Stewart D Jeremy, Fahmy Hesham, Roth Bryan L, Yan Feng, Zjawiony Jordan K
Department of Pharmacognosy and National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, Mississippi 38677-1848, USA.
Arzneimittelforschung. 2006;56(4):269-75. doi: 10.1055/s-0031-1296720.
Salvinorin A ((2S,4aR,6aR,7R,9S,10aS, 10bR)-2H-naphtho[2,1-c]pyran-7-carboxylic acid, 9-(acetyloxy)-2-(3-furanyl)dodecahydro-6a,10b-dimethyl-4,10-dioxo methyl ester, 1, CAS 83729-01-5) has been shown to bind with high affinity and selectivity to the kappa-opioid receptor (KOR) as an agonist. Bioisosteres of 1 were developed and biologically evaluated in binding and functional assays. The C-2 thioacetate isoster produced comparable activity to 1, but nitrogen substitution had a diminishing effect. Intermediates, which lack a beta-carbonyl at C-2, displayed moderate affinity. The derivatives were tested against all opioid subtypes and were selective towards KOR.
Salvinorin A（(2S,4aR,6aR,7R,9S,10aS,10bR)-2H-萘并[2,1-c]吡喃-7-羧酸，9-(乙酰氧基)-2-(3-呋喃基)十二氢-6a,10b-二甲基-4,10-二氧代甲酯，1，CAS 83729-01-5）已被证明作为激动剂与κ-阿片受体（KOR）具有高亲和力和选择性结合。开发了1的生物电子等排体，并在结合和功能测定中进行了生物学评估。C-2硫代乙酸酯等排体产生了与1相当的活性，但氮取代有减弱作用。在C-2处缺乏β-羰基的中间体表现出中等亲和力。对这些衍生物针对所有阿片类亚型进行了测试，并且它们对KOR具有选择性。
