Ukrainets Igor V, Petrushova Lidiya A, Sidorenko Lyudmila V, Davidenko Alexandra A, Duchenko Marina A
Department of Pharmaceutical Chemistry, National University of Pharmacy, 53 Pushkinska St., Kharkiv 61002, Ukraine.
Department of Pharmaceutical Chemistry, N. I. Pirogov Vinnitsa National Medical University, 56 Pirogov St., Vinnitsa 21018, Ukraine.
Sci Pharm. 2016 Apr 18;84(3):497-506. doi: 10.3390/scipharm84030497.
In continuing the search for new analgesics among derivatives of 2,1-benzothiazines, a series of corresponding toluidides and xylidides of 4-hydroxy-2,2-dioxo-1-2λ⁶,1-benzothiazine-3-carboxylic acid has been synthesized by the reaction of ethyl 4-hydroxy-2,2-dioxo-1-2λ⁶,1-benzothiazine-3-carboxylate with equimolar amounts of mono- and dimethyl-substituted anilides in boiling dry xylene. Their structure has been confirmed by the data of elemental analysis, nuclear magnetic resonance (NMR) spectroscopy (¹Н and С), as well as mass spectrometry. All compounds obtained were subjected to pharmacological screening to identify their analgesic properties. Testing was carried out in male rats using the standard model of the thermal tail-flick (tail immersion test) in parallel and in comparison with the structurally related drugs meloxicam and piroxicam. Among the substances studied, highly active oral painkillers have been found; they exceed the analgesic effect of the reference drugs using the same dose. Interesting structural and biological regularities have been described; they will be useful in further research on creating promising new analgesics based on 4-hydroxy-2,2-dioxo-1-2λ⁶,1-benzothiazine-3-carboxamides.
在继续从2,1-苯并噻嗪衍生物中寻找新型镇痛药的过程中，通过使4-羟基-2,2-二氧代-1-2λ⁶,1-苯并噻嗪-3-羧酸乙酯与等摩尔量的单甲基和二甲基取代的苯胺在沸腾的无水二甲苯中反应，合成了一系列相应的4-羟基-2,2-二氧代-1-2λ⁶,1-苯并噻嗪-3-羧酸甲苯胺盐和二甲苯胺盐。通过元素分析、核磁共振（NMR）光谱（¹H和C）以及质谱数据确认了它们的结构。对所得到的所有化合物进行了药理筛选，以确定其镇痛特性。使用热甩尾（尾部浸入试验）标准模型在雄性大鼠中进行测试，并与结构相关药物美洛昔康和吡罗昔康平行比较。在所研究的物质中，发现了高活性口服止痛药；它们在相同剂量下超过了参比药物的镇痛效果。已经描述了有趣的结构和生物学规律；它们将有助于基于4-羟基-2,2-二氧代-1-2λ⁶,1-苯并噻嗪-3-羧酰胺开发有前景的新型镇痛药的进一步研究。
