The search for novel TRPV1-antagonists: from carboxamides to benzimidazoles and indazolones.
Based on a series of diaryl amides the corresponding inverse amides have been found to be potent TRPV1 receptor antagonists. Benzimidazole and indazolone derivatives prepared retained good potency in vitro and indazolone 4a was identified as a novel TRPV1 receptor antagonist suitable for evaluating orally in animal models of analgesia.
Fletcher
Stephen Robert
SR
Merck Sharp & Dohme, The Neuroscience Research Centre, Terlings Park, Harlow, Essex CM20 2QR, UK. stephen_fletcher@merck.com
McIver
Edward
E
Lewis
Stephen
S
Burkamp
Frank
F
Leech
Clare
C
Mason
Glenn
G
Boyce
Susan
S
Morrison
Denise
D
Richards
Gillian
G
Sutton
Kathy
K
Jones
Anthony Brian
AB
D000588:Amines / Q000737:chemistry; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000588:Amines; D001562:Benzimidazoles; D007093:Imidazoles; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; C031000:benzimidazole