title: Identification of potent, soluble, and orally active TRPV1 antagonists.
abstract: 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.
authors: Department of Chemistry, MSD, Newhouse, Lanarkshire ML1 5SH, UK. Paul.Ratcliffe@grunenthal.com
authors: Paul
authors: P
authors: Ratcliffe
authors: John
authors: J
authors: Maclean
authors: Lynn
authors: L
authors: Abernethy
authors: Tom
authors: T
authors: Clarkson
authors: Maureen
authors: M
authors: Dempster
authors: Anna-Marie
authors: AM
authors: Easson
authors: Darren
authors: D
authors: Edwards
authors: Katy
authors: K
authors: Everett
authors: Helen
authors: H
authors: Feilden
authors: Peter
authors: P
authors: Littlewood
authors: Duncan
authors: D
authors: McArthur
authors: Deborah
authors: D
authors: McGregor
authors: Hazel
authors: H
authors: McLuskey
authors: Olaf
authors: O
authors: Nimz
authors: Lesley-Anne
authors: LA
authors: Nisbet
authors: Ronnie
authors: R
authors: Palin
authors: Heather
authors: H
authors: Tracey
authors: Glenn
authors: G
authors: Walker
mesh_terms: D000284:Administration, Oral; D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D007555:Isoxazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy; D051381:Rats; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000577:Amides; D007555:Isoxazoles; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human