Thiazolyl N-benzyl-substituted acetamide derivatives: Synthesis, Src kinase inhibitory and anticancer activities

被引：62

作者：

Fallah-Tafti, Asal ^{[2
]}

Foroumadi, Alireza ^{[2
]}

Tiwari, Rakesh ^{[1
]}

Shirazi, Amir Nasrolahi ^{[1
]}

Hangauer, David G. ^{[3
]}

Bu, Yahao ^{[3
]}

Akbarzadeh, Tahmineh ^{[2
]}

Parang, Keykavous ^{[1
]}

Shafiee, Abbas ^{[2
]}

机构：

[1] Univ Rhode Isl, Coll Pharm, Dept Biomed & Pharmaceut Sci, Kingston, RI 02881 USA

[2] Univ Tehran Med Sci, Dept Med Chem, Fac Pharm & Pharmaceut Sci, Res Ctr, Tehran 14176, Iran

[3] Kinex Pharmaceut, Buffalo, NY 14203 USA

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2011年 / 46卷 / 10期

基金：

美国国家科学基金会;

关键词：

Anticancer; Cell proliferation; KX-2; Inhibitor; Src kinase; Thiazole; CONSTRAINED PEPTIDE ANALOGS; SH2; INHIBITORS; DISCOVERY; BINDING; BMS-354825; BLOCKADE; AGENTS;

D O I：

10.1016/j.ejmech.2011.07.050

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

KX2-391 (KX-01/Kinex Pharmaceuticals), N-benzyl-2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl) acetamide, is a highly selective Src substrate binding site inhibitor. To understand better the role of pyridine ring and N-benzylsubstitution in KX2-391 and establish the structure activity relationship, a number of N-benzyl substituted (((2-morpholinoethoxy)phenyl)thiazol-4-yl)acetamide derivatives containing thiazole instead of pyridine were synthesized and evaluated for Src kinase inhibitory activities. The unsubstituted N-benzyl derivative (8a) showed the inhibition of c-Src kinase with GI(50) values of 1.34 mu M and 2.30 mu M in NIH3T3/c-Src527F and SYF/c-Src527F cells, respectively. All the synthesized compounds were evaluated for inhibition of cell proliferation of human colon carcinoma (HT-29), breast carcinoma (BT-20), and leukemia (CCRF-CEM) cells. 4-Fluorobenzylthiazolyl derivative 8b exhibited 64 -71% inhibition in the cell proliferation of BT-20 and CCRF cells at concentration of 50 mu M. (C) 2011 Elsevier Masson SAS. All rights reserved.

引用

页码：4853 / 4858

页数：6

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