Dihydropyridine KATP potassium channel openers

1,4-Dihydropyridine Scaffold in Medicinal Chemistry, The Story so Far And Perspectives (Part 1): Action in Ion Channels and GPCRs

“…The presence in cromakalim (Fig. 14), a prototypic K ATP channel agonist, and in many analogues of an electron deficient aromatic ring perpendicular to a second ring containing an adjacent hydrogen bond acceptor [128] suggest that 1,4-DHP-acridinediones could act on the same channel as activator. In fact, some structural and electronic features of cromakalin could be found in the 1,4-DHPacridinediones.…”

Pharmacology of ZM244085: A Novel Bladder‐Selective Dihydropyridine KATP Channel Activator

“…Based on the relaxant activity in the bladder and portal vein smooth muscles, the selectivity of ZM244085 for bladder over vascular tissue can be presented graphically as shown in Fig. 2, which includes also the selectivity data generated in-house for Compound 1, diazoxide, cromakalim, YM-934, a potent benzoxazine K' channel activator, and Compound 3 in reference 7, a more potent acridinedione (dihydropyndine) K' channel activator (7). Both ZM244085 and Compound 1 are relatively more bladder selective than cromakalim, although they are not as potent.…”

Investigation of myorelaxant activity of 9-aryl-3,4,6,7-tetrahydroacridine-1,8-(2H,5H,9H,10H)-diones in isolated rabbit gastric fundus

“…Some DHP derivatives have also potassium channel opener activity (Klöckner and Trieschmann, 1989;Davis-Taber, et al, 2003;Grissmer and Cahalan, 1989;Mannhold, 2004;Gopalakrishnan et al, 2003). Frank and coworkers synthesized 9-(3-nitrophenyl)-3,4,6,7-tetrahydroacridine-1,8-(2H,5H,9H,10H)-dione and showed its potassium channel opener activity (Frank et al 1993). It has been shown that imidazolylacridinedione derivatives possess potassium channel modulatory activity (Hadizadeh and Mehri, 2006).…”