Synthesis of New Thiazolopyrimidine, Pyrazole, Stilbene-Triazine Derivatives and Tropane Auxiliary

Abstract

This research work describes the synthesis and characterizationof some novel thiazolopyrimidine,pyrazole, stilbene-triazine derivatives and that of a tropane auxiliary. The in vitro and in silico studiesof synthesized compounds were also carried out.  Synthesis of thiazolopyrimidine derivatives (56-67) was carried out by one-pot multicomponent acid-catalyzed reaction of ethylacetoacetate and 2-aminothiazole and benzaldehyde substituted with electron-donating and electron-withdrawing groups with the aim to find some more potent antidiabetic and antibacterial drugs. An in vitro antidiabetic effect was evaluated in adult male BALB/c mice and antibacterial activities were tested against Gram positive and Gram negative bacteria. Some of the tested compounds proved to possess good to excellent activities compared to the reference drugs. An in silico molecular docking was also performed on synthesized compounds. The current study is expected to provide useful insights into the designof antidiabetic and antibacterial drugs and understanding the mechanism by which such drugs interact with RNA and diabetes target and exert their biochemical action.  A series of phenylhydrazono-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one derivatives (68-91)were conveniently synthesizedby the reaction of different anilines with ethylacetoacetate or acetylacetonefollowed by treatment with phenyl hydrazine.  Synthesis of pyrazole carboxamide derivatives (92-101) was carried out by multistep pathway starting from the reaction of substituted anilines and diethylmalonate. The resulting intermediate was then treated with benzaldehyde to afford ethyl 3-phenyl-2-(phenylcarbamoyl)acrylate which was converted to pyrazole derivatives by reacting with hydrazine hydrate.In vitro antidiabetic studies showed thatsome compounds possess better activities than the reference drugs and thederivative (94) having 2,4-dichloro substituents on phenyl ring was found to be most potent compound and was identified as the lead molecule for furtherstructural modifications.  A series of new optical brighteners (102-113)were efficiently synthesized by a facile three-step approach. 2,4,6-Trichloro-1,3,5-triazine was treated with different anilines and the resulting dichlorotriazinyl intermediates were further condensed with 4,4´-diaminostilbene-2,2´-disulfonic acid followed by nucleophilic substitution with ethanolamine to furnish new hybrid brighteners. UV/Visible absorptions were determined using freshly-prepared solutions in deionized water. The synthesized optical brighteners were also assessed for their efficacy as fluorescent brightening agents.  Synthesis of new thiourea-based bis-monochlorotriazine optical brighteners (114-125)was effected out by multistep synthetic pathway in good yields.  An efficient synthesis of some thioureas (126-145) was also accomplished.Substituted benzoyl chlorides were reacted with potassium thiocyanate to give the corresponding isothiocyantes intermediates, which on addition of separately-synthesized amino-2,4,6-triphenylpyridine, afforded thiourea derivatives in good yields.  In order to synthesize the enantio-pure α-alkylated aldehydes (which are widely recognized as important building blocks in asymmetric induction) from tropane-derived enamine, a highly efficient asymmetric multistep synthesis of a tropane auxiliary (153)was developed.  All the synthesized compounds were characterized on the basis of their physiochemical parameters and spectral data.