biostudies-literatureUnknown358(3)Gunduz MGHacettepe University Scientific Research Projects Coordination Unit (THD-2020-18712).Biginelli dihydropyrimidines (DHPMs) are considered superior over 1,4-dihydropyridines (DHPs) in terms of both light and metabolic stabilities. Nevertheless, DHPs dominate the market as the most prescribed calcium channel blockers with strong therapeutic potential in managing cardiovascular ailments. To overcome the restrictions that complicate the formulation and postadministration of DHPs, employing bioisosteric replacement by exchanging the DHP ring with DHPM appears as a logical approach for the improved formulations of new calcium channel blockers. In this study, we obtained DHPM derivatives via Biginelli synthesis and acetylated their N-3 position by heating them in acetic anhydride (GD1-GD12). We also incorporated the DHPM scaffold into a condensed ring system (GD13 and GD14). TheseArchiv der Pharmaziee2400584https://www.ebi.ac.uk/biostudies/studies/S-EPMC11933517biostudies-literatureBiginelli dihydropyrimidines and their acetylated derivatives as L-/T-type calcium channel blockers: Synthesis, enantioseparation, and molecular modeling studies.PMC11933517Huang SNafie JWZamponi GWDenzinger KLee JTDengiz CArmstrong DWWolber GGunduz MGfalseBiginelli dihydropyrimidines and their acetylated derivatives as L-/T-type calcium channel blockers: Synthesis, enantioseparation, and molecular modeling studies.Biginelli dihydropyrimidines (DHPMs) are considered superior over 1,4-dihydropyridines (DHPs) in terms of both light and metabolic stabilities. Nevertheless, DHPs dominate the market as the most prescribed calcium channel blockers with strong therapeutic potential in managing cardiovascular ailments. To overcome the restrictions that complicate the formulation and postadministration of DHPs, employing bioisosteric replacement by exchanging the DHP ring with DHPM appears as a logical approach for the improved formulations of new calcium channel blockers. In this study, we obtained DHPM derivatives via Biginelli synthesis and acetylated their N-3 position by heating them in acetic anhydride (GD1-GD12). We also incorporated the DHPM scaffold into a condensed ring system (GD13 and GD14). These2025-01-01T00:00:00Z2025 Mar2026-06-02T21:12:26.498Z2026-05-29T03:06:28.18ZS-EPMC119335174012886410.1002/ardp.202400584