| Autor: |
Kiev S. Ly, Andrew Richard Hudson, Christine Hoffmaster, James T. Limberis, J. Guy Breitenbucher, Richard Barido, De Michael Chung, Yingzhuo Yan, Gary Anderson, Vincent J. Santora, Dany Gitnick, Dong Lee, Brett C. Bookser, Anne Danks, Robert E. Petroski, Graeme Freestone, Varsha Gupta, Clifford Cabebe, Andrew Morse, Michael R. Kennedy, Kristen Sebring, Zachary W. Yoder, Douglas Zook, Marco Peters, Chih-Kun Chai, Joel Renick, Jim Na, Theresa A. Almos, Shouzhen Xia, Ali Tabatabaei, John Nikpur, Samantha Sevidal, Stephine Chow, Mi Chen, Jillian Basinger, Chris L. Bellows, Lindsay Heger, David Neul, Jenny Wen, Brittany Masatsugu, Nicola J. Broadbent, Alan P. Kaplan, Chi Ching Mak |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
Bioorganicmedicinal chemistry letters. 30(14) |
| ISSN: |
1464-3405 |
| Popis: |
A strategy to conformationally restrain a series of GlyT1 inhibitors identified potent analogs that exhibited slowly interconverting rotational isomers. Further studies to address this concern led to a series of azetidine-based inhibitors. Compound 26 was able to elevate CSF glycine levels in vivo and demonstrated potency comparable to Bitopertin in an in vivo rat receptor occupancy study. Compound 26 was subsequently shown to enhance memory in a Novel Object Recognition (NOR) behavioral study after a single dose of 0.03 mg/kg, and in a contextual fear conditioning (cFC) study after four QD doses of 0.01–0.03 mg/kg. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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Full Text from ScienceDirect 