Identification of potent, soluble, and orally active TRPV1 antagonists.

Paul Ratcliffe,John Maclean,Lynn Abernethy,Tom Clarkson,Maureen Dempster,Anna-Marie Easson,Darren Edwards,Katy Everett,Helen Feilden,Peter Littlewood,Duncan McArthur,Deborah McGregor,Hazel McLuskey,Olaf Nimz,Lesley-Anne Nisbet,Ronnie Palin,Heather Tracey,Glenn Walker

Bioorganic & Medicinal Chemistry Letters（2011）

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摘要

Optimization of a water soluble, moderately potent lead series of isoxazole-3-carboxamides was conducted, affording a compound with the requisite balance of potency, solubility and physicochemical properties for in vivo use. Compound 8e was demonstrated to be efficacious in a rat model of inflammatory pain, following oral administration.

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关键词

TRPV1 antagonist,Antihyperalgesia,Isoxazoles

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