Asymmetric syntheses, opioid receptor affinities, and antinociceptive effects of 8-amino-5,9-methanobenzocyclooctenes, a new class of structural analogues of the morphine alkaloids.
Asymmetric syntheses, opioid receptor affinities, and antinociceptive effects of 8-amino-5,9-methanobenzocyclooctenes, a new class of structural analogues of the morphine alkaloids.
复制标题
8-氨基-5,9-亚甲基苯并环辛烯（一类新的吗啡生物碱结构类似物）的不对称合成、阿片受体亲和力和镇痛作用。
DOI：
10.1021/jm950817g
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发表时间：
1996
影响因子：
7.3
通讯作者：
Bidlack,JM
中科院分区：
文献类型：
--
作者：
Schultz,AG;Wang,A;Alva,C;Sebastian,A;Glick,SD;Deecher,DC;Bidlack,JM
Several 8-amino-5,9-methanobenzocyclooctenes have been prepared by asymmetric organic synthesis techniques. Opioid receptor affinity studies have revealed the virtual absence of enantioselectivity for receptor binding, particularly at the μ-receptor, for the (+)-3a−fand the (−)-3a−fseries. It is noteworthy that inversion of configuration at the nitrogen-bearing carbon atom [(5S,8S,9S)-8-amino-3-hydroxy-5,9-methano-9-(methoxymethyl)-5-methylbenzocyclooctene, (+)-3avs (5S,8S,9R)-8-amino-3-hydroxy-5,9-methano-9-(methoxymethyl)-5-methylbenzocyclooctene, (dl)-22] resulted in a >10-fold increase in κ-receptor affinity. Antinociceptive studies demonstrated that (dl)-22was a full κ-agonist while (+)-3aand (−)-3adid not possess κ-activity. Although both (dl)-22and (+)-3a/(−)-3ahad high affinity for the μ-receptor, these compounds did not act as high-affinity agonists or antagonists at this receptor.
