Guanidine-containing compounds useful as muscarinic receptor antagonists
AssigneeTheravance Biopharma R&D IP, LLC
InventorsYuHua Ji, Craig Husfeld, YongQi Mu, Rick Lee, Li Li
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Abstract
The invention provides compounds of formula I: or a pharmaceutically acceptable salt thereof, wherein R1-3, R5-7, a, X, Y, Y′, Y″, and Z are as defined in the specification. These compounds are muscarinic receptor antagonists. The invention also provides pharmaceutical compositions containing such compounds, processes for preparing such compounds and methods of using such compounds to, for example, treat pulmonary disorders such as chronic obstructive pulmonary disease and asthma.
Claims1
A process for preparing a compound selected from 4-((R)-2-cyclopentyl-2-hydroxy-2-phenylacetyl)-N-furan-2-ylmethylpiperazine-1-carboxamidine and 4-((R)-2-cyclopentyl-2-hydroxy-2-phenylacetyl)-N-thiophen-2-ylmethyl-piperazine-1-carboxamidine, or a pharmaceutically acceptable salt thereof, comprising:
- (a) coupling compound (1) and compound (2) under amide bond-forming conditions and deprotecting the product to form compound (3):
- where a is 0;
- R1 is cyclopentyl;
- R2 is phenyl;
- R3 is —OH;
- and P is an amino-protecting group;
- (b) reacting compound (3) with compound (6) to form compound (7):
- where X is a bond, Y is —CH2—, Y′ is —N—, Y″ is —CH2—, and R6 is H;
- and;
- (c) reacting compound (7) and compound (8) to provide a compound of formula I:
- where R7 is H, Z is —CH2-Q, and Q is furanyl or thiophenyl.
Dependencies are inferred from the claim text.