Stavropoulou Konstantina, Kaimaki Angeliki, Nikolaou Maria, Brown Ana K, Tsotinis Andrew, Taylor Martin C, Kelly John M, Papanastasiou Ioannis P
Division of Pharmaceutical Chemistry, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens Panepistimiopoli-Zografou 157 71 Athens Greece
Department of Chemistry, University of San Francisco 2130 Fulton Street San Francisco California CA 94117 USA.
RSC Med Chem. 2025 Apr 25. doi: 10.1039/d5md00135h.
In this work, we describe the design, synthesis and evaluation of novel functionalised 1-(4-phenyl)adamantane and 1-(4-phenoxyphenyl)adamantane derivatives. Based on previous findings, we incorporated a phenyl ring between the adamantane core and the pharmacophoric side chain to enhance the activity and selectivity index (SI). The aromatic imidazolines 1a-d and the linear amidines 2a,b and 3a,b exhibited notable activity against . The 1-(4-phenyl)adamantane 1-(4-phenoxyphenyl)adamantane core was further functionalized with the aminoguanylhydrazone and thiosemicarbazone moieties. 2-[()-4-(1-adamantyl)benzylidene]hydrazine-1-carbothioamide 4c emerged as a promising trypanocidal agent with an EC of 0.16 μM and an SI of 17. Future studies will focus on optimizing the length and the distance of the side chain between the aromatic ring and the chromophores to further enhance the activity and selectivity of these molecules.
在本研究中，我们描述了新型功能化的1-(4-苯基)金刚烷和1-(4-苯氧基苯基)金刚烷衍生物的设计、合成及评估。基于先前的研究结果，我们在金刚烷核心与药效基团侧链之间引入一个苯环，以提高活性和选择性指数（SI）。芳香咪唑啉1a-d以及线性脒2a、b和3a、b对……表现出显著活性。1-(4-苯基)金刚烷和1-(4-苯氧基苯基)金刚烷核心进一步用氨基胍腙和硫代氨基脲部分进行功能化。2-[()-4-(1-金刚烷基)亚苄基]肼-1-碳硫酰胺4c成为一种有前景的杀锥虫剂，其半数有效浓度（EC）为0.16 μM，选择性指数（SI）为17。未来的研究将集中于优化芳香环与发色团之间侧链的长度和距离，以进一步提高这些分子的活性和选择性。
