Syntheses and biological evaluation of 2- and 9-aminobenzonorbornenes as conformationally rigid analogs of amphetamines.
Syntheses and biological evaluation of 2- and 9-aminobenzonorbornenes as conformationally rigid analogs of amphetamines.
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作为安非他明构象刚性类似物的 2- 和 9- 氨基苯并降冰片烯的合成和生物学评价。
DOI：
10.1002/jps.2600700222
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发表时间：
1981
影响因子：
3.8
通讯作者：
J. E. Gearienx
中科院分区：
文献类型：
--
作者：
L. E. Wood;R. Daniels;Ludwig Bauer;J. E. Gearienx
制备了2-和9-氨基苯冰片烯的异构体作为苯丙胺的刚性类似物，并用于研究间接作用的交感神经递质的构象要求。在这一系列异构胺中，外氧-2和抗-9异构体非常类似于苯丙胺的完全扩展构象。另外两个胺，endo-2和syn-9异构体，在构象上类似于苯丙胺的折叠构象。类似安非他明扩展构象的异构体增加了小鼠的自发运动活动，而类似折叠形式的异构体对运动活动要么减少，要么没有影响。还研究了这些化合物加速去甲肾上腺素从离体灌流兔心房的囊泡和非囊泡储存部位流出的能力；分别使用α-甲基-对酪氨酸和利血平处理的兔。苯丙胺和氨基苯冰片的exo-2和抗9异构体在所研究的浓度下可加速去甲肾上腺素从任一室流出，而endo-2和syn-9异构体则只促进非囊泡室的去甲肾上腺素外流。芬氟拉明和哌醋甲酯也被用来研究它们加速外排的能力。芬氟拉明和哌甲酸甲酯与苯丙胺折叠构象的氨基苯冰片相似，因为它们能够加速非囊泡储存的外流。然而，芬氟拉明也类似于苯丙胺和与苯丙胺扩展构象相对应的氨基苯冰片，其加速从囊泡储存部位外流的能力。对哌甲酸甲酯的反应类似于苯丙胺的折叠构象的氨基苯冰片。
Isomers of the 2- and 9-aminobenzonorbornenes were prepared as rigid analogs of amphetamine and were employed to study the conformational requirements of indirectly acting sympathomimetic agents. Of this series of isomeric amines, the exo-2 and anti-9 isomers closely resemble the fully extended conformation of amphetamine. The other two amines, the endo-2 and syn-9 isomers, conformationally resemble the folded conformation of amphetamine. The isomers that resemble the extended conformation of amphetamine increased the spontaneous motor activity in mice while the isomers resembling the folded form either decreased or had no effect on motor activity. These compounds also were studied for their ability to accelerate the efflux of tritiated norepinephrine from vesicular and nonvesicular storage sites of isolated perfused rabbit atria; either alpha-methyl-p-tyrosine- or reserpine-pretreated rabbits were used. Amphetamine and the exo-2 and anti-9 isomers of aminobenzonorbornene could accelerate norepinephrine efflux from either compartment while the endo-2 and syn-9 isomers could accelerate the efflux from only the nonvesicular compartment at the concentrations studied. Fenfluramine and methylphenidate also were studied for their ability to accelerate efflux. Fenfluramine and methylphenidate resembled the aminobenzonorbornenes that correspond to the folded conformation of amphetamine in their ability to accelerate the efflux from nonvesicular storage. However, fenfluramine also resembled amphetamine and the aminobenzonorbornenes corresponding to the extended conformation of amphetamine in its ability to accelerate efflux from vesicular storage sites. The response to methylphenidate was similar to that of the aminobenzonorbornenes resembling the folded conformation of amphetamine.