Synthesis, modification, and evaluation of (R)-de-O-methyllasiodiplodin and analogs as nonsteroidal antagonists of mineralocorticoid receptor

被引：33

作者：

Jiang, Cheng-Shi ^{[1
]}

Zhou, Rong ^{[2
]}

Gong, Jing-Xu ^{[1
]}

Chen, Li-Li ^{[1
]}

Kurtan, Tibor ^{[3
]}

Shen, Xu ^{[1
,2
]}

Guo, Yue-Wei ^{[1
]}

机构：

[1] Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China

[2] E China Univ Sci & Technol, Shanghai 200237, Peoples R China

[3] Univ Debrecen, Dept Organ Chem, H-4010 Debrecen, Hungary

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 04期

关键词：

Macrolide; (R)-De-O-methyllasiodiplodin; Mineralocorticoid receptor; Antagonist; Ring-closing-metathesis reaction; RING-CLOSING-METATHESIS; POTENT; METABOLITES; MACROLIDE; BIOLOGY; (R)-(+)-LASIODIPLODIN; LASIODIPLODIN; CONSTITUENTS; ALDOSTERONE; CONGENERS;

D O I：

10.1016/j.bmcl.2010.12.101

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Macrolide (R)-de-O-methyllasiodiplodin (1), discovered to be a potent nonsteroidal antagonist of the mineralocorticoid receptor (MR), was synthesized via an efficient method and evaluated for MR antagonistic activity together with its analogs. Among all the tested compounds, compounds 18a, 18b and 18c, exhibited more potent antagonistic activity against MR with IC50 values ranging from 0.58 to 1.11 mu M. Generally, it was obviously demonstrated that acetylation at phenolic hydroxyl groups and the ring size in analogs of 1 were very important for MR antagonist activity. (c) 2010 Elsevier Ltd. All rights reserved.

引用

页码：1171 / 1175

页数：5

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