Antituberculosis agents

The main use of y-picoline (4) is in the production of the antituberculosis agent, isonia2id (31). Compound (4) is also used to make 4-vinylpyridine, and subsequendy polymers. 

As far as sinusoidal uptake is concerned, drug-drug interactions have also been reported between antituberculosis agents (rifamycin SV and rifampicin) and bromosulfophthalein in humans both drugs reduce the clearance of bromosul-fophthalein and also induce hyperbilirubinemia [108]. These results may be ac-... 

Treatment of tuberculosis Use in conjunction with other effective antituberculosis agents. 

Tuberculosis Initial treatment of active tuberculosis in adults and children when combined with other antituberculosis agents. 

Intended for use concomitantly with other antituberculosis agents in pulmonary infections caused by capreomycin-susceptible strains of Mycobacterium tuberculosis, when the primary agents (eg, isoniazid, rifampin) have been ineffective or cannot be used because of toxicity or the presence of resistant tubercle bacilli. Administration and Dosage... 

Sivakumar, P.M., Babu, S.K.G., Mukesh, D. QSAR studies on chalcones and flavonoids as antituberculosis agents using genetic function approximation (GFA) method. Chem. Pharm. Bull. 2007, 55, 44-9. 

Ethionamide (Trecator) is a derivative of isonicotinic acid and is chemically related to isoniazid. It is a secondary agent used in combination when primary agents are ineffective or contraindicated it is a bacteriostatic antituberculosis agent. Its exact mechanism of action is unknown but is believed to involve inhibition of oxygen-dependent mycolic acid synthesis. It is thought that mutations in the region of the (tnhA) gene that are involved in mycolic acid synthesis can cause both isoniazid and ethionamide resistance. 

Moving to the 2,4,l-diheteraborin-3-ones, we find that Martin s group prepared a set of 2,4,1-benzodiazaborin-3-ones and -thiones (52-54) as potential antituberculosis agents <98BMCL843>. Compounds 52b and S3 were determined to be the most active. 

Combination antituberculosis agents isoniazid/pyrazinamide/rifampin... 

Various antituberculosis agents ethambutol hydrochloride pyrazinamide... 

Andrade CH, Salum Lde B, Castilho MS et al (2008) Fragment-based and classical quantitative structure-activity relationships for a series of hydrazides as antituberculosis agents. Mol Divers 12 47-59... 

Prakash O, Ghosh I (2006) Developing an antituberculosis compounds database and data mining in the search of a motif responsible for the activity of a diverse class of antituberculosis agents. J Chem Inf Model 46 17-23... 

Garcia-Garcia A, Galvez J, de Julian-Ortiz JV, Guna R et al (2005) Search of chemical scaffolds for novel antituberculosis agents. J Biomol Screen 10 206-214... 

Lu T, Drlica K. In vitro activity of C-8-methoxy fluoroquinolones against mycobacteria when combined with antituberculosis agents. /. Antimicrob. Chemother., 2003, 52, 1025-1028. 

The first TCAs (imipramine and amitriptyline) and MAOIs appeared between 1957 and 1961 (Fig. 19.1). The MAOIs were developed from antituberculosis agents which had been noted to elevate mood. Independently, imipramine was synthesised from the antipsychotic drug chlorpro-mazine and found to have antidepressant rather than antipsychotic properties. Over the next 25... 

Several herbal products have been claimed to mitigate drug-induced hepatitis caused by antituberculosis agents. However, few of them have undergone rigorous randomized controlled trials. 

There is a lack of consensus on the best re-treatment protocol for patients who develop hepatotoxicity during treatment with standard antituberculosis agents. Investigators from Turkey have reported a high risk of recurrence of hepatitis (in six of 25 patients) on re-introduction of all drugs in full doses after recovery from hepatitis (31). This risk was less when rifampicin and isonia-zid were re-introduced sequentially in increasing doses and when pyrazinamide was replaced by streptomycin. 

Pyridine derivatives are precursors of many chemical products of medicinal, agricultural, and industrial importance. Pyridine itself is used not only as a solvent, but also as a starting material for pharmaceuticals, herbicides, insecticides, and fungicides. a-Picoline is a precursor for 2-vinylpyridine which is used in the production of an adhesive for textile tire cord. The major use of y-picoline is in the production of isonicotinic hydrazide, an antituberculosis agent. / -Picoline and 2-methyl-5-ethylpyridine are important intermediates in the production of two members of the vitamin B family, nicotinamide, and nicotinic acid (also known as vitamin B3). All this shows there is a substantial need for the production of picolines. The following text describes a novel route to a-picoline which might in the future lead to new processes. 

Ethionamide is an antituberculosis agent that causes inhibition of peptide synthesis in susceptible organisms. It is indicated in the treatment of tuberculosis, in combination with other agents, in patients with M. tuberculosis resistant to isoniazid or rifampin, or when there is intolerance to other antituberculous agents. 

Pyrazinamide is an antituberculosis agent. Pyrazine analog of nicotinamide may be bacteriostatic or bactericidal against Mycobacterium tuberculosis. It is indicated in an initial treatment of active tuberculosis in adults and selected children when combined with other antituberculosis agents. 

Rifapentine is an antituberculosis agent that inhibits DNA-dependent RNA polymerase in susceptible strains of Mycobacterium tuberculosis. It is bactericidal for intracellular and extracellular M. tuberculosis organisms. It is indicated in the treatment of pulmonary tuberculosis in conjunction with one or more other antituberculosis drugs to which the isolate is susceptible. 

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