6-Amino-4-aryl-7-phenyl-3-(phenylimino)-4,7-dihydro-3H-[1,2]dithiolo[3,4-b]pyridine-5-carboxamides: Synthesis, Biological Activity, Quantum Chemical Studies and In Silico Docking Studies
-
Published:2024-01-07
Issue:2
Volume:25
Page:769
-
ISSN:1422-0067
-
Container-title:International Journal of Molecular Sciences
-
language:en
-
Short-container-title:IJMS
Author:
Dotsenko Victor V.12ORCID, Bespalov Alexander V.1, Sinotsko Anna E.1, Temerdashev Azamat Z.3ORCID, Vasilin Vladimir K.4, Varzieva Ekaterina A.1ORCID, Strelkov Vladimir D.1, Aksenov Nicolai A.2, Aksenova Inna V.2
Affiliation:
1. Department of Organic Chemistry and Technologies, Kuban State University, 149 Stavropolskaya St., 350040 Krasnodar, Russia 2. Department of Chemistry, North Caucasus Federal University, 1a Pushkin St., 355017 Stavropol, Russia 3. Department of Analytical Chemistry, Kuban State University, 149 Stavropolskaya St., 350040 Krasnodar, Russia 4. Department of Bioorganic Chemistry, Kuban State Technological University, 2 Moskovskaya St., 350072 Krasnodar, Russia
Abstract
New [1,2]dithiolo[3,4-b]pyridine-5-carboxamides were synthesized through the reaction of dithiomalondianilide (N,N′-diphenyldithiomalondiamide) with 3-aryl-2-cyanoacrylamides or via a three-component reaction involving aromatic aldehydes, cyanoacetamide and dithiomalondianilide in the presence of morpholine. The structure of 6-amino-4-(2,4-dichloro- phenyl)-7-phenyl-3-(phenylimino)-4,7-dihydro-3H-[1,2]dithiolo[3,4-b]pyridine-5-carboxamide was confirmed using X-ray crystallography. To understand the reaction mechanism in detail, density functional theory (DFT) calculations were performed with a Grimme B97-3c composite computational scheme. The results revealed that the rate-limiting step is a cyclization process leading to the closure of the 1,4-dihydropyridine ring, with an activation barrier of 28.8 kcal/mol. Some of the dithiolo[3,4-b]pyridines exhibited moderate herbicide safening effects against 2,4-D. Additionally, ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) parameters were calculated and molecular docking studies were performed to identify potential protein targets.
Funder
Russian Science Foundation
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
|
|