Design, synthesis, and evaluation of 4-(substituted)phenyl-2-thioxo-3,4-dihydro-1H-chromino[4,3-d]pyrimidin-5-one and 4-(substituted)phenyl-3,4-dihydro-1H-chromino[4, 3-d]pyrimidine-2,5-dione analogs as antitubercular agents

摘要

Tuberculosis (TB) is the world's second leading cause of death as an infectious disease after acquired immune deficiency syndrome (AIDS) (Jindani et al, 1980). The current treatment of TB is an exceedingly lengthy therapy spanning 6-9 months (Jarvis and Lamb, 1998), which makes patient compliance difficult and is a frequent source of drug-resistant strains (Marinis and Legakis, 1985; Cohen and Tartasky, 1997). The need for a lengthy treatment is a consequence of the presence of a population of persistent bacilli that are not effectively eliminated by the current TB drugs (Jarvis and Lamb, 1998; Kawakami et al, 2000). Given the difficulties in successful completion of treatment and the increasing incidences of drug-resistant strains, additional targets for development of new drags need to be researched (Krajewski et al, 2005). Special efforts are needed to find and develop new leads against the many validated TB targets. New leads with novel modes of action are urgently required to combat the drag-resistant strains of M. tuberculosis and stop the emerging TB pandemic (Miyakawa et al, 1996).