Biphenylsulfonamide endothelin receptor antagonists. Part 3: structure-activity relationship of 4'-heterocyclic biphenylsulfonamides.
A number of 4'-heterocyclic biphenylsulfonamide derivatives, formally derived from BMS-193884 (1) by replacing the oxazole ring with other heterocyclic rings, are potent and selective endothelin A (ET(A)) receptor antagonists. Among the analogues examined, the pyrimidine derivative 18 is the most potent (K(i)=0.9 nM) and selective for the ET(A) receptor, approximately equivalent to 1.
Murugesan
Natesan
N
Department of Chemistry, Cardiovascular Agents, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-5400, USA. natesan.murugesan@bms.com
Gu
Zhengxiang
Z
Stein
Philip D
PD
Spergel
Steven
S
Bisaha
Sharon
S
Liu
Eddie C-K
EC
Zhang
Rongan
R
Webb
Maria L
ML
Moreland
Suzanne
S
Barrish
Joel C
JC
D000818:Animals; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D065128:Endothelin Receptor Antagonists; D006801:Humans; D011485:Protein Binding; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014162:Transfection
D001713:Biphenyl Compounds; D065128:Endothelin Receptor Antagonists; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; D013449:Sulfonamides