Synthesis and anticancer evaluation of novel 2-cyclopropylimidazo[2,1-b] [1,3,4]-thiadiazole derivatives

被引：115

作者：

Noolvi, Malleshappa N. ^{[1
]}

Patel, Harun M. ^{[1
]}

Singh, Navjot ^{[1
]}

Gadad, Andanappa K. ^{[2
]}

Cameotra, Swaranjit Singh ^{[3
]}

Badiger, Arvind ^{[4
]}

机构：

[1] ASBASJSM Coll Pharm, Dept Pharmaceut Chem, Ropar 140111, Punjab, India

[2] Univ W Indies, Fac Med Sci, Sch Pharm, St Augustine, Trinidad Tobago

[3] Inst Microbial Technol, Chandigarh, India

[4] Shree Dhanvantary Pharmaceut Anal & Res Ctr, Surat 394110, Gujarat, India

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2011年 / 46卷 / 09期

关键词：

Antitumor agents; Imidazo[2,1-b][1,3,4]thiadiazole derivatives; Five-dose assay; NCI-USA; KINASE EGFR INHIBITOR; QUINAZOLINE DERIVATIVES; 2D QSAR; SERIES; AGENTS;

D O I：

10.1016/j.ejmech.2011.07.012

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 2,5,6-trisubstituted imidazo[2,1-b][1,3,4]-thiadiazole derivatives 4(a-k) have been prepared by reaction of 2-amino-5-cyclopropyl-1,3,4-thiadiazole and an appropriate phenacyl bromide. Further 5-bromo 5(a-k) and 5-thiocyanato 6(a-k) derivatives were synthesized in order to study the effect of these substituents on antitumor activity. Structures of these compounds were established by IR, H-1 NMR, C-13 NMR and Mass spectroscopy. Seven compounds were granted NSC code at National Cancer Institute (NCI), USA for anticancer activity at a single high dose (10-5 M) in full NCI 60 cell panel. Among the compounds tested, 5-bromo-6-(4-chlorophenyl)-2-cyclopropylimidazo[2,1-b][1,3,4]thiadiazole 5b (NSC D-96022/1) was found to be the most active candidate of the series at five dose level screening with degree of selectivity toward Leukemic cancer cell line. (C) 2011 Elsevier Masson SAS. All rights reserved.

引用

页码：4411 / 4418

页数：8