Abstract
The B1 receptor is an attractive target for the treatment of pain and inflammation. A series of 3-carboxamido-5-phenacylamino pyrazole B1 receptor antagonists are described that exhibit good potency against B1 and high selectivity over B2. Initially, N-unsubstituted pyrazoles were studied, but these compounds suffered from extensive glucuronidation in primates. This difficulty could be surmounted by the use of N-substituted pyrazoles. Optimization efforts culminated in compound 41, which has high receptor potency and metabolic stability.
MeSH terms
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Benzamides / chemical synthesis*
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Benzamides / chemistry
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Benzamides / pharmacology
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Bradykinin B1 Receptor Antagonists*
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Crystallography, X-Ray
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Fibroblasts / metabolism
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Humans
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In Vitro Techniques
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Lung / cytology
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Molecular Structure
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Pyrazoles / chemical synthesis*
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Pyrazoles / chemistry
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Pyrazoles / pharmacology
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Radioligand Assay
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Structure-Activity Relationship
Substances
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4-bromo-5-((2-chlorobenzoyl)amino)-1-phenyl-N-(2-(1-(4-pyridinyl)-4-piperidinyl)ethyl)-1H-pyrazole-3-carboxamide
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Benzamides
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Bradykinin B1 Receptor Antagonists
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Pyrazoles