Design and synthesis of new prostaglandin D₂ receptor antagonists

Maki Iwahashi; Eiji Takahashi; Motoyuki Tanaka; Yoko Matsunaga; Yutaka Okada; Ryoji Matsumoto; Fumio Nambu; Hisao Nakai; Masaaki Toda

doi:10.1016/j.bmc.2011.08.007

Design and synthesis of new prostaglandin D₂ receptor antagonists

Bioorg Med Chem. 2011 Sep 15;19(18):5361-71. doi: 10.1016/j.bmc.2011.08.007. Epub 2011 Aug 8.

Authors

Maki Iwahashi¹, Eiji Takahashi, Motoyuki Tanaka, 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: 21885288
DOI: 10.1016/j.bmc.2011.08.007

Abstract

To identify new cost-effective prostaglandin D₂ (DP) receptor antagonists, a series of novel 3-benzoylaminophenylacetic acids were synthesized and biologically evaluated. Among those tested, some representative compounds were found to be orally available. Receptor selectivity and rat PK profiles were also evaluated. The structure-activity relationship (SAR) study is presented.

MeSH terms

Animals
Benzamides / chemical synthesis
Benzamides / chemistry
Benzamides / pharmacology*
Binding, Competitive / drug effects
CHO Cells
Cricetinae
Dose-Response Relationship, Drug
Drug Design*
Male
Molecular Conformation
Phenylacetates / chemical synthesis
Phenylacetates / chemistry
Phenylacetates / pharmacology*
Rats
Receptors, Immunologic / antagonists & inhibitors*
Receptors, Prostaglandin / antagonists & inhibitors*
Stereoisomerism
Structure-Activity Relationship
Tissue Distribution

Substances

Benzamides
Phenylacetates
Receptors, Immunologic
Receptors, Prostaglandin
prostaglandin D2 receptor