2018年2月1日
Design, synthesis, and evaluation of novel inhibitors for wild-type human serine racemase
Bioorganic and Medicinal Chemistry Letters
- 巻
- 28
- 号
- 3
- 開始ページ
- 441
- 終了ページ
- 445
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.bmcl.2017.12.021
- 出版者・発行元
- Elsevier Ltd
Most of the endogenous free D-serine (about 90%) in the brain is produced by serine racemase (SR). D-Serine in the brain is involved in neurodegenerative disorders and epileptic states as an endogenous co-agonist of the NMDA-type glutamate receptor. Thus, SR inhibitors are expected to be novel therapeutic candidates for the treatment of these disorders. In this study, we solved the crystal structure of wild-type SR, and tried to identify a new inhibitor of SR by in silico screening using the structural information. As a result, we identified two hit compounds by their in vitro evaluations using wild-type SR. Based on the structure of the more potent hit compound 1, we synthesized 15 derivatives and evaluated their inhibitory activities against wild-type SR. Among them, the compound 9C showed relatively high inhibitory potency for wild-type SR. Compound 9C was a more potent inhibitor than compound 24, which was synthesized by our group based upon the structural information of the mutant-type SR.
- リンク情報
- ID情報
-
- DOI : 10.1016/j.bmcl.2017.12.021
- ISSN : 1464-3405
- ISSN : 0960-894X
- PubMed ID : 29277459
- SCOPUS ID : 85038848519