Custom Pharmaceutical Services, Dr. Reddy's Laboratories Limited, Bollaram Road Miyapur, Hyderabad 500049, India.
Bioorg Med Chem Lett. 2012 Sep 1;22(17):5639-47. doi: 10.1016/j.bmcl.2012.06.100. Epub 2012 Jul 20.
Novel polysubstituted pyrroles have been designed and accessed via a one-pot multicomponent reaction followed by Pd-mediated C-C bond forming reactions. All the compounds synthesized were tested for their PDE4B inhibitory properties in vitro and two of them obtained via Heck reaction showed significant inhibition. The docking results suggested that these alkenyl derivatives containing ester moiety interact well with the PDE4B protein in silico where the ester carbonyl oxygen played a key role. The pyrrole framework presented here could be a new template for the identification of small molecule based novel inhibitors of PDE4. The single crystal X-ray data of a representative compound is presented.
新型多取代吡咯已通过一锅多组分反应以及 Pd 介导的 C-C 键形成反应进行设计和获得。所有合成的化合物均在体外进行 PDE4B 抑制特性测试，其中通过 Heck 反应获得的两种化合物表现出显著的抑制作用。对接结果表明，这些含有酯基的烯基衍生物与 PDE4B 蛋白在体内相互作用良好，其中酯羰基氧起着关键作用。本文提出的吡咯骨架可能是识别基于小分子的新型 PDE4 抑制剂的新模板。还呈现了代表性化合物的单晶 X 射线数据。
