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Tuberculosis (TB) is still one of the major causes of bacterial infections and mortality in the world. In 1944, streptomycin was introduced as a first antibiotic remedy to cure TB effectively. After that, in the 1940s and 50s, with the introduction of pyrazinamide (PZA), rifampicin (RIF), isoniazid (INH), ethambutol and streptomycin as well as cocktail-drug treatment of tuberculosis, a cure for tuberculosis was considered reasonable. This period was a period of optimism, as it was believed that TB could be cured and eliminated. Hence, the United Nations targeted elimination of TB by 2025. These expectations were dashed as a worldwide pandemic of tuberculosis began in 1987 and the World Health Organization declared that tuberculosis posed a global emergency in 1993. The estimates of the global burden of the disease caused by Mycobacterium tuberculosis in 2009 are as follows: 9.4 million incident cases, 14 million prevalent cases, 1.3 million deaths among HIV-negative people and 0.38 million deaths among HIV-positive people. It is estimated that among TB patients notified in 2009, 250 000 had multidrug resistant TB (MDR-TB). The situation is worsening because of the increasing incidence of single-drug resistant, multidrug resistant and extensively drug-resistant (XDR-TB) TB (WHO report, 2010; The Stop TB Partnership, 2010; Velayati et al., 2009). This chapter deals with pyrazinecarboxamide (amide of pyrazinecarboxylic acid, PZA, see Fig. 1, structure I) and its derivatives. PZA was introduced to clinical practice in 1952, and it has been among the first-line antituberculosis (anti-TB) drugs (Kushner et al., 1952; Solotorovsky, 1952; Steele & Des Prez, 1988).

Pyrazinecarboxylic Acid Derivatives with Antimycobacterial Activity