181052-61-9Relevant articles and documents
Development of dual-acting benzofurans for thromboxane A2 receptor antagonist and prostacyclin receptor agonist: Synthesis, structure-activity relationship, and evaluation of benzofuran derivatives
Ohno, Michihiro,Miyamoto, Mitsuko,Hoshi, Kazuhiro,Takeda, Takahiro,Yamada, Naohiro,Ohtake, Atsushi
, p. 5279 - 5294 (2007/10/03)
Prostacyclin (PGI2) is an unstable, powerful endogenous inhibitor of platelet aggregation, and thromboxane A2 (TXA 2) is an unstable endogenous arachidonic acid metabolite that plays a pivotal role in platelet aggregation and vasoconstriction. The balance between TXA2 and PGI2 greatly affects maintenance of the homeostasis of the circulatory system. A novel series of benzofuran-7- yloxyacetic acid derivatives was discovered as potent dual-acting agents to block the thromboxane A2 receptor and to activate the prostacyclin receptor. Synthesis, structure-activity relationship, and in vitro and ex vivo pharmacology of this series of compounds are described. The most potent in the series was {3-[2-(1,1-diphenylethylsulfanyl)ethyl]-2-hydroxymethylbenzofuran-7- yloxy}acetic acid diethanolamine salt (7) with Ki of 4.5 nM for thromboxane receptor antagonism and Ki of 530 nM for prostacyclin receptor agonism. Remarkably, compound 7 is a promising candidate for novel treatment as an antithrombotic agent with other cardiovascular actions to avoid hypotensive side effects.
