title: Identification of novel and orally active spiroindoline NPY Y5 receptor antagonists.
abstract: A series of spiroindoline-3,4'-piperidine derivatives were synthesized and evaluated for their binding affinities and antagonistic activities at Y5 receptors. Potent Y5 antagonists were tested for their oral bioavailabilities and brain penetration in rats. Some of the antagonists showed good oral bioavailability and/or good brain penetration. In particular, compound 6e was orally bioavailable and brain penetrant, and oral administration of 6e inhibited bPP-induced food intake in rats with a minimum effective dose of 10mg/kg.
authors.affiliation: Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd, Okubo 3, Tsukuba 300-2611, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Minoru
authors.initials: M
authors.lastname: Moriya
authors.forename: Yuji
authors.initials: Y
authors.lastname: Haga
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Takunobu
authors.initials: T
authors.lastname: Shibata
authors.forename: Osamu
authors.initials: O
authors.lastname: Okamoto
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Nonoshita
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Kitazawa
authors.forename: Masayasu
authors.initials: M
authors.lastname: Hidaka
authors.forename: Akira
authors.initials: A
authors.lastname: Gomori
authors.forename: Hisashi
authors.initials: H
authors.lastname: Iwaasa
authors.forename: Akane
authors.initials: A
authors.lastname: Ishihara
authors.forename: Akio
authors.initials: A
authors.lastname: Kanatani
authors.forename: Takehiro
authors.initials: T
authors.lastname: Fukami
authors.forename: Ying-Duo
authors.initials: YD
authors.lastname: Gao
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Macneil
authors.forename: Lihu
authors.initials: L
authors.lastname: Yang
mesh_terms: D000284:Administration, Oral; D000588:Amines / Q000737:chemistry; D000818:Animals; D001682:Biological Availability; D001921:Brain / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D007211:Indoles / Q000008:administration & dosage* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D017953:Isocyanates / Q000737:chemistry; D008956:Models, Chemical; D019151:Peptide Library; D051381:Rats; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D014508:Urea / Q000737:chemistry
chemical_list: D000588:Amines; D007211:Indoles; D017953:Isocyanates; D019151:Peptide Library; D017476:Receptors, Neuropeptide Y; C100568:neuropeptide Y5 receptor; C057812:indoline; D014508:Urea