Synthesis and calcium antagonistic activity of 2,6,6-trimethyl-3-carbomethoxy(ethoxy)-4-aryl-1,4,5,6,7,8-hexahydroquinoline derivatives.
Twelve new 2,6,6-trimethyl-3-carbomethoxy(ethoxy)-4-aryl-1,4.5,6.7,8-hexahydroquinoline derivatives have been prepared. Their structures were confirmed by IR, 1H NMR, mass and elemental analysis. The calcium antagonistic activity of these compounds was tested in rat aortic rings precontracted with 30 mM K+. The compounds IVa, IVc, IVe, IVf, IVh-l induced concentration dependent relaxation response in precontracted aortic rings. The concentrations that cause 50% relaxation of K+-contraction were also calculated for the compounds IVe, IVf, IVj. According to pharmacological results, compound IVl exert the most activity and compound IVc has been found to be least active in this series. The methyl ester derivatives carrying mono halogensubstitutent in the phenyl ring, the activity order is F > Br > Cl. Replacement of the substituted phenyl ring with the pyridine ring increases the activity.
Simşek
R
R
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.
Ismailoğlu
U B
UB
Safak
C
C
Sahin-Erdemli
I
I
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000494:pharmacology; D004095:Dihydropyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D013055:Spectrophotometry, Infrared; D017550:Spectroscopy, Fourier Transform Infrared
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D011804:Quinolines