الفهرس 
Vascular smooth muscle contraction and hypertensionOnly 14 pages are availabe for public view
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Abstract
1,4-dihydropyridine(DHP)is one of the leading classes of calcium channel blockers. It inhibits the influx of extracellular Ca2+ through L-type voltage dependent calcium channels. Consequently, new candidates were designed based on a Field-Based QSAR model. Field-Based QSAR was applied to a chosen set of 1,4-DHPs to build a 3D-QSAR model with good predictive ability indicated by high Q2 value of 0.519. The model has utilized in predicting the activity of novel 1,4-DHPs.As a result, two novel series of nifedipine analogues in which the orthonitrophenylring of nifedipine was replaced by ortho- or meta-iodophenyl substituent were designed. Nine symmetrical analogues(4a-i)were prepared by condensing two equivalents of alkyl acetoacetate, one equivalent of ammonium acetate with one equivalent of the corresponding aldehyde, in a classical Hantzsch synthesis. Whereas fourteen asymmetrical analogues (7a-n) were synthesized by a modified Hantzsch reaction, that involved, condensation of one equivalent of alkyl acetoacetate and one equivalent of alkyl 3-aminocrotonate with the correspondin
one equivalent of aldehyde. All synthesized compounds were evaluated as calcium antagonist using the high K+ contraction of the guinea pig ileal longitudinal smooth muscle. The results of IC50 demonstrate that all the synthesized compounds were active with similar to lower potency than the reference drug nifedipine. Substituents of suitable bulkiness, such as benzyl ester, at 3- and 5-positions of DHP ring having ortho-iodophenyl substituent at 4-postion gives 4d with
IC50 of 0.87X 10-9 that is equally active as nifedipine. Molecular docking
study was performed for all compounds at the 1,4-dihydropyridine receptor
model active site to explain the differences in calcium channel antagonist activities