Discovery of novel phenethylpyridone derivatives as potent melanin-concentrating hormone 1 receptor antagonists.
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.
Ando
Makoto
M
Department of Medicinal Chemistry, Tsukuba Research Institute, Merck Research Laboratories, Banyu Pharmaceutical Co. Ltd, Okubo-3, Tsukuba, Ibaraki, Japan. andoumkt@gmail.com
Sekino
Etsuko
E
Haga
Yuji
Y
Moriya
Minoru
M
Ito
Masahiko
M
Ito
Junko
J
Iwaasa
Hisashi
H
Ishihara
Akane
A
Kanatani
Akio
A
Ohtake
Norikazu
N
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
D019440:Anti-Obesity Agents; C103263:MCHR1 protein, human; D011728:Pyridones; D017481:Receptors, Somatostatin; D011994:Recombinant Proteins