Benzimisazo[4,5-f]isoquinolinone derivatives

• US 20040176601A1
• Filed: 01/30/2004
• Published: 09/09/2004
• Est. Priority Date: 08/01/2001
• Status: Active Grant

• Current Assignee: Merck Sharp & Dohme LLC (Merck & Co., Inc.)
• Original Assignee: Merck & Co., Inc.
• Inventors: Goulet, Joung L., Thompson, James E, Cubbon, Rose M, Sinclair, Peter J, Cummings, Richard T, Hong, Xingfang
• Granted Patent: US 6,852,727 B2
• Time in Patent Office: Days
• US Class Current: 546/46
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 39/00 General protective or antinoxious agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/14 of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 7/10 Antioedematous agents; Diuretics
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 471/14 Ortho-condensed systems

Abstract

Benzimidazo[4,5-f]isoquinolinone derivatives are inhibitors of Janus protein tyrosine kinases (Jak), and as such are useful as immunosuppressants, and in the treatment of diseases including asthma, allergies, autoimmune diseases.

Claims

1. A compound of formula I:

2. A compound of claim 1 wherein R¹ is selected from hydrogen, C_1-6alkyl, C_3-6cycloalkyl and aryl-C_1-3alkyl wherein alkyl, cycloalkyl and aryl are optionally substituted with one or two groups independently selected from X.

3. A compound of claim 1 wherein R³ and R⁴ are independently selected from hydrogen, halogen and trifluoromethyl.

4. A compound of claim 1 wherein Q is C and one of R³ and R⁴ is halogen or trifluoromethyl at the 9-position, and the other is H, halogen or trifluoromethyl.

5. A compound of claim 1 wherein R⁵ is selected from C_1-6alkyl and Cy wherein each is optionally substituted with one to three groups independently selected from X.

6. A compound of claim 1 wherein R⁵ is phenyl optionally substituted with one to three groups independently selected from X.

7. A compound of claim 1 wherein Q is C.

8. A compound of claim 1 wherein Q is N.

9. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

10. A method for the treatment of Janus protein tyrosine kinase mediated diseases in a mammal which comprises administering to said mammal a therapeutically effective amount of a compound of claim 1.