Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad 500 046, AP, India.
Bioorg Med Chem Lett. 2012 Jul 1;22(13):4418-27. doi: 10.1016/j.bmcl.2012.04.109. Epub 2012 May 2.
Novel thieno[3,2-c]pyran-4-one based small molecules were designed as potential anticancer agents. Expeditious synthesis of these compounds was carried out via a multi-step sequence consisting of few steps such as Gewald reaction, Sandmeyer type iodination, Sonogashira type coupling followed by iodocyclization and then Pd-mediated various C-C bond forming reactions. The overall strategy involved the construction of thiophene ring followed by the fused pyranone moiety and then functionalization at C-7 position of the resultant thieno[3,2-c]pyran-4-one framework. Some of the compounds synthesized showed selective growth inhibition of cancer cells in vitro among which two compounds for example, 5d and 6c showed IC(50) values in the range of 2.0-2.5 μM. The crystal structure analysis of an active compound along with hydrogen bonding patterns and molecular arrangement present within the molecule is described.
新型噻吩并[3,2-c]吡喃-4-酮类小分子被设计为有潜力的抗癌药物。通过多步序列，包括 Gewald 反应、Sandmeyer 型碘化、Sonogashira 型偶联、随后的碘环化以及然后 Pd 介导的各种 C-C 键形成反应，快速合成了这些化合物。总体策略涉及噻吩环的构建，然后是稠合吡喃酮部分，然后在所得噻吩并[3,2-c]吡喃-4-酮骨架的 C-7 位置进行功能化。合成的一些化合物在体外显示出对癌细胞的选择性生长抑制作用，其中两种化合物（例如 5d 和 6c）的 IC50 值在 2.0-2.5 μM 范围内。描述了一个活性化合物的晶体结构分析以及分子内氢键模式和分子排列。
