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.
Dack
K N
KN
Department of Discovery Chemistry, Pfizer Central Research, Sandwich, Kent, U.K. Kevin_Dack@sandwich.pfizer.com
Dickinson
R P
RP
Long
C J
CJ
Steele
J
J
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D015195:Drug Design; D007202:Indicators and Reagents; D015394:Molecular Structure; D010666:Phenylpropionates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D007202:Indicators and Reagents; D010666:Phenylpropionates; D010975:Platelet Aggregation Inhibitors; D017482:Receptors, Thromboxane; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid