Pyrrolo[2,3-b]pyridin-4-yl-amines and pyrrolo[2,3-b]pyrimidin-5-yl-amines as Janus kinase inhibitors
First Claim
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1. A method of treating allograft rejection or graft versus host a disease in a patient, comprising administering to said patient a therapeutically effective amount of a compound of Formula I:
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Abstract
The present invention provides pyrrolo[2,3-b]pyridine-4-yl amines pyrrolo[2,3-b]pyrimidin-4-yl amines that modulate the activity of Janus kinases and are useful in the treatment of diseases related to activity of Janus kinases including, for example, immune-related diseases and cancer.
81 Citations
32 Claims
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1. A method of treating allograft rejection or graft versus host a disease in a patient, comprising administering to said patient a therapeutically effective amount of a compound of Formula I:
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32)
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2. The method of claim 1 wherein R1 is H.
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3. The method of claim 1 wherein R2 is H.
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4. The method of claim 1 wherein R3 is H.
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5. The method of claim 1 wherein R4 is H or C1-4 alkyl.
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6. The method of claim 1 wherein R4 is methyl.
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7. The method of claim 1 wherein R5 is 3-8 membered heterocycloalkyl substituted by one R6 and 0, 1 or 2 R7.
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8. The method of claim 1 wherein R5 is 6-membered heterocycloalkyl substituted by one R6 and 0, 1 or 2 R7.
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9. The method of claim 1 wherein R5 is piperidinyl substituted by one R6 and 0, 1 or 2 R7.
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10. The method of claim 1 wherein R5 is piperidin-3-yl substituted by one R6 and 0, 1 or 2 R7.
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11. The method of claim 10 wherein R6 is substituted on the piperidinyl N-atom.
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12. The method of claim 1 wherein R5 is -L-pyrrolidinyl;
- L is C1-4 alkylenyl; and
said pyrrolidinyl is substituted by one R6 and 0, 1 or 2 R7.
- L is C1-4 alkylenyl; and
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13. The method of claim 1 wherein R5 is -L-pyrrolidin-2-yl;
- L is C1-4 alkylenyl and said pyrrolidin-2-yl is substituted by one R6 and 0, 1 or 2 R7.
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14. The method of claim 1 wherein W2 is SO2, CO, COO, C(S)NR12, or CONR12.
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15. The method of claim 1 wherein W2 is SO2, CO, COO, C(S)NH, CONH or —
- CON(C1-4 alkyl)-.
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16. The method of claim 1 wherein W2 is SO2 or CO.
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17. The method of claim 1 wherein W3 is C1-4alkylenyl or cycloalkyl.
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18. The method of claim 1 wherein R13 is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl or heterocycloalkylalkyl, each optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from:
C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, heterocycloalkylalkyl, halo, CN, NO2, ORa″
, SRa″
, C(O)Rb″
, C(O)NRc″
Rd″
, C(O)ORa″
, OC(O)Rb″
, OC(O)NRc″
Rd″
, NRc″
Rd″
, NRc″
C(O)Rd″
, NRc″
C(O)ORa″
, S(O)Rb″
, S(O)NRc″
Rd″
, S(O)2Rb″
, S(O)2NRc″
Rd″
, —
(C1-6 alkyl)-CN, —
(C1-6 alkyl)-NO2, —
(C1-6 alkyl)-ORa″
, —
(C1-6 alkyl)-SRa″
, —
(C1-6 alkyl)-C(O)Rb″
, —
(C1-6 alkyl)-C(O)NRc″
Rd″
, —
(C1-6 alkyl)-C(O)ORa″
, —
(C1-6 alkyl)-OC(O)Rb″
, —
(C1-6 alkyl)-OC(O)NRc″
Rd″
, —
(C1-6 alkyl)-NRc″
Rd″
, —
(C1-6 alkyl)-NRc″
C(O)Rd″
, —
(C1-6 alkyl)-NRc″
C(O)ORa″
, —
(C1-6 alkyl)-S(O)Rb″
, —
(C1-6 alkyl)-S(O)NRc″
Rd″
, —
(C1-6 alkyl)-S(O)2Rb″
, and —
(C1-6 alkyl)-S(O)2NRc″
Rd″
.
