scientia pharmaceutica--外文学术期刊【掌桥科研】

来自 : www.zhangqiaokeyan.com/academi 发布时间：2021-03-24

作者：Winfried Wendelin;Josef Zarfl;Edith G nitzer;Dalal Abou El Ella; 刊名：Scientia pharmaceutica 1996年第3/4期 摘要：The dihydrobenzo[f]quinolin-3-amine hydroiodides 9a - e.HI were prepared from 3-chloro-N-(2-naphthyl)propionamide 10 via dihydrobenzoquinolinone 11, thione 12 and 3-methylthio-benzoquinoline hydroiodide 13.HI as intermediates. Heating of salts 13.HI with ammonia, methyl-, ethyl-, isopropyl- and tert-butylamine in butanol yielded 40 - 86% of salts 9a - e.HI. N~3-methyl compound 9b.HCl was also directly synthesized from lactam 11 and methylamine hydrochloride in the presence of phosphorus pentoxide (yield 23%). Structure, (Z,E)-isomerism, tautomerism and conformation of the hydroiodides 9a - e.HI and of N~3-methylbenzoquinolin-amine 9c were studied by one and two dimensional nmr spectroscopy including NOE-experiments. The pharmacological tests showed that amino- and isopropylamino compound 9a and d.HI do not exert remarkable effects to the cardiovascular system in rats. At the Langendorff heart 9a and 9d.HI reduced cardiac output and myocardial contractile force similar to the calcium influx-blocking drug prenylamine. The testing of methylamino analogue 9b.HI for 5-HTP potentiation and tetrabenazine antagonism pointed to strong antidepressant properties. Salts 9a,b and d.HI exert weak saluretic, but strong carbonic anhydrase inhibitor effects. Tests for hypoglycemic (9a.HI), antiarrhythmic and analgesic (9a und d.HI) and antiepileptic effects (9d.HI) revealed no significant effects. The toxicity of 9a, b and d.HI is rather high (LD_(50), mice, 50 - 80 mg/kg).