Tuberculosis, due to its relentless nature, is now a major public health threat. The concomitant resurgence of TB with the MDR- or XDR-TB and HIV/AIDS pandemic has exposed the frailties of the current drug armatorium. Based on good structural similarity between BM-212, a novel antimycobacterial agent undergoing clinical trials, and diaryl thiophenes, we have designed novel diaryl thiophenes. Alkyl or aryl isothiocyanates were reacted with substituted phenylacetonitrile in the presence of NaH to afforded 3-mercapto-3-(substitutedamino)-2- [(un)substitutedphenyl]acrylonitrile (5a-h). The designed molecules, 3-amino-2-cyano-5-(substitutedamino)-4- [(un)substitutedphenyl]thiophenes (6a-h) were synthesized by cyclocondention of 3-mercapto-3-(substitutedamino)- 2-[(un)substitutedphenyl]acrylonitrile (5a-h) with chloroacetonitrile in ethanol. All the compounds were screened for their antimycobacterial activity on mycobacterium tuberculosis using H37Rv strain by 1% proportion method. Some of the synthesized compounds exhibited potent antimycobacterial activity with MIC values in the range of 12.5-100 µg/mL.