Synthesis of benzamide derivatives as TRPV1 antagonists

Yuji Shishido; Madoka Jinno; Takafumi Ikeda; Fumitaka Ito; Masaki Sudo; Naoya Makita; Atsuko Ohta; Ayako Iki-Taki; Takashi Ohmi; Yoshihito Kanai; Tetsuya Tamura; Masato Shimojo

doi:10.1016/j.bmcl.2007.12.007

Synthesis of benzamide derivatives as TRPV1 antagonists

Bioorg Med Chem Lett. 2008 Feb 1;18(3):1072-8. doi: 10.1016/j.bmcl.2007.12.007. Epub 2007 Dec 10.

Authors

Yuji Shishido¹, Madoka Jinno, Takafumi Ikeda, Fumitaka Ito, Masaki Sudo, Naoya Makita, Atsuko Ohta, Ayako Iki-Taki, Takashi Ohmi, Yoshihito Kanai, Tetsuya Tamura, Masato Shimojo

Affiliation

¹ Pfizer Global Research & Development, Nagoya Laboratories, 5-2 Taketoyo, Aichi 470-2394, Japan. Yuji.Shishido@pfizer.com

PMID: 18155908
DOI: 10.1016/j.bmcl.2007.12.007

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.

MeSH terms

Analgesics / chemical synthesis*
Analgesics / chemistry
Analgesics / pharmacology*
Animals
Benzamides / chemical synthesis*
Benzamides / chemistry
Benzamides / pharmacology*
Combinatorial Chemistry Techniques*
Humans
Mice
Molecular Structure
Rats
Structure-Activity Relationship
TRPV Cation Channels / antagonists & inhibitors*

Substances

Analgesics
Benzamides
TRPV Cation Channels
TRPV1 protein, human