Rational design, synthesis and characterization of potent, drug-like monomeric Smac mimetics as pro-apoptotic anticancer agents
Rational design, synthesis and characterization of potent, drug-like monomeric Smac mimetics as pro-apoptotic anticancer agents
复制标题
DOI：
10.1016/j.bmcl.2012.01.098
复制
发表时间：
2012-03-15
影响因子：
2.7
通讯作者：
Seneci, Pierfausto
中科院分区：
文献类型：
--
作者：
Bianchi, Aldo;Ugazzi, Marcello;Seneci, Pierfausto
合成了一组先导化合物2a的苯基取代的Smac模拟物/IAP抑制剂类似物，旨在保留其强的无细胞效力，同时增加其生物利用度。制备了17个化合物2b-r，并使用无细胞和细胞测定进行了体外表征。其中，p-CF 3取代的类似物2 m显示出最好的细胞膜渗透性，并被选择用于进一步的体外和体内研究，由于其强大的亚微摩尔细胞效力。(C)2012爱思唯尔有限公司保留所有权利。
A set of phenyl-substituted Smac mimetics/IAP inhibitor analogues of lead compound 2a was synthesized, aiming to retain its strong cell-free potency while increasing its bioavailability. Seventeen compounds 2b-r were prepared and characterized in vitro, using cell-free and cellular assays. Among them, the p-CF3 substituted analogue 2m showed the best permeability through cell membranes, and was selected for further in vitro and in vivo studies due to its strong, sub-micromolar cellular potency. (C) 2012 Elsevier Ltd. All rights reserved.