Discovery of novel phenethylpyridone derivatives as potent melanin-concentrating hormone 1 receptor antagonists

  • Bioorg Med Chem Lett. 2009 Sep 1;19(17):5186-90. doi: 10.1016/j.bmcl.2009.07.023.
Makoto Ando  1 ,  Etsuko Sekino ,  Yuji Haga ,  Minoru Moriya ,  Masahiko Ito ,  Junko Ito ,  Hisashi Iwaasa ,  Akane Ishihara ,  Akio Kanatani ,  Norikazu Ohtake
Affiliations
  • 1. Department of Medicinal Chemistry, Tsukuba Research Institute, Merck Research Laboratories, Banyu Pharmaceutical Co. Ltd, Okubo-3, Tsukuba, Ibaraki, Japan. [email protected]
PMID: 19632840 DOI: 10.1016/j.bmcl.2009.07.023
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.