Weinstock J, Ladd D L, Wilson J W, Brush C K, Yim N C, Gallagher G, McCarthy M E, Silvestri J, Sarau H M, Flaim K E
J Med Chem. 1986 Nov;29(11):2315-25. doi: 10.1021/jm00161a029.
Certain 6-halo-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines were found to be potent D-1 dopamine agonists. The 1-(4-hydroxyphenyl) analogues did not have central nervous system activity because their high polarity inhibited entry into the brain. However, these compounds were potent renal vasodilators. Fenoldopam, the 6-chloro analogue, is an especially significant member of the series, and its synthesis, pharmacology, and clinical properties have been studied extensively. The 6-methyl and 6-iodo congeners were potent renal vasodilators, but nonpotent partial D-1 agonists as measured by stimulation of rat caudate adenylate cyclase. A possible rationalization suggests different receptor reserves for these activities. The 9-substituted benzazepines were either inactive or of low potency as dopamine agonists, while the N-methyl analogues had significant antagonist potency as measured by inhibition of dopamine stimulation of rat caudate adenylate cyclase.
某些6-卤代-1-苯基-2,3,4,5-四氢-1H-3-苯并氮杂䓬被发现是强效的D-1多巴胺激动剂。1-(4-羟基苯基)类似物没有中枢神经系统活性，因为它们的高极性抑制了其进入大脑。然而，这些化合物是强效的肾血管扩张剂。非诺多泮，即6-氯类似物，是该系列中特别重要的一个成员，并且对其合成、药理学和临床特性进行了广泛研究。6-甲基和6-碘同系物是强效的肾血管扩张剂，但通过刺激大鼠尾状核腺苷酸环化酶测定，它们是低效的部分D-1激动剂。一种可能的解释表明这些活性存在不同的受体储备。9-取代的苯并氮杂䓬作为多巴胺激动剂要么无活性要么活性低，而N-甲基类似物通过抑制多巴胺对大鼠尾状核腺苷酸环化酶的刺激测定具有显著的拮抗活性。
