3-(2-氨基乙基)-5-(4-乙氧基苯亚甲基)-噻唑烷-2,4-二酮的构效关系（SAR）研究：潜在的ERK1/2 特异性底物抑制剂的开发。
Structure-activity relationship (SAR) studies of 3-(2-amino-ethyl)-5-(4-ethoxy-benzylidene)-thiazolidine-2,4-dione: development of potential substrate-specific ERK1/2 inhibitors.
机构信息
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298-0540, USA.
出版信息
Bioorg Med Chem Lett. 2009 Nov 1;19(21):6042-6. doi: 10.1016/j.bmcl.2009.09.057. Epub 2009 Sep 18.
Abstract
A series of analogs of 3-(2-amino-ethyl)-5-(4-ethoxy-benzylidene)-thiazolidine-2,4-dione, a putative substrate-specific ERK1/2 inhibitor, were synthesized and biologically characterized in human leukemia U937 cells to define its pharmacophore. It was discovered that shift of ethoxy substitution from the 4- to the 2-position on the phenyl ring significantly improved functional activities of inhibiting cell proliferation and inducing apoptosis. This may provide access to a new lead for developing ERK1/2 substrate-specific inhibitors.
摘要
一系列 3-(2-氨基乙基)-5-(4-乙氧基苄叉基)-噻唑烷-2,4-二酮的类似物，一种假定的 ERK1/2 抑制剂的底物特异性，被合成并在人白血病 U937 细胞中进行了生物学表征，以确定其药效团。研究发现，苯环上乙氧基取代基从 4-位转移到 2-位，可显著提高抑制细胞增殖和诱导细胞凋亡的功能活性。这可能为开发 ERK1/2 底物特异性抑制剂提供了新的途径。
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