Ukrainets Igor V, Petrushova Lidiya A, Shishkina Svitlana V, Sidorenko Lyudmila V, Sim Galina, Kryvanych Olga V
Department of Pharmaceutical Chemistry, National University of Pharmacy, 53 Pushkinska St., Kharkiv 61002, Ukraine.
STC "Institute for Single Crystals", National Academy of Sciences of Ukraine, 60 Nauki Ave., Kharkiv 61001, Ukraine.
Sci Pharm. 2016 Jun 17;84(3):523-535. doi: 10.3390/scipharm84030523.
As potential new analgesics, the corresponding 4-hydroxy-2,2-dioxo-1-2λ⁶,1-benzothiazine-3-carboxanilides have been obtained by amidation of ethyl 4-hydroxy-2,2-dioxo-1-2λ⁶,1-benzothiazine-3-carboxylate with aniline and its halogenated analogsin boiling dry xylene. The peculiarities of the mass and nuclear magnetic resonance (¹Н and С) spectra of the synthesized compounds are discussed. Using X-ray diffraction analysis, the ability of the compounds to form stable solvates with ,-dimethylformamide has been shown on the example of 4-bromo-substituted derivative. It should be further studied to be considered in their crystallization. According to the results of the pharmacological testing conducted on the model of the thermal tail-flick (tail immersion test) among halogen-substituted 4-hydroxy-2,2-dioxo-1-2λ⁶,1-benzothiazine-3-carboxanilides, substances which are considerably superior to meloxicam and piroxicam by their analgesic activity have been found. They are of interest for further profound studies.
作为潜在的新型镇痛药，通过在沸腾的干燥二甲苯中将4-羟基-2,2-二氧代-1,2λ⁶,1-苯并噻嗪-3-羧酸乙酯与苯胺及其卤代类似物进行酰胺化反应，得到了相应的4-羟基-2,2-二氧代-1,2λ⁶,1-苯并噻嗪-3-甲酰苯胺。讨论了合成化合物的质谱和核磁共振（¹Н和С）光谱的特点。以4-溴取代衍生物为例，通过X射线衍射分析表明了这些化合物与N,N-二甲基甲酰胺形成稳定溶剂化物的能力。在其结晶过程中应进一步研究加以考虑。根据在热甩尾（尾部浸入试验）模型上进行的药理测试结果，在卤代4-羟基-2,2-二氧代-1,2λ⁶,1-苯并噻嗪-3-甲酰苯胺中，发现了镇痛活性明显优于美洛昔康和吡罗昔康的物质。它们值得进一步深入研究。
