Synthesis, Evaluation of Pharmacological Activities and Quantitative Structure–Activity Relationship Studies of a Novel Group of bis(4‐Nitroaryl‐1,4‐dihyropyridine)

Abstract

Voltage-dependent calcium channels are crucial targets for a wide range of clinically active pharmacological agents. From these agents, 1,4-dihydropyridines constitute a group of small organic compounds are based on a core pyridine structure which can both block and enhance calcium currents. They are considered specific for L-Type calcium channels; however, other channel types, and in particular certain T-Type channels, may show sensitivity to dihydropyridine compounds. In this study, we synthesized a novel group of bis-1,4-dihydropyridines using the procedure reported by Dagnino that involved the condensation of n-alkyl diacetoacetate (n = 2-7) with methyl-3-aminocrotonate and nitrophenylaldehyde. The synthesis was run under two conditions: (i) reflux and (ii) microwave. Calcium channels antagonist activity were determined in vitro using guinea-pig ileum longitudinal smooth muscle assay. Synthesis of these compounds was confirmed with 1H-NMR, IR and mass spectrometry. Then IC(50) of them are calculated and compared with Nifedipine. Finally, the result of this pharmacological assay was used in quantitative structure-activity relationship studies utilizing multiple linear regression analysis. Most of these compounds are less active compared with Nifedipine. Decrease in activity is the result of increase in steric hindrance. The quantitative structure-activity relationship study indicates that the activity is related to the electrostatic and topological parameters and the distance between two C5-esteric groups of 1,4-dihydropyridine rings.

Design, synthesis and 3D-QSAR studies of novel 1,4-dihydropyridines as TGFβ/Smad inhibitors

“…QSAR analyses have become a widely used technique in drug design (13) aside from classic calcium channel antagonist activity in guinea pig ileum smooth muscle assays. (19) In all cases, the requirement for calculating a QSAR model is the assumption that all evaluated derivatives share the same target or target binding site, and unspecific effects, such as permeability, have no significance influence or do not decisively determine the desired activity, respectively.…”

Synthesis, Biological Evaluation, in silico ADMET and Molecular Docking of new 1,4‐Dihydropyridine Derivatives Bearing Ether Substitution as Calcium Channel Blockers

“…The IC 50 values of all synthesized compounds were evaluated by guinea pig ileal longitudinal smooth muscle (GPILSM) assay. [24] In this method, the CCB effect of the synthesized compounds was considered as the required concentration to inhibit 50 % of the longitudinal contraction of guinea pig smooth muscle. [25] The nifedipine.…”

Hantzsch reaction with 6-aminouracil: Synthesis of novel tetrakis(6-aminouracil-5-yl)methanes and bis(decahydropyrido[2,3-d:6,5-d']dipyrimidine-tetraones) linked to aliphatic or aromatic cores via ether-amide or ester-amide linkages

“…Hantzsch reaction is one of the most common routes for the synthesis of 1,4-dihydropyridines (1, having therapeutic and pharmacological properties. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] In addition, Uracil is considered to be one of the major motifs present in the biopolymer RNA 20,21 and it plays several roles in our life. 22,23 The uracil scaffold and its derivatives exhibit a wide range of biological activities, including anticancer agents, [24][25][26] antihypertensive agents, 27 antiallergic compounds 28 and antiviral agents.…”