Benzofuro[3,2-b]pyridines as mixed ET(A)/ET(B) and selective ET(B) endothelin receptor antagonists.
The discovery, synthesis and structure-activity relationships of a series of novel benzofuro[3,2-b]pyridines as non-selective endothelin ET(A)/ET(B) as well as selective ET(B) receptor antagonists are described. The most potent non-selective inhibitor 7s displayed an IC50 of 21 nM and 41 nM for ET(A) and ET(B) receptors, respectively, whereas 7ee merely showed affinity for the ET(B) receptor (IC50 = 3.6 nM).
Mederski
W W
WW
Merck KGaA, Preclinical Pharmaceutical Research, Darmstadt, Germany. mederski@merck.de
Osswald
M
M
Dorsch
D
D
Christadler
M
M
Schmitges
C J
CJ
Wilm
C
C
D000818:Animals; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D013329:Structure-Activity Relationship; D013552:Swine
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D011725:Pyridines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B