Imidazo [4, 5-C] quinoline derivatives as bromodomain inhibitors

• US 8,557,984 B2
• Filed: 11/03/2010
• Issued: 10/15/2013
• Est. Priority Date: 11/05/2009
• Status: Expired due to Fees

• Current Assignee: GlaxoSmithKline LLC (GSK plc)
• Original Assignee: GlaxoSmithKline LLC (GSK plc)
• Inventors: Bouillot, Anne Marie Jeanne, Donche, Frederic, Gellibert, Francoise Jeanne, Lamotte, Yann, Mirguet, Olivier
• Primary Examiner(s): Andres, Janet L.
• Assistant Examiner(s): Rozof, Timothy R
• Application Number:
  US13/503,722
• Publication Number:
  US 20120232074A1
• Time in Patent Office: 1,077 Days
• Field of Search: None
• US Class Current: 544/126
• 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: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 471/04 Ortho-condensed systems

Abstract

Novel compounds of formula (I)

and salts thereof, pharmaceutical compositions containing such compounds and their use in therapy.

Claims

1. A compound of formula (I) or a salt thereof

2. A compound or a salt thereof according to claim 1 which is a compound of formula (IA)

3. A compound or a salt thereof according to claim 2 in which R⁴ is hydrogen and A is a group of formula (I) or (ii) wherein n is 1.

4. A compound or a salt thereof according to claim 1 in which A is a group of formula (II) wherein R^2b represents (CH₂)₂C_1-6alkoxy.

5. A compound or a salt thereof according to claim 1 which is a compound of formula (IB)

6. A compound or a salt thereof according to claim 5 in which R⁵ is —

OCH₃.

7. A compound or a salt thereof according to claim 1 which is a compound of formula (1C)

8. A compound or a salt thereof according to claim 7 in which R^2a represents H, C_1-3alkyl, (CH₂)_mOH, (CH₂)_mC_1-3alkoxy, (CH₂)_mNR^aR^b or (CHR⁶)_pheterocyclyl,

wherein

R^a represents H, C_1-3alkyl, or heterocyclyl;

R^b represents H or C_1-3alkyl, or

R^a and R^b together with the N to which they are attached form a 5 or 6 membered heterocyclyl;

R⁶ represents H or C_1-3alkyl;

m represents 1, 2 or 3; and

p represents 0, 1, 2.

9. A compound or a salt thereof according to claim 7 in which R^2a is tetrahydropyranyl.

10. A compound or a salt thereof according to claim 1 in which n is 1.

11. A compound or a salt thereof according to claim 1 in which R² is hydrogen or methyl.

12. A compound or a salt thereof according claim 1 in which R¹ represents a heteroaromatic group optionally substituted by one or two groups selected from hydroxy, C_1-3alkyl, C_1-3alkoxy, hydroxyC_1-4-alkyl and C_1-4alkoxyC_1-4alkyl.

13. A compound or a salt thereof according to claim 12 in which the heteroaromatic group is pyridyl.

14. A compound or a salt thereof according to claim 12 in which the heteroaromatic group is selected from furanyl, thienyl, isoxazolyl, thiazolyl, pyrazolyl, pyrazinyl and pyrimidinyl.

17. A pharmaceutical composition which comprises a compound or a salt thereof as defined in claim 1 and one or more pharmaceutically acceptable carriers, diluents or excipients.

15. A compound which is any of one of Examples 1-226 or a salt thereof.

16. A compound which is 7-(3,5-dimethyl-4-isoxazolyl)-8-(methyloxy)-1-[(1R)-1-(2-pyridinyl)ethyl]-1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-one