New groups of antimycobacterial agents: 6-chloro-3-phenyl-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones and 6-chloro-3-phenyl-2H-1,3-benzoxazine-2,4(3H)-dithiones.
A series of 6-chloro-3-phenyl-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones 3 and a series of 6-chloro-3-phenyl-2H-1,3-benzoxazine-2, 4(3H)-dithiones 4 were synthesized by melting 6-chloro-3-phenyl-2H-1, 3-benzoxazine-2,4(3H)-dione and its derivatives substituted on the phenyl ring 2 with tetraphosphorus decasulfide. Compounds 2c-e, 3 and 4 exhibited in vitro activity against Mycobacterium tuberculosis, M. kansasii (two strains) and M. avium better than or comparable to that of isoniazid. Replacement of the oxo group by a thioxo group at position 4 led to improvement in activity against M. tuberculosis and M. kansasii. The Free-Wilson method and procedure developed by the authors were used to analyse the structure-activity and structure-antimycobacterial profile relationships, respectively.
Waisser
K
K
Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, 500 05, Hradec Králové, Czech Republic. waisser@faf.cuni.cz
Gregor
J
J
Kubicová
L
L
Klimesová
V
V
Kunes
J
J
Machácek
M
M
Kaustová
J
J
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009161:Mycobacterium / Q000187:drug effects*; D010078:Oxazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013045:Species Specificity
D000900:Anti-Bacterial Agents; D010078:Oxazines