PYRROLO[2,3-b]PYRIDIN-4-YL-AMINES AND PYRROLO[2,3-b]PYRIMIDIN-5-YL-AMINES AS JANUS KINASE INHIBITORS

US 20140228346A1
Filed: 04/17/2014
Published: 08/14/2014
Est. Priority Date: 12/22/2004
Status: Active Grant

First Claim

Patent Images

1. A compound of Formula I:

View all claims

3 Assignments

Timeline View

Assignment View

0 Petitions

Accused Products

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.

58 Citations

View as Search Results

45 Claims

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, 41, 43, 44)
- - 2. The compound of claim 1 wherein R¹is H.
  - 3. The compound of claim 1 wherein R²is H.
  - 4. The compound of claim 1 wherein R³is H.
  - 5. The compound of claim 1 wherein R⁴is H or C_1-4alkyl.
  - 6. The compound of claim 1 wherein R⁴is methyl.
  - 7. The compound of claim 1 wherein R⁵is 3-8 membered heterocycloalkyl substituted by one R⁶and 0, 1 or 2 R⁷.
  - 8. The compound of claim 1 wherein R⁵is 6-membered heterocycloalkyl substituted by one R⁶and 0, 1 or 2 R⁷.
  - 9. The compound of claim 1 wherein R⁵is piperidinyl substituted by one R⁶and 0, 1 or 2 R⁷.
  - 10. The compound of claim 1 wherein R⁵is piperidin-3-yl substituted by one R⁶and 0, 1 or 2 R⁷.
  - 11. The compound of claim 10 wherein R⁶is substituted on the piperidinyl N-atom.
  - 12. The compound of claim 1 wherein R⁵is L-pyrrolidinyl;
    - L is C_1-4alkylenyl; and
      
      said pyrrolidinyl is substituted by one R⁶and 0, 1 or 2 R⁷.
  - 13. The compound of claim 1 wherein R⁵is L-pyrrolidin-2-yl;
    - L is C_1-4alkylenyl and said pyrrolidin-2-yl is substituted by one R⁶and 0, 1 or 2 R⁷.
  - 14. The compound of claim 1 wherein W²is SO₂, CO, COO, C(S)NR¹², or CONR¹².
  - 15. The compound of claim 1 wherein W²is SO₂, CO, COO, C(S)NH, CONH or —
    - CON(C_1-4alkyl)-.
  - 16. The compound of claim 1 wherein W²is SO₂or CO.
  - 17. The compound of claim 1 wherein W³is C_1-4alkylenyl or cycloalkyl.
  - 18. The compound of claim 1 wherein R¹³is C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl or heterocycloalkylalkyl, each optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from:
    - C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, heterocycloalkylalkyl, halo, CN, NO₂, OR^a″, S R^a″, C(O)R^b″, C(O)NR^c″R^d″, C(O)OR^a″, OC(O)R^b″, OC(O)NR^c″R^d″, NR^c″R^d″, NR^c″C(O)R^d″, NR^c″C(O)OR^a″, S(O)R^b″, S(O)NR^c″R^d″, S(O)₂R^b″, S(O)₂NR^c″
      
      R^d″, —
      
      (C_1-6alkyl)-CN, —
      
      (C_1-6alkyl)-NO₂, —
      
      (C_1-6alkyl)-OR^a″, —
      
      (C_1-6alkyl)-SR^a″, —
      
      (C_1-6alkyl)-C(O)R^b″, —
      
      (C_1-6alkyl)-C(O)NR^c″R^d″, —
      
      (C_1-6alkyl)-C(O)OR^a″, —
      
      (C_1-6alkyl)-OC(O)R^b″, —
      
      (C_1-6alkyl)-OC(O)NR^c″R^d″, —
      
      (C_1-6alkyl)-NR^c″R^d″, —
      
      (C_1-6alkyl)-NR^c″C(O)R^d″, —
      
      (C_1-6alkyl)-NR^c″C(O)OR^a″, —
      
      (C_1-6alkyl)-S(O)R^b″, —
      
      (C_1-6alkyl)-S(O)NR^c″R^d″, —
      
      (C_1-6alkyl)-S(O)₂R^b″, and —
      
      (C_1-6alkyl)-S(O)₂NR^c″R^d″.
  - 19. The compound of claim 1 wherein R¹³is C_1-6alkyl, C_1-6haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl or heterocycloalkylalkyl, each optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from:
    - C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, heterocycloalkylalkyl, halo, CN, NO₂, OR^a″, SR^a″, C(O)R^b″, C(O)NR^c″R^d″, C(O)OR^a″, OC(O)R^b″, OC(O)NR^c″R^d″, NR^c″R^d″, NR^c″C(O)R^d″, NR^c″C(O)OR^a″, S(O)R^b″, S(O)NR^c″R^d″, S(O)₂R^b″, S(O)₂NR^c″R^d″, —
      
