Dimeric 1,4-dihydropyridines as calcium channel antagonists.
A series of 1,n-alkanediylbis(1,4-dihydropyridines) (n = 2, 4, 6, 8, 10, 12) bridged at C3 of 2,6-dimethyl-3-carboxy-5-carbethoxy-4-(3-nitrophenyl)-1,4-dihydropyridin e were synthesized and evaluated in a radioligand binding assay, [3H]nitrendipine in intestinal smooth muscle, as Ca2+ channel ligands. Binding activity was comparable to that of nitrendipine itself but independent of chain length, suggesting the lack of a major binding contribution by the second 1,4-dihydropyridine group. Analogues lacking the second 1,4-dihydropyridine nucleus or possessing an inactive function (4-nitrophenyl) were no less active, confirming that this series of ligands likely does not bridge adjacent 1,4-dihydropyridine receptors of the Ca2+ channel.
Joslyn
A F
AF
Department of Biochemical Pharmacology, School of Pharmacy, State University of New York, Buffalo 14260.
Luchowski
E
E
Triggle
D J
DJ
D000818:Animals; D002121:Calcium Channel Blockers / Q000138:chemical synthesis*; D015220:Calcium Channels; D055598:Chemical Phenomena; D002621:Chemistry; D004095:Dihydropyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects; D013329:Structure-Activity Relationship
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D011978:Receptors, Nicotinic