Discovery and biological profile of 4-(1-aryltriazol-4-yl)-tetrahydropyridines as an orally active new class of metabotropic glutamate receptor 1 antagonist

  • Bioorg Med Chem. 2008 Nov 15;16(22):9817-29. doi: 10.1016/j.bmc.2008.09.060.
Satoru Ito  1 ,  Atsushi Satoh ,  Yasushi Nagatomi ,  Yukari Hirata ,  Gentaroh Suzuki ,  Toshifumi Kimura ,  Akio Satow ,  Shunsuke Maehara ,  Hirohiko Hikichi ,  Mikiko Hata ,  Hiroshi Kawamoto ,  Hisashi Ohta
Affiliations
  • 1. Tsukuba Research Institute, Banyu Pharmaceutical CO., LTD, 3 Okubo, Tsukuba 300-2611, Japan. [email protected]
PMID: 18849168 DOI: 10.1016/j.bmc.2008.09.060
Abstract

We describe here the discovery and the structure-activity relationship (SAR) of a series of 4-(1-Aryltriazol-4-yl)-tetrahydropyridines as novel mGluR1 antagonists. Our extensive chemical modification of lead compound 2 successfully led to fluoropyridine analogs 7j and 1 with improved in vivo antagonistic activities. Among the evaluated compounds, chemically stable urea analog 1 showed oral antagonistic activity at dose ranges of 10-30mg/kg in an animal model.