title: Discovery and in vitro and in vivo profiles of 4-fluoro-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide as novel class of an orally active metabotropic glutamate receptor 1 (mGluR1) antagonist.
abstract: We identified 4-fluoro-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide 27 as a potent mGluR1 antagonist. The compound possessed excellent subtype selectivity and good PK profile in rats. It also demonstrated relatively potent antipsychotic-like effects in several animal models. Suitable for development as a PET tracer, compound 27 would have great potential for elucidation of mGluR1 functions in human.
authors.affiliation: Tsukuba Research Institute, Merck Research Laboratories, Banyu Pharmaceutical Co., Ltd, Okubo 3, Tsukuba, Ibaraki 300-2611, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Satoh
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nagatomi
authors.forename: Yukari
authors.initials: Y
authors.lastname: Hirata
authors.forename: Satoru
authors.initials: S
authors.lastname: Ito
authors.forename: Gentaroh
authors.initials: G
authors.lastname: Suzuki
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Kimura
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Maehara
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Hikichi
authors.forename: Akio
authors.initials: A
authors.lastname: Satow
authors.forename: Mikiko
authors.initials: M
authors.lastname: Hata
authors.forename: Hisashi
authors.initials: H
authors.lastname: Ohta
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawamoto
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D001549:Benzamides / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D014150:Antipsychotic Agents; D001549:Benzamides; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; C038530:N-methylbenzamide