Search for new pharmacophores for antimalarial activity. Part II: Synthesis and antimalarial activity of new 6-ureido-4-anilinoquinazolines

被引：102

作者：

Madapa, S. ^{[1
]}

Tusi, Z. ^{[1
]}

Mishra, A. ^{[1
]}

Srivastava, K. ^{[2
]}

Pandey, S. K. ^{[2
]}

Tripathi, R. ^{[2
]}

Puri, S. K. ^{[2
]}

Batra, S. ^{[1
]}

机构：

[1] Cent Drug Res Inst, Med & Proc Chem Div, Lucknow 226001, Uttar Pradesh, India

[2] Cent Drug Res Inst, Div Parasitol, Lucknow 226001, Uttar Pradesh, India

来源：

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

关键词：

Quinazoline; Antimalarial; Urea; In vitro; In vivo; P; falciparum; PLASMODIUM-FALCIPARUM; INHIBITORS; DERIVATIVES; KINASE; POTENT; QUINAZOLINES; GROWTH; EGFR; SAR;

D O I：

10.1016/j.bmc.2008.11.005

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：

Synthesis of new 6-ureido-4-anilinoquinazolines have been accomplished and their in vitro antimalarial activity against chloroquine-sensitive P. falciparum have been examined. Out of 64 compounds evaluated, the IC50 of 16 compounds which have displayed MIC of 0.25 mu g/mL were also recorded. One of the compounds (24g) had IC50 value of 2.27 ng/mL which was equipotent to the standard drug chloroquine used in the bioassay. The in vivo evaluation of a few compounds among the series led to discovery of one analog (30g) displaying 40% curative activity (28 days) against mdr P. yoeilli nigeriensis at an oral dose of 100 mg/kg x 4days. (c) 2008 Elsevier Ltd. All rights reserved.

引用

页码：222 / 234

页数：13

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