Pyrrolo[2,3-b]pyridin-4-yl-amines and pyrrolo[2,3-b]pyrimidin-4-yl-amines as Janus kinase inhibitors
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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.
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Citations
38 Claims
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1. 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, 33)
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2. The compound of claim 1, or pharmaceutically acceptable salt thereof, wherein R1 is H.
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3. The compound of claim 1, or pharmaceutically acceptable salt thereof, wherein R2 is H.
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4. The compound of claim 1, or pharmaceutically acceptable salt thereof, wherein R3 is H.
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5. The compound of claim 1, or pharmaceutically acceptable salt thereof, wherein R4 is H or C1-4 alkyl.
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6. The compound of claim 1, or pharmaceutically acceptable salt thereof, wherein R4 is methyl.
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7. The compound of claim 1, or pharmaceutically acceptable salt thereof, wherein R5 is 3-8 membered heterocycloalkyl substituted by one R6 and 0, 1 or 2 R7.
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8. The compound of claim 1, or pharmaceutically acceptable salt thereof, wherein R5 is 6-membered heterocycloalkyl substituted by one R6 and 0, 1 or 2 R7.
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9. The compound of claim 1, or pharmaceutically acceptable salt thereof, wherein R5 is piperidinyl substituted by one R6 and 0, 1 or 2R7.
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10. The compound of claim 1, or pharmaceutically acceptable salt thereof, wherein R5 is piperidin-3-yl substituted by one R6 and 0, 1 or 2 R7.
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11. The compound of claim 10, or pharmaceutically acceptable salt thereof, wherein R6 is substituted on the piperidinyl N-atom.
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12. The compound of claim 1, or pharmaceutically acceptable salt thereof, 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—
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13. The compound of claim 1, or pharmaceutically acceptable salt thereof, 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.
- L—
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14. The compound of claim 1, or pharmaceutically acceptable salt thereof, wherein W2 is SO2, CO, COO, C(S)NR12, or CONR12.
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15. The compound of claim 1, or pharmaceutically acceptable salt thereof, wherein W2 is SO2, CO, COO, C(S)NH, CONH or —
- CON(C1-4 alkyl)-.
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16. The compound of claim 1, or pharmaceutically acceptable salt thereof, wherein W2 is SO2 or CO.
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17. The compound of claim 1, or pharmaceutically acceptable salt thereof, wherein W3 is C1-4 alkylenyl or cycloalkyl.
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18. The compound of claim 1, or pharmaceutically acceptable salt thereof, 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)ORd″
, —
(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 compound of claim 1, or pharmaceutically acceptable salt thereof, 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 compound of claim 1, or pharmaceutically acceptable salt thereof, 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 compound of claim 1, or pharmaceutically acceptable salt thereof, 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 compound of claim 1, or pharmaceutically acceptable salt thereof, where R13 is OH or CN.
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23. The compound of claim 1, or pharmaceutically acceptable salt thereof, 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 compound of claim 1, or pharmaceutically acceptable salt thereof, wherein R6 is —
- W2—
W3—
R13.
- W2—
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25. The compound of claim 1, or pharmaceutically acceptable salt thereof, wherein R6 is —
- CO—
CH2—
CN.
- CO—
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26. The compound of claim 1, or pharmaceutically acceptable salt thereof, wherein R6 is —
- W2—
R13.
- W2—
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27. The compound of claim 1, or pharmaceutically acceptable salt thereof, wherein:
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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″
—
(C1-6alkyl)-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 compound of claim 1 having the structure of Formula I-A:
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29. The compound of claim 28, or pharmaceutically acceptable salt thereof, 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)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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30. The compound of claim 1 having the structure of Formula I-B:
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31. The compound of claim 30, or pharmaceutically acceptable salt thereof, 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.
- , SRa″
-
32. A compound of claim 1 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-(1H-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; (2S)-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-(1H-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-(1H-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; (3S)-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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33. A composition comprising a compound of claim 1, or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
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2. The compound of claim 1, or pharmaceutically acceptable salt thereof, wherein R1 is H.
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34. A pharmaceutical composition for topical administration comprising a compound of Formula II:
- View Dependent Claims (35, 36, 37, 38)
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35. The composition of claim 34 wherein said topical administration comprises transdermal administration.
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36. The composition of claim 34 which is in the form of a transdermal patch, ointment, lotion, cream, or gel.
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37. The composition of claim 34 wherein A is CR1.
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38. The composition of claim 34 wherein A is N.
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35. The composition of claim 34 wherein said topical administration comprises transdermal administration.
Specification
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Current AssigneeIncyte Holdings Corporation And Incyte Corporation
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Original AssigneeIncyte Corporation
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InventorsCombs, Andrew P., Wang, Haisheng, Sparks, Richard B., Rodgers, James D.
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Primary Examiner(s)Seaman; Margaret D.
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Assistant Examiner(s)Rahmani; Niloofar
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Application NumberUS11/313,394Publication NumberTime in Patent Office797 DaysField of Search546/113, 514/300, 514/233.8, 544/235, 544/116US Class Current514/300CPC 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