title: Discovery of novel spiro-piperidine derivatives as highly potent and selective melanin-concentrating hormone 1 receptor antagonists.
abstract: Optimization of high-throughput screening hit 1a led to the identification of a novel spiro-piperidine class of melanin-concentrating hormone 1 receptor (MCH-1R) antagonists. Compound 3c was identified as a highly potent and selective MCH-1R antagonist, which has an IC(50) value of 0.09 nM at hMCH-1R. The synthesis and structure-activity relationships of the novel spiro-piperidine MCH-1R antagonists are described.
authors.affiliation: Department of Medicinal Chemistry, Tsukuba Research Institute, Merck Research Laboratories, Banyu Pharmaceutical Co, Ltd, Tsukuba, Ibaraki, Japan. takao_suzuki@merck.com
authors.forename: Takao
authors.initials: T
authors.lastname: Suzuki
authors.forename: Minoru
authors.initials: M
authors.lastname: Moriya
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Takuya
authors.initials: T
authors.lastname: Suga
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kishino
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Takahashi
authors.forename: Makoto
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Keita
authors.initials: K
authors.lastname: Nagai
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Imai
authors.forename: Etsuko
authors.initials: E
authors.lastname: Sekino
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ito
authors.forename: Hisashi
authors.initials: H
authors.lastname: Iwaasa
authors.forename: Akane
authors.initials: A
authors.lastname: Ishihara
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tokita
authors.forename: Akio
authors.initials: A
authors.lastname: Kanatani
authors.forename: Nagaaki
authors.initials: N
authors.lastname: Sato
authors.forename: Takehiro
authors.initials: T
authors.lastname: Fukami
mesh_terms: D002460:Cell Line; D055808:Drug Discovery; D006801:Humans; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: C103263:MCHR1 protein, human; D010880:Piperidines; D017481:Receptors, Somatostatin; D013141:Spiro Compounds