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Updated: Jan 17, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Structure-activity relationship studies on 2-thienylidene substituted 3-oxo-2,3-dihydrobenzofuran-7-carboxamides as
Abosede Salami1, Ugochi Adiele1, Griffin Coate1
1Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, New York 11439, United States.
Abstract:
A series of 2-thienylidene substituted 3-oxo-2,3-dihydrobenzofuran-7-carboxamide derivatives was synthesized and evaluated to investigate structure-activity relationship for inhibiting PARP1 enzyme activity. These efforts led to the identification of a new isosteric lead compound 2, (Z)-5-((7-carbamoyl-3-oxobenzofuran-2(3H)-ylidene)methyl) thiophene-2-carboxylic acid (PARP1 IC50 = 20 nM). Subsequently, the pendant carboxyl group of 2 was coupled with several amines to access adenine binding pocket (ABP) of PARP1 active site. Among the resulting analogs, several derivatives with a structural diversity in PARP1 ABP binding motifs showed PARP1 IC50 values in the range of 17 nM - 640 nM. These derivatives also showed improved cellular inhibition of PARylation compared to lead 2. Collectively, PARP1 ABP binding moieties such as (R)-3-aminoquinuclidine in 9, 1-methylspiro[indoline-3,3'-piperidin]-2-one in 11 and benzimidazole in 13 and 15 were favorable and thus these derivatives will serve as refined leads for future SAR optimization.
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