Synthesis Of Sulfonamide-Containing Aryl β-Diketo Acid And Quinoxalone Derivatives

β-diketo acid derivatives are the only HIV-1 integrase with anti-viral activity in cell until now. It can selectively inhibit strand transfer reaction of HIV-1 IN catalytic domain. The inhibitory molecular basis of diketoacid derivatives is to interact with catalytic domain of IN selectively. In the paper, the synthesis of sulfonamide arylβ-diketo acids and quinoxalinone derivatives is the aim of our research based on the analysis priminary fact of arylβ-diketo acids HIV-1 integrase inhibitors.We have investigated the detailed synthesis of sulfonamide-containing arylβ-diketo acid derivatives and quinoxalinone derivatives. We design and synthesize ten different sulfonamide-containing arylβ-diketo acid derivatives 50a-e and 51a-e with the substitute of -H, -Cl, -CH3, -OCH3, -NO2 respectively. The existence of carboxyl make the diketo acid derivatives instability in chemistry and biology and also have the disadvantage of low utilization in the body, so we design quinoxalinone derivatives as its bioisostere and synthesize ten quinoxalinone derivatives from 52a to 53e. The above compounds were confirmed by the methods of NMR, IR and MS.The X-ray crystal structure of 52a, 53b, 53c and 53d were further analysed. Because of the existence of intramolecular hydrogen bond and the sp2 hybrid configuration of two N atoms, there was a similar arrangement between the chain of quinoxalinone derivatives and diketo acid derivatives, which further confirmed our above design.We investigated the recognition and affinity of target compounds covalent with metal ion by UV-Vis spectro in organic solvent. The experiment results demonstrated that the quinoxalone derivatives could selectively recognize Cu²⁺, and the Ks of the sulfonamide unit in the meta position of phenyl ring is 100 times than that in the para position.