Scapecchi Serena, Martini Elisabetta, Manetti Dina, Ghelardini Carla, Martelli Cecilia, Dei Silvia, Galeotti Nicoletta, Guandalini Luca, Novella Romanelli Maria, Teodori Elisabetta
Dipartimento di Scienze Farmaceutiche, Università di Firenze, Via G. Capponi 9, I-50121, Firenze, Italy.
Bioorg Med Chem. 2004 Jan 2;12(1):71-85. doi: 10.1016/j.bmc.2003.10.025.
Structure-activity relationships on two novel potent cognition enhancing drugs, unifiram (DM232, 1) and sunifiram (DM235, 2), are reported. Although none of the compounds synthesised reached the potency of the parent drugs, some fairly active compounds have been identified that may represent new leads to develop other cognition enhancing drugs. An interesting result of this research is the identification of two compounds (13 and 14) that are endowed with amnesing activity (the opposite of the activity of the original molecules) and are nearly equipotent to scopolamine. Moreover, two compounds of the series (5 and 6) were found endowed with analgesic activity on a rat model of neuropathic pain at the dose of 1 mg/kg.
报道了两种新型强效认知增强药物——unifiram（DM232，1）和sunifiram（DM235，2）的构效关系。尽管合成的化合物均未达到母体药物的效力，但已鉴定出一些活性相当的化合物，它们可能代表开发其他认知增强药物的新先导物。该研究的一个有趣结果是鉴定出两种具有遗忘活性（与原始分子的活性相反）且效力与东莨菪碱相近的化合物（13和14）。此外，该系列中的两种化合物（5和6）在1 mg/kg剂量下对大鼠神经性疼痛模型具有镇痛活性。