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19. The method of claim 1 wherein R13 is C1-6 alkyl, C1-6 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl or heterocycloalkylalkyl, each optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from:
C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, heterocycloalkylalkyl, halo, CN, NO2, ORa″
, SRa″
, C(O)Rb″
, C(O)NRc″
Rd″
, C(O)ORa″
, OC(O)Rb″
, OC(O)NRc″
Rd″
, NRc″
Rd″
, NRc″
C(O)Rd″
, NRc″
C(O)ORa″
, S(O)Rb″
, S(O)NRc″
Rd″
, S(O)2Rb″
, S(O)2NRc″
Rd″
, —
(C1-6 alkyl)-CN, —
(C1-6 alkyl)-NO2, —
(C1-6 alkyl)-ORa″
, —
(C1-6 alkyl)-SRa″
, —
(C1-6 alkyl)-C(O)Rb″
, —
(C1-6 alkyl)-C(O)NRc″
Rd″
, —
(C1-6 alkyl)-C(O)ORa″
, —
(C1-6 alkyl)-OC(O)Rb″
, —
(C1-6 alkyl)-OC(O)NRc″
Rd″
, —
(C1-6 alkyl)-NRc″
Rd″
, —
(C1-6 alkyl)-NRc″
C(O)Rd″
, —
(C1-6 alkyl)-NRc″
C(O)ORa″
, —
(C1-6 alkyl)-S(O)Rb″
, —
(C1-6 alkyl)-S(O)NRc″
Rd″
, —
(C1-6 alkyl)-S(O)2Rb″
, and —
(C1-6 alkyl)-S(O)2NRc″
Rd″
.
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20. The method of claim 1 wherein R13 is C1-6 alkyl, C1-6 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl or heterocycloalkylalkyl, each optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from C1-6 alkyl, C1-6 haloalkyl, aryl, heteroaryl, halo, CN, ORa″
- , SRa″
, C(O)Rb″
, C(O)ORa″
, NRc″
C(O)Rd″
, S(O)2Rb″
, and —
(C1-6 alkyl)-CN.
- , SRa″
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21. The method of claim 1 wherein R13 is C1-6 alkyl, C1-6 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl or heterocycloalkylalkyl, each optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from C1-6 alkyl, C1-6 haloalkyl, aryl, heteroaryl, halo, CN, OH, C1-4-alkoxy, C1-4-haloalkoxy, heteroaryloxy, aryloxy, —
- SC1-6 alkyl, —
C(O)—
C1-6 alkyl, —
C(O)OC1-6 alkyl, —
S(O)2C1-6 alkyl, —
NHC(O)—
C1-6 alkyl, and —
(C1-6 alkyl)-CN.
- SC1-6 alkyl, —
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22. The method of claim 1 where R13 is OH or CN.
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23. The method of claim 1 wherein W1 is absent, W2 is CO or SO2, W3 is C1-4 alkyleneyl or cycloalkyl, W4 is absent, W5 is absent, W6 is absent, and R13 is CN or OH.
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24. The method of claim 1 wherein R6 is —
- W2—
W3—
R13.
- W2—
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25. The method of claim 1 wherein R6 is —
- CO—
CH2—
CN.
- CO—
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26. The method of claim 1 wherein R6 is —
- W2—
R13.
