Synthesis And Bioactivities Of Thiazole And Pyrimidine Derivatives Base On4,4-Dimethyl-1-arylpent-1-en-3-one

Heterocyclic compounds are highly appreciated by medicinal chemists due to their broad-spectrum of biological activities, and have become one of significant fields to reserch new drugs. Thiazole derivatives and pyrimidine-based compounds are two important sorts of heterocyclic compounds containing N-heterocycles. They are not only known to exhibit insecticidal, antibacterial, antifungal, antitumor and antivirus activities, but also low toxicities to mammal and friendly compatibility to environment. So, to research and develop the derivaties of thiazole and pyrimidine has important theoretical value and extensive application value. In order to search for novel compounds with high activities, we analyzed structural features and active-informations of thiazole derivatives and pyrimidine-based compounds, designed and synthesized four series of novel thiazole and pyrimidine derivatives using the principle of combination of bioactive sub-structures. The main research contents and results are shown as follows:1. The Adol condensation of arylaldehydes and pinacolone was catalyzed by sodium hydrate, and the influence of the reaction temperature was investigated.2-Bromo-4,4-dimethyl-1-arylpentan-3-ones was obtained by the reactions of hydrogenation and bromination to4,4-dimethyl-1-arylpent-l-en-3-ones. The target compounds5-benzyl-4-tert-butyl-2-arylamino thiazole hydrobromates were synthesized by the reactions of2-bromo-4,4-dimethyl-1-arylpentan-3-ones and N-aryl substituted thioureas. And influences of solvent and temperature of the reaction were investigated. The target compounds were confirmed by1H NMR, ESI-MS and elementary analyses. The antitumor activities of the target compounds were measured by using MTT assay, and the preliminary bioassay showed that some compounds exhibited good inhibitory activities against A549. Meanwhile, some compounds showed insecticidal activity against Aphis fabae.2.5-Benzyl-4-tert-butyl-2-aminothiazole hydrobromates was synthesized by the reaction of2-bromo-4,4-dimethyl-l-arylpentan-3-ones and thiourea in ethanol, and neutralized with ammonia, we obtained the key intermediate5-benzyl-4-tert-butyl-2-aminothiazoles. Using DMAP as catalyst and DCC as condensing agent, the target compounds were synthesized by the reactions of5-benzyl-4-tert-butyl-2-aminothiazoles with anhydrides, acyl chlorides and aryl carboxylic acids, respectively. And the influence of additive sequences of DMAP and DCC was investigated. The structures of target compounds were confirmed by1H NMR, ESI-MS, elementary analyses and X-ray single crystal diffraction. The preliminary bioassay showed that some compounds exhibited good inhibitory activities against A549and Hela. Meanwhile, some compounds showed insecticidal activities against Aphis fabae and Tetranychus urtica.3.2,2-Dimethyl-5-aryl-6-nitrohexan-3-ones was synthesized by the Michael addiction of4,4-dimethyl-1-arylpent-1-en-3-ones and nitromethane, and the influence of catalyst (diethylamine and potassium carbonate) was investigated. For the bromination of2,2-dimethyl-5-aryl-6-nitrohexan-3-ones, we investigated the difference between hydrogen peroxide/sodium bromide/concentrated sulfuric acid and bromine. The target compounds were obtained after cyclization and N-acylation of2,2-dimethyl-4-bromo-5-aryl-6-nitrohexan-3-ones, and confirmed by1H NMR, ESI-MS and elementary analyses. The preliminary bioassay showed that some compounds exhibited good inhibitory activities against A549and Hela. Meanwhile, some compounds showed insecticidal activities against Mythimna sepatara, Aphis fabae and Tetranychus urtica.4.6-tert-Butyl-4-aryl-3,4-dihydropyrimidine-2-(1H)-2-thiones were synthesized by the reaction of4,4-dimethyl-1-arylpent-1-en-3-ones and thiourea via "Atwal" reaction, which were catalyzed by sodium hydrate. And their stuctures were confirmed by1H NMR and13C NMR.6-Methyl-5-ethoxycarbonyl-4-aryl-3,4-dihydropyrimidine-2-(1H-2-thiones were synthesized by the reaction of arylaldehydes, thiourea and ethyl acetoacetate via Biginelli reaction, which were catalyzed by concentrated sulfuric acid. The preliminary bioassay showed that some compounds exhibited good inhibitory activity of5-HT transporter(SERT).