title: Novel orally active NPY Y5 receptor antagonists: Synthesis and structure-activity relationship of spiroindoline class compounds.
abstract: 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.
authors.affiliation: Tsukuba Research Institute, Merck Research Laboratories, Banyu Pharmaceutical Co., Ltd, Okubo-3, Tsukuba, Ibaraki 300-2611, Japan. toshihiro_sakamoto@merck.com
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Minoru
authors.initials: M
authors.lastname: Moriya
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Tsuge
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Haga
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Nonoshita
authors.forename: Osamu
authors.initials: O
authors.lastname: Okamoto
authors.forename: Hirobumi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Aya
authors.initials: A
authors.lastname: Sakuraba
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hirohashi
authors.forename: Takunobu
authors.initials: T
authors.lastname: Shibata
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kanno
authors.forename: Junko
authors.initials: J
authors.lastname: Ito
authors.forename: Hisashi
authors.initials: H
authors.lastname: Iwaasa
authors.forename: Akira
authors.initials: A
authors.lastname: Gomori
authors.forename: Akane
authors.initials: A
authors.lastname: Ishihara
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fukuroda
authors.forename: Akio
authors.initials: A
authors.lastname: Kanatani
authors.forename: Takehiro
authors.initials: T
authors.lastname: Fukami
mesh_terms: 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
chemical_list: D019440:Anti-Obesity Agents; D007211:Indoles; D017476:Receptors, Neuropeptide Y; D013141:Spiro Compounds; C100568:neuropeptide Y5 receptor; C057812:indoline