Synthesis、characterization And Biological Activity Of The Quinazoline/pyrazoline Compounds Containing 1,3,4-thiadiazole

Nitrogen-containing heterocyclic compounds as common research object which are extensively used as the synthetic drugs、natural products、pharmaceuticals and pesticide chemicals. Quinazoline and pyrazoline skeletons as the "master key" of heterocycle were used in drug researchs with a variety of biological activity due to the advantages of low toxicity、high efficiency and low-residue. In addition,1,3,4-thiadiazole skeleton containing both nitrogen and sulfur atom playing a pivotal role in the field of medicine because of its potential biological activity, and its unique "nitrogen-carbon-sulfur" structure as an active center can be combined with certain metal ions in vivo, to give full play to drug efficacy by the improvement of cell permeability, which has caused widely concern.In order to find out bioactive molecules with the advantages of easy synthesis, easy separation and higher biological activity, we are try to introduce 2-amino-5-phenyl-1,3,4-thiadiazole structure into quinazoline and pyrazoline skeleton, which expected to get more efficient biological compounds. In this paper, a total of two types 26 new compounds were synthesized including quinazoline compounds containing 1,3,4-thiadiazole and pyrazoline compounds containing 1,3,4-thiadiazole with simple synthesis and processing conditions. All the newly synthesized compounds were characterized by 1H NMR、13C NMR、IR、HRMS and their spectral characteristics were analyzed. All the new compounds’ structures have been identified correctly. In addition, compounds 1j and 2a also carried out X-Ray characterization. At the same time, the melting point of new compounds were tested and synthesis condition were discussed. Structured as follows:(1) quinazoline compounds containing 1,3,4-thiadiazole(2) pyrazoline compounds containing 1,3,4-thiadiazoleAll new compounds with the structure identified have been carried out to investigated the preliminary antifungal activity (Pythium solani、Gibberlla saubinetii、Gibberlla nicotiancola). The results shows that all the compounds exhibited different degrees inhibition for the three plant fungi. Compounds 1c, 1h,2j,2k have shown a higher antifungal activity,1c and 2h have special inhibitory effect for Gibberlla saubinetii equivalent to or even better than the standard drug. The inhibitory of Compound 1h for Gibberlla nicotiancola is equivalent to standard drug. By comparion of different substituents, the compounds of aromatic ring substituted by furan、thiophene and pyridine exhibited the highest inhibitory activity, and substituted by benzene connecting halogen bromine or chlorine showed higher inhibitory activity than those compounds with other substituted groups or unsubstituted. The antifungal activity of ortho-substituted may have contributed to the greater inhibitory potency than para-substituted in the same compound.