M. Saddala, Jangampalli Adi Pradeepkiran
Nov 4, 2019
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Quality indicators
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Current topics in medicinal chemistry
Abstract
AIMS The aim of the present study to synthesis and biological evaluation of 3-ethyl 5-methyl 2-(2-aminoethoxy)-4-(2-chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylate derivatives. Dihydropyridine (DHP) is an important class of calcium antagonist structure, the structure of the compound pyridine natured with semi-saturated with two substituents replacing one double bond. DHP inhibits the influx of extracellular Ca2+ through L-type voltage-dependent calcium channels in earlier reports. OBJECTIVE The aim of the present study to synthesis and biological evaluation of 3-ethyl 5-methyl 2-(2-aminoethoxy)-4-(2-chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylate derivatives. Dihydropyridine (DHP) is an important class of calcium antagonist structure, the structure of the compound pyridine natured with semi-saturated with two substituents replacing one double bond. DHP inhibits the influx of extracellular Ca2+ through L-type voltage-dependent calcium channels in earlier reports. METHOD An efficient synthesis of two series of novel carbamate and sulfonamide derivatives of amlodipine, 3-ethyl 5-methyl 2-(2-aminoethoxy)-4-(2-chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylate (Amlodipine) 1 was done with chemical synthesis process. In this process various chloroformates 2(a-e) and sulfonyl chlorides 4(a-e) on reaction with 1 in the presence of N,N-dimethylpiperazine as a base in THF at 50-550 C yielded the corresponding title compounds 3(a-e) and 5(a-e) in high yields. These synthesized compounds 3(a-e) and 5(a-e) validated by in vitro and in silico methods such as antioxidant activity, hemolytic activity, cytotoxicity assays, molecular docking studies and ADMET tests Result: The compounds 3(a-e) and 5(a-e) exhibited moderate to high antioxidant, hemolytic, cytotoxicity due to the presence of different substituted functional groups at carbamate and sulfonamide moieties of amlodipine. All 3(a-e) and 5(a-e) synthesized compounds futher validated like in silico ADMET and molecular docking studies for further confirmations. CONCLUSION Furthermore, we are going validate these compounds in vivo and experimental validation to confirm their potential calcium channel blockers activity for therapeutic validated applications in drug discovery.