大环锥虫半胱氨酸蛋白酶抑制剂的合成。
Synthesis of macrocyclic trypanosomal cysteine protease inhibitors.
作者信息
Chen Yen Ting, Lira Ricardo, Hansell Elizabeth, McKerrow James H, Roush William R
机构信息
Department of Chemistry, Scripps Florida, 5353 Parkside Drive, RE-2, Jupiter, FL 33458, USA.
出版信息
Bioorg Med Chem Lett. 2008 Nov 15;18(22):5860-3. doi: 10.1016/j.bmcl.2008.06.012. Epub 2008 Jun 10.
Abstract
The importance of cysteine proteases in parasites, compounded with the lack of redundancy compared to their mammalian hosts makes proteases attractive targets for the development of new therapeutic agents. The binding mode of K11002 to cruzain, the major cysteine protease of Trypanosoma cruzi was used in the design of conformationally constrained inhibitors. Vinyl sulfone-containing macrocycles were synthesized via olefin ring-closing metathesis and evaluated against cruzain and the closely related cysteine protease, rhodesain.
摘要
半胱氨酸蛋白酶在寄生虫中的重要性，加之与它们的哺乳动物宿主相比缺乏冗余性，使得蛋白酶成为开发新型治疗药物的有吸引力的靶点。K11002与克氏锥虫主要半胱氨酸蛋白酶克鲁兹蛋白酶的结合模式被用于设计构象受限抑制剂。通过烯烃闭环复分解反应合成了含乙烯砜的大环化合物，并对克鲁兹蛋白酶和密切相关的半胱氨酸蛋白酶罗德西亚蛋白酶进行了评估。
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