Chemical compounds

• US 7,294,636 B2
• Filed: 05/06/2004
• Issued: 11/13/2007
• Est. Priority Date: 05/09/2003
• Status: Expired due to Fees

• Current Assignee: Astrazeneca AB (Astrazeneca PLC)
• Original Assignee: Astrazeneca AB (Astrazeneca PLC)
• Inventors: Faull, Alan, Cumming, John
• Primary Examiner(s): Seaman; Margaret D.
• Assistant Examiner(s): Rahmani; Niloofar
• Application Number:
  US10/556,023
• Publication Number:
  US 20070015788A1
• Time in Patent Office: 1,286 Days
• Field of Search: 546/124, 546/199, 546/208, 546/210, 514/304, 514/321, 514/322, 514/326
• US Class Current: 514/304
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/16 Otologicals
• 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 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/18 for HIV
• 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 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/08 Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock artificial tears A61P27/04
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 401/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 413/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 417/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 451/02 : containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof

Abstract

Compounds of formula (I): compositions comprising them, processes for preparing them and their use in medical therapy (for example modulating CCR5 receptor activity in a warm blooded animal)

Claims

1. A compound of formula (I):

2. A compound of formula (I) as claimed in claim 1 wherein A is absent.

3. A compound of formula (I) as claimed in claim 1 wherein R¹ is halo, cyano, S(O)₂(C_1-6 alkyl), OS(O)₂(C_1-6 alkyl), CO₂(C_1-6 alkyl), NHC(O)(C_1-6 alkyl), NHS(O)₂(C_1-6 alkyl), NHC(O)phenyl, NHC(O)heteroaryl, NHC(O)(C_1-4 alkyl)phenyl, NHC(O)(C_1-4 alkyl)heteroaryl, NHS(O)₂phenyl, NHS(O)₂heteroaryl, NHS(O)₂(C_1-4 alkyl)phenyl or NHS(O)₂(C_1-4 alkyl)heteroaryl;

wherein the foregoing phenyl and heteroaryl groups are optionally substituted by halo, hydroxy, nitro, S(O)₂(C_1-4 alkyl), S(O)₂NH₂, S(O)₂NH(C_1-4 alkyl), S(O)₂N(C_1-4 alkyl)₂, cyano, C_1-4 alkyl, C_1-4 alkoxy, C(O)NH₂, C(O)NH(C_1-4 alkyl), C(O)N(C_1-4 alkyl)₂, CO₂H, CO₂(C_1-4 alkyl), NHC(O)(C_1-4 alkyl), NHS(O)₂(C_1-4 alkyl), C(O)(C_1-4 alkyl), CF₃ or OCF₃.

4. A compound of formula (I) as claimed in claim 1 wherein R¹ is halo, cyano, S(O)₂(C_1-6 alkyl), OS(O)₂(C_1-6 alkyl), CO₂(C_1-6 alkyl), NHC(O)(C_1-6 alkyl) or NHS(O)₂(C_1-6 alkyl).

5. A compound of formula (I) as claimed in claim 1 wherein R² is phenyl or halophenyl.

6. A compound of formula (I) as claimed in claim 1 wherein R³ is hydrogen.

7. A compound of formula (I) as claimed in claim 1 wherein R⁴ is imidazolyl, 1,2,4-triazolyl, 1,2,4-oxadiazolyl, tetrazolyl, pyrazolyl, 1,3-thiazolyl, or isoxazolyl optionally substituted as described in claim 1.

8. A process for preparing a compound of formula (I) as claimed in claim 1, the process comprising reductive amination of a compound of formula (II):

9. A pharmaceutical composition which comprises a therapeutically effective amount of a compound as claimed in claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable adjuvant, diluent or carrier.

10. A compound as claimed in claim 2 wherein R¹ is halo, cyano, S(O)₂(C_1-6 alkyl), OS(O)₂(C_1-6 alkyl), CO₂(C_1-6 alkyl), NHC(O)(C_1-6 alkyl), NHS(O)₂(C_1-6 alkyl), NHC(O)phenyl, NHC(O)heteroaryl, NHC(O)(C_1-4 alkyl)phenyl, NHC(O)(C_1-4 alkyl)heteroaryl, NHS(O)₂phenyl, NHS(O)₂heteroaryl, NHS(O)₂(C_1-4 alkyl)phenyl or NHS(O)₂(C_1-4 alkyl)heteroaryl;

wherein the foregoing phenyl and heteroaryl groups are optionally substituted by halo, hydroxy, nitro, S(O)₂(C_1-4 alkyl), S(O)₂NH₂, S(O)₂NH(C_1-4 alkyl), S(O)₂N(C_1-4 alkyl)₂, cyano, C_1-4 alkyl, C_1-4 alkoxy, C(O)NH₂, C(O)NH(C_1-4 alkyl), C(O)N(C_1-4 alkyl)₂, CO₂H, CO₂(C_1-4 alkyl), NHC(O)(C_1-4 alkyl), NHS(O)₂(C_1-4 alkyl), C(O)(C_1-4 alkyl), CF₃ or OCF₃.

11. A compound as claimed in claim 2 wherein R¹ is halo, cyano, S(O)₂(C_1-6 alkyl), OS(O)₂(C_1-6 alkyl), CO₂(C_1-6 alkyl), NHC(O)(C_1-6 alkyl) or NHS(O)₂(C_1-6 alkyl).

12. A compound as claimed in claim 2 wherein R² is phenyl or halophenyl.

13. A compound as claimed in claim 2 wherein R³ is hydrogen.

14. A compound as claimed in claim 2 wherein R⁴ is imidazolyl, 1,2,4-triazolyl, 1,2,4-oxadiazolyl, tetrazolyl, pyrazolyl, 1,3-thiazolyl, or isoxazolyl optionally substituted as described in claim 1.

15. A compound as claimed in claim 3 wherein R² is phenyl or halophenyl.

16. A compound as claimed in claim 3 wherein R³ is hydrogen.

17. A compound as claimed in claim 3 wherein R⁴ is imidazolyl, 1,2,4-triazolyl, 1,2,4-oxadiazolyl, tetrazolyl, pyrazolyl, 1,3-thiazolyl, or isoxazolyl optionally substituted as described in claim 1.