- W2—
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27. The method of claim 1 wherein:
-
R6 is —
W2—
R13;W2 is SO2, CO, COO, C(S)NR12, or CONR12; and R13 is C1-6 alkyl, C1-6 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl or heterocycloalkylalkyl, each optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from; C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, heterocycloalkylalkyl, halo, CN, NO2, ORa″
, SRa″
, C(O)Rb″
, C(O)NRc″
Rd″
, C(O)ORa″
, OC(O)Rb″
, OC(O)NRc″
Rd″
, NRc″
Rd″
, NRc″
C(O)Rd″
, NRc″
C(O)ORa″
, S(O)Rb″
, S(O)NRc″
Rd″
, S(O)2Rb″
, S(O)2NRc″
Rd″
, —
(C1-6 alkyl)-CN, —
(C1-6 alkyl)-NO2, —
(C1-6 alkyl)-ORa″
, —
(C1-6 alkyl)-SRa″
, —
(C1-6 alkyl)-C(O)Rb″
, —
(C1-6 alkyl)-C(O)NRc″
Rd″
, —
(C1-6 alkyl)-C(O)ORa″
, —
(C1-6 alkyl)-OC(O)Rb″
, —
(C1-6 alkyl)-OC(O)NRc″
Rd″
, —
(C1-6 alkyl)-NRc″
Rd″
, —
(C1-6 alkyl)-NRc″
C(O)Rd″
, —
(C1-6 alkyl)-NRc″
C(O)ORa″
, —
(C1-6 alkyl)-S(O)Rb″
, —
(C1-6 alkyl)-S(O)NRc″
Rd″
, —
(C1-6 alkyl)-S(O)2Rb″
, and —
(C1-6 alkyl)-S(O)2NRc″
Rd″
.
-
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28. The method of claim 1 wherein said compound has the structure of Formula I-A:
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29. The method of claim 28 wherein:
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W2 is SO2, CO, COO, C(S)NR12, or CONR12; and R13 is C1-6 alkyl, C1-6 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl or heterocycloalkylalkyl, each optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from; C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, heterocycloalkylalkyl, halo, CN, NO2, ORa″
, SRa″
, C(O)Rb″
, C(O)NRc″
Rd″
, C(O)ORa″
, OC(O)Rb″
, OC(O)NRc″
Rd″
, NRc″
Rd″
, NRc″
C(O)Rd″
, NRc″
C(O)ORa″
, S(O)Rb″
, S(O)NRc″
Rd″
, S(O)2Rb″
, S(O)2NRc″
Rd″
, —
(C1-6 alkyl)-CN, —
(C1-6 alkyl)-NO2, —
(C1-6 alkyl)-ORa″
, —
(C1-6 alkyl)-SRa″
, —
(C1-6 alkyl)-C(O)Rb″
, —
(C1-6 alkyl)-C(O)NRc″
Rd″
, —
(C1-6 alkyl)-C(O)ORa″
, —
(C1-6 alkyl)-OC(O)Rb″
, —
(C1-6 alkyl)-OC(O)NRc″
Rd″
, —
(C1-6 alkyl)-NRc″
Rd″
, —
(C1-6 alkyl)-NRc″
C(O)Rr, —
(C1-6 alkyl)-NRc″
C(O)ORa″
, —
(C1-6 alkyl)-S(O)Rb″
, —
(C1-6 alkyl)-S(O)NRc″
Rd″
, —
(C1-6 alkyl)-S(O)2Rb″
, and —
(C1-6 alkyl)-S(O)2NRc″
Rd″
.
-
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30. The method of claim 1 wherein the compound has the structure of Formula I-B:
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31. The method of claim 30 wherein:
-
R13 is C1-6 alkyl, C1-6 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl or heterocycloalkylalkyl, each optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from C1-6 alkyl, C1-6 haloalkyl, aryl, heteroaryl, halo, CN, ORa″
, SRa″
, C(O)Rb″
, C(O)ORa″
, NRc″
C(O)Rd″
, S(O)2Rb″
, and —
(C1-6 alkyl)-CN;W2 is SO2, CO, COO, C(S)NH, CONH or —
CON(C1-4 alkyl)-; andR4 is C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, S(O)2R9, SOR9, cycloalkyl, or heterocycloalkyl, wherein said C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, cycloalkyl, heterocycloalkyl are each optionally substituted with 1, 2 or 3 substituents selected from halo, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO2, ORa, SRa, C(O)Rb, C(O)NRcRd, C(O)ORa, OC(O)Rb, OC(O)NRcRd, NRcRd, NRcC(O)Rd, NRcC(O)ORa, S(O)Rb, S(O)NRcRd, S(O)2Rb, and S(O)2NRcRd.
