IP Library › Granted Patent US 12,258,316
Granted Patent B2
US 12,258,316 · App. 17/569,255 · Granted Mar 25, 2025

Biphenyl compounds useful as muscarinic receptor antagonists

Inventors: Mathai Mammen (Menlo Park, CA); YuHua Ji (Palo Alto, CA); YongQi Mu (Los Altos, CA); Craig Husfeld (Redwood City, CA); Li Li (Sunnyvale, CA)
Assignee: THERAVANCE BIOPHARMA R&D IP, LLC
C07D211/62A61K9/124A61K9/1623A61K9/1652A61K31/4545A61K45/06C07D401/12
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Quick Facts
Patent No.
US 12,258,316
App. No.
17/569,255
Granted
Mar 25, 2025
Kind
B2
Abstract

This invention provides compounds of formula I: wherein a, b, c, d, m, n, p, s, t, W, Ar 1 , R 1 , R 2 , R 3 , R 4 , R 6 , R 7 , and R 8 are as defined in the specification. The compounds of formula I are muscarinic receptor antagonists. The invention also provides pharmaceutical compositions containing such compounds, processes and intermediates for preparing such compounds and methods of using such compounds to treat pulmonary disorders.

Claims (13)

1. A process for preparing Compound 1 having the structure:

comprising:

(a) contacting Compound 4 having the structure:

with 4-carboxybenzaldehyde in the presence of a coupling agent under conditions sufficient to form Compound 5 having the structure:

and

(b) contacting Compound 5 with isonipecotamide in the presence of acetic acid, sodium sulfate, and sodium triacetoxyborohyride under conditions sufficient to form Compound 1.

2. The process of claim 1 , wherein step (b) is carried out at a temperature of 0 to 10° C.

3. The process of claim 1 , wherein step (a) is carried out at room temperature.

4. The process of claim 1 , further comprising contacting Compound 3 having the structure:

with hydrogen in the presence of palladium on activated carbon and acetic acid under conditions sufficient to form Compound 4.

5. The process of claim 4 , further comprising contacting biphenyl-2-ylcarbamic acid piperidin-4-yl ester and N-benzyl-N-methylaminoacetaldehyde in the presence of sodium triacetoxyborohydride to form Compound 3.

6. The process of claim 1 , further comprising contacting Compound 1 in the presence of an acid to form a salt of Compound 1.

7. The process of claim 6 , wherein the acid is phosphoric acid, sulfuric acid, or oxalic acid.

Assignments (1)
SECURITY INTEREST Recorded Sep 24, 2026
From: THERAVANCE BIOPHARMA R&D IP, LLC
To: U.S. BANK TRUST COMPANY, NATIONAL ASSOCIATION
Reel/Frame 076134/0790 →
Continuity (16)
Continuation 16744565 · Jan 16, 2020
Continuation 16420421 · May 23, 2019
Continuation 16130076 · Sep 13, 2018
Continuation 15876525 · Jan 22, 2018
Continuation 15251144 · Aug 30, 2016
Continuation 15016528 · Feb 5, 2016
Continuation 14539550 · Nov 12, 2014
Continuation 14023794 · Sep 11, 2013
Continuation 13592713 · Aug 23, 2012
Continuation 13438105 · Apr 3, 2012
Continuation 13226677 · Sep 7, 2011
Continuation 12814629 · Jun 14, 2010
Continuation 11879835 · Jul 19, 2007
Continuation 11077433 · Mar 10, 2005
Provisional Application 60552443 · Mar 11, 2004
Related Publication 20220306579A1 · Sep 29, 2022
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