合成和评估儿茶素二醚类化合物作为原虫磷酸二酯酶 B1（TbrPDEB1）的抑制剂。
Synthesis and assessment of catechol diether compounds as inhibitors of trypanosomal phosphodiesterase B1 (TbrPDEB1).
机构信息
Northeastern University, Department of Chemistry and Chemical Biology, 417 Egan Research Center, 360 Huntington Avenue, Boston, MA 02115, USA.
出版信息
Bioorg Med Chem Lett. 2013 Nov 1;23(21):5971-4. doi: 10.1016/j.bmcl.2013.08.057. Epub 2013 Aug 21.
Abstract
Human African trypanosomiasis (HAT) is a parasitic neglected tropical disease that affects 10,000 patients each year. Current treatments are sub-optimal, and the disease is fatal if not treated. Herein, we report our continuing efforts to repurpose the human phosphodiesterase 4 (hPDE4) inhibitor piclamilast to target trypanosomal phosphodiesterase TbrPDEB1. We prepared a range of substituted heterocyclic replacements for the 4-amino-3,5-dichloro-pyridine headgroup of piclamilast, and found that these compounds exhibited weak inhibitory activity of TbrPDEB1.
摘要
人类非洲锥虫病（HAT）是一种寄生虫性被忽视的热带病，每年影响 10000 名患者。目前的治疗方法并不理想，如果不治疗，这种疾病是致命的。在此，我们报告我们继续努力重新利用人类磷酸二酯酶 4（hPDE4）抑制剂匹拉米特来靶向锥虫磷酸二酯酶 TbrPDEB1。我们制备了一系列取代的杂环取代物，用于匹拉米特的 4-氨基-3,5-二氯-吡啶头基，发现这些化合物对 TbrPDEB1 表现出较弱的抑制活性。
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2
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