Biphenyl derivatives

• US 7,345,175 B2
• Filed: 06/07/2006
• Issued: 03/18/2008
• Est. Priority Date: 02/14/2003
• Status: Active Grant

• Current Assignee: Theravance Biopharma R&D IP, LLC (Theravance Biopharma, Inc.)
• Original Assignee: Theravance, Inc
• Inventors: Hughes, Adam, Mammen, Mathai, Chen, Yan
• Primary Examiner(s): DESAI, RITA J
• Application Number:
  US11/448,293
• Publication Number:
  US 20060223858A1
• Time in Patent Office: 650 Days
• Field of Search: 546/242
• US Class Current: 546/242
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/452 Piperidinium derivatives pancuronium A61K31/58
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 11/08 Bronchodilators
• CPC Class Codes: A61P 11/12 Mucolytics
• 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 5/40 Mineralocorticosteroids, e.g. aldosterone; Drugs increasing or potentiating the activity of mineralocorticosteroids
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07D 211/46 having a hydrogen atom as the second substituent in position 4
• CPC Class Codes: C07D 211/48 having an acyclic carbon atom attached in position 4
• CPC Class Codes: C07D 211/58 attached in position 4
• CPC Class Codes: C07D 401/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 409/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 453/02 containing not further condensed quinuclidine ring systems
• CPC Class Codes: C07D 471/08 : Bridged systems
• CPC Class Codes: G01N 33/9433 : (Nor)adrenaline

Abstract

This invention provides biphenyl derivatives of formula I:

• • wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, W, a, b and c are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The biphenyl derivatives of this invention possess both β₂ adrenergic receptor agonist and muscarinic receptor antagonist activity and therefore, such biphenyl derivatives are useful for treating pulmonary disorders, such as chronic obstructive pulmonary disease and asthma.

Claims

1. A compound of the formula:

2. The compound of claim 1, wherein o is 2 or 3.

3. The compound of claim 1, wherein o is 2.

4. The compound of claim 1, wherein p is 1 or 2.

5. The compound of claim 1, wherein p is 1.

6. The compound of claim 1, wherein o is 2 and p is 1.

7. The compound of claim 1, wherein the phen-1,4-ylene group has one substituent.

8. The compound of claim 1, wherein the phen-1,4-ylene group has two substituents.

9. The compound of claim 1, wherein the phen-1,4-ylene group is substituted with from 1 to 4 substituents and at least one of the substituents is halo.

10. The compound of claim 1, wherein the phen-1,4-ylene group is substituted with from 1 to 4 substituents and at least one of the substituents is chloro.

11. The compound of claim 1, wherein the phen-1,4-ylene group is substituted with from 1 to 4 substituents and at least one of the substituents is (1-4C)alkoxy.

12. The compound of claim 1, wherein the phen-1,4-ylene group is substituted with from 1 to 4 substituents and at least one of the substituents is methoxy.

13. The compound of claim 1, wherein the phen-1,4-ylene group is substituted with from 1 to 4 substituents and at least one of the substituents is (1-4C)alkyl.

14. The compound of claim 1, wherein the phen-1,4-ylene group is substituted with from 1 to 4 substituents and at least one of the substituents is methyl.

15. The compound of claim 1, wherein the compound has the (R) configuration at the carbon atom of the group —

CH(OH)—

.

16. The compound of claim 1, wherein the compound is in the form of a pharmaceutically acceptable salt.

17. The compound of claim 1, wherein the compound is in the form of a free base.