Biphenyl derivatives

• US 7,514,558 B2
• Filed: 11/27/2006
• Issued: 04/07/2009
• 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, Stangeland, Eric, Mammen, Mathai, Chen, Yan
• Primary Examiner(s): SEAMAN, D MARGARET M
• Application Number:
  US11/604,607
• Publication Number:
  US 20070088054A1
• Time in Patent Office: 862 Days
• Field of Search: 546/157, 514/314
• US Class Current: 546/157
• 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 formula II:

2. The compound of claim 1, wherein W is O.

3. The compound of claim 1, wherein Q^f is hydrogen.

4. The compound of claim 1, wherein e is 0.

5. The compound of claim 1, wherein g is 0.

6. The compound of claim 1, wherein R^4a is (1-10C)alkylene.

7. The compound of claim 1, wherein R^4a is —

CH₂CH₂—

.

8. The compound of claim 1, wherein A² is phenylene.

9. The compound of claim 1, wherein A² is phen-1,4-ylene.

10. The compound of claim 1, wherein A² is phen-1,3-ylene.

11. The compound of claim 1, wherein R^4d is (1-10C)alkylene.

12. The compound of claim 1, wherein R^4d is —

CH₂CH₂—

.

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

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

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

16. A method of treating a patient having a pulmonary disorder, the method comprising administering to the patient a therapeutically effective amount of a compound of claim 1.

17. A method of treating a patient having chronic obstructive pulmonary disease or asthma, the method comprising administering to the patient a therapeutically effective amount of a compound of claim 1.

18. A method of producing bronchodilation in a patient, the method comprising administering to the patient a bronchodilation-producing amount of a compound of claim 1.