title: Discovery of novel phenethylpyridone derivatives as potent melanin-concentrating hormone 1 receptor antagonists.
abstract: Novel phenethylpyridone derivatives were identified as potent human melanin-concentrating hormone 1 receptor (MCH-1R) antagonists. A search for surrogates for the 4-(2-aminoethoxy)phenyl moiety of 1 resulted in discovery of 2-[4-(aminomethyl)phenyl]ethyl substructure as in 6a. Successive optimization of the right-hand moiety led to the identification of a number of potent derivatives.
authors.affiliation: Department of Medicinal Chemistry, Tsukuba Research Institute, Merck Research Laboratories, Banyu Pharmaceutical Co. Ltd, Okubo-3, Tsukuba, Ibaraki, Japan. andoumkt@gmail.com
authors.forename: Makoto
authors.initials: M
authors.lastname: Ando
authors.forename: Etsuko
authors.initials: E
authors.lastname: Sekino
authors.forename: Yuji
authors.initials: Y
authors.lastname: Haga
authors.forename: Minoru
authors.initials: M
authors.lastname: Moriya
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ito
authors.forename: Junko
authors.initials: J
authors.lastname: Ito
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: Norikazu
authors.initials: N
authors.lastname: Ohtake
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D055808:Drug Discovery; D006801:Humans; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D011728:Pyridones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D019440:Anti-Obesity Agents; C103263:MCHR1 protein, human; D011728:Pyridones; D017481:Receptors, Somatostatin; D011994:Recombinant Proteins