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.
Merck Sharp & Dohme, The Neuroscience Research Centre, Terlings Park, Harlow, Essex CM20 2QR, UK. stephen_fletcher@merck.com
Stephen Robert
SR
Fletcher
Edward
E
McIver
Stephen
S
Lewis
Frank
F
Burkamp
Clare
C
Leech
Glenn
G
Mason
Susan
S
Boyce
Denise
D
Morrison
Gillian
G
Richards
Kathy
K
Sutton
Anthony Brian
AB
Jones
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