl)-1H-pyrrolo[2,- 3-b]pyridin-5-yl]pyridine- P-0191 2-carboxamide; 6-[3-chloro-2-(1-isopropyl-3-methyl-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin- -5-yl]-N-(1-cyano-1-methyl- P-0192 ethyl)pyridine-2-carboxamide; N-(1-cyano-1-methyl-ethyl)-6-[2-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]-1H-- pyrrolo[2,3- P-0193 b]pyridin-5-yl]pyridine-2-carboxamide; 6-[2-[4-(1-cyanocyclopropyl)phenyl]-1H-pyrrolo[2,3-b]pyridin-5-yl]-N-(1-cy- ano-1-methyl-ethyl)pyridine- P-0194 2-carboxamide; N-(1-cyano-1-methyl-ethyl)-6-(2-pyrimidin-5-yl-1H-pyrrolo[2,3-b]pyridin-5-- yl)pyridine-2-carboxamide; P-0195 N-(1-cyano-1-methyl-ethyl)-6-[2-(2-methoxypyrimidin-5-yl)-1H-pyrrolo[2,3-b- ]pyridin-5-yl]pyridine- P-0196 2-carboxamide; N-(1-cyano-1-methyl-ethyl)-6-[2-(6-morpholino-3-pyridyl)-1H-pyrrolo[2,3-b]- pyridin-5-yl]pyridine- P-0197 2-carboxamide; N-(1-cyano-1-methyl-ethyl)-6-[2-(2-morpholinopyrimidin-5-yl)-1H-pyrrolo[2,- 3-b]pyridin-5-yl]pyridine- P-0198 2-carboxamide; N-(1-cyano-1-methyl-ethyl)-6-[2-[3-(1,1-dioxo-1,2-thiazolidin-2-yl)phenyl]- -1H-pyrrolo[2,3-b]pyridin-5 P-0199 -yl]pyridine-2-carboxamide; N-(2-amino-1,1-dimethyl-2-oxo-ethyl)-6-[2-[1-(4-piperidyl)pyrazol-4-yl]-1H- -pyrrolo[2,3-b]pyridin-5- P-0200 yl]pyridine-2-carboxamide; N-(1-cyano-1-methyl-ethyl)-6-[2-[6-(trifluoromethyl)-3-pyridyl]-1H-pyrrolo- [2,3-b]pyridin-5-yl]pyridine- P-0201 2-carboxamide; N-(1-cyano-1-methyl-ethyl)-6-[2-(2-pyrrolidin-1-ylpyrimidin-5-yl)-1H-pyrro- lo[2,3-b]pyridin-5-yl]pyridine- P-0202 2-carboxamide; N-(1-cyano-1-methyl-ethyl)-6-[2-(2-ethoxypyrimidin-5-yl)-1H-pyrrolo[2,3-b]- pyridin-5-yl]pyridine- P-0203 2-carboxamide; N-(1-cyano-1-methyl-ethyl)-6-[2-[2-(trifluoromethyl)pyrimidin-5-yl]-1H-pyr- rolo[2,3-b]pyridin- P-0204 5-yl]pyridine-2-carboxamide; N-(1-cyano-1-methyl-ethyl)-6-[2-(2-ethylpyrimidin-5-yl)-1H-pyrrolo[2,3-b]p- yridin- P-0205 5-yl]pyridine-2-carboxamide; N-(1-cyano-1-methyl-ethyl)-6-[2-(2-propoxypyrimidin-5-yl)-1H-pyrrolo[2,3- - P-0206 b]pyridin-5-yl]pyridine-2-carboxamide; 6-[3-chloro-2-[1-(4-piperidyl)pyrazol-4-yl]-1H-pyrrolo[2,3-b]pyridin-5-yl]- - P-0207 N-(1-cyano-1-methyl-ethyl)pyridine-2-carboxamide; N-(1-cyano-1-methyl-ethyl)-6-[2-(6-fluoro-3-pyridyl)-1H-pyrrolo[2,3-b]pyri- din-5-yl]pyridine-2-carboxamide; P-0208 N-(1-cyano-1-methyl-ethyl)-6-[2-(2-fluoro-4-pyridyl)-1H-pyrrolo[2,3-b]pyri- din-5- P-0209 yl]pyridine-2-carboxamide; N-(1-cyano-1-methyl-ethyl)-6-2-(2-methyl-4-pyridyl)-1H-pyrrolo[2,3-b]pyrid- in-5-yl]pyridine-2-carboxamide; P-0210 N-(1-cyano-1-methyl-ethyl)-6-[2-[2-(1-hydroxy-1-methyl-ethyl)pyrimidin-5-y- l]- P-0211 1H-pyrrolo[2,3-b]pyridin-5-yl]pyridine-2-carboxamide; N-(2-cyanopropan-2-yl)-6-(2-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)- - P-0212 1H-pyrrolo[2,3-b]pyridin-5-yl)picolinamide; N-(2-cyanopropan-2-yl)-6-(2-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)-1H-pyr- rolo[2,3-b]pyridin-5-yl)picolinamide; P-0213 N-(2-cyanopropan-2-yl)-6-(2-(1-(oxetan-3-ylmethyl)-1H-pyrazol-4-yl)-1H-pyr- rolo[2,3-b]pyridin-5-yl)picolinamide; P-0214 and N-(2-cyanopropan-2-yl)-6-(2-(1-((methylsulfonyl)methyl)-1H-pyrazol-4-y- l)-1H-pyrrolo[2,3-b]pyridin-5- P-0215 yl)picolinamide;

or a pharmaceutically acceptable salt or a solvate of any one of the above compounds.

24. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier.

25. The pharmaceutical composition according to claim 24, further comprising a second pharmaceutical agent selected from the group consisting of an anti-proliferative agent, an anti-inflammatory agent, an immunomodulatory agent, and an immunosuppressive agent.

26. The pharmaceutical composition according to claim 24, further comprising a second pharmaceutical agent, wherein the second pharmaceutical agent is: i) an alkylating agent selected from adozelesin, altretamine, bizelesin, busulfan, carboplatin, carboquone, carmustine, chlorambucil, cisplatin, cyclophosphamide, dacarbazine, estramustine, fotemustine, hepsulfam, ifosfamide, improsulfan, irofulven, lomustine, mechlorethamine, melphalan, oxaliplatin, piposulfan, semustine, streptozocin, temozolomide, thiotepa, and treosulfan; ii) an antibiotic selected from bleomycin, dactinomycin, daunorubicin, doxorubicin, epirubicin, idarubicin, menogaril, mitomycin, mitoxantrone, neocarzinostatin, pentostatin, and plicamycin; an antimetabolite selected from the group consisting of azacitidine, capecitabine, cladribine, clofarabine, cytarabine, decitabine, floxuridine, fludarabine, 5-fluorouracil, ftorafur, gemcitabine, hydroxyurea, mercaptopurine, methotrexate, nelarabine, pemetrexed, raltitrexed, thioguanine, and trimetrexate; iii) an antibody therapy agent selected from alemtuzumab, bevacizumab, cetuximab, galiximab, gemtuzumab, panitumumab, pembrolizumab, pertuzumab, rituximab, tositumomab, trastuzumab, and 90 Y ibritumomab tiuxetan; a hormone or hormone antagonist selected from the group consisting of anastrozole, androgens, buserelin, diethylstilbestrol, exemestane, flutamide, fulvestrant, goserelin, idoxifene, letrozole, leuprolide, magestrol, raloxifene, tamoxifen, and toremifene; iv) a taxane selected from DJ-927, docetaxel, TPI 287, paclitaxel and DHA-paclitaxel; v) a retinoid selected from alitretinoin, bexarotene, fenretinide, isotretinoin, and tretinoin; vi) an alkaloid selected from etoposide, homoharringtonine, teniposide, vinblastine, vincristine, vindesine, and vinorelbine; vii) an antiangiogenic agent selected from AE-941 (GW786034, Neovastat), ABT-510, 2-methoxyestradiol, lenalidomide, and thalidomide; viii) a topoisomerase inhibitor selected from amsacrine, edotecarin, exatecan, irinotecan, SN-38 (7-ethyl-10-hydroxy-camptothecin)), rubitecan, topotecan, and 9-aminocamptothecin; ix) a kinase inhibitor selected from erlotinib, gefitinib, flavopiridol, imatinib mesylate, lapatinib, sorafenib, sunitinib malate, AEE-788, AG-013736, AMG 706, AMN107, BMS-354825, BMS-599626, UCN-01 (7-hydroxystaurosporine), vemurafenib, dabrafenib, trametinib, cobimetinib selumetinib and vatalanib; x) a targeted signal transduction inhibitor selected from bortezomib, geldanamycin, and rapamycin; xi) a biological response modifier selected from imiquimod, interferon-.alpha., and interleukin-2; xii) an IDO inhibitor; and xiii) a chemotherapeutic agent selected from 3-AP (3-amino-2-carboxyaldehyde thiosemicarbazone), altrasentan, aminoglutethimide, anagrelide, asparaginase, bryostatin-1, cilengitide, elesclomol, eribulin mesylate (E7389), ixabepilone, lonidamine, masoprocol, mitoguanazone, oblimersen, sulindac, testolactone, tiazofurin, a mTOR inhibitor, a PI3K inhibitor, a Cdk4 inhibitor, an Akt inhibitor, a Hsp90 inhibitor, a farnesyltransferase inhibitor and an aromatase inhibitor (anastrozole letrozole exemestane); xiii) a Mek inhibitor; xiv) a tyrosine kinase inhibitor; or xv) an EGFR inhibitor.

27. A method for treatment of a disease or condition modulated by a FLT3 protein kinase, wherein the disease or condition is an inflammatory disease, an inflammatory condition, an autoimmune disease or cancer, said method comprising administering to a subject suffering from the disease or condition a therapeutically effective amount of a compound according to claim 1.

28. A method for treatment of a disease or condition mediated by a FLT3 or c-Kit protein kinase, said method comprising administering to a subject suffering from the disease or condition a therapeutically effective amount of a compound according to claim 1, wherein the disease or condition is acute myeloid leukemia, stem cell ablation and myelopreparation for stem cell transplant, primary progressive multiple sclerosis, complex regional pain syndrome, reflex sympathetic dystrophy, muscular dystrophy, duchenne muscular dystrophy, causalgia, neuro-inflammation, neuroinflammatory disorders, benign forgetfulness, HIV, binswager type dementia, dementia with lewy bodie, prosencephaly, microencepahy, cerebral palsy, congenital hydrocephalus, abdominal dropsy, progressive supranuclear palsy, glaucoma, addiction disorders, dependencies, alcoholism, tremors, Wilson's disease, vascular dementias, multi infarct dementia, fronto temporal dementia, pseudo-dementia, bladder cancer, basal cell carcinoma, cholangiocarcinoma, colon cancer, endometrial cancer, esophageal cancer, Ewing's sarcoma, gastric cancer, glioma, hepatocellular carcinoma, Hodgkin lymphoma, laryngeal carcinoma, leukemia, liver cancer, lung cancer, melanoma, mesothelioma, pancreatic cancer, rectal cancer, renal cancer, squamous cell carcinoma, t cell lymphoma, thyroid cancer, monocytic leukemia, pheochromocytoma, malignant peripheral nerve cell tumors, malignant peripheral nerve sheath tumors (MPNST), cutaneous and plexiform neurofibromas, leiomyoadenomatoid tumor, fibroids, uterine fibroids, leiomyosarcoma, papillary thyroid cancer, anaplastic thyroid cancer, medullary thyroid cancer, follicular thyroid cancer, hurthle cell carcinoma, thyroid cancer, ascites, malignant ascites, mesothelioma, salivary gland tumors, mucoepidermoid carcinoma of the salivary gland, acinic cell carcinoma of the salivary gland, gastrointestinal stromal tumors (GIST), tumors that cause effusions in potential spaces of the body, pleural effusions, pericardial effusions, peritoneal effusions aka ascites, giant cell tumors (GCT), GCT of bone other sarcomas, tumor angiogenesis, or paracrine tumor growth.

