Diversified Synthetic Pathway of 1, 4-Dihydropyridines: A Class of Pharmacologically Important Molecules

Abstract

: The current review discusses the different synthetic pathways for one of the most important and interesting heterocyclic ring systems 1,4-dihydropyridine. This cyclic system depicts diverse pharmacological action at several receptors, channels, and enzymes. Dihydropyridine moiety plays an important role in several calcium-channel blockers. Moreover, it has been exploited for the treatment of a variety of cardiovascular diseases due to its potential antihypertensive, anti-angina, vasodilator, and cardiac depressant activities. Furthermore, it also shows antibacterial, anticancer, antileishmanial, anticoagulant, anticonvulsant, anti-tubercular, antioxidant, antiulcer, and neuroprotective properties. Several reports have demonstrated dihydropyridine derivatives as a potentiator of cystic fibrosis transmembrane conductance regulator protein, potent antimalarial agent and HIV-1 protease inhibitor. Herein, we have briefly reviewed different novel chemistry and synthesis of 1,4-dihydropyridine.

Thermodynamics of the elementary steps of organic hydride chemistry determined in acetonitrile and their applications

“…•+ ) and ΔH PD (DH [60][61][62][63] and great reduction ability. 24,25 Given that our research interest has been focused on exploring the thermodynamic driving forces on each elementary step of organic hydride compounds releasing hydride, in 2018, we successfully synthesized 23 3,5-disubstituted-1,4-dihydropyridines (denoted as OH 2 here for clarity) with diverse electron-withdrawing groups at the 3,5position and N 1 -position (Scheme 9), 39 and established 23 "Molecule ID Cards" of OH 2 to quantitatively scale the ) hydride-, hydrogen-, proton-, and electron-donating abilities of OH 2 and its reaction active intermediates in acetonitrile to be used to accurately deduce the reduction mechanism.…”

Tandem Protocol of Hexahydroquinoline Synthesis Using [H2-DABCO][HSO4]2 Ionic Liquid as a Green Catalyst at Room Temperature

“…1,4-Dihydropyridine (1,4-DHP) nuclei are key fragments in various natural compounds as well as in synthetic molecules because of their interaction properties with different proteins . Since 1,4-DHP is an analogue of the coenzyme NADH (nicotinamide adenine dinucleotide), biochemists are highly attracted toward its green synthesis with its applications in medicinal chemistry. − The 1,4-DHP skeleton works as a calcium channel modulator and cardiovascular agent (nicardipine, amlodipine, and nifedipine) and shows antitubercular, antitumor, antiatherosclerotic, vasodilator, neuroprotective, hepatoprotective, and bronchodilator activity. − Polyhydroquinoline (PHQ) is a derivative of 1,4-DHP, a large family of medicinal and industrially important compounds, and has fascinated researchers…”

Quantitative Estimation of the Hydrogen-Atom-Donating Ability of 4-Substituted Hantzsch Ester Radical Cations

“…4-Substituted Hantzsch esters (XRH, Scheme 1 ), known as dipine drugs, are used to treat hypertensive and cardiovascular diseases as calcium channel modulators, 1 , 2 which also have the 1,4-dihydropyridine structure and used as excellent NADH coenzyme models. 3 − 5 XRH were investigated as antioxidants to quench active radicals (R • , RO • , ROO • , RS • or RNH • , and so on) in vivo and vitro in many papers.…”

“…4-Substituted Hantzsch esters (XRH, Scheme ), known as dipine drugs, are used to treat hypertensive and cardiovascular diseases as calcium channel modulators, , which also have the 1,4-dihydropyridine structure and used as excellent NADH coenzyme models. − XRH were investigated as antioxidants to quench active radicals (R • , RO • , ROO • , RS • or RNH • , and so on) in vivo and vitro in many papers. − In recent years, XRH have been examined as alkyl reagents to synthetize various bioactive molecules, and the key elementary step is XRH •+ releasing R • (XRH •+ → XH + + R • ). − However, not all XRH •+ can release R • ; for example, 4-phenyl-Hantzsch ester could not release Ph • itself . We wonder that could XRH •+ be used as H • donors served as radical scavengers just like NADH and NADH •+ (Scheme ).…”