Synthesis And Antibacterial Activity Of 5-amino-3,4-dihydroquinoline-2(1H)-one And Derivatives

Chitin was the essential component of fungal cell wall and did not exist in mammalian biological tissue. Chitin biosynthesis was catalysed by chitin synthase. The synthesis would cease and fungi would die if the enzyme was inhibited. Therefore, chitin synthase was an ideal target for antifungal drug. It was significant for antimycotic drug development to research the chitin synthase inhibitors.At the present stage, there were three ways to get strong chitin synthase inhibitors:modifying an available inhibitor to gain new one; extracting active ingredient from natural products; searching for potential chemical structure of chitin synthase inhibitor from antibiotics. However, all the lead compounds were somewhat randomLy chosen in the mentioned methods above.Combined the application of computer technology with biochemistry, we simulated 3D protein structure of chitin synthase and docked it with several compounds to screen suitable compound which was matching with chitin synthase extremely. And then, queried literatures reported the compound or structural analogues to assess the antimycotic potential. Ultimately, we determined 5-amino-dihydroquinoline-2(1H)-one as the key intermediate and synthesized a series of drug molecules for obtaining strong chitin synthase inhibitors. The main work was summarized as follows: 1. Preparation of 5-amino-dihydroquinoline-2(1H)-one 50:starting from 1,3-cyclohexanedione, the key intermediate 5-amino-3,4-dihydro-quinoline-2 (1H)-one 50 was obtained via multistep reactions such as Michael addition, oximation reaction, SemmLer-wolff aromatization reaction hydrolysis reaction and so on.2. Preparation of novel 5-amino-dihydroquinoline-2(1H)-one amide derivatives 64a-1:the target compounds were obtained via acylation between 5-amino-3,4-dihydro-quinoline-2 (1H)-one 50 and acyl chloride which were synthesized from different aromatic carboxylic acids. 3. The novel compounds were characterized by NMR, and MS spectra. 4. The condition for preparation of intermediate or target compounds were explored to find the optimum reaction conditions.5. The in vitro antibacterial and antifungal assays indicated that some amide derivatives could inhibit growth of the tested microorganisms medium and some of them showed no activities in comparison with the reference drugs.6. The preliminary structure-activity relationship showed that the amide derivatives substituted at ortho-position generally showed better anti-microbial activity than those substituted at para-position.33 compounds were synthesized in this thesis. Among this,12 new compounds had not been reported, including 11 benzene-substituted amide derivatives and one heterocyclic-substituted amide derivative.