Identification of alpha-substituted acylamines as novel, potent, and orally active mGluR5 negative allosteric modulators. Issue 16 (15th August 2015)

• Record Type: Journal Article
• Authors: Yoshikawa, Keita; Ohyama, Tomofumi; Takahashi, Eiki; Numajiri, Yoshitaka; Konno, Mitsuhiro; Moriyama, Masaki; Takemi, Natsumi; Kunita, Kana; Nishimura, Kazumi; Hayashi, Ryoji
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 16(2015)
• Page Start: 3135
• Page End: 3141
• Publication Date: 2015-08-15
• Subjects: Metabotropic glutamate receptor -- mGluR5 negative allosteric modulators -- Acylamines; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.06.008
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: This Letter describes the identification of a series of novel non-acetylenic mGluR5 negative allosteric modulators based on the alpha-substituted acylamine structure. An initial structure–activity relationship study suggested that ( R )-19b and ( R )-19j might have good in vitro activity. When administered orally, these compounds were found to have an anxiolytic-like effect in a mouse model of stress-induced hyperthermia.