Heilman W P, Heilman R D, Scozzie J A, Wayner R J, Gullo J M, Ariyan Z S
J Pharm Sci. 1980 Mar;69(3):282-7. doi: 10.1002/jps.2600690310.
To develop nonacidic, nonsteroidal anti-inflammatory agents without GI complications, a series of asymmetric triazines was synthesized and evaluated for anti-inflammatory efficacy in the carrageenan-induced pedal edema assay. Toxicity was estimated by determination of approximate LD50 values in mice. Twenty-five compounds possessed activity comparable to the standard, indomethacin. Thirteen of the 25 compounds were selected for dose-response evaluation in the carrageenan assay based on their relative toxicity and anti-inflammatory activity. Neurotoxicity of the 13 triazines was estimated by determination of NTD50 values in mice. Five of the 13 compounds tested in the dose-response assay were active in terms of anti-inflammatory efficacy (ED50 values) and lack of overt neurotoxicity (NTD50 values) when compared to indomethacin. To determine the effect of these five developmental triazines on chronic inflammation, they were evaluated in the adjuvant-induced polyarthritis assay. One was comparable to indomethacin in reducing adjuvant-induced inflammation in this assay.
为了开发无胃肠道并发症的非酸性、非甾体类抗炎药，合成了一系列不对称三嗪，并在角叉菜胶诱导的足爪肿胀试验中评估其抗炎效果。通过测定小鼠的近似半数致死量（LD50）值来评估毒性。25种化合物具有与标准药物吲哚美辛相当的活性。基于它们的相对毒性和抗炎活性，从这25种化合物中选择了13种进行角叉菜胶试验中的剂量反应评估。通过测定小鼠的半数神经毒性剂量（NTD50）值来评估这13种三嗪的神经毒性。与吲哚美辛相比，在剂量反应试验中测试的13种化合物中有5种在抗炎效果（半数有效量[ED50]值）和无明显神经毒性（NTD50值）方面具有活性。为了确定这5种处于研发阶段的三嗪对慢性炎症的影响，在佐剂诱导的多关节炎试验中对它们进行了评估。在该试验中，有一种在减轻佐剂诱导的炎症方面与吲哚美辛相当。
