The design and synthesis of a novel series of indole derived selective ET(A) antagonists.
Conformational constraint has been used as the key design element in the identification of a series of potent and selective ET(A) antagonists. The most potent antagonist, 32, (ET(A) IC(50)=0.55nM) is 722-fold selective over the ET(B) receptor, as measured by binding experiments.
Rawson
David J
DJ
Department of Discovery Chemistry, Pfizer Central Research, Sandwich, Kent CT13 9NJ, UK. david_rawson@sandwich.pfizer.com
Dack
Kevin N
KN
Dickinson
Roger P
RP
James
Kim
K
D065128:Endothelin Receptor Antagonists; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology; D044022:Receptor, Endothelin A; D013329:Structure-Activity Relationship
D065128:Endothelin Receptor Antagonists; D007211:Indoles; D044022:Receptor, Endothelin A