Carbonic anhydrase inhibitors: synthesis and inhibition of cytosolic/tumor-associated carbonic anhydrase isozymes I, II, and IX with sulfonamides derived from 4-isothiocyanato-benzolamide

被引：41
作者：
Cecchi, A
Winum, JY
Innocenti, A
Vullo, D
Montero, JL
Scozzafava, A
Supuran, CT
机构：
[1] Univ Florence, Polo Sci, Lab Chim Bioinorgan, I-50019 Florence, Italy
[2] Univ Montpellier 2, Ecole Natl Super Chim Montpellier, UMR 5032, Lab Chim Biomol, F-34296 Montpellier, France
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 23期
关键词：
D O I：
10.1016/j.bmcl.2004.09.062
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of sulfonamides incorporating 4-thioureido-benzolamide moieties have been prepared from aminobenzolamide and thiophosgene followed by the reaction of the thiocyanato intermediate with aliphatic/aromatic amines or hydrazines. The new derivatives have been investigated as inhibitors of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), and more precisely of the cytosolic isozymes hCA I and II, as well as the tumor-associated isozyme hCA IX (all of human origin). The new compounds showed excellent inhibitory properties against all three isozymes with inhibition constants in the range of 0.6-62nM against hCA I, 0.5-1.7nM against hCA Il and 3.2-23nM against hCA IX, respectively. These derivatives are interesting candidates for the development of novel therapies targeting hypoxic tumors. (C) 2004 Elsevier Ltd. All rights reserved.
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收藏
页码：5775 / 5780
页数：6
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