-
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32. The method of claim 1 wherein the compound is selected from:
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3-{3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidin-1-yl}-3-oxopropanenitrile; 3-{(3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidin-1-yl}-3-oxopropanenitrile; N-methyl-N-[(3R,4R)-4-methyl-1-(phenylsulfonyl)piperidin-3-yl]-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-[(3R,4R)-1-(methoxyacetyl)-4-methylpiperidin-3-yl]-N-methyl-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; (3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]-N-phenylpiperidine-1-carboxamide; (3R,4R)—
N-benzyl-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidine-1-carboxamide;(3R,4R)—
N-ethyl-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidine-1-carboxamide;(3R,4R)—
N-isopropyl-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidine-1-carboxamide;N-[(3R,4R)-1-isobutyryl-4-methylpiperidin-3-yl]-N-methyl-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-methyl-N-[(3R,4R)-4-methyl-1-(morpholin-4-ylcarbonyl)piperidin-3-yl]-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-[(3R,4R)-1-acetyl-4-methylpiperidin-3-yl]-N-methyl-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-methyl-N-[(3R,4R)-4-methyl-1-(3-methylbutanoyl)piperidin-3-yl]-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-[(3R,4R)-1-benzoyl-4-methylpiperidin-3-yl]-N-methyl-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; (3R,4R)—
N,N,4-trimethyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidine-1-carboxamide;4-({(3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidin-1-yl}carbonyl)benzonitrile; N-[(3R,4R)-1-(cyclopropylcarbonyl)-4-methylpiperidin-3-yl]-N-methyl-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-[(3R,4R)-1-isonicotinoyl-4-methylpiperidin-3-yl]-N-methyl-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-{(3R,4R)-1-[(1-acetylpiperidin-4-yl)carbonyl]-4-methylpiperidin-3-yl}-N-methyl-N-(1 H-pyrrolo[2,3-b]pyridin-4-yl)-amine; Phenyl (3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidine-1-carboxylate; Methyl (3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidine-1-carboxylate; N-methyl-N-[(3R,4R)-4-methyl-1-(trifluoroacetyl)piperidin-3-yl]-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-[(3R,4R)-1-(2-furoyl)-4-methylpiperidin-3-yl]-N-methyl-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; (3R,4R)—
N-(4-cyanophenyl)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidine-1-carboxamide;(3R,4R)—
N-(3-cyanophenyl)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidine-1-carboxamide;(3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]-N-(2-phenylethyl)piperidine-1-carboxamide; (3R,4R)—
N-(2-furylmethyl)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidine-1-carboxamide;N-methyl-N-[(3R,4R)-4-methyl-1-(propylsulfonyl)piperidin-3-yl]-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-[(3R,4R)-1-(isopropylsulfonyl)-4-methylpiperidin-3-yl]-N-methyl-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; 4-({(3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidin-1-yl}sulfonyl)benzonitrile; 2-({(3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidin-1-yl}sulfonyl)benzonitrile; N-methyl-N-[(3R,4R)-4-methyl-1-(methylsulfonyl)piperidin-3-yl]-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-methyl-N-{(3R,4R)-4-methyl-1-[(trifluoromethyl)sulfonyl]piperidin-3-yl}-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-methyl-N-[(3R,4R)-4-methyl-1-(pyridin-3-ylsulfonyl)piperidin-3-yl]-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; 2-fluoro-5-({(3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidin-1-yl}sulfonyl)benzonitrile; N-methyl-N-[(3R,4R)-4-methyl-1-(3-pyridin-3-ylpropanoyl)piperidin-3-yl]-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-methyl-N-[(3R,4R)-4-methyl-1-(3,3,3-trifluoropropanoyl)piperidin-3-yl]-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-methyl-N-[(3R,4R)-4-methyl-1-(tetrahydrofuran-2-ylcarbonyl)piperidin-3-yl]-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; (2R)-1-{(3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidin-1-yl}-1-oxopropan-2-ol; (2R)-1-{(3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidin-1-yl}-1-oxopropan-2-ol; N-methyl-N-[(3R,4R)-4-methyl-1-(3-phenylpropanoyl)piperidin-3-yl]-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; (3R,4R)—
