1,4-Dihydropyridines bearing a pharmacophoric fragment of lidoflazine.
A series of 1,4-dihydropyridines bearing a pharmacophoric fragment of lidoflazine was synthesized. The compounds were evaluated for inotropic, chronotropic, and calcium antagonist activities. All compounds behave as inotropic and chronotropic agents, except for compounds 4b, 5a, and 5b, which exhibit a rather weak calcium antagonism in vascular smooth muscle (like aorta). Compound 5b is about twofold more potent in decreasing both chronotropy and inotropy, while compound 5c is about fivefold more potent in decreasing inotropy than nifedipine. Moreover, compound 5b is the most potent calcium antagonist derivative of the series.
Chiarini
A
A
Department of Pharmaceutical Sciences, University of Bologna, Italy.
Rampa
A
A
Budriesi
R
R
Bisi
A
A
Fabbri
G
G
Valenti
P
P
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000737:chemistry* / Q000494:pharmacology; D004095:Dihydropyridines / Q000737:chemistry* / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D008013:Lidoflazine / Q000737:chemistry* / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D014665:Vasodilator Agents / Q000737:chemistry* / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D014665:Vasodilator Agents; C038806:1,4-dihydropyridine; D008013:Lidoflazine