Biphenyl derivatives

• US 7,879,879 B2
• Filed: 06/07/2006
• Issued: 02/01/2011
• 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, Dunham, Sarah, Husfeld, Craig, Chen, Yan
• Primary Examiner(s): CHANG, CELIA C
• Application Number:
  US11/448,317
• Publication Number:
  US 20060223860A1
• Time in Patent Office: 1,700 Days
• Field of Search: 514/314, 514/317, 546/157, 546/216, 546/223
• US Class Current: 514/317
• 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 method of antagonizing a muscarinic receptor or agonizing a β

₂ adrenergic receptor in a biological system or sample, the method comprising;

(a) contacting a biological system or sample having a muscarinic receptor or a β

₂ adrenergic receptor with a muscarinic receptor-antagonizing or a β

₂ adrenergic receptor-agonizing amount of a compound of formula I;

2. The method of claim 1, wherein the biological system or sample is a cell or cellular extract.

3. The method of claim 1, wherein the biological system or sample is a plasma membrane or tissue sample.

4. The method of claim 1, wherein the biological system or sample is a mammal.

5. The method of claim 1, wherein the mammal is a mouse, rat, guinea pig, rabbit, dog or pig.

6. The method of claim 1, wherein R⁴ in the compound of formula I is (4-10C)alkylene.

7. The method of claim 1, wherein the compound of formula I used in the method at a concentration in the range from about 0.1 nanomolar to about 100 nanomolar.