N-(4-cyanophenyl)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidine-1-carbothioamide;N-methyl-N-{(3R,4R)-4-methyl-1-[(5-methylisoxazol-4-yl)sulfonyl]piperidin-3-yl}-N-(1 H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-methyl-N-{(3R,4R)-4-methyl-1-[(1-methyl-1H-imidazol-4-yl)sulfonyl]piperidin-3-yl}-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-{(3R,4R)-1-[(3,5-dimethylisoxazol-4-yl)carbonyl]-4-methylpiperidin-3-yl}-N-methyl-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; (3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]-N-2-thienylpiperidine-1-carboxamide; N-[(3R,4R)-1-(isoxazol-5-ylcarbonyl)-4-methylpiperidin-3-yl]-N-methyl-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-{(3R,4R)-1-[(1,2-dimethyl-1H-imidazol-4-yl)sulfonyl]-4-methylpiperidin-3-yl}-N-methyl-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-[4-methyl-5-({(3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidin-1-yl}sulfonyl)-1,3-thiazol-2-yl]acetamide; N-{(3R,4R)-1-[(2,4-dimethyl-1,3-thiazol-5-yl)sulfonyl]-4-methylpiperidin-3-yl}-N-methyl-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-methyl-N-{(3R,4R)-4-methyl-1-[(1,3,5-trimethyl-1H-pyrazol-4-yl)sulfonyl]piperidin-3-yl}-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-{(3R,4R)-1-[(3,5-dimethylisoxazol-4-yl)sulfonyl]-4-methylpiperidin-3-yl}-N-methyl-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-methyl-N-{(3R,4R)-4-methyl-1-[(pyridin-4-ylmethyl)sulfonyl]piperidin-3-yl}-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-methyl-N-{(3R,4R)-4-methyl-1-[(pyridin-3-ylmethyl)sulfonyl]piperidin-3-yl}-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-methyl-N-{(3R,4R)-4-methyl-1-[(pyridin-2-ylmethyl)sulfonyl]piperidin-3-yl}-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; 4-({(3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidin-1-yl}sulfonyl)benzonitrile; (3R,4R)—
N-(4-cyanophenyl)-N,4-dimethyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidine-1-carboxamide;(3R,4R)—
N-(4-cyanophenyl)-N-ethyl-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidine-1-carboxamide;(3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]-N-1,3-thiazol-2-ylpiperidine-1-carboxamide; (3R,4R)-4-methyl-N-(3-methylisoxazol-5-yl)-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidine-1-carboxamide; 3-chloro-4-({(3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidin-1-yl}sulfonyl)benzonitrile; (3R,4R)-4-methyl-N-(5-methylisoxazol-3-yl)-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidine-1-carboxamide; (3R,4R)—
N-isoxazol-3-yl-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidine-1-carboxamide;N-methyl-N-{(3R,4R)-4-methyl-1-[(5-pyridin-3-yl-2-thienyl)sulfonyl]piperidin-3-yl}-N-(1 H-pyrrolo[2,3-b]pyridin-4-yl)-amine; (3R,4R)—
N-(3-cyano-2-thienyl)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidine-1-carboxamide;(3R,4R)—
N-1,3-benzothiazol-2-yl-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidine-1-carboxamide;N-[(3R,4R)-1-(2,3-dihydro-1H-indol-1-ylcarbonyl)-4-methylpiperidin-3-yl]-N-methyl-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-methyl-N-{(3R,4R)-4-methyl-1-[(methylthio)acetyl]piperidin-3-yl}-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; (3R,4R)—
