Discovery of selective indole-based prostaglandin D₂ receptor antagonist

Maki Iwahashi; Atsushi Shimabukuro; Takahiro Onoda; Yoko Matsunaga; Yutaka Okada; Ryoji Matsumoto; Fumio Nambu; Hisao Nakai; Masaaki Toda

doi:10.1016/j.bmc.2011.06.014

Discovery of selective indole-based prostaglandin D₂ receptor antagonist

Bioorg Med Chem. 2011 Aug 1;19(15):4574-88. doi: 10.1016/j.bmc.2011.06.014. Epub 2011 Jun 16.

Authors

Maki Iwahashi¹, Atsushi Shimabukuro, Takahiro Onoda, Yoko Matsunaga, Yutaka Okada, Ryoji Matsumoto, Fumio Nambu, Hisao Nakai, Masaaki Toda

Affiliation

¹ Minase Research Institute, Ono Pharmaceutical Co., Ltd, 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan. iwahashi@ono.co.jp

PMID: 21737285
DOI: 10.1016/j.bmc.2011.06.014

Abstract

A series of N-benzoyl-2-methylindole-3-acetic acids were synthesized and biologically evaluated as prostaglandin (PG) D₂ receptor antagonists. Some of the selected compounds significantly inhibited OVA-induced vascular permeability in guinea pig conjunctiva after oral dosing. Structure-activity relationship study is presented.

MeSH terms

Animals
CHO Cells
Capillary Permeability / drug effects*
Conjunctiva / blood supply
Cricetinae
Cricetulus
Drug Discovery
Guinea Pigs
Humans
Indoles / chemistry*
Indoles / pharmacology*
Receptors, Immunologic / antagonists & inhibitors*
Receptors, Immunologic / metabolism*
Receptors, Prostaglandin / antagonists & inhibitors*
Receptors, Prostaglandin / metabolism*

Substances

Indoles
Receptors, Immunologic
Receptors, Prostaglandin
prostaglandin D2 receptor