Paglietti G, Sanna P, Carta A, Sparatore F, Vazzana I, Peana A, Satta M
Istituto di Chimica Farmaceutica e Tossicologica, Università di Sassari.
Farmaco. 1994 Nov;40(11):693-702.
In order to investigate the influence of structural modifications on the high choleretic activity of 3-(benzotriazol-1-yl)butanoic acid, a set of new benzotriazolyl alkanoic and alkenoic acids was prepared and, together with some other acids previously described, tested in rats by i.v. administration at the dose of 0.5 mmol/kg. Most of the tested compounds exhibited a good choleretic activity comparable with or higher than that of the model acid and of dehydrocholic acid (+56% mean increase of bile volume during 4 hours). Influence of nature and position of substituents was shown in some cases: a moderate decrease of activity was observed for methoxy derivatives and for the introduction of a methyl group in position 6, while a trifluoromethyl group in the same position enhanced the activity (10). Activity was maintained after the introduction of unsaturation in the chain (17,18), but was completely suppressed when unsaturation was associated with a shortening of the alkenoic chain (16). Moving the butanoic chain from position 1 to position 2 in the case of the nitroderivative (15) produced a striking increase of activity (from +42 to +118 mean variation of bile volume during 4 hours), while the same change in the unsubstituted acid 1 abolished the activity.
为了研究结构修饰对3-(苯并三唑-1-基)丁酸高利胆活性的影响，制备了一组新的苯并三唑基链烷酸和链烯酸，并与先前描述的其他一些酸一起，以0.5 mmol/kg的剂量通过静脉注射在大鼠中进行测试。大多数测试化合物表现出良好的利胆活性，与模型酸和去氢胆酸相当或更高（4小时内胆汁体积平均增加56%）。在某些情况下显示了取代基的性质和位置的影响：甲氧基衍生物以及在6位引入甲基时观察到活性适度降低，而在相同位置的三氟甲基增强了活性(10)。在链中引入不饱和键后活性得以保持(17,18)，但当不饱和键与链烯酸链缩短相关联时活性完全被抑制(16)。对于硝基衍生物(15)，将丁酸链从1位移至2位时活性显著增加（4小时内胆汁体积平均变化从+42增至+118），而未取代的酸1中的相同变化则消除了活性。
