Effect of a 6-cyano substituent in 14-oxygenated N-methylmorphinans on opioid receptor binding and antinociceptive potency.
Effect of a 6-cyano substituent in 14-oxygenated N-methylmorphinans on opioid receptor binding and antinociceptive potency.
复制标题
14-氧化 N-甲基吗啡喃中的 6-氰基取代基对阿片受体结合和镇痛效力的影响。
DOI：
10.1021/jm0580205
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发表时间：
2005
影响因子：
7.3
通讯作者：
Schmidhammer,Helmut
中科院分区：
文献类型：
--
作者：
Spetea,Mariana;Greiner,Elisabeth;Aceto,MarioD;Harris,LouisS;Coop,Andrew;Schmidhammer,Helmut
在持续的努力中，在吗啡烷中寻找新的取代模式，以产生强的抗伤害感受，同时诱导更少的副作用，合成了4，5-氧桥开放的6-氰基取代的N-甲基吗啡烷（1−3）。所有化合物在低纳摩尔范围内对μ阿片受体表现出高亲和力，并降低与δ和κ受体的相互作用，因此具有μ选择性。当在体内测试时，6-氰基吗啡烷作为有效的抗伤害剂，其活性或等效于其6-酮类似物4 −6。
In a continued effort to find new substitution patterns in morphinans that would produce strong antinociception while inducing lesser side effects, 4,5-oxygen bridge-opened 6-cyano-substitutedN-methylmorphinans (1−3) were synthesized. All compounds showed high affinities in the low nanomolar range to the μ opioid receptor and decreased interaction with δ and κ receptors, thus being μ selective. When tested in vivo,the 6-cyanomorphinanas acted as potent antinociceptive agents which were either more active or equipotent to their 6-keto analogues4−6.