1H-imidazo[4,5-d]thieno[3,2-b]pyridine based tricyclic compounds and pharmaceutical compositions comprising same

• US 7,683,171 B2
• Filed: 02/03/2006
• Issued: 03/23/2010
• Est. Priority Date: 02/04/2005
• Status: Active Grant

• Current Assignee: Bristol-Myers Squibb Company
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Qiu, Yuping, Pitts, William J., Das, Jagabandhu, Spergel, Steven H.
• Primary Examiner(s): Desai; Rita J
• Application Number:
  US11/346,986
• Publication Number:
  US 20060178393A1
• Time in Patent Office: 1,509 Days
• Field of Search: 546/83, 514/293
• US Class Current: 546/83
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C07D 495/14 Ortho-condensed systems

Abstract

The present invention provides for thiazolopyridine-based tricyclic compounds having the formula (I),

wherein R¹, R², R⁵, R⁶ and R⁷ are as described herein. The present invention further provides pharmaceutical compositions comprising such compounds, as well as the use of such compounds for treating inflammatory and immune diseases.

Claims

1. A compound of formula (I),

2. A compound of claim 1 wherein

R¹ is methyl, ethyl, propyl, or i-propyl.

3. A compound of claim 1, wherein

R⁶ is phenyl optionally independently substituted as valence allows with one or more Z^1d, Z^2d and Z^3d.

4. A compound of claim 3, wherein

R¹ is methyl, ethyl, propyl, or i-propyl.

5. A compound of claim 3, wherein

R⁶ is

6. A pharmaceutical composition comprising (a) at least one compound according to claim 1, or a pharmaceutically acceptable salt thereof, and (b) a pharmaceutically-acceptable carrier or diluent.

7. A pharmaceutical composition comprising (a) at least one compound according to claim 5, or a pharmaceutically acceptable salt thereof, and (b) a pharmaceutically-acceptable carrier or diluent.

8. A compound of claim 1, wherein the compound of formula is

N,1-Dimethyl-7-phenyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-4-amine;

N-Ethyl-1-methyl-7-phenyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-4-amine;

1-methyl-7-phenyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-4-amine;

7-(3-Fluorophenyl)-1-methyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-4-amine;

6-Bromo-7-(3-fluorophenyl)-N,1-dimethyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-4-amine;

7-(3-fluorophenyl)-N,1-dimethyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-4-amine;

7-(3,5-difluorophenyl)-N,1-dimethyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-4-amine;

7-[3-(aminomethyl)phenyl]-1-methyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-4-amine;

N-[[3-(4-amino-1-methyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl)phenyl]methyl]-1-methyl-4-piperidinecarboxamide;

N-[[3-(4-amino-1-methyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl)phenyl]methyl]acetamide;

2-amino-N-[[3-(4-amino-1-methyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl)phenyl]methyl]-(2S)-propanamide;

N-[[3-(4-amino-1-methyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl)phenyl]methyl]-, (2S)-2-pyrrolidinecarboxamide;

alpha-amino-N-[[3-(4-amino-1-methyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-1-yl)phenyl]methyl]-, (alphaR)-benzenepropanamide;

N-[[3-(4-amino-1-methyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl)phenyl]methyl]-1,2,3-thiadiazole-4-carboxamide;

N-[[3-(4-amino-1-methyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl)phenyl]methyl]-2,2-dimethylpropanamide;

N-[[3-(4-amino-1-methyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl)phenyl]methyl]cyclopropanecarboxamide;

N-[[3-(4-amino-1-methyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl)phenyl]methyl]-3-pyridinecarboxamide;

N-[[3-(4-amino-1-methyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl)phenyl]methyl]-4-pyridinecarboxamide;

N-[[3-(4-amino-1-methyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl)phenyl]methyl]-4-pyridazinecarboxamide;

N-[[3-(4-amino-1-methyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl)phenyl]methyl]-2-(2-methoxyethoxy)acetamide;

2-(acetylamino)-N-[[3-(4-amino-1-methyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl)phenyl]methyl]acetamide;

N-[[3-(4-amino-1-methyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl)phenyl]methyl]-1-methyl-1H-imidazole-4-acetamide;

N-[[3-(4-amino-1-methyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl)phenyl]methyl]-5-methyl-3-isoxazolecarboxamide;

N-[[3-(4-amino-1-methyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl)phenyl]methyl]-2-methyl propanamide;

N-[[3-(4-amino-1-methyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl)phenyl]methyl]-1-methyl-cyclopropanecarboxamide;

N-[[3-(4-amino-1-methyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl)phenyl]methyl]-4-(methylsulfonyl)benzamide;

N-[[3-(4-amino-1-methyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl)phenyl]methyl]-3-(methylsulfonyl)benzamide;

N-[[3-(4-amino-1-methyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-1-yl)phenyl]methyl]-2-(methylsulfonyl)benzamide;

2-amino-N-[[3-(4-amino-1-methyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl)phenyl]methyl]acetamide;

2-amino-N-[[3-(4-amino-1-methyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl)phenyl]methyl]-(2R)-propanamide;

7-[3-(Aminomethyl)phenyl]-N,1-dimethyl-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-4-amine;

N-[[3-[1-methyl-4-(methylamino)-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl]phenyl]methyl]acetamide;

N-[[3-[1-methyl-4-(methylamino)-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl]phenyl]methyl]-1,2,3-thiadiazole-4-carboxamide;

N-[[3-[1-methyl-4-(methylamino)-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl]phenyl]methyl]-2-pyridinecarboxamide;

N-[[3-[1-methyl-4-(methylamino)-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl]phenyl]methyl]-2,2-dimethylpropanamide;

N-[[3-[1-methyl-4-(methylamino)-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-1-yl]phenyl]methyl]-cyclopropanecarboxamide;

N-[[3-[1-methyl-4-(methylamino)-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl]phenyl]methyl]-3-pyridinecarboxamide;

N-[[3-[1-methyl-4-(methylamino)-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl]phenyl]methyl]-4-pyridinecarboxamide;

N-[[3-[1-methyl-4-(methylamino)-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl]phenyl]methyl]-4-pyridazinecarboxamide;

N-[[3-[1-methyl-4-(methylamino)-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl]-phenyl]methyl]-2-pyrazinecarboxamide;

2-cyano-N-[[3-[1-methyl-4-(methylamino)-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl]phenyl]methyl]acetamide;

N-[[-[1-methyl-4-(methylamino)-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl]phenyl]methyl]-2-(2-methoxyethoxy)acetamide;

N-[[3-[1-methyl-4-(methylamino)-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-1-yl]phenyl]methyl]-2-(acetylamino)acetamide;

1-methyl-N-[[3-[1-methyl-4-(methylamino)-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl]phenyl]methyl]-1H-imidazole-4-acetamide;

N-[[3-[1-methyl-4-(methylamino)-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl]phenyl]methyl]-5-methyl-3-isoxazolecarboxamide;

N-[[3-[1-methyl-4-(methylamino)-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl]phenyl]methyl]-5-methyl-4-isoxazolecarboxamide;

N-[[3-[1-methyl-4-(methylamino)-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl]phenyl]methyl]-2-methyl-propanamide;

N-[[3-[1-methyl-4-(methylamino)-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl]phenyl]methyl]-1-methylcyclopropanecarboxamide;

N-[[3-[1-methyl-4-(methylamino)-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl]phenyl]methyl]-alpha,alpha-dimethyl benzeneacetamide;

N-[[3-[1-methyl-4-(methylamino)-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl]phenyl]methyl]-4-(methylsulfonyl)benzamide;

N-[[3-[1-methyl-4-(methylamino)-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl]phenyl]methyl]-3-(methylsulfonyl)benzamide;

N-[[3-[1-methyl-4-(methylamino)-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl]phenyl]methyl]-2-(methylsulfonyl)benzamide;

1-methyl-N-[[3-[1-methyl-4-(methylamino)-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl]phenyl]methyl]-4-piperidinecarboxamide;

N-[[3-[1-methyl-4-(methylamino)-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl]phenyl]methyl]-(2S)-2-aminopropanamide;

2-amino-N-[[3-[1-methyl-4-(methylamino)-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl]phenyl]methyl]-(2R)-propanamide;

N-[[3-[1-methyl-4-(methylamino)-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl]phenyl]methyl]-(2S)-2-pyrrolidinecarboxamide;

N-[[3-[1-methyl-4-(methylamino)-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl]phenyl]methyl]-alpha-amino-(alphaR)benzenepropanamide;

or

N-[[3-[1-methyl-4-(methylamino)-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-7-yl]phenyl]methyl]-2-amino-acetamide;

or pharmaceutically acceptable salt thereof.

9. A pharmaceutical composition comprising (a) at least one compound according to claim 8, or a pharmaceutically acceptable salt thereof, and (b) a pharmaceutically-acceptable carrier or diluent.