Synthesis and calcium channel blocker activity of alkyl 1,4-dihydro-2,6-dimethyl-4-nitrobenzyl thioimidazolyl-3,5-pyridinedicarboxylates.
New alkyl ester analogues of nifedipine, in which the orthonitrophenyl group of position 4 is replaced by 1-methyl 2-(p-nitrobenzyl)thio-5-imidazolyl substituent, were synthesized and evaluated as calcium-channel antagonists using the high K+ contraction of guinea-pig ileal longitudinal smooth muscle. The results for the symmetrical esters showed that increasing the length of methylen chain in C3 and C5 ester substituents decreased activity. When the presence of bulky lipophilic esters increased activity. In unsymmetrical diester series, the results showed when R1 is a small substituent (R1 = Me), increasing of the lipophilic property in R2 substituent increased the activity if this high lipophilicity don't accompany with steric hinderance. Our results demonstrate that the most active compound was diphenyl ester derivative and it was almost seven times more active than the reference drug nifedipine.
Zarghi
A
A
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Shaheed Beheshti University of Medical Sciences, Tehran, Iran.
Faizi
M
M
Abdolahnejad
R
R
Fassihi
A
A
D000818:Animals; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000494:pharmacology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007202:Indicators and Reagents; D009543:Nifedipine