      (C_1-6alkyl)-CN, —
      
      (C_1-6alkyl)-NO₂, —
      
      (C_1-6alkyl)-OR^a″, —
      
      (C_1-6alkyl)-SR^a″, —
      
      (C_1-6alkyl)-C(O)R^b″, —
      
      (C_1-6alkyl)-C(O)NR^c″R^d″, —
      
      (C_1-6alkyl)-C(O)OR^a″, —
      
      (C_1-6alkyl)-OC(O)R^b″, —
      
      (C_1-6alkyl)-OC(O)NR^c″R^d″, —
      
      (C_1-6alkyl)-NR^c″R^d″, —
      
      (C_1-6alkyl)-NR^c″C(O)R^d″, —
      
      (C_1-6alkyl)-NR^c″C(O)OR^a″, —
      
      (C_1-6alkyl)-S(O)R^b″, —
      
      (C_1-6alkyl)-S(O)NR^c″R^d″, —
      
      (C_1-6alkyl)-S(O)₂R^b″, and —
      
      (C_1-6alkyl)-S(O)₂NR^c″R^d″.
  - 20. The compound of claim 1 wherein R¹³is C_1-6alkyl, C_1-6haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl or heterocycloalkylalkyl, each optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from C_1-6alkyl, C_1-6haloalkyl, aryl, heteroaryl, halo, CN, OR^a″
    - , SR^a″, C(O)R^b″, C(O)OR^a″, NR^c″C(O)R^d″, S(O)₂R^b″, and —
      
      (C_1-6alkyl)-CN.
  - 21. The compound of claim 1 wherein R¹³is C_1-6alkyl, C_1-6haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl or heterocycloalkylalkyl, each optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from C_1-6alkyl, C_1-6haloalkyl, aryl, heteroaryl, halo, CN, OH, C_1-4alkoxy, C_1-4haloalkoxy, heteroaryloxy, aryloxy, —
    - SC_1-6alkyl, —
      
      C(O)—
      
      C_1-6alkyl, —
      
      C(O)OC_1-6alkyl, —
      
      S(O)₂C_1-6alkyl, —
      
      NHC(O)—
      
      C_1-6alkyl, and —
      
      (C_1-6alkyl)-CN.
  - 22. The compound of claim 1 where R¹³is OH or CN.
  - 23. The compound of claim 1 wherein W¹is absent, W²is CO or SO₂, W³is C_1-4alkyleneyl or cycloalkyl, W⁴is absent, W⁵is absent, W⁶is absent, and R¹³is CN or OH.
  - 24. The compound of claim 1 wherein R⁶is W²—
    - W³—
      
      R¹³.
  - 25. The compound of claim 1 wherein R⁶is CO—
    - CH₂—
      
      CN.
  - 26. The compound of claim 1 wherein R⁶is W²—
    - R¹³.
  - 27. The compound of claim 1 wherein:
    - R⁶is W²—
      
      R¹³;
      
      W²is SO₂, CO, COO, C(S)NR¹², or CONR¹²; and
      
      R¹³is C_1-6alkyl, C_1-6haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl or heterocycloalkylalkyl, each optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from;
      
      C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, heterocycloalkylalkyl, halo, CN, NO₂, OR^a″, SR^a″, C(O)R^b″, C(O)NR^c″R^d″, C(O)OR^a″, OC(O)R^b″, OC(O)NR^c″R^d″, NR^c″R^d″, NR^c″C(O)R^d″, NR^c″C(O)OR^a″, S(O)R^b″, S(O)NR^c″R^d″, S(O)₂R^b″, S(O)₂NR^c″R^d″, —
      
      (C_1-6alkyl)-CN, —
      
      (C_1-6alkyl)-NO₂, —
      
      (C_1-6alkyl)-OR^a″, —
      
      (C_1-6alkyl)-SR^a″, —
      
      (C_1-6alkyl)-C(O)R^b″, —
      
      (C_1-6alkyl)-C(O)NR^c″R^d″, —
      
      (C_1-6alkyl)-C(O)OR^a″, —
      
      (C_1-6alkyl)-OC(O)R^b″, —
      
      (C_1-6alkyl)-OC(O)NR^c″R^d″, —
      
      (C_1-6alkyl)-NR^c″R^d″, —
      
      (C_1-6alkyl)-NR^c″C(O)R^d″, —
      
      (C_1-6alkyl)-NR^c″C(O)OR^a″, —
      
      (C_1-6alkyl)-S(O)R^b″, —
      
      (C_1-6alkyl)-S(O)NR^c″R^d″, —
      
      (C_1-6alkyl)-S(O)₂R^b″, and —
      
      (C_1-6alkyl)-S(O)₂NR^c″R^d″.
  - 28. The compound of claim 1 having the structure of Formula I-A:
  - 29. The compound of claim 28 wherein:
    - W²is SO₂, CO, COO, C(S)NR¹², or CONR¹²; and
      
      R¹³is C_1-6alkyl, C_1-6haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl or heterocycloalkylalkyl, each optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from;
      
      C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, heterocycloalkylalkyl, halo, CN, NO₂, OR^a″, SR^a″, C(O)R^b″, C(O)NR^c″R^d″, C(O)OR^a″, OC(O)R^b″, OC(O)NR^c″R^d″, NR^c″R^d″, NR^c″C(O)R^d, NR^c″C(O)OR^a″, S(O)R^b″, S(O)NR^c″R^d″, S(O)₂R^b″, S(O)₂NR^c″
      
