Synthesis of Novel Alkyl Amide Functionalized Trifluoromethyl Substituted Furo/thieno Pyridine Derivatives: Their Anticancer Activity and CoMFA and CoMSIA Studies

A series of novel alkyl amide functionalized trifluoromethyl substituted furo/thieno pyridine derivatives 4a–h , 5a–d , and 6a–h were prepared starting from 2‐oxo/thioxo‐6‐phenyl/thien‐2‐yl‐4‐(trifluoromethyl)‐1,2‐dihydropyridine‐3‐carbonitrile 1 on reaction with bromoethylacetate followed by reaction with different primary aliphatic amines, cyclic secondary amines, or l ‐amino acids under different set of conditions. All the synthesized compounds 4a–h , 5a–d , and 6a–h were screened for anticancer activity against four cancer cell lines such as HeLa—cervical cancer (CCL‐2), COLO205—colon cancer (CCL‐222), HepG2—liver cancer (HB‐8065), and MCF7—breast cancer (HTB‐22). Compounds 4g and 4h are found to have promising anticancer activity at micromolar concentration. CoMFA and CoMSIA methods were applied to derive 3D‐QSAR models for alkyl amide tagged furo/thieno pyridine derivatives as potential anticancer inhibitors. 3D‐QSAR models provided a strong basis for future rational design of more active and selective HeLa, COLO205, HepG2, and MCF‐7 cell line inhibitors.