N-(4,5-dihydro-1,3-thiazol-2-yl)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidine-1-carboxamide;(3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]-N-(1,3-thiazol-2-ylmethyl)piperidine-1-carboxamide; 1-({(3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidin-1-yl}carbonyl)piperidine-4-carbonitrile; 1-({(3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidin-1-yl}carbonyl)piperidine-3-carbonitrile; 1-({(3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidin-1-yl}carbonyl)pyrrolidine-3-carbonitrile; (3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]-N-(3-thienylmethyl)piperidine-1-carboxamide; (3R,4R)—
N-(2-benzothien-1-ylmethyl)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidine-1-carboxamide;(3R,4R)—
N-(1,3-benzothiazol-2-ylmethyl)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidine-1-carboxamide;N-[(3R,4R)-1-(3-furylacetyl)-4-methylpiperidin-3-yl]-N-methyl-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; 3-(2-{(3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidin-1-yl}-2-oxoethyl)-1,3-thiazolidine-2,4-dione; 3-(2-{(3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidin-1-yl}-2-oxoethyl)-1,3-benzothiazol-2(3H)-one; (3R,4R)—
N-[5-(cyanomethyl)-4,5-dihydro,-1,3-thiazol-2-yl]-3-[methyl-(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]-4-methyl-piperidine-1-carboxamide;(3R)-1-({(3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidin-1-yl}carbonyl)pyrrolidine-3-carbonitrile; (3R)-1-({(3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidin-1-yl}carbonyl)pyrrolidine-3-carbonitrile; 1-({(3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidin-1-yl}carbonyl)-4-phenylpiperidine-4-carbonitrile; N-methyl-N-((3R,4R)-4-methyl-1-{[3-(trifluoromethyl)pyrrolidin-1-yl]carbonyl}piperidin-3-yl)-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; 1-({(3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidin-1-yl}carbonyl)azetidine-3-carbonitrile; 4-methyl-1-({(3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidin-1-yl}carbonyl)pyrrolidine-3-carbonitrile; 1-({(3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidin-1-yl}carbonyl)pyrrolidine-3,4-dicarbonitrile; 3-methyl-1-({(3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidin-1-yl}carbonyl)pyrrolidine-3-carbonitrile; (3R,4R)—
N-(2-cyanoethyl)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidine-1-carboxamide;4-methoxy-1-({(3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidin-1-yl}carbonyl)pyrrolidine-3-carbonitrile; N-{(3R,4R)-1-[(2R)-2-aminopropanoyl]-4-methylpiperidin-3-yl}-N-methyl-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-[(3R,4R)-1-(aminoacetyl)-4-methylpiperidin-3-yl]-N-methyl-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; 1-(2-{(3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidin-1-yl}-2-oxoethyl)piperidine-4-carbonitrile; N-methyl-N-[(3R,4R)-4-methyl-1-(1,3-thiazol-4-ylcarbonyl)piperidin-3-yl]-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine bis(trifluoroacetate); 4-(2-2S-{[methyl-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amino]-methyl}-pyrrolidin-1-yl-sulfonyl)-benzonitrile trifluoroacetate; N-[(1-methanesulfonyl-2S-pyrrolidin-2-yl)-methyl]-N-methyl-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine trifluoroacetate; 3-((2S)-2-{[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]methyl}pyrrolidin-1-yl)-3-oxopropanenitrile trifluoroacetate; Methyl 3-[({(3R,4R)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidine-1-yl}carbonyl)-amino]benzoate; (3R,4R)—
N-(4-trifluoromethoxyphenyl)-4-methyl-3-[methyl-(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidine-1-carboxamide;(3R,4R)—
N-(4-fluorophenyl)-4-methyl-3-[methyl-(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidine-1-carboxamide;(3R,4R)—
N-(3-fluorophenyl)-4-methyl-3-[methyl-(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidine-1-carboxamide;(3R,4R)—
N-(2-fluorophenyl)-4-methyl-3-[methyl-(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidine-1-carboxamide;(3R,4R)—
N-(4-trifluoromethylphenyl)-4-methyl-3-[methyl-(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidine-1-carboxamide;(3R,4R)—
