Diethyl 3,6-dihydro-2,4-dimethyl-2,6-methano-1,3-benzothiazocine-5,11- dicarboxylates as calcium entry antagonists: new conformationally restrained analogues of Hantzsch 1,4-dihydropyridines related to nitrendipine as probes for receptor-site conformation.
The pharmacological activity of rigid analogues of 1,4-dihydropyridine calcium entry antagonists 9-16 is demonstrated by dose-dependent inhibition of the calcium contraction in depolarized rat aortic strips and by a [3H]nitrendipine binding assay in using cardiac sarcolemmal membranes. From the results, a model is proposed as the receptor-bound conformation of the dihydropyridine calcium entry antagonists.
D000818:Animals; D001011:Aorta / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D004095:Dihydropyridines; D004305:Dose-Response Relationship, Drug; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects; D008297:Male; D009568:Nitrendipine / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship; D013552:Swine; D013729:Terpenes / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D006571:Heterocyclic Compounds; D007473:Ion Channels; D011725:Pyridines; D013729:Terpenes; C038806:1,4-dihydropyridine; D009568:Nitrendipine