| Title: | Cyclopropane-based conformational restriction of GABA by a stereochemical diversity-oriented strategy: Identification of an efficient lead for potent inhibitors of GABA transports |
| Authors: | Nakada, Kazuaki Browse this author |
| Yoshikawa, Mamie Browse this author |
| Ide, Soichiro Browse this author →KAKEN DB |
| Suemasa, Akihiro Browse this author |
| Kawamura, Shuhei Browse this author |
| Kobayashi, Takaaki Browse this author |
| Masuda, Eiji Browse this author |
| Ito, Yoshihiko Browse this author |
| Hayakawa, Wataru Browse this author |
| Katayama, Takahiro Browse this author →KAKEN DB |
| Yamada, Shizuo Browse this author |
| Arisawa, Mitsuhiro Browse this author →KAKEN DB |
| Minami, Masabumi Browse this author →KAKEN DB |
| Shuto, Satoshi Browse this author →KAKEN DB |
| Keywords: | GABA transporter |
| GAT3 |
| BGT1 |
| Cyclopropane |
| Conformational restriction |
| Issue Date: | 1-Sep-2013 |
| Publisher: | Pergamon-elsevier science ltd |
| Journal Title: | Bioorganic & medicinal chemistry |
| Volume: | 21 |
| Issue: | 17 |
| Start Page: | 4938 |
| End Page: | 4950 |
| Publisher DOI: | 10.1016/j.bmc.2013.06.063 |
| PMID: | 23886812 |
| Abstract: | A series of cyclopropane-based conformationally restricted gamma-aminobutyric acid (GABA) analogs with stereochemical diversity, that is, the trans- and cis-2,3-methano analogs Ia and Ib and their enantiomers ent-Ia and ent-Ib, and also the trans- and cis-3,4-methano analogs IIa and IIb and their enantiomers ent-IIa and ent-Iib, were synthesized from the chiral cyclopropane units Type-a and Type-b that we developed. These analogs were systematically evaluated with four GABA transporter (GAT) subtypes. The trans-3,4-methano analog IIa had inhibitory effects on GAT3 (IC50 = 23.9 mu M) and betaine-GABA transporter1 (5.48 mu M), indicating its potential as an effective lead compound for the development of potent GAT inhibitors due to its hydrophilic and low molecular weight properties and excellent ligand efficiency. (C) 2013 Elsevier Ltd. All rights reserved. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/54095 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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