Waisser Karel, Matyk Josef, Kunes Jirí, Dolezal Rafael, Kaustová Jarmila, Dahse Hans-Martin
Department of Inorganic and Organic Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Hradec Králové, Czech Republic.
Arch Pharm (Weinheim). 2008 Dec;341(12):800-3. doi: 10.1002/ardp.200800004.
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.
合成了一系列6-氯-3-(4-烷基苯基)-4-硫代-2H-1,3-苯并恶嗪-2(3H)-酮、7-氯-3-(4-烷基苯基)-4-硫代-2H-1,3-苯并恶嗪-2(3H)-酮、6-溴-3-(4-烷基苯基)-4-硫代-2H-1,3-苯并恶嗪-2(3H)-酮、6,8-二溴-3-(4-烷基苯基)-4-硫代-2H-1,3-苯并恶嗪-2(3H)-酮、6-氯-3-(4-烷基苯基)-2H-1,3-苯并恶嗪-2,4(3H)-二硫酮、7-氯-3-(4-烷基苯基)-2H-1,3-苯并恶嗪-2,4(3H)-二硫酮、6-溴-3-(4-烷基苯基)-2H-1,3-苯并恶嗪-2,4(3H)-二硫酮和6,8-二溴-3-(4-烷基苯基)-2H-1,3-苯并恶嗪-2,4(3H)-二硫酮。这些化合物对结核分枝杆菌、堪萨斯分枝杆菌（两株）和鸟分枝杆菌具有体外活性。6-溴-3-(4-丙基苯基)-4-硫代-2H-1,3-苯并恶嗪-2(3H)-酮和6-溴-3-(4-丙基苯基)-2H-1,3-苯并恶嗪-2,4(3H)-二硫酮是对结核分枝杆菌活性最强的化合物。其活性与异烟肼（INH）相似。所研究的化合物对潜在致病菌株具有广泛的活性。3-(4-烷基苯基)-2H-1,3-苯并恶嗪-2,4(3H)-二酮的氧代基团被硫代基团取代通常会导致对结核分枝杆菌的抗分枝杆菌活性提高。
