Relationships between the chemical structure of substances and their antimycobacterial activity against atypical strains. Part 18. 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-diones and isosteric 3-phenylquinazoline-2,4 (1H, 3H)-diones

A series of 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-diones 2 and 3-phenylquinaz oline-2, 4(1H,3H)-diones 5 substituted on the phenyl rings were synthesized . The target compounds as well as the intermediates were tested against Myc obacterium tuberculosis, M. kanasii, and M. avium. The replacement of the o xygen atom by nitrogen resulted in a decrease or loss of antimycobacterial activity. 2-[(Ethoxycarbonyl)amino]benzanilides 4 appeared to be inactive. Salicylanilides 1 and 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-diones 2 exhibit significant activity against both M. tuberculosis and nontuberculous mycoba cteria (the MICs within thf range of 4-250 mu mol/l for all compounds). The antimycobacterial activity of the compounds increases with increasing both electron-withdrawing properties and hydrophobicity of the substituent(s) o n the phenyl moiety. The antimycobacterial profile of the compounds was ana lyzed according to the criteria based on vector algebra, such as cosine coe fficients. Moreover, salicylanilides 1 exhibit activity against other micro organisms tested by the agar diffusion method.