Synthesis and antituberculosis activity of n-r-amides 1- hydroxy-3-oxo-6,7 dihydro-3h, 5h-pyrido [3,2,1-ij] quinoline-2-carbonic acids

Abstract

The main modern problem in the treatment of tuberculosis is the rapid development of resistance of the causative agent of this dangerous infectious disease to antimycobacterial drugs. According to the World Health Organization, today, drug-resistant tuberculosis is diagnosed in an average of 7% of patients today, and may soon seriously destabilize the epidemiological situation in the world and develop into a global threat to humanity. In addition to improving preventive and diagnostic measures, today three research areas are being intensively developed, designed, if not to remove the problem of multidrug-resistant strains from the agenda, then at least to reduce its severity. The first of them provides for the development of strictly controlled schemes of intensive treatment with short courses of chemotherapy using combinations of existing drugs, significantly postponing the development of resistance to them. The second direction combines genetic studies to decipher the sequence of nucleotides in the genome of Mycobacterium tuberculosis in order to identify genes corresponding to the mutation and, therefore, involved in the mechanisms of antibiotic resistance. In the future, this approach will make it possible to create fundamentally new means and methods for combating tuberculosis. However, at the present level of development of science, the third direction has not yet lost its significance, which is based mainly on the empirical selection of a leader structure from a series of synthesized compounds that have passed different levels of pharmacological tests.