2. Academic Validation
  3. Lead optimization of 4-(dimethylamino)quinazolines, potent and selective antagonists for the melanin-concentrating hormone receptor 1

Lead optimization of 4-(dimethylamino)quinazolines, potent and selective antagonists for the melanin-concentrating hormone receptor 1

  • Bioorg Med Chem Lett. 2005 Sep 1;15(17):3853-6. doi: 10.1016/j.bmcl.2005.05.121.
Kosuke Kanuma 1,  Katsunori Omodera,  Mariko Nishiguchi,  Takeo Funakoshi,  Shigeyuki Chaki,  Graeme Semple,  Thuy-Anh Tran,  Bryan Kramer,  Debbie Hsu,  Martin Casper,  Bill Thomsen,  Yoshinori Sekiguchi
Affiliations

Affiliation

  • 1 Medicinal Research Laboratories, Taisho Pharmaceutical Co. Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama, Saitama 331-9530, Japan.
PMID: 16002290 DOI: 10.1016/j.bmcl.2005.05.121
Abstract

The optimization of a series of 4-(dimethylamino)quinazoline antagonists of the melanin-concentrating hormone receptor 1 (MCH-R1) is described. The combination of the elaboration of both the linker portion and the terminal phenyl ring provided N-(cis-4-{[4-(dimethylamino)quinazolin-2-yl]amino}cyclohexyl)-3,4-difluorobenzamide hydrochloride 28 (ATC0175), which showed excellent antagonist activity at the MCH-R1 (IC50 = 3.4 nM) as well as good selectivity over the Y5 and the alpha2A receptors.

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