title: Highly active potential antituberculotics: 3-(4-alkylphenyl)-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones and 3-(4-alkylphenyl)-2H-1,3-benzoxazine-2,4(3H)-dihiones substituted in ring-B by halogen.
abstract: A series of 6-chloro-3-(4-alkylphenyl)-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones, 7-chloro-3-(4-alkylphenyl)-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones, 6-bromo-3-(4-alkylphenyl)-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones, 6,8-dibromo-3-(4-alkylphenyl)-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones, 6-chloro-3-(4-alkylphenyl)-2H-1,3-benzoxazine-2,4(3H)-dithiones, 7-chloro-3-(4-alkylphenyl)-2H-1,3-benzoxazine-2,4(3H)-dithiones, 6-bromo-3-(4-alkylphenyl)-2H-1,3-benzoxazine-2,4(3H)-dithiones and 6,8-dibromo-3-(4-alkylphenyl)-2H-1,3-benzoxazine-2,4(3H)-dithiones was synthesized. The compounds exhibited in-vitro activity against Mycobacterium tuberculosis, M. kansasii (two strains), and M. avium. 6-bromo-3-(4-propylphenyl)-4-thioxo-2H-1,3-benzoxazin-2(3H)-one and 6-bromo-3-(4-propylphenyl)-2H-1,3-benzoxazin-2,4(3H)-dithione are the most active compounds against M. tuberculosis. The activity is similar to isoniazid (INH). The compounds under study have a broad spectrum of activity against potential pathogenic strains. The replacement of the oxo group by thioxo group of 3-(4-alkylphenyl)-2H-1,3-benzoxazine-2,4(3H)-diones often led to an improvement in the antimycobacterial activity against M. tuberculosis.
authors.affiliation: Department of Inorganic and Organic Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Hradec Králové, Czech Republic. waisser@faf.cuni.cz
authors.forename: Karel
authors.initials: K
authors.lastname: Waisser
authors.forename: Josef
authors.initials: J
authors.lastname: Matyk
authors.forename: Jirí
authors.initials: J
authors.lastname: Kunes
authors.forename: Rafael
authors.initials: R
authors.lastname: Dolezal
authors.forename: Jarmila
authors.initials: J
authors.lastname: Kaustová
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Dahse
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D048588:Benzoxazines / Q000138:chemical synthesis* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000995:Antitubercular Agents; D048588:Benzoxazines