Muscarinic receptor antagonists

• US 7,456,203 B2
• Filed: 04/29/2003
• Issued: 11/25/2008
• Est. Priority Date: 02/16/1999
• Status: Expired due to Fees

• Current Assignee: Theravance Biopharma R&D IP, LLC (Theravance Biopharma, Inc.)
• Original Assignee: Theravance, Inc
• Inventors: Moran, Edmund J., Mammen, Mathai, Marquess, Daniel, Griffin, John H., Oare, David, Aggen, James
• Primary Examiner(s): SHIBUYA, MARK LANCE
• Application Number:
  US10/425,368
• Publication Number:
  US 20040110229A1
• Time in Patent Office: 2,037 Days
• Field of Search: 514/346, 514/351, 546/247
• US Class Current: 514/346
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: C07C 211/32 containing dibenzocycloheptane or dibenzocycloheptene ring systems or condensed derivatives thereof
• CPC Class Codes: C07C 2603/32 Dibenzocycloheptenes; Hydrogenated dibenzocycloheptenes
• CPC Class Codes: C07D 207/08 with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
• CPC Class Codes: C07D 209/48 with oxygen atoms in positions 1 and 3, e.g. phthalimide
• CPC Class Codes: C07D 211/46 having a hydrogen atom as the second substituent 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 403/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 519/00 Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
• CPC Class Codes: G01N 33/566 using specific carrier or receptor proteins as ligand binding reagents where possible specific carrier or receptor proteins are classified with their target compounds

Abstract

Disclosed are multibinding compounds which are muscarinic receptor antagonists. The multibinding compounds of this invention containing from 2 to 10 ligands covalently attached to one or more linkers. Each ligand is, independently of each other, a muscarinic receptor antagonist or an allosteric modulator provided that at least one of said ligand is a muscarinic receptor antagonist. The multibinding compounds of this invention are useful in the treatment and prevention of diseases such as chronic obstructive pulmonary disease, chronic bronchitis, irritable bowel syndrome, urinary incontinence, and the like.

Claims

1. A compound of the formula:

2. The compound of claim 1, wherein L^b is formula (j).

3. The compound of claim 1, wherein L^b is formula (i).

4. The compound of claim 1, wherein R⁴⁶ is alkyl.

5. The compound of claim 1, wherein R⁴⁶ is substituted alkyl.

6. The compound of claim 1, wherein R⁴⁶ is cycloalkyl.

7. The compound of claim 1, wherein R⁴⁶ is heterocycle.

8. The compound of claim 1, wherein R⁴⁷ is alkyl.

9. The compound of claim 1, wherein R⁴⁷ is substituted alkyl.

10. The compound of claim 1, wherein R⁴⁷ is aryl.

11. The compound of claim 1, wherein R⁴⁷ is acyl.

12. The compound of claim 1, wherein R⁴⁷ is heterocycle.

13. The compound of claim 1, wherein R⁴⁶ and R⁴⁷ together with the nitrogen atom to which they are attached form heterocycle.

14. A pharmaceutical composition comprising a pharmaceutically-acceptable carrier and a therapeutically effective amount of a compound of any one of claims 1 to 13.