New dihydropyridine derivatives: Anti-inflammatory, analgesic and docking studies
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Date
2013
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Abstract
The present article describes synthesis of new diethyl 2,6-dimethyl-4-(4- (2-substituted amino-2-oxoethoxy) phenyl)-1,4-dihydropyridine-3,5-dicarboxylates (6a-10b) following multistep synthetic route. Structures of newly synthesized intermediates and title compounds were established by spectral and elemental analyses. The final compounds were screened for their in vivo anti-inflammatory and analgesic activities by carrageenan-induced paw oedema and tail immersion methods, respectively. Moreover, molecular docking studies were carried out for active compounds 6c, 6d, 7d, 8 and 10b to study their mode of action, meanwhile in vivo results indicated that these compounds displayed rapid onset of anti-inflammatory action and exhibited prominent activity when compared with the standard drug. Compounds 6d and 7d carrying amide functionality showed the highest anti-inflammatory as well as analgesic activities. The molecular docking results emphasised the in vivo data and all docked molecules were found to display very low binding constant values in nanomolar scale. © 2012 Springer Science+Business Media, LLC.
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Keywords
4 (2 (2 (4 (3,5 bis(ethoxycarbonyl) 2,6 dimethyl 1,4 dihydropyridin 4 yl)phenoxy)acetyl)hydrazinyl) 4 oxobutanoic acid, analgesic agent, antiinflammatory agent, carrageenan, diclofenac, diethyl 4 (4 ((5 mercapto 1,3,4 oxadiazol 2 yl)methoxy)phenyl) 2,6dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, diethyl 4 (4 (2 (1,3 dioxoisoindolin 2 ylamino) 2 oxoethoxy)phenyl) 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, diethyl 4 (4 (2 (benzothiazol 2 ylamino) 2 oxoethoxy)phenyl) 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, diethyl 4 (4 (2 (benzylamino) 2 oxoethoxy)phenyl) 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, diethyl 4 (4 (2 (p toluidino) 2 oxoethoxy)phenyl) 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, diethyl 4 (4 (2,6 dimethylphenylamino) 2 oxoethoxy)phenyl) 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, diethyl 4 (n' (3 chloro thiophene 2 carbonyl) 2 phenoxyacetohydrazide) 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, diethyl 4 (n' (4 methyl benzoyl) 2 phenoxyacetohydrazide) 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, diethyl 4 (n' (benzoyl) 2 phenoxyacetohydrazide) 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, diethyl 4 (n' (thiophene 2 carbonyl) 2 phenoxyacetohydrazide) 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, diethyl 4-(4 (2 (3,5 dimethyl 1h pyrazol 1 yl) 2 oxoethoxy)phenyl) 2,6 dimethyl 1,4 dihydropyridine 3,5 dicarboxylate, dihydropyridine derivative, unclassified drug, analgesic activity, animal experiment, animal model, antiinflammatory activity, article, binding affinity, carbon nuclear magnetic resonance, controlled study, drug mechanism, drug potency, drug structure, drug synthesis, female, immersion, in vivo study, infrared spectroscopy, male, mass spectrometry, molecular docking, nonhuman, paw edema, proton nuclear magnetic resonance, rat
Citation
Medicinal Chemistry Research, 2013, 22, 4, pp. 1549-1562