Design, synthesis and structure-activity relationships of novel benzoxazolone derivatives as 18 kDa translocator protein (TSPO) ligands.

Selective 18 kDa translocator protein (TSPO) ligands are expected to be therapeutic agents with a wide spectrum of action on psychiatric disorders and fewer side effects. We designed novel benzoxazolone derivatives and examined the structure-activity relationship (SAR) of a series of compounds with various substituents at the amide part and C-5 position. Although a number of the synthesized compounds showed high TSPO binding affinity, these compounds had poor drug-like properties. Further optimization of pharmacokinetic properties of these compounds led to discovery of compound 74, which exhibited anxiolytic effect in the rat Vogel conflict model. Copyright © 2012 Elsevier Ltd. All rights reserved.

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Takayuki Fukaya, Toru Kodo, Takeo Ishiyama, Hiroyoshi Kakuyama, Hiroyuki Nishikawa, Satoko Baba, Shuji Masumoto. Design, synthesis and structure-activity relationships of novel benzoxazolone derivatives as 18 kDa translocator protein (TSPO) ligands. Bioorganic & medicinal chemistry. 2012 Sep 15;20(18):5568-82

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PMID: 22884355

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