title: Synthesis of benzamide derivatives as TRPV1 antagonists.
abstract: 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.
authors.affiliation: Pfizer Global Research & Development, Nagoya Laboratories, 5-2 Taketoyo, Aichi 470-2394, Japan. Yuji.Shishido@pfizer.com
authors.forename: Yuji
authors.initials: Y
authors.lastname: Shishido
authors.forename: Madoka
authors.initials: M
authors.lastname: Jinno
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ikeda
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Ito
authors.forename: Masaki
authors.initials: M
authors.lastname: Sudo
authors.forename: Naoya
authors.initials: N
authors.lastname: Makita
authors.forename: Atsuko
authors.initials: A
authors.lastname: Ohta
authors.forename: Ayako
authors.initials: A
authors.lastname: Iki-Taki
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohmi
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Kanai
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tamura
authors.forename: Masato
authors.initials: M
authors.lastname: Shimojo
mesh_terms: 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*
chemical_list: D000700:Analgesics; D001549:Benzamides; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human