Discovery of substituted biphenyl imidazoles as potent, bioavailable bombesin receptor subtype-3 agonists.
We report SAR studies on a novel non-peptidic bombesin receptor subtype-3 (BRS-3) agonist lead series derived from high-throughput screening hit RY-337. This effort led to the discovery of compound 22e with significantly improved potency at both rodent and human BRS-3.
He
Shuwen
S
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. shuwen_he@merck.com
Dobbelaar
Peter H
PH
Liu
Jian
J
Jian
Tianying
T
Sebhat
Iyassu K
IK
Lin
Linus S
LS
Goodman
Allan
A
Guo
Cheng
C
Guzzo
Peter R
PR
Hadden
Mark
M
Henderson
Alan J
AJ
Ruenz
Megan
M
Sargent
Bruce J
BJ
Yet
Larry
L
Kelly
Theresa M
TM
Palyha
Oksana
O
Kan
Yanqing
Y
Pan
Jie
J
Chen
Howard
H
Marsh
Donald J
DJ
Shearman
Lauren P
LP
Strack
Alison M
AM
Metzger
Joseph M
JM
Feighner
Scott D
SD
Tan
Carina
C
Howard
Andrew D
AD
Tamvakopoulos
Constantin
C
Peng
Qianping
Q
Guan
Xiao-Ming
XM
Reitman
Marc L
ML
Patchett
Arthur A
AA
Wyvratt
Matthew J
MJ
Nargund
Ravi P
RP
D000818:Animals; D001682:Biological Availability; D055808:Drug Discovery; D006801:Humans; D007093:Imidazoles / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D018004:Receptors, Bombesin / Q000819:agonists*; D013329:Structure-Activity Relationship
D007093:Imidazoles; D018004:Receptors, Bombesin; C107120:bombesin receptor subtype 3