Discovery of imidazole carboxamides as potent and selective CCK1R agonists.
High-throughput screening revealed diaryl pyrazole 3 as a selective albeit modest cholecystokinin 1 receptor (CCK1R) agonist. SAR studies led to the discovery and optimization of a novel class of 1,2-diaryl imidazole carboxamides. Compound 44, which was profiled extensively, showed good in vivo mouse gallbladder emptying (mGBE) and lean mouse overnight food intake (ONFI) reduction activities.
Zhu
Cheng
C
Department of Medicinal Chemistry, Merck Research Laboratories, Merck & Co. Inc., PO Box 2000, Rahway, NJ 07065, USA. cheng_zhu@merck.com
Hansen
Alexa R
AR
Bateman
Thomas
T
Chen
Zhesheng
Z
Holt
Tom G
TG
Hubert
James A
JA
Karanam
Bindhu V
BV
Lee
Susan J
SJ
Pan
Jie
J
Qian
Su
S
Reddy
Vijay B G
VB
Reitman
Marc L
ML
Strack
Alison M
AM
Tong
Vincent
V
Weingarth
Drew T
DT
Wolff
Michael S
MS
MacNeil
Doug J
DJ
Weber
Ann E
AE
Duffy
Joseph L
JL
Edmondson
Scott D
SD
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D019742:Chemokines, CC; D020650:Combinatorial Chemistry Techniques; D004435:Eating / Q000187:drug effects; D016473:Gallbladder Emptying / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D015394:Molecular Structure; D011949:Receptors, Cholecystokinin / Q000819:agonists*; D013329:Structure-Activity Relationship
D000577:Amides; D019440:Anti-Obesity Agents; C511142:Ccl28 protein, mouse; D019742:Chemokines, CC; D007093:Imidazoles; D011949:Receptors, Cholecystokinin