Synthesis and antimalarial activity of new 4-amino-7-chloroquinolyl amides, sulfonamides, ureas and thioureas

被引：70

作者：

Ekoue-Kovi, Kekeli ^{[1
]}

Yearick, Kimberly ^{[1
]}

Iwaniuk, Daniel P. ^{[1
]}

Natarajan, Jayakumar K. ^{[1
,2
]}

Alumasa, John ^{[1
]}

de Dios, Angel C. ^{[1
,3
]}

Roepe, Paul D. ^{[1
,2
,3
]}

Wolf, Christian ^{[1
,3
]}

机构：

[1] Georgetown Univ, Dept Chem, Washington, DC 20057 USA

[2] Georgetown Univ, Dept Biochem & Cellular & Mol Biol, Washington, DC 20057 USA

[3] Georgetown Univ, Ctr Infect Dis, Washington, DC 20057 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 01期

关键词：

Chloroquine; 4-Aminoquinolines; Sulfonamides; Ureas; Thioureas; Amides; Malaria; COPPER-CATALYZED AMINATION; PLASMODIUM-FALCIPARUM; IN-VITRO; CHLOROQUINE RESISTANCE; ANTIPLASMODIAL ACTIVITY; DRUG DISCOVERY; SIDE-CHAIN; MULTICOMPONENT REACTIONS; POTENTIAL ANTIMALARIAL; PARALLEL SYNTHESIS;

D O I：

10.1016/j.bmc.2008.11.009

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：

We report the synthesis and in vitro antimalarial activities of more than 50 7-chloro-4-aminoquinolyl-derived sulfonamides 3-8 and 11-26, ureas 19-22, thioureas 23-26, and amides 27-54. Many of the CQ analogues prepared for this study showed submicromolar antimalarial activity versus HB3 (chloroquine sensitive) and Dd2 (chloroquine resistant strains of Plasmodium falciparum) and low resistance indices were obtained in most cases. Systematic variation of the side chain length and introduction of fluorinated aliphatic and aromatic termini revealed promising leads that overcome CQ resistance. In particular, sulfonamide 3 exhibiting a short side chain with a terminal dansyl moiety combined high anti-plasmodial potency with a low resistance index and showed IC(50)s of 17.5 and 22.7 nM against HB3 and Dd2 parasites. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：270 / 283

页数：14

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