      R^d″, —
      
      (C_1-6alkyl)-CN, (C_1-6alkyl)-NO₂, —
      
      (C_1-6alkyl)-OR^a″, —
      
      (C_1-6alkyl)-SR^a″, —
      
      (C_1-6alkyl)-C(O)R^b″, —
      
      (C_1-6alkyl)-C(O)NR^c″R^d″, —
      
      (C_1-6alkyl)-C(O)OR^a″, —
      
      (C_1-6alkyl)-OC(O)R^b″, —
      
      (C_1-6alkyl)-OC(O)NR^c″R^d″, —
      
      (C_1-6alkyl)-NR^c″R^d″, —
      
      (C_1-6alkyl)-NR^c″C(O)R^d″, —
      
      (C_1-6alkyl)-NR^c″C(O)OR^a″, —
      
      (C_1-6alkyl)-S(O)R^b″, —
      
      (C_1-6alkyl)-S(O)NR^c″R^d″, —
      
      (C_1-6alkyl)-S(O)₂R^b″, and —
      
      (C_1-6alkyl)-S(O)₂NR^c″R^d″.
  - 30. The compound of claim 1 having the structure of Formula I-B:
  - 31. The compound of claim 30 whereinR¹³is C_1-6alkyl, C_1-6haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl or heterocycloalkylalkyl, each optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from C_1-6alkyl, C_1-6haloalkyl, aryl, heteroaryl, halo, CN, O R^a″
    - , S R^a″, C(O)R^b″, C(O)OR^a″, NR^c″C(O)R^d″, S(O)₂R^b″, and —
      
      (C_1-6alkyl)-CN;
      
      W²is SO₂, CO, COO, C(S)NH, CONH or —
      
      CON(C_1-4alkyl)-; and
      
      R⁴is C_1-4alkyl, C_2-4alkenyl, C_2-4alkynyl, S(O)₂R⁹, SOR⁹, cycloalkyl, or heterocycloalkyl, wherein said C_1-4alkyl, C_2-4alkenyl, C_2-4alkynyl, cycloalkyl, heterocycloalkyl are each optionally substituted with 1, 2 or 3 substituents selected from halo, C_1-4alkyl, C_2-4alkenyl, C_2-4alkynyl, C_1-4haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO₂, OR^a, SR^a, C(O)R^b, C(O)NR^cR^d, C(O)OR^a, OC(O)R^b, OC(O)NR^cR^d, NR^cR^d, NR^cC(O)R^d, NR^cC(O)OR^a, S(O)R^b, S(O)NR^cR^d, S(O)₂R^b, and S(O)₂NR^cR^d.
  - 32. A compound of claim 1 selected from:
    - 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.
  - 41. A method of treating a disease in a patient, wherein said disease is associated with JAK activity, comprising administering to said patient a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof.
  - 43. The method of claim 41 wherein said disease is an autoimmune disease.
  - 44. The method of claim 43 wherein said autoimmune disease is a skin disorder, multiple sclerosis, rheumatoid arthritis, juvenile arthritis, type I diabetes, lupus, psoriasis, inflammatory bowel disease, Crohn'"'"'s disease, or autoimmune thyroid disorder.

33-40. -40. (canceled)

42. (canceled)

45-60. -60. (canceled)

Specification

Resources

Litigation Campaign Assessment

Current Assignee
Incyte Holdings Corporation And Incyte Corporation
Original Assignee
Incyte Corporation
Inventors
Rodgers, James D., Wang, Haisheng, Combs, Andrew P., Sparks, Richard B.

Granted Patent

US 9,090,611 B2
Time in Patent Office

Days
Field of Search
US Class Current

514/210.18
CPC Class Codes

A61P 1/04   for ulcers, gastritis or re...

A61P 17/00   Drugs for dermatological di...

A61P 17/06   Antipsoriatics

A61P 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   Antivirals

A61P 31/14   for RNA viruses

A61P 31/18   for HIV

A61P 31/20   for DNA viruses

A61P 35/00   Antineoplastic agents

A61P 37/00   Drugs for immunological or ...

A61P 37/02   Immunomodulators

A61P 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 systems

C07D 487/04   Ortho-condensed systems

PYRROLO[2,3-b]PYRIDIN-4-YL-AMINES AND PYRROLO[2,3-b]PYRIMIDIN-5-YL-AMINES AS JANUS KINASE INHIBITORS

First Claim

3 Assignments

0 Petitions

Accused Products

Abstract

58 Citations

45 Claims

Specification

Solutions

Use Cases

Quick Links

PYRROLO[2,3-b]PYRIDIN-4-YL-AMINES AND PYRROLO[2,3-b]PYRIMIDIN-5-YL-AMINES AS JANUS KINASE INHIBITORS

First Claim

3 Assignments

Subscription Required

Subscription Required

0 Petitions

Subscription Required

Accused Products

Subscription Required

Abstract

58 Citations

45 Claims

Specification

Subscription Required

Solutions

Use Cases

Quick Links