Synthesis, Binding Affinity, and Functional In Vitro Activity of 3-Benzylaminomorphinan and 3-Benzylaminomorphine Ligands at Opioid Receptors
作者： John L. Neumeyer , Bin Zhang , Tangzhi Zhang , Anna W. Sromek , Brian I. Knapp
DOI: 10.1021/JM3001086
关键词:
摘要: A series of 3-benzylamino-3-desoxymorphinan (I) and 3-benzylamino-3-desoxymorphine (II) derivatives were synthesized evaluated for their binding affinities, functional activity data are presented at MOR, KOR, DOR. Some these ligands found to have high affinity MOR KOR displayed increased selectivity over DOR compared butorphan or cyclorphan. The most selective compound, 3-(3'-hydroxybenzyl)amino-17-methylmorphinan (4g) (24-fold 1700-fold DOR) also showed (0.42 nM MOR) was a full agonist in the [(35)S]GTPγS assay. 2-(3'-Hydroxybenzyl)amino-17-cyclopropylmethylmorphinan (17) be KOR-selective ligand (150-fold >10000-fold DORs). Most 3-benzylaminomorphinan partial agonists
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