Development of a prostaglandin D2 receptor antagonist: discovery of a new chemical lead.

作者信息

Torisu Kazuhiko, Kobayashi Kaoru, Iwahashi Maki, Egashira Hiromu, Nakai Yoshihiko, Okada Yutaka, Nanbu Fumio, Ohuchida Shuichi, Nakai Hisao, Toda Masaaki

机构信息

Minase Research Institute, Ono Pharmaceutical Co., Ltd., Shimamoto, Mishima, Osaka 618-8585, Japan.

出版信息

Eur J Med Chem. 2005 May;40(5):505-19. doi: 10.1016/j.ejmech.2004.11.011.

DOI:10.1016/j.ejmech.2004.11.011

PMID:15893024

Abstract

A series of N-(p-alkoxy)benzoyl-5-methoxy-2-methylindole-3-acetic acids and N-(p-butoxy)benzoyl-2-methylindole-4-acetic acid were discovered as new chemical leads for a prostaglandin D2 (PGD2) receptor antagonist. Most of them exhibited PGD2 receptor binding and blocked cyclic adenosine 3',5'-monophosphate (cAMP) formation in vitro. In particular, 2-methylindole-4-acetic acid analog 1 showed markedly increased receptor affinity and cAMP antagonist activity. Chemistry and structure activity relationship (SAR) data are also presented.

摘要

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