Synthesis of benzamide derivatives as TRPV1 antagonists.
From hit compounds identified by high throughput screening (HTS), we have found compound 1 as a lead TRPV1 antagonist and confirmed its potential as a treatment for pain. Compound 1 has led to potent TRPV1 antagonistic benzamide derivatives ((+/-)-2: human IC(50)=23 nM, (+/-)-3: human IC(50)=14 nM in the capsaicin-induced calcium influx assay) containing indole and naphthyl moieties, obtained by elaboration of the tryptamine scaffold or via bioisosteric replacements.
D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D051381:Rats; D013329:Structure-Activity Relationship; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*
D000700:Analgesics; D001549:Benzamides; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human