(S)-N-{3-[1-cyclopropyl-1-(2,4-difluoro-phenyl)-ethyl]-1H-indol-7-yl}-methanesulfonamide: a potent, nonsteroidal, functional antagonist of the mineralocorticoid receptor.
A novel, potent series of indole analogs were recently developed as MR antagonists, culminating in 14. This compound represents the first MR antagonist in this class of molecules, exhibiting picomolar binding affinity and in vivo blood pressure lowering at pharmaceutically relevant doses.
Bell
Michael G
MG
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. bell_michael_g@Lilly.com
Gernert
Douglas L
DL
Grese
Timothy A
TA
Belvo
Matthew D
MD
Borromeo
Peter S
PS
Kelley
Sally A
SA
Kennedy
Joseph H
JH
Kolis
Stanley P
SP
Lander
Peter A
PA
Richey
Rachel
R
Sharp
V Scott
VS
Stephenson
Gregory A
GA
Williams
Jeffrey D
JD
Yu
Hannah
H
Zimmerman
Karen M
KM
Steinberg
Mitchell I
MI
Jadhav
Prabhakar K
PK
D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000451:Mineralocorticoid Receptor Antagonists; D008958:Models, Molecular; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000959:Antihypertensive Agents; D007211:Indoles; D000451:Mineralocorticoid Receptor Antagonists; C527716:N-(3-(1-cyclopropyl-1-(2,4-difluorophenyl)ethyl)-1H-indol-7-yl)methanesulfonamide; D013449:Sulfonamides