Synthesis of some new fluorine substituted thiobarbituric acid derivatives as anti HIV1 and cyclin-dependent kinase 2 (CDK2) for cell tumor division: Part I

Abstract

New potential enzyme inhibitors, fluorine-substituted thiobarbituric acid derivatives (2, 3, 9, 8 and 12) and their fused/isolated heterocyclic nitrogen systems (5, 6, 10 and 14) have been obtained from heterocyclization of fluorinated N, Nʹ-disubstituted thiourea (1, 7 and 11) with malonic acid followed by ring closure reactions with primary nitrogen reagents. Structures of the synthesized products have been deduced from their elemental analysis and spectral data. Anti-HIV-1 and inhibition of cyclin-dependent kinase2 (CDK2) for cell tumor division for the synthesized compounds were also evaluated.

Synthesis of Some New Barbituric and Thiobarbituric Acids Bearing 1,2,4-Triazine Moiety and Their Related Systems as Herbicidal Agents

“…Recent studies reported that the barbituric and thiobarbituric acids have many tautomers, which led to a high degree of stability [8,9]. Also, 1,2,4-triazine moiety exhibited a wide range of biological, pharmacological, and medicinal properties [10,14].…”

“…e polyfunctional systems of compounds 8-10 were obtained via Knoevenagel condensation by the reaction of compounds 5-7 with 4-chlorobenzaldehyde in EtOH-piperidine to give the 5-arylidene barbituric/thiobarbituric acid derivatives 8-10 (Scheme 2). e introduction of fluorine atoms to heterocyclic nitrogen systems, especially thiobarbituric acid derivatives, enhances their physical, chemical, and biological properties [8,9]. us, fluoroacylation of compounds 5-7 by refluxing with 2,2,2-trifluoroacetic anhydride in DMF yielded 1-(5′,6′-diphenyl-1,2,4triazin-3′-yl)-3-cyclohexyl-5-di(trifluoroacetyl)barbituric acid (11) and/or 1-(5′,6′-diphenyl-1,2,4-triazin-3′-yl)-3-methyl/phenyl-5-di(trifluoroacetyl)thiobarbituric acids (12 and 13), respectively (Scheme 3).…”

“…Moreover, thiobarbituric acids bearing various heterocyclic moieties were used as potent anticonvulsant agents [7] in MES and PTZ models. Recently, Al-Harbi et al [8,9] synthesized fluorinated N 1 ,N 3 -disubstituted thiobarbituric acids that can be used as anti-HIV1 agents and as inhibitors for cyclin-dependent kinase 2 (CDK2) in cell tumor division [8,9]. Based upon these facts, the present work tends to synthesize newer 1,3-disubstituted barbituric and thiobarbituric acid derivatives from 3-amino-5,6-diphenyl-1,2,4-triazine (1) [10] and study their chemical reactivity as well as evaluate them as herbicidal agents.…”

“…Found, %: C, 66.41; H, 3.70; N, 15.39; and S, 7.02.4.3. N 1 -(Substituted)-N 3 -(5,6-diphenyl-1,2,4-triazin-3′-yl)-5-(4′-chlorobenzylidene)barbituric/thiobarbituric Acids(8)(9)(10). Equimolar mixtures of 5, 6, and 7 and 4-chlorobenzaldehyde in EtOH (50 ml) with a few drops of piperidine were refluxed for 6-8 h, cooled, and then poured onto ice.…”

Synthesis of New Fluorinated 1,2,4-Triazino [3,4-b][1,3,4]thiadiazolones as Antiviral Probes-Part II-Reactivities of Fluorinated 3-Aminophenyl-1,2,4-triazinothiadiazolone

“…Abdel-Rahmanetal reported [1] [25], fluorine substituted thiobarbituric acid derivatives use as anti HIV-1 and cyclin dependent kinase 2 (CDK2) for cell tumor division, thus ring closure reaction of compound 3 with malonic acid in boiling with glacial acetic acid afforded the fluorine substituted N,N'-disubstitutedthiobarbituric acid 13 (Scheme 7). Formation of compound 13 was deduced from ring closure reaction of substituted thiourea 3 with malonic acid (Figure 2).…”