Thromboxane modulating agents. 4. Design and synthesis of 3-(2-[{(4-chlorophenyl)sulfonyl}amino]ethyl)benzenepropanoic acid derivatives as potent thromboxane receptor antagonists

The design of a series of thromboxane receptor antagonists based on 3-(2-[{(4-chlorophenyl)sulfonyl}amino]ethyl)benzenepropanoic acid (1) is described. Addition of an arylmethyl group at the 5-position of 1 gave exceptionally potent agents in vitro and in vivo, with 13a (UK-147,535) giving complete blockade of the TxA2 receptor for greater than 12 hours in dogs, following an oral dose of 0.1 mg/kg.