Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
Department of Pharmacy, "G. D'Annunzio" University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy.
Molecules. 2019 Jan 29;24(3):484. doi: 10.3390/molecules24030484.
New -acetyl/-thiocarbamoylpyrazoline derivatives were designed and synthesized in high yields to assess their inhibitory activity and selectivity against human monoamine oxidase A and B. The most important chiral compounds were separated into their single enantiomers and tested. The impact of the substituents at N1, C3 and C5 positions as well the influence of the configuration of the C5 on the biological activity were analyzed. Bulky aromatic groups at C5 were not tolerated. -Prenyloxyaryl moiety at C3 oriented the selectivity toward the B isoform. The results were also corroborated by molecular modelling studies providing new suggestions for the synthesis of privileged structures to serve as lead compounds for the treatment of mood disorders and neurodegenerative diseases.
新型 N-乙酰基/-硫代碳酰基吡唑啉衍生物被设计和高收率合成，以评估它们对人单胺氧化酶 A 和 B 的抑制活性和选择性。最重要的手性化合物被分离成它们的单一对映异构体并进行测试。分析了 N1、C3 和 C5 位置取代基以及 C5 构型对生物活性的影响。C5 上的大体积芳基基团是不能耐受的。C3 上的 -prenyloxyaryl 部分使选择性朝向 B 同工酶。分子建模研究也证实了这一结果，为合成作为治疗情绪障碍和神经退行性疾病的先导化合物的优势结构提供了新的建议。
