- PYRIDYL COMPOUND SUITABLE FOR THE TREATMENT OF METABOLIC DISORDERS
-
The description relates to a pyridyl compound of Formula 1 wherein A, B, X, R1, R2, R3, R4, R5, R6, and n are as defined in the specification, in all their isotopic forms, stereoisomeric and tautomeric forms and mixtures thereof in all ratios, their pharmaceutically acceptable salts, N-oxides, pharmaceutically acceptable solvates, isosteres and prodrugs thereof, which are useful in treating metabolic disorders related to insulin resistance or hyperglycemia. The description also relates to a process for the manufacture of the pyridyl compound and a pharmaceutical composition containing the pyridyl compound.
- -
-
Page/Page column 56
(2015/01/16)
-
- New 2-Thiopyridines as potential candidates for killing both actively growing and dormant mycobacterium tuberculosis cells
-
From in vivo observations, a majority of M. tuberculosis cells in latently infected individuals are in a dormant and probably nonculturable state, display little metabolic activity, and are phenotypically resistant to antibiotics. Despite many attempts, no specific antimicrobials effective against latent tuberculosis have yet been found, partly because of a lack of reliable and adequate in vitro models for screening of drug candidates. We propose here a novel in vitro model of M. tuberculosis dormancy that meets the important criteria of latency, namely, nonculturability of cells, considerable reduction of metabolic activity, and significant phenotypic resistance to the first-line antibiotics rifampin and isoniazid. Using this model, we found a new group of 2-thiopyridine derivatives that had potent antibacterial activity against both actively growing and dormant M. tuberculosis cells. By means of the model of M. tuberculosis nonculturability, several new 2-thiopyridine derivatives were found to have potent antitubercular activity. The compounds are effective against both active and dormant M. tuberculosis cells. The bactericidal effects of compounds against dormant M. tuberculosis was confirmed by using three different in vitro models of tuberculosis dormancy. The model of nonculturability could be used as a reliable tool for screening drug candidates, and 2-thiopyridine derivatives may be regarded as prominent compounds for further development of new drugs for curing latent M. tuberculosis infection.
- Salina, Elena,Ryabova, Olga,Kaprelyants, Arseny,Makarov, Vadim
-
-