Bioorganic & Medicinal Chemistry Letters 2009-09-15

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.

Atsushi Satoh, Yasushi Nagatomi, Yukari Hirata, Satoru Ito, Gentaroh Suzuki, Toshifumi Kimura, Shunsuke Maehara, Hirohiko Hikichi, Akio Satow, Mikiko Hata, Hisashi Ohta, Hiroshi Kawamoto

Index: Bioorg. Med. Chem. Lett. 19(18) , 5464-8, (2009)

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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.