mGlu5 negative allosteric modulators: a patent review (2013-2016)

被引:30
作者
Emmitte, Kyle A. [1 ]
机构
[1] Univ North Texas, Hlth Sci Ctr, UNT Syst Coll Pharm, Dept Pharmaceut Sci, Ft Worth, TX 76107 USA
关键词
Basimglurant; dipraglurant; mavoglurant; metabotropic glutamate receptor subtype 5; negative allosteric modulator; anxiety; depression; fragile X syndrome; Parkinson's disease; levodopa-induced dyskinesia; METABOTROPIC GLUTAMATE-RECEPTOR; MGLUR5 ANTAGONIST MPEP; LEVODOPA-INDUCED DYSKINESIA; FRAGILE-X-SYNDROME; MOUSE MODEL; GLUTAMATE-RECEPTOR-5; ANTAGONIST; PARKINSONS-DISEASE; ANXIOLYTIC-LIKE; CLINICAL DEVELOPMENT; NUCLEUS-ACCUMBENS;
D O I
10.1080/13543776.2017.1280466
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Introduction: The pursuit of small molecule mGlu(5) NAMs as treatments for a variety of psychiatric and neurodegenerative disorders has developed into a mature field. In addition to extensive preclinical studies, multiple compounds have advanced into clinical trials with the most advanced studies occurring in patients with FXS, PD-LID, and MDD. Areas covered: This review begins with an update of the clinical activity with mGlu(5) NAMs, and then moves into a summary of patent applications filed since 2013. The summaries are organized into three separate sections: (1) inventions centered on improvements to existing clinical compounds; (2) new small molecules that maintain the prototypical disubstituted alkyne chemotype found in many mGlu(5) NAM compounds; and (3) new small molecules that are not from a disubstituted alkyne chemotype. Expert opinion: It is a critical moment for mGlu(5) NAM research as recent reports from clinical trials have included some significant disappointments that have blunted prior optimism. Still, research in this area remains active, and recent years have added several more attractive small molecules to this field. There is now an arsenal of diverse chemotypes available to continue to probe this target in the hopes that a drug may yet emerge.
引用
收藏
页码:691 / 706
页数:16
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