YM-254890 analogues, novel cyclic depsipeptides with Gαq/11 inhibitory activity from Chromobacterium sp QS3666

被引：60

作者：

Taniguchi, M ^{[1
]}

Suzumura, K ^{[1
]}

Nagai, K ^{[1
]}

Kawasaki, T ^{[1
]}

Takasaki, J ^{[1
]}

Sekiguchi, M ^{[1
]}

Moritani, Y ^{[1
]}

Saito, T ^{[1
]}

Hayashi, K ^{[1
]}

Fujita, S ^{[1
]}

Tsukamoto, S ^{[1
]}

Suzuki, K ^{[1
]}

机构：

[1] Yamanouchi Pharmaceut Co Ltd, Inst Drug Discovery Res, Tsukuba, Ibaraki 3058585, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2004年 / 12卷 / 12期

关键词：

YM-254890; depsipeptide; G alpha(q/11) inhibitor; platelet aggregation;

D O I：

10.1016/j.bmc.2004.04.006

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The structure elucidation and biological activity of novel YM-254890 (1) analogues and semi-synthetic derivatives are described. Three natural analogues, YM-254891 (2), YM-254892 (3), and YM-280193 (4), were isolated from the fermentation broth of Chromobacterium sp. QS3666, and two hydrogenated derivatives, YM-385780 (5) and YM-385781 (6), were synthesized from YM-254890. Their structures were determined by one- and two-dimensional NMR studies and mass spectrometry. Among these compounds, two natural analogues 2-3 which possessed acyl groups at beta-HyLeu-1 and one derivative 6 whose conformation was similar to that of 1 showed comparable Galpha(q/11) inhibitory activity to that of 1. This indicates that the acyl beta-HyLeu residue plays an important role in activity and also that the alpha,beta-unsaturated carbonyl group of the N-MeDha residue is not critical to activity. The other hydrogenated derivative 5 had significantly less activity, which could be attributed to conformational differences. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：3125 / 3133

页数：9

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