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

K N Dack; R P Dickinson; C J Long; J Steele

doi:10.1016/s0960-894x(98)00242-x

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

Bioorg Med Chem Lett. 1998 Aug 18;8(16):2061-6. doi: 10.1016/s0960-894x(98)00242-x.

Authors

K N Dack¹, R P Dickinson, C J Long, J Steele

Affiliation

¹ Department of Discovery Chemistry, Pfizer Central Research, Sandwich, Kent, U.K. [email protected]

PMID: 9873486
DOI: 10.1016/s0960-894x(98)00242-x

Abstract

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.

MeSH terms

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology
Animals
Dogs
Drug Design
Indicators and Reagents
Molecular Structure
Phenylpropionates / chemical synthesis*
Phenylpropionates / chemistry
Phenylpropionates / pharmacology
Platelet Aggregation / drug effects
Platelet Aggregation Inhibitors / chemical synthesis*
Platelet Aggregation Inhibitors / chemistry
Platelet Aggregation Inhibitors / pharmacology
Receptors, Thromboxane / antagonists & inhibitors*
Structure-Activity Relationship

Substances

Indicators and Reagents
Phenylpropionates
Platelet Aggregation Inhibitors
Receptors, Thromboxane
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid