New potent C2-symmetric malaria plasmepsin I and II inhibitors

被引：30

作者：

Oscarsson, K

Oscarson, S

Vrang, L

Hamelink, E

Hallberg, A

Samuelsson, B

机构：

[1] Stockholm Univ, Dept Organ Chem, Arrhenius Lab, S-10691 Stockholm, Sweden

[2] Medivir AB, S-14144 Huddinge, Sweden

[3] Uppsala Univ, BMC, Dept Organ Pharmaceut Chem, S-75123 Uppsala, Sweden

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2003年 / 11卷 / 07期

关键词：

D O I：

10.1016/S0968-0896(02)00643-0

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：

A series of malaria plasmepsin (Pim) I and II inhibitors containing a C-2-symmetric core structure have been synthesised and tested for protease inhibition activity. These compounds can be prepared using a straightforward synthesis involving a phenol nucleophilic ring opening of a diepoxide. Exemplar compounds synthesised exhibited remarkable inhibitory activity against both Plm I and II, notably 15c with K-i values of 2.7 nM and 0.25 nM respectively, as well as showing > 100-fold selectivity against Cathepsin D. (C) 2003 Elsevier Science Ltd. All rights reserved.

引用

页码：1235 / 1246

页数：12

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