Synthesis and evaluation of 5,5-diphenylimidazolones as potent human neuropeptide Y5 receptor antagonists.
A series of novel 5,5-diphenylimidazolones was synthesized and evaluated for activity against the human neuropeptide Y5 receptor. The 3-pyridyl analog 46 demonstrated an IC(50) of 8.3 nM with a favorable pharmacokinetic profile in rats, but was ineffective in reducing food intake.
Gillman
Kevin W
KW
Bristol-Myers Squibb Pharmaceutical Research Institute, Richard L. Gelb Center for Pharmaceutical Research and Development, Wallingford, CT 06492, USA. gillmank@bms.com
Higgins
Mendi A
MA
Poindexter
Graham S
GS
Browning
Marc
M
Clarke
Wendy J
WJ
Flowers
Sharon
S
Grace
James E
JE
Hogan
John B
JB
McGovern
Rachel T
RT
Iben
Lawrence G
LG
Mattson
Gail K
GK
Ortiz
Astrid
A
Rassnick
Stefanie
S
Russell
John W
JW
Antal-Zimanyi
Ildiko
I
D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013997:Time Factors
D019440:Anti-Obesity Agents; D007093:Imidazoles; D017476:Receptors, Neuropeptide Y; C100568:neuropeptide Y5 receptor