Since the pioneering studies of Fleckenstein and co-workers, L-Type Calcium Channel (LTCC) blockers have attracted large interest due to their effectiveness in treating several cardiovascular diseases. Medicinal chemists achieved high potency and tissue selectivity by decorating the 1-4-DHP nucleus, the most studied scaffold among LTCC blockers. Nowadays it is clear that the 1,4-DHP nucleus is a privileged scaffold since, when appropriately substituted, it can selectively modulate diverse receptors, channels and enzymes. Therefore, the 1,4-DHP scaffold could be used to treat various diseases by a single-ligand multi-target approach. In this review, we describe the structure-activity relationships of 1,4-DHPs at ion channels, G-protein coupled receptors, and outline the potential for future therapeutic applications.
Ioan P, Carosati E, Micucci M, Cruciani G, Broccatelli F, ZhorovBS, et al. (2011). 1,4-Dihydropyridine Scaffold in Medicinal Chemistry, The Story so Far And Perspectives. (Part 1): Action in Ion Channels and GPCRs. CURRENT MEDICINAL CHEMISTRY, 18, 4901-4922 [10.2174/092986711797535173].
1,4-Dihydropyridine Scaffold in Medicinal Chemistry, The Story so Far And Perspectives. (Part 1): Action in Ion Channels and GPCRs.
IOAN, PIERFRANCO;MICUCCI, MATTEO;CHIARINI, ALBERTO;BUDRIESI, ROBERTA
2011
Abstract
Since the pioneering studies of Fleckenstein and co-workers, L-Type Calcium Channel (LTCC) blockers have attracted large interest due to their effectiveness in treating several cardiovascular diseases. Medicinal chemists achieved high potency and tissue selectivity by decorating the 1-4-DHP nucleus, the most studied scaffold among LTCC blockers. Nowadays it is clear that the 1,4-DHP nucleus is a privileged scaffold since, when appropriately substituted, it can selectively modulate diverse receptors, channels and enzymes. Therefore, the 1,4-DHP scaffold could be used to treat various diseases by a single-ligand multi-target approach. In this review, we describe the structure-activity relationships of 1,4-DHPs at ion channels, G-protein coupled receptors, and outline the potential for future therapeutic applications.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
