3-苯基-4(1H)喹啉酮羟基衍生物的合成及其抗骨质疏松活性

SYNTHESIS AND ANTIOSTEOPOROSIS ACTIVITY OF 3-PHENYL-4(1H) QUINOLINONE DERIVATIVES

目的 设计并合成 7 羟基 3 (取代 )苯基 4 (1H)喹啉酮化合物及其相应的 5 羟基 3 (取代 )苯基 4 (1H)喹啉酮化合物并考察其抗骨质疏松活性。方法 以间氨基酚为原料 ,选择改良的Gould Jacobs反应路线同时合成 7 羟基 3 (取代 )苯基 4 (1H)喹啉酮 4个 (A1～ 4)及其相应的 5 羟基 3 (取代 )苯基 4 (1H)喹啉酮 4个 (B1～ 4) ,通过骨细胞筛选实验以及羟磷灰石吸附实验分别考察其促骨形成作用和趋骨性。结果 共合成了新化合物 8个 (A1～ 4,B1～ 4) ,其结构经IR ,MS ,1 HNMR和元素分析确证。骨细胞筛选实验结果表明 ,B3 有促骨形成作用 ,但作用弱于芒柄花黄素 ;羟磷灰石吸附实验结果表明 ,羟磷灰石对B1 ,B2 和B4有一定的吸附 ,其中对B1 和B2 的吸附作用强于四环素。结论5 羟基 3 (取代 )苯基 4 (1H)喹啉酮化合物有促骨形成作用并具有一定的趋骨活性。

AIM To design and synthesize 7-hydroxy-3-(substituted) phenyl-4(1H) quinolinone and 5-hydroxy-3-(substituted) phenyl-4(1H) quinolinone and to study the antiosteoporosis activity of these compounds. METHODS The compounds of 7-hydroxy and 5-hydroxy were prepared simultaneously by improved Gould-Jacobs reaction and resorcin was used as starting material. Eight compounds (A 1～4, B 1～4) were synthesized and their chemical structures were determined by IR, MS, 1HNMR and elemental analysis. Their osteoplastic activity was evaluated by the absorptive test to Ca 2+ of hydroxyapatite crystal. RESULTS Compounds (A 1～4,B 1～4) are new compounds. Compounds B 1 and B 2 showed antiosteoporosis activities and was stronger than the control drug of tetracycline. CONCLUSION Compounds B 1 and B 2 are worthy to be intensively studied.