Studies of the KATP Channel Opening Activity of the New Dihydropyridine Compound 9-(3-Cyanophenyl)-3,4,6,7,9,10-Hexahydro-1,8-(2H, 5H)-Acridinedione in Bladder Detrusor In Vitro

Pharmacological characterization of a 1,4‐dihydropyridine analogue, 9‐(3,4‐dichlorophenyl)‐3,3,6,6‐tetramethyl‐3,4,6,7,9,10‐hexahydro‐1,8(2H,5H)‐acridinedione (A‐184209) as a novel KATP channel inhibitor

“…Frank et al . (1993) and, subsequently, Li et al . (1996) reported dihydropyridines such as ZM244085 and the corresponding 3‐nitro analogue, as openers of K ATP channels, devoid of L‐type calcium channel activity.…”

“…For example, PNU‐99963 is a potent K ATP channel blocker (IC 50 =18 n M ; Khan et al ., 1997) of the cyanoguandine class that is structurally related to the prototypical opener, P1075. Analogues belonging to the dihydropyridine series such as ZM‐244085 (Li et al ., 1996) and A‐278637 (Gopalakrishnan et al ., 2002b) have been shown to activate K ATP channels and suppress smooth muscle contractility in vitro . In the present study, we describe the activator and inhibitory profiles of a pair of 1,4‐dihydropyridine analogues at native smooth muscle K ATP channels.…”

“…In the present study, we describe the activator and inhibitory profiles of a pair of 1,4‐dihydropyridine analogues at native smooth muscle K ATP channels. These studies show that 9‐(3,4‐dichlorophenyl) ‐3,3,6,6 ‐ tetramethyl ‐ 3,4,6,7,9,10‐ hexahydro‐1,8(2 H ,5 H )‐acridinedione (A‐184209; Figure 1), is a K ATP channel blocker, whereas its analogue, lacking the gemdimethyl substitutions, 9‐(3,4‐dichlorophenyl)‐3,4,6,7,9,10‐hexahydro‐1,8(2 H ,5 H )‐acridinedione (A‐184208), behaves as a K ATP channel opener, the latter consistent with previous observations (Frank et al ., 1993; Li et al ., 1996). The structural overlap between openers and blockers belonging to the dihydropyridine and cyanoguanidine class support the notion that both openers and blockers bind to similar or very closely coupled sites on the sulfonylurea receptor and that subtle changes in the pharmacophore could switch the functional properties from channel activation to channel inhibition.…”

Organocatalytic Domino Entry to an Octahydroacridine Scaffold Bearing Three Contiguous Stereocenters

“…Acridine, containing a tricyclic skeleton, can be found in a variety of natural products with important biologic activities . As a subclass of acridines, octahydroacridines bearing a privileged structure of tetrahydroquinoline core have received limited attention on pharmacological studies so far, mainly due to their restricted availability.…”

Substituted 9-aryl-1,8-acridinedione derivatives and their effects on potassium channels

“…DHP derivatives have also potassium channel opener activities (Grissmer and Cahalan, 1989;Mannhold, 2004;Davis-Taber et al, 2003;. In addition, these compounds affect urinary bladder smooth muscle (Li et al, 1996;Trivedi et al, 1995;Wein, 1998 (Hadizadeh and Mehri, 2006). In this study, we aimed to synthesize 3,6-dimethyl-9-aryl-3,4,6,7-tetrahydroacridine-1,8(2H,5H,9H,10H)-diones and investigate their effects on vascular potassium channels on phenylephrine-induced contractile responses in isolated rat aorta rings.…”