口服活性前列腺素D2受体拮抗剂的发现。

Discovery of orally active prostaglandin D2 receptor antagonists.

作者信息

Torisu Kazuhiko, Kobayashi Kaoru, Iwahashi Maki, Nakai Yoshihiko, Onoda Takahiro, Nagase Toshihiko, Sugimoto Isamu, Okada Yutaka, Matsumoto Ryoji, Nanbu Fumio, Ohuchida Shuichi, Nakai Hisao, Toda Masaaki

机构信息

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

出版信息

Bioorg Med Chem Lett. 2004 Oct 4;14(19):4891-5. doi: 10.1016/j.bmcl.2004.07.039.

DOI:10.1016/j.bmcl.2004.07.039

PMID:15341946

Abstract

A series of N-(p-alkoxy)benzoyl-2-methylindole-4-acetic acids were synthesized and evaluated for prostaglandin D(2) (DP) receptor affinity and antagonist activity. Some of them exhibited strong receptor binding and were potent in the cAMP formation assays. These antagonists also suppressed allergic inflammatory responses such as the PGD(2)-induced increase of microvascular permeability. Structure-activity relationship (SAR) data are presented.

摘要

合成了一系列N-（对烷氧基）苯甲酰基-2-甲基吲哚-4-乙酸，并对其前列腺素D2（DP）受体亲和力和拮抗剂活性进行了评估。其中一些表现出强烈的受体结合能力，并且在环磷酸腺苷（cAMP）形成试验中具有强效。这些拮抗剂还抑制了过敏炎症反应，如PGD2诱导的微血管通透性增加。并给出了构效关系（SAR）数据。