Discovery and synthesis of a potent sulfonamide ET(B) selective antagonist.
The synthesis and structure activity relationships of a series of sulfonamide endothelin antagonists are described. In the course of our modification studies, we discovered ET(B) selective antagonists. The most potent compound 15f displays IC50 values of 1.7 microM and 0.002 microM to ET(A) and ET(B) receptors, respectively.
Kanda
Y
Y
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan. yasuhiko.kanda@shionogi.co.jp
Takahashi
T
T
Araki
Y
Y
Konoike
T
T
Mihara
S
S
Fujimoto
M
M
D000818:Animals; D001011:Aorta; D019556:COS Cells; D002460:Cell Line; D065128:Endothelin Receptor Antagonists; D015394:Molecular Structure; D009131:Muscle, Smooth, Vascular; D011869:Radioligand Assay; D051381:Rats; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000378:metabolism; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
D065128:Endothelin Receptor Antagonists; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D013449:Sulfonamides