一种新型吡唑并吡啶，基于对近期发现的抗疟咪唑并哒嗪核心结构进行的构效关系研究，在感染伯氏疟原虫和恶性疟原虫的小鼠模型中具有体内活性。
A Novel Pyrazolopyridine with in Vivo Activity in Plasmodium berghei- and Plasmodium falciparum-Infected Mouse Models from Structure-Activity Relationship Studies around the Core of Recently Identified Antimalarial Imidazopyridazines.
作者信息
Le Manach Claire, Paquet Tanya, Brunschwig Christel, Njoroge Mathew, Han Ze, Gonzàlez Cabrera Diego, Bashyam Sridevi, Dhinakaran Rajkumar, Taylor Dale, Reader Janette, Botha Mariette, Churchyard Alisje, Lauterbach Sonja, Coetzer Theresa L, Birkholtz Lyn-Marie, Meister Stephan, Winzeler Elizabeth A, Waterson David, Witty Michael J, Wittlin Sergio, Jiménez-Díaz María-Belén, Santos Martínez María, Ferrer Santiago, Angulo-Barturen Iñigo, Street Leslie J, Chibale Kelly
机构信息
Division of Clinical Pharmacology, Department of Medicine, University of Cape Town , Observatory 7925, South Africa.
Syngene International Ltd. , Biocon Park, Plot No. 2 & 3, Bommasandra IV Phase, Jigani Link Road, Bangalore 560099, India.
出版信息
J Med Chem. 2015 Nov 12;58(21):8713-22. doi: 10.1021/acs.jmedchem.5b01605. Epub 2015 Nov 2.
Toward improving pharmacokinetics, in vivo efficacy, and selectivity over hERG, structure-activity relationship studies around the central core of antimalarial imidazopyridazines were conducted. This study led to the identification of potent pyrazolopyridines, which showed good in vivo efficacy and pharmacokinetics profiles. The lead compounds also proved to be very potent in the parasite liver and gametocyte stages, which makes them of high interest.
为了改善药代动力学、体内疗效以及对人乙醚-a-去极化钾通道（hERG）的选择性，我们围绕抗疟咪唑并哒嗪的核心结构开展了构效关系研究。该研究鉴定出了强效的吡唑并吡啶，其显示出良好的体内疗效和药代动力学特征。先导化合物在疟原虫肝脏期和配子体期也表现出很强的活性，这使其备受关注。
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