Development of 3,4-dihydro-2H-benzo[1,4]oxazine derivatives as dual thromboxane A2 receptor antagonists and prostacyclin receptor agonists

We discovered a novel series of 3,4-dihydro-2H-benzo[1,4]oxazin-8-yloxyacetic acid derivatives as potent dual-acting PGl(2) receptor. We report the synthesis, structure-activity relationship, agents to block the TXA receptor and to activate the PGl(2) i and in vitro, ex vivo, and in vivo pharmacology of this series of compounds. 4-[2-(1,1-Diphenylethylsulfanyl)ethyl]-3,4-dihydro2H-benzo[1,4]oxazin-8-yloxyacetic acid N-inethyl-D-glucamine salt (7) is a promising candidate for a novel treatment in the antithrombotic and the cardioscular fields avoiding hypotensive side effects. (c) 2005 Elsevier Ltd. All rights reserved.