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.
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.
Satoh
Atsushi
A
Tsukuba Research Institute, Merck Research Laboratories, Banyu Pharmaceutical Co., Ltd, Okubo 3, Tsukuba, Ibaraki 300-2611, Japan.
Nagatomi
Yasushi
Y
Hirata
Yukari
Y
Ito
Satoru
S
Suzuki
Gentaroh
G
Kimura
Toshifumi
T
Maehara
Shunsuke
S
Hikichi
Hirohiko
H
Satow
Akio
A
Hata
Mikiko
M
Ohta
Hisashi
H
Kawamoto
Hiroshi
H
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
D014150:Antipsychotic Agents; D001549:Benzamides; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; C038530:N-methylbenzamide