Merck Research Laboratories, Kirkland, QC, Canada.
Bioorg Med Chem Lett. 2010 Dec 15;20(24):7444-9. doi: 10.1016/j.bmcl.2010.10.015. Epub 2010 Oct 12.
Identification of potent and reversible cruzipain inhibitors for the treatment of Chagas disease is described. The identified inhibitors bearing an amino nitrile warhead in P1 exhibit low nanomolar in vitro potency against cruzipain. Further SAR in P2 portion led to the identification of compounds, such as 26, that have a unique selectivity profile against other cysteine proteases and offering new opportunities for safer treatment of Chagas disease.
本文描述了用于治疗恰加斯病的有效且可逆的克氏锥虫蛋白酶抑制剂的鉴定。鉴定出的抑制剂在 P1 中带有氨基腈弹头，对克氏锥虫蛋白酶具有低纳摩尔的体外效力。进一步在 P2 部分进行 SAR 研究，鉴定出了具有独特的选择性针对其他半胱氨酸蛋白酶的化合物，如 26，为更安全地治疗恰加斯病提供了新的机会。
