Angeli P, Brasili L, Brancia E, Giardinà D, Quaglia W, Melchiorre C
J Med Chem. 1985 Nov;28(11):1643-7. doi: 10.1021/jm00149a017.
Several N,N''-(dithiodi-2,1-ethanediyl)bis[N'-(arylmethyl)-1,6-hex anediamines] were prepared and evaluated for their blocking activity on postsynaptic alpha 1-adrenoreceptors in the isolated rat vas deferens. The results were compared with those obtained for benextramine (1). N,N''-(Dithiodi-2,1-ethanediyl)bis[N'-(pyrrol-2-ylmethyl)-1, 6 -hexanediamine] (pyrextramine, 29) was the most potent among the tetraamine disulfides investigated. Thus, it was selected for further pharmacological evaluation to assess its receptor specificity. At a concentration of 10 microM it did not affect the responses elicited by 5-hydroxytryptamine and histamine in guinea pig ileum and by isoproterenol in guinea pig atria and tracheal chain. Furthermore, it was more specific than benextramine (1) toward the muscarinic receptor, being significantly less potent in inhibiting the carbachol-induced response in rat jejunum. These results show that pyrextramine (29) is an irreversible alpha-blocking agent that is more potent and specific than benextramine (1). In conclusion, 29 may be a useful tool in the elucidation and characterization of the peripheral alpha 1-adrenoreceptor.
合成了几种N,N''-(二硫代二-2,1-亚乙基)双[N'-(芳基甲基)-1,6-己二胺]，并对其在离体大鼠输精管中对突触后α1-肾上腺素能受体的阻断活性进行了评估。将结果与苯苄胺(1)的结果进行了比较。在研究的四胺二硫化物中，N,N''-(二硫代二-2,1-亚乙基)双N'-(吡咯-2-基甲基)-1,6-己二胺活性最强。因此，选择它进行进一步的药理学评估，以评估其受体特异性。在10微摩尔浓度下，它不影响5-羟色胺和组胺在豚鼠回肠中以及异丙肾上腺素在豚鼠心房和气管链中引起的反应。此外，它对毒蕈碱受体的特异性比苯苄胺(1)更高，在抑制大鼠空肠中卡巴胆碱诱导的反应方面效力明显更低。这些结果表明，吡咯苄胺(29)是一种不可逆的α阻断剂，比苯苄胺(1)更有效且更具特异性。总之，29可能是阐明和表征外周α1-肾上腺素能受体的有用工具。
