Development of prostaglandin D2 receptor antagonist: discovery of highly potent antagonists

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

doi:10.1016/j.bmc.2004.06.024

Development of prostaglandin D2 receptor antagonist: discovery of highly potent antagonists

Bioorg Med Chem. 2004 Sep 1;12(17):4685-700. doi: 10.1016/j.bmc.2004.06.024.

Authors

Kazuhiko Torisu¹, Kaoru Kobayashi, Maki Iwahashi, Yoshihiko Nakai, Takahiro Onoda, Toshihiko Nagase, Isamu Sugimoto, Yutaka Okada, Ryoji Matsumoto, Fumio Nanbu, Shuichi Ohuchida, Hisao Nakai, Masaaki Toda

Affiliation

¹ Minase Research Institute, Ono Pharmaceutical Co. Ltd., Shimamoto, Mishima, Osaka 618-8585, Japan. [email protected]

PMID: 15358295
DOI: 10.1016/j.bmc.2004.06.024

Abstract

The process of discovery for highly potent prostaglandin D(2) (PGD(2)) receptor antagonists is reported. A series of N-(p-alkoxy)benzoyl-2-methylindole-4-acetic acids were synthesized and identified as a new class of selective PGD(2) receptor antagonists. Most of them exhibited strong PGD(2) receptor antagonism in binding studies and the cAMP formation assay. The structure-activity relationships (SAR), including subtype selectivity of the synthesized compounds, are also discussed.

MeSH terms

Anti-Allergic Agents / chemical synthesis
Anti-Allergic Agents / pharmacology*
Binding Sites
Cyclic AMP / metabolism
Drug Design
Indoleacetic Acids / chemistry
Indoleacetic Acids / pharmacology*
Receptors, Immunologic / antagonists & inhibitors*
Receptors, Prostaglandin / antagonists & inhibitors*
Structure-Activity Relationship

Substances

Anti-Allergic Agents
Indoleacetic Acids
Receptors, Immunologic
Receptors, Prostaglandin
Cyclic AMP
prostaglandin D2 receptor