Department of Biomedicinal Chemistry, Inje University, Gimhae 621 749, Gyeongnam, South Korea.
Bioorg Med Chem Lett. 2011 Nov 15;21(22):6678-86. doi: 10.1016/j.bmcl.2011.09.063. Epub 2011 Sep 21.
A series of twenty 2,6-diarylpiperidin-4-one O-methyloximes were synthesized with fluoro/chloro/bromo/methyl/methoxy/ethoxy/isopropyl substituents on various positions of the phenyl at C-2 and C-6 in association with/without methyl substituent on the secondary amino group and methyl/ethyl/isopropyl substituents on the active methylene centers. Regardless of their substitution all compounds predominantly exist in the chair conformation except 3m, which adopts a twist-boat conformation. All the synthesized compounds were evaluated for their in vitro antiproliferative activity against human cervical carcinoma (HeLa) cell line. The cytotoxicity of the test compounds was determined by measuring the number of live cells after 24 h of treatment by MTT assay method. This preliminary SAR suggests some lead molecules 3c-f, 3j-k, 4d-g, and 4i with a scope of further structural optimization of the piperidone pharmacophore toward the development of anticancer drug synthesis.
合成了一系列二十个 2,6-二芳基哌啶-4-酮-O-甲肟，它们在 C-2 和 C-6 位的苯基上具有氟/氯/溴/甲基/甲氧基/乙氧基/异丙基取代基，并且与/或不具有仲氨基上的甲基取代基以及活性亚甲基中心上的甲基/乙基/异丙基取代基。除了 3m 外，所有化合物都主要以椅式构象存在，3m 采用扭船式构象。所有合成的化合物都通过 MTT 测定法测定 24 小时处理后活细胞数量的方法评估其对人宫颈癌（HeLa）细胞系的体外增殖活性。该初步 SAR 表明，一些先导化合物 3c-f、3j-k、4d-g 和 4i 具有进一步结构优化的范围，对哌啶酮药效团进行了优化，以开发抗癌药物合成。
