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ID: ALA1137896

Journal: Bioorg Med Chem Lett

Title: Synthesis and AMPA receptor antagonistic activity of a novel 7-imidazolyl-6-trifluoromethyl quinoxalinecarboxylic acid with a substituted phenyl group and improved its good physicochemical properties by introduced CF3 group.

Authors: Takano Y, Shiga F, Asano J, Hori W, Anraku T, Uno T.

Abstract: We describe the synthesis, physicochemical, and biological properties of a novel series of 7-imidazolyl-6-trifluoromethyl quinoxalinecarboxylic acids with a substituted phenyl group attached through a urethane linkage at the C-7 position. We found that the introduction of trifluoromethyl group at the C-6 position brought about good biological activity and physicochemical properties. Among them, compound 9k (KRP-199), which has a 4-carboxyphenyl group, was found to possess high potency and selectivity for the AMPA-R in vitro and to exhibit good neuroprotective effects in vivo. Furthermore, the compound showed good physicochemical properties such as stability to light and good solubility in aqueous solutions.

CiteXplore: 15380209

DOI: 10.1016/j.bmcl.2004.07.093