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Despite a significant work has been done on thiophenes, continuous efforts are still being made by the researchers to identify novel heterocyclic compounds with potential bioactivities. This review may help the medicinal chemists and researchers to develop novel leads having thiophene nucleus with higher efficacy and reduced side effects. Exhaustive study has been done in screening the thophene derivatives developed till now and potential ones are isolated from them. This review throws the light on synthetic approaches which have been used for synthesis of potential thiophene derivatives followed by the depth analysis of them with respect to their pharmacological significance.