Benzo[b]thiophene-based 5-lipoxygenase inhibitors: A comprehensive review of therapeutic advances

Heterocyclic compounds have an irreplaceable position in medicinal chemistry. Almost all bioactive natural products have heteroatoms in their active components. Benzo[b]thiophene is one of the important compounds among them. Several drugs contain benzo[b]thiophene as a potential portion responsible for pharmacological action. Zileuton, a potential 5-LOX inhibitor, is such a compound, having a benzo[b]thiophene ring as a crucial structural feature. Some of the previous research works revealed that a major side effect of zileuton is hepatotoxicity, which is found to be due to the presence of N-hydroxyurea attached to the benzo[b]thiophene ring. In this review article, we performed a systematic review of previous works for structural modification on the benzo[b]thiophene ring to improve its biological activity against the 5-LOX enzyme. Also, we compared the structure and biological activity and conducted a brief study of the structural activity relationship of the benzo[b]thiophene ring against the 5-LOX enzyme. Finally, we concluded that some positions of the benzo[b]thiophene ring are literally prone to an increase in 5-LOX inhibition after substituting with privileged motifs. So, substitution on the benzo[b]thiophene ring is able to develop much better 5-LOX inhibitors in the future.