SAR studies of 1,5-diarylpyrazole-based CCK1 receptor antagonists.
A high throughput screening campaign revealed compound 1 as a potent antagonist of the human CCK(1) receptor. Here, we report the syntheses and SAR studies of 1,5-diarylpyrazole analogs with various structural modifications of the alkane side chain of the molecule. The difference in affinity between the two enantiomers for the CCK(1) receptor and the flexible nature of the linker led to the design of constrained analogs with increased potency.
Gomez
Laurent
L
Johnson & Johnson Pharmaceutical Research and Development L.L.C., 3210 Merryfield Row, San Diego, CA 92121, USA. lgomez4@prdus.jnj.com
Hack
Michael D
MD
McClure
Kelly
K
Sehon
Clark
C
Huang
Liming
L
Morton
Magda
M
Li
Lina
L
Barrett
Terrance D
TD
Shankley
Nigel
N
Breitenbucher
J Guy
JG
D000818:Animals; D006801:Humans; D011720:Pyrazoles / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D043886:Receptor, Cholecystokinin A / Q000037:antagonists & inhibitors* / Q000502:physiology; D013329:Structure-Activity Relationship
D011720:Pyrazoles; D043886:Receptor, Cholecystokinin A