title: 1,4-Dihydropyridine scaffold in medicinal chemistry, the story so far and perspectives (part 1): action in ion channels and GPCRs.
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.
authors: Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Bologna, Via Belmeloro 6, 40126 Bologna, Italia.
authors: P
authors: P
authors: Ioan
authors: E
authors: E
authors: Carosati
authors: M
authors: M
authors: Micucci
authors: G
authors: G
authors: Cruciani
authors: F
authors: F
authors: Broccatelli
authors: B S
authors: BS
authors: Zhorov
authors: A
authors: A
authors: Chiarini
authors: R
authors: R
authors: Budriesi
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D004095:Dihydropyridines / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007473:Ion Channels / Q000737:chemistry* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines; D007473:Ion Channels; D043562:Receptors, G-Protein-Coupled; C038806:1,4-dihydropyridine