Discovery and synthesis of a potent sulfonamide ET(B) selective antagonist

Y Kanda; T Takahashi; Y Araki; T Konoike; S Mihara; M Fujimoto

doi:10.1016/s0960-894x(00)00366-8

Discovery and synthesis of a potent sulfonamide ET(B) selective antagonist

Bioorg Med Chem Lett. 2000 Aug 21;10(16):1875-8. doi: 10.1016/s0960-894x(00)00366-8.

Authors

Y Kanda¹, T Takahashi, Y Araki, T Konoike, S Mihara, M Fujimoto

Affiliation

¹ Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan. yasuhiko.kanda@shionogi.co.jp

PMID: 10969989
DOI: 10.1016/s0960-894x(00)00366-8

Abstract

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.

MeSH terms

Animals
Aorta
COS Cells
Cell Line
Endothelin Receptor Antagonists*
Molecular Structure
Muscle, Smooth, Vascular
Radioligand Assay
Rats
Receptor, Endothelin B
Receptors, Endothelin / metabolism
Sulfonamides / chemical synthesis*
Sulfonamides / chemistry
Sulfonamides / metabolism
Sulfonamides / pharmacology*

Substances

Endothelin Receptor Antagonists
Receptor, Endothelin B
Receptors, Endothelin
Sulfonamides