Design, synthesis, and biological evaluation of a new class of MT2-selective agonists

被引：1
|
作者：
Zhang, Xuan [1 ]
Wang, Zhilong [2 ]
Huang, Qingqing [1 ]
Luo, Yu [1 ]
Xie, Xin [2 ]
Lu, Wei [1 ]
机构：
[1] E China Normal Univ, Inst Drug Discovery & Dev, Shanghai Engn Res Ctr Mol Therapeut & New Drug De, Shanghai 200062, Peoples R China
[2] Chinese Acad Sci, Natl Ctr Drug Screening, CAS Key Lab Receptor Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
来源：
RSC ADVANCES | 2014年 / 4卷 / 49期
基金：
中国国家自然科学基金;
关键词：
MELATONIN RECEPTOR AGONISTS; ANTIPROLIFERATIVE ACTIVITY; DOUBLE-BLIND; MT2; DERIVATIVES; ANTAGONISTS; LIGANDS; ANALOGS; CANCER; SLEEP;
D O I：
10.1039/c4ra03728f
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
A novel class of chiral 2,3-dihydro-1H-indene derivatives were designed and synthesized as melatonergic ligands. Most of the reported MT2-selective ligands behave as antagonists. By contrast, our exploration of 2,3-dihydro-1H-indene showed that the introduction of a lipophilic group at the 2- or 3-position of this scaffold could afford highly selective MT2 agonists. Among all these synthesized molecules, compounds 10b, 12a, 17a, 20a exhibited powerful MT2 agonistic activity (EC50 < 50 nM) as well as excellent MT2 selectivity (more than 2200-fold).
引用
收藏
页码：25871 / 25874
页数：4
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