Malinka W, Swiatek P, Filipek B, Sapa J, Jezierska A, Koll A
Department of Chemistry of Drugs, Wrocław Medical University, ul. Tamka 1, 50-137 Wrocław, Poland.
Farmaco. 2005 Nov-Dec;60(11-12):961-8. doi: 10.1016/j.farmac.2005.08.005. Epub 2005 Oct 11.
A series of new 4-arylpiperazine derivatives of isothiazolopyridine of Mannich base type and their non-4-arylpiperazine analogues (3 and 4) were synthesized and assayed as potential analgesic agents. Pharmacological assay demonstrated that all the compounds prepared, without exception, displayed significant activity in the mouse writhing assay. The analgesic action, expressed as ED50, was found to be 2-10 times more potent than that of acetylsalicylic acid and 1.5-10 times weaker than that of morphine, these being used as standards. The toxicities (LD50) of the investigated derivatives varied and ranged from 250 to 2000 mg/kg. Additionally, the computational investigations were performed in order to find correlation between molecular structure and biological effects (toxicity, analgesic action) of discussed compounds. Useful model was found for toxicity assessment.
合成了一系列曼尼希碱型异噻唑并吡啶的新型4-芳基哌嗪衍生物及其非4-芳基哌嗪类似物（3和4），并作为潜在的镇痛剂进行了测定。药理试验表明，所制备的所有化合物无一例外在小鼠扭体试验中均表现出显著活性。以ED50表示的镇痛作用比乙酰水杨酸强2至10倍，比吗啡弱1.5至10倍，这些用作标准。所研究衍生物的毒性（LD50）各不相同，范围为250至2000 mg/kg。此外，进行了计算研究，以找出所讨论化合物的分子结构与生物效应（毒性、镇痛作用）之间的相关性。发现了用于毒性评估的有用模型。
