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Open AccessArticle

Scale-Up Synthesis and Identification of GLYX-13, a NMDAR Glycine-Site Partial Agonist for the Treatment of Major Depressive Disorder

1
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
2
Jiangsu Nhwa Pharmaceutical Co., Ltd., 69 Democratic South Road, Xuzhou 221116, Jiangsu, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this paper.
Molecules 2018, 23(5), 996; https://doi.org/10.3390/molecules23050996
Received: 21 March 2018 / Revised: 11 April 2018 / Accepted: 21 April 2018 / Published: 24 April 2018
(This article belongs to the Section Medicinal Chemistry)
GLYX-13, a NMDAR glycine-site partial agonist, was discovered as a promising antidepressant with rapidly acting effects but no ketamine-like side effects. However, the reported synthetic process route had deficiencies of low yield and the use of unfriendly reagents. Here, we report a scaled-up synthesis of GLYX-13 with an overall yield of 30% on the hectogram scale with a column chromatography-free strategy, where the coupling and deprotection reaction conditions were systematically optimized. Meanwhile, the absolute configuration of precursor compound of GLYX-13 was identified by X-ray single crystal diffraction. Finally, the activity of GLYX-13 was verified in the cortical neurons of mice through whole-cell voltage-clamp technique. View Full-Text
Keywords: GLYX-13; NMDA receptor; chromatography-free synthesis; crystal structure; whole-cell voltage-clamp GLYX-13; NMDA receptor; chromatography-free synthesis; crystal structure; whole-cell voltage-clamp
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MDPI and ACS Style

Li, W.; Liu, J.; Fan, M.; Li, Z.; Chen, Y.; Zhang, G.; Huang, Z.; Zhang, L. Scale-Up Synthesis and Identification of GLYX-13, a NMDAR Glycine-Site Partial Agonist for the Treatment of Major Depressive Disorder. Molecules 2018, 23, 996.

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