ArticleChemMedChem2026
Streamlined Synthesis and Structure-Activity Relationship Analysis of 2-Amidothiophene-3-Carboxamides Targeting Influenza Polymerase PA-PB1 Heterodimerization.
Article in ChemMedChem, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Influenza viruses remain a major global health threat due to their rapid evolution and ability to evade current therapies. Among viral targets, the PA-PB1 interface of the RNA polymerase complex has emerged as an attractive site for small-molecule inhibition. Based on compound 1, a previously identified PA-PB1 interaction inhibitor featuring a cycloheptathiophene-3-carboxamide scaffold, we designed and synthesized a new series of derivatives to investigate the role of the cycloheptyl moiety in antiviral activity and water solubility. In parallel, we developed an improved three-step synthetic route to access 2-amidothiophene-3-carboxamide analogs more efficiently. The new derivatives (2-16) provided valuable structure-activity relationship insights, highlighting how modifications at C-5 influence both anti-influenza potency and solubility. Among them, the C-5 phenyl analog 9 displayed the strongest antiviral activity, achieving sub-micromolar EC
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