Simpson Denise S, Katavic Peter L, Lozama Anthony, Harding Wayne W, Parrish Damon, Deschamps Jeffrey R, Dersch Christina M, Partilla John S, Rothman Richard B, Navarro Hernan, Prisinzano Thomas E
Division of Medicinal & Natural Products Chemistry, College of Pharmacy, The University of Iowa, Iowa City, Iowa 52242, USA.
J Med Chem. 2007 Jul 26;50(15):3596-603. doi: 10.1021/jm070393d. Epub 2007 Jun 20.
Further modification of salvinorin A (1a), the major active component of Salvia divinorum, has resulted in the synthesis of novel neoclerodane diterpenes with opioid receptor affinity and activity. We report in this study that oxadiazole 11a and salvidivin A (12a), a photooxygenation product of 1a, have been identified as the first neoclerodane diterpenes with kappa antagonist activity. This indicates that additional structural modifications of 1a may lead to analogues with higher potency and utility as drug abuse medications.
对鼠尾草属植物主要活性成分Salvinorin A（1a）的进一步修饰，已导致合成出具有阿片受体亲和力和活性的新型新克罗烷二萜。我们在本研究中报告，恶二唑11a和Salvidivin A（12a），即1a的光氧化产物，已被鉴定为首批具有κ拮抗剂活性的新克罗烷二萜。这表明对1a进行额外的结构修饰可能会产生效力更高且作为药物滥用治疗药物更有用的类似物。
