||3D-QSAR using CoMFA and CoMSIA were developed for a series of 26 2,6-disubstituted 4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide derivatives for prediction of anti-mycobacterial activity. Both COMFA and COMSIA models were obtained with LOO cross-validation q2 values of 0.825 and 0.503 were obtained respectively. The models were validated by external test set of six compounds with conventional r2 value of 0.971 and 0.920 for CoMFA and CoMSIA analysis respectively. The contour maps from 3D-QSAR CoMFA and CoMSIA models show better interpret the structure activity relationship. Molecular docking studies were also performed to most and least active compounds.