Nonpeptide endothelin antagonists: from lower affinity pyrazol-5-ols to higher affinity pyrazole-5-carboxylic acids.
Random screening of compounds in endothelin receptor (ET(A) and ET(B)) binding assays led to the discovery of a new class of pyrazol-5-ol ligands. Characterization of structural features crucial for binding activities of these pyrazol-5-ols, by structure activity-relationship (SAR) studies, allowed us to design a novel class of pyrazole-5-carboxylic acids as more potent ET antagonists.
Zhang
J
J
Medicinal Chemistry, Hoechst Marion Roussel, Romainville, France. jidong.zhang@aventis.com
Didierlaurent
S
S
Fortin
M
M
Lefrançois
D
D
Uridat
E
E
Vevert
J P
JP
D002264:Carboxylic Acids / Q000378:metabolism*; D016232:Endothelins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011720:Pyrazoles / Q000378:metabolism*; D013329:Structure-Activity Relationship
D002264:Carboxylic Acids; D016232:Endothelins; D011720:Pyrazoles