29. A method for treatment of a disease or condition mediated by a FLT3 protein kinase, said method comprising administering to a subject suffering from the disease or condition a therapeutically effective amount of a compound according to claim 1, wherein the disease or condition is lysosomal storage selected from the group consisting of mucolipodosis, alpha-mannosidosis; aspartylglucosaminuria; Batten disease; beta-mannosidosis; cystinosis; Danon disease; Fabry disease; Farber disease; fucosidosis; galactosialidosis; Gaucher disease; gangliosidosis; Krabbe disease; metachromatic leukodystrophy; mucopolysaccharidoses disorders; aspartylglucosaminuria; Batten disease; beta-mannosidosis; cystinosis; Danon disease; Fabry disease; Farber disease; fucosidosis; galactosialidosis; Gaucher disease; gangliosidosis; Krabbe disease; metachromatic leukodystrophy; mucopolysaccharidoses disorders; mucolipidosis type I (Sialidosis); Mucolipidosis type II (I-Cell disease); Mucolipidosis type III (Pseudo-Hurler polydystrophy); Mucolipidosis type IV; multiple sulfatase deficiency; Niemann-Pick types A, B, C; Pompe disease (glycogen storage disease); pycnodysostosis; Sandhoff disease; Schindler disease; Salla disease/sialic acid storage disease; Tay-Sachs; and Wolman disease.

30. The method according to claim 27, wherein FLT3 kinase is a mutated form comprising a FLT3 internal tandem duplication (ITD) mutation.

31. The method according to claim 30, wherein mutated FLT3 kinase further comprises a D835 mutation, a F691L mutation, or both D835 and F691L mutations.

32. The method according to claim 31, wherein mutated FLT3 kinase further comprises a D835Y mutation, a F691L mutation, or both D835Y and F691L mutations.

33. A method for treatment of a disease or condition mediated by a (TGF-.beta.) receptor type 2, said method comprising administering to a subject suffering from the disease or condition a therapeutically effective amount of a compound according to claim 1, wherein the disease or condition is fibrosis, cardiovascular disease or cancer.

34. A compound having the structure: ##STR00300## or a pharmaceutically acceptable salt or a solvate thereof.

35. A compound having the structure: ##STR00301## or a pharmaceutically acceptable salt or a solvate thereof.

36. A compound having the structure: ##STR00302## or a pharmaceutically acceptable salt or a solvate thereof.

37. A compound having the structure: ##STR00303## or a pharmaceutically acceptable salt or a solvate thereof.

38. A compound having the structure: ##STR00304## or a pharmaceutically acceptable salt or a solvate thereof.

39. A compound having the structure: ##STR00305## or a pharmaceutically acceptable salt or a solvate thereof.

40. A compound having the structure: ##STR00306## or a pharmaceutically acceptable salt or a solvate thereof.

41. A compound having the structure: ##STR00307## or a pharmaceutically acceptable salt or a solvate thereof.

42. A compound having the structure: ##STR00308## or a pharmaceutically acceptable salt or a solvate thereof.

43. A compound having the structure: ##STR00309## or a pharmaceutically acceptable salt or a solvate thereof.

Details for Patent 9,938,273

Applicant Tradename Biologic Ingredient Dosage Form BLA Number Approval Date Patent No. Assignee Estimated Patent Expiration Status Orphan Source
Merck ELSPAR asparaginase VIAL 101063 001 1978-01-10   See Pricing Plexxikon Inc. (Berkeley, CA) 2035-12-07 RX search
Genentech RITUXAN rituximab VIAL 103705 001 1997-11-26   See Pricing Plexxikon Inc. (Berkeley, CA) 2035-12-07 RX search
Genentech HERCEPTIN trastuzumab VIAL; INTRAVENOUS 103792 001 1998-09-25   See Pricing Plexxikon Inc. (Berkeley, CA) 2035-12-07 RX Orphan search
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Number >Approval Date >Patent No. >Assignee >Estimated Patent Expiration >Status >Orphan >Source

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