Design, Synthesis And Action Investigation Of Ortho-hydroxy-N-(Pyridin-4-yl) Benzamides As Tuberculostatic Agent

N-pyridinylsalicylanilides with broad applications in current medicinal and chemical fields have become not only an intermediate, a catalyst or an antihypertensive agent as potassium channel opener, but also an antibiotic of the possible high selectivity and the possible excellent efficacy to Mycobacterium avium complex and Mycobacterium kansasii due to the inhibition of two-component regulatory system. So the antituberculosis action of 8 designed compounds(tl-t8) not reported in the literature was investigated for discovery of the novel antituberculosis drugs with high selectivity, good safty, and excellent efficacy, and solution of the emerging globle problems led by severe liver or kidney toxicity and multiple-drug resistance of the antituberculosis drug to date.Salicylic acid derivatives in the present of phenol gave the corresponding phenyl esters. The mixture of the corresponding substitued acetylsalicyloyl phenyl esters and substituted 4-amino-pyridines under the temperature of 190-210℃carried out the condensation reaction. Then the recrystallization of reation residue resulted in the target compounds. The structural assignment was based on 1HNMR,13CNMR, IR spectra and HRMS high resolution mass spectrum. Investigation of the condition of condensation reaction and post set-up optimized synthetic technics of the target compounds with the more than 65% yields. The logP determination by UV predicted the relationship between liposolubility and antituberculosis action of the target compounds. 2-fold serial dilution prepared solution with a serious concentration of the target compounds. In the antituberculosis in vitro test of H37Rv as the standard strain, the determination of the minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), and the half inhibitory concentration (IC50) by colorimetry showed that MIC of t2-t7 were almostly equal to the ones of rifampicin and pyrazinamide, their IC50 adjacent to the one of streptomycin, and MBC of t4, t5, and t7 also contiguous to the one of streptomycin. It was noted that MIC as well as MBC and IC50 of t5 and t7 were all more excellent than the ones of streptomycin, and nearly equal to the ones of rifampicin, pyrazinamide and retozide as the clinical first-line antituberculosis drugs. So t5 and t7 are of the big perspective due to the worth of further clinical development.