Novel orally active NPY Y5 receptor antagonists: Synthesis and structure-activity relationship of spiroindoline class compounds.
Spiroindoline urea derivatives, designed to act as NPY Y5 receptor antagonists, were synthesized and their structure-activity relationships were investigated. Of these derivatives, compound 3a showed good Y5 binding affinity with favorable pharmacokinetic properties. Compound 3a significantly inhibited bPP Y5 agonist-induced food intake in rats, and suppressed body weight gain in DIO mice.
Sakamoto
Toshihiro
T
Tsukuba Research Institute, Merck Research Laboratories, Banyu Pharmaceutical Co., Ltd, Okubo-3, Tsukuba, Ibaraki 300-2611, Japan. toshihiro_sakamoto@merck.com
Moriya
Minoru
M
Tsuge
Hiroyasu
H
Takahashi
Toshiyuki
T
Haga
Yuji
Y
Nonoshita
Katsumasa
K
Okamoto
Osamu
O
Takahashi
Hirobumi
H
Sakuraba
Aya
A
Hirohashi
Tomoko
T
Shibata
Takunobu
T
Kanno
Tetsuya
T
Ito
Junko
J
Iwaasa
Hisashi
H
Gomori
Akira
A
Ishihara
Akane
A
Fukuroda
Takahiro
T
Kanatani
Akio
A
Fukami
Takehiro
T
D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D013329:Structure-Activity Relationship
D019440:Anti-Obesity Agents; D007211:Indoles; D017476:Receptors, Neuropeptide Y; D013141:Spiro Compounds; C100568:neuropeptide Y5 receptor; C057812:indoline