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Novel antimycobacterial heterocyclic amides

A kind of technology of carboxamide, methyl bicyclic, applied in the pharmaceutical composition of novel compound, the field of preparing described novel compound

Pending Publication Date: 2021-02-26
REPLIDYNE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Therefore, it is not surprising that the overall clinical and microbiological cure rate of Mabs infection is only 41% (Diel, R. et al., Chest 152, 120-142, 2017)

Method used

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  • Novel antimycobacterial heterocyclic amides
  • Novel antimycobacterial heterocyclic amides
  • Novel antimycobacterial heterocyclic amides

Examples

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preparation example Construction

[0077] The preparation of the pharmaceutical compositions of the present invention involves the inclusion of inert, solid or liquid pharmaceutically acceptable carriers. Solid form preparations include powders, tablets, dispersible granules, capsules, cachets, and suppositories. The powders and tablets may contain from about 5% to about 95% active ingredient. Suitable solid carriers are known in the art, such as magnesium carbonate, magnesium stearate, talc, silicon dioxide, sucrose, lactic acid, starch or cellulose derivatives. Tablets, powders, cachets, and capsules can be used as solid dosage forms suitable for oral administration. Pharmaceutically acceptable carriers and methods for the preparation of various compositions can be found in A. Gennaro (ed.), Remington's Pharmaceutical Sciences, 18th Edition, (1990), Mack Publishing Co., Easton, Pa. instance.

[0078] Liquid form preparations include solutions, suspensions and emulsions. As an example, water or water-polye...

Embodiment 193

[0140] Example 193: Description of anti-mycobacterial effects and mechanism of action.

[0141] Multiple pathogenic organisms (including Mycobacterium abscessus, Mycobacterium chelonis, Mycobacterium fortuitum, Mycobacterium peregrinum, Mycobacterium avium, Mycobacterium intracellulare, Chimera Mycobacterium and Mycobacterium tuberculosis) were tested for antimycobacterial activity to determine the minimum inhibitory concentration (MIC). All compounds were tested according to CLSI guidelines (Clinical and Laboratory Standards Institute, document M24-A) using standard methods and conditions. Against Mycobacterium abscessus, the compounds described in Examples 1-101 have MICs of 0.03-1 μg / mL, and Examples 102-192 have MICs of 2-32 μg / mL; but against other pathogens (including Staphylococcus aureus (S .aureus), Streptococcus pneumoniae (S.pneumoniae), Streptococcus pyogenes (S.pyogenes), Enterococcus faecalis (E.faecalis), Escherichia coli (E.coli), Pseudomonas aeruginosa (P.aer...

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Abstract

The present invention provides novel heterocylic amide compounds having useful antimycobacterial activity. Use of these compounds as pharmaceutical compositions and method of their production are alsoprovided.

Description

technical field [0001] The present disclosure relates to novel heterocyclic amide compounds useful in the treatment of infections caused by mycobacteria, such as nontuberculous Mycobacteria and Mycobacterium tuberculosis. The present disclosure also relates to methods for the preparation of the novel compounds and pharmaceutical compositions comprising the novel compounds useful in the treatment of mycobacterial infections. [0002] Background of the invention [0003] Mycobacteria remain important, often drug-resistant human pathogens worldwide, including M. tuberculosis and the historically lesser identified nontuberculous mycobacteria (NTM). Pulmonary NTM disease has steadily increased in the United States from 86,000 cases in 2010 to an estimated 181,000 cases in 2014, with associated direct medical costs of $1.7 billion (Strollo, S.E. et al., Ann Am Thorac Soc 12, 1458-1464, 2015). Underlying pulmonary conditions leading to increased susceptibility include bronchiectas...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/40A61K31/407A61K31/437A61K31/55
CPCC07D333/72C07D277/68C07D263/58C07D235/30A61P31/06A61P31/04C07D277/82
Inventor J·达伊J·格雷哈姆T·贾维斯E·麦克法丁U·奥克斯纳孙喜成C·翁
Owner REPLIDYNE
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