Drugs Used in Tuberculosis and Leprosy

Smith, M. I.; Accinelli, A.; Tejada, Frederick R.; Kharel, Madan K.

doi:10.1016/bs.seda.2016.08.015

Cited by 6 publications

(2 citation statements)

References 85 publications

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“…A preparative-scale reaction for the synthesis of ( S )- 2a was also performed using AmDH-M 0 . This afforded the desired product in 84% isolated yield with >99% ee, which thus achieved a formal synthesis of the active ( S , S )-form of the tuberculosis drug ethambutol (Scheme B) . This route to ( S )- 2a could be more advantageous than those currently employed, as it avoids the need for chiral pool starting materials or precious-metal catalysis and also exclusively generates the ( S )-enantiomer required for the active form of the drug …”

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confidence: 99%

Enantioselective Synthesis of Chiral Vicinal Amino Alcohols Using Amine Dehydrogenases

et al. 2019

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Chiral vicinal amino alcohols are an important motif found in many biologically active molecules. In this study, biocatalytic reductive amination of α-hydroxy ketones with ammonia was investigated using engineered amine dehydrogenases (AmDHs) derived from the leucine amino acid dehydrogenase (AADH) from Lysinibacillus fusiformis. The AmDHs thus identified enabled the synthesis of (S)-configured vicinal amino alcohols from the corresponding α-hydroxy ketones in up to 99% conversions and >99% ee. One of the AmDH variants was used to prepare a key intermediate for the antituberculosis pharmaceutical ethambutol.

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confidence: 99%

Enantioselective Synthesis of Chiral Vicinal Amino Alcohols Using Amine Dehydrogenases

et al. 2019

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“…Studies have shown that the DM effect on QT interval appears to be dose-dependent and that this effect is negligible at recommended therapeutic concentrations of DM (100 mg twice daily) [ 90 ]. In randomized clinical trials, where MDR-TB patients received DM 100 mg, 200 mg, or placebo each twice daily, the drug exhibited asymptomatic QT segment prolongation in both treatment groups (13.1% and 9.9%) compared to the placebo group (3.8%) [ 91 , 92 ]. Noteworthy, DM is not a substrate, inhibitor, nor an inducer of CYP450 isozymes; it is also not conjugated, acetylated, or excreted renally.…”

Section: Novel Anti-mtb Agentsmentioning

confidence: 99%

Chemical Classes Presenting Novel Antituberculosis Agents Currently in Different Phases of Drug Development: A 2010–2020 Review

2021

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Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a curable airborne disease currently treated using a drug regimen consisting of four drugs. Global TB control has been a persistent challenge for many decades due to the emergence of drug-resistant Mtb strains. The duration and complexity of TB treatment are the main issues leading to treatment failures. Other challenges faced by currently deployed TB regimens include drug-drug interactions, miss-matched pharmacokinetics parameters of drugs in a regimen, and lack of activity against slow replicating sub-population. These challenges underpin the continuous search for novel TB drugs and treatment regimens. This review summarizes new TB drugs/drug candidates under development with emphasis on their chemical classes, biological targets, mode of resistance generation, and pharmacokinetic properties. As effective TB treatment requires a combination of drugs, the issue of drug-drug interaction is, therefore, of great concern; herein, we have compiled drug-drug interaction reports, as well as efficacy reports for drug combinations studies involving antitubercular agents in clinical development.

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