N-(2-methoxyphenyl)-4-methyl-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)amino]piperidine-1-carboxamide;(3R,4R)-4-methyl-N-(4-methylphenyl)-3-[methyl(1H-pyrrolo[2,3-b]pyridin-4-yl)-amino]piperidine-1-carboxamide; N-methyl-N-{(3R,4R)-4-methyl-1-[4-(pyridin-2-yloxy)phenyl]sulfonyl-piperidin-3-yl}-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-methyl-N-{(3R,4R)-4-methyl-1-[4-(1,3-oxazol-5-yl)phenyl]sulfonyl-piperidin-3-yl}-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-methyl-N-{(3R,4R)-4-methyl-1-[5-(1,3-oxazol-5-yl)thienyl]sulfonyl-piperidin-3-yl}-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-methyl-N-{(3R,4R)-4-methyl-1-[(6-phenoxy-pyridin-3-yl)sulfonyl]piperidin-3-yl}-(1H-pyrrolo[2,3-b]pyridin-4-yl)amine; N-{(3R,4R)-1-[(2,6-dichlorophenyl)sulfonyl]-4-methylpiperidin-3-yl}-N-methyl-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-{(3R,4R)-1-[(4-fluorophenyl)sulfonyl]-4-methylpiperidin-3-yl}-N-methyl-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-{(3R,4R)-1-[(3-fluorophenyl)sulfonyl]-4-methylpiperidin-3-yl}-N-methyl-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-{(3R,4R)-1-[(2-fluorophenyl)sulfonyl]-4-methylpiperidin-3-yl}-N-methyl-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-{(3R,4R)-4-methyl-1-[4-(trifluoromethyl)phenyl]sulfonyl-piperidin-3-yl}-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-{(3R,4R)-4-methyl-1-[3-(trifluoromethyl)phenyl]sulfonyl-piperidin-3-yl}-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-{(3R,4R)-4-methyl-1-[2-(trifluoromethyl)phenyl]sulfonyl-piperidin-3-yl}-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-{(3R,4R)-1-[(4-methoxyphenyl)sulfonyl]-4-methylpiperidin-3-yl}-N-methyl-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-{(3R,4R)-1-[(3-methoxyphenyl)sulfonyl]-4-methylpiperidin-3-yl}-N-methyl-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-methyl-N-{(3R,4R)-4-methyl-1-[(4-methylphenyl)sulfonyl]piperidin-3-yl}-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-methyl-N-{(3R,4R)-4-methyl-1-[(3-methylphenyl)sulfonyl]piperidin-3-yl}-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-methyl-N-{(3R,4R)-4-methyl-1-[(2-methylphenyl)sulfonyl]piperidin-3-yl}-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-{(3R,4R)-1-[(4-chlorophenyl)sulfonyl]-4-methylpiperidin-3-yl}-N-methyl-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; N-{(3R,4R)-1-[(3-chlorophenyl)sulfonyl]-4-methylpiperidin-3-yl}-N-methyl-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine; and N-{(3R,4R)-1-[(2-chlorophenyl)sulfonyl]-4-methylpiperidin-3-yl}-N-methyl-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)-amine, or a pharmaceutically acceptable salt thereof.
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2. The method of claim 1 wherein R1 is H.
Specification
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Current AssigneeIncyte Holdings Corporation And Incyte Corporation
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Original AssigneeIncyte Corporation
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InventorsRodgers, James D., Wang, Haisheng, Combs, Andrew P., Sparks, Richard B.
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Primary Examiner(s)Rahmani, Niloofar
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Application NumberUS13/889,618Publication NumberTime in Patent Office391 DaysField of Search514/233.8, 514/300US Class Current514/233.8CPC Class CodesA61P 1/04 for ulcers, gastritis or re...A61P 17/00 Drugs for dermatological di...A61P 17/06 AntipsoriaticsA61P 19/02 for joint disorders, e.g. a...A61P 25/00 Drugs for disorders of the ...A61P 29/00 Non-central analgesic, anti...A61P 3/10 for hyperglycaemia, e.g. an...A61P 31/12 AntiviralsA61P 31/14 for RNA virusesA61P 31/18 for HIVA61P 31/20 for DNA virusesA61P 35/00 Antineoplastic agentsA61P 37/00 Drugs for immunological or ...A61P 37/02 ImmunomodulatorsA61P 37/06 Immunosuppressants, e.g. dr...A61P 37/08 Antiallergic agents antiast...A61P 43/00 Drugs for specific purposes...A61P 5/14 of the thyroid hormones, e....C07D 471/04 Ortho-condensed systemsC07D 487/04 Ortho-condensed systems