新型基于氰胺的组织蛋白酶C抑制剂的发现
Discovery of novel cyanamide-based inhibitors of cathepsin C.
作者信息
Lainé Dramane, Palovich Michael, McCleland Brent, Petitjean Emilie, Delhom Isabelle, Xie Haibo, Deng Jianghe, Lin Guoliang, Davis Roderick, Jolit Anais, Nevins Neysa, Zhao Baoguang, Villa Jim, Schneck Jessica, McDevitt Patrick, Midgett Robert, Kmett Casey, Umbrecht Sandra, Peck Brian, Davis Alicia Bacon, Bettoun David
机构信息
GlaxoSmithKline, Respiratory CEDD, 709 Swedeland Road, P.O. Box 1539, King of Prussia, Pennsylvania 19406-0939, United States.
出版信息
ACS Med Chem Lett. 2010 Nov 10;2(2):142-7. doi: 10.1021/ml100212k. eCollection 2011 Feb 10.
Abstract
The discovery of potent and selective cyanamide-based inhibitors of the cysteine protease cathepsin C is detailed. Optimization of the template with regard to plasma stability led to the identification of compound 17, a potent cathepsin C inhibitor with excellent selectivity over other cathepsins and potent in vivo activity in a cigarette smoke mouse model.
摘要
强效且具有选择性的基于氰胺的半胱氨酸蛋白酶组织蛋白酶C抑制剂的发现过程得到了详细阐述。针对血浆稳定性对模板进行优化，从而确定了化合物17，它是一种强效的组织蛋白酶C抑制剂，对其他组织蛋白酶具有出色的选择性，并且在香烟烟雾小鼠模型中具有强大的体内活性。
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1
[22] Preparation and specificity of dipeptidyl aminopeptidase I.[22] 二肽基氨基肽酶I的制备及特异性
Methods Enzymol. 1972;25:272-81. doi: 10.1016/S0076-6879(72)25024-8.
2
Inhibitors of cathepsin C (dipeptidyl peptidase I).组织蛋白酶 C（二肽基肽酶 I）抑制剂。
Expert Opin Ther Pat. 2010 Apr;20(4):497-506. doi: 10.1517/13543771003657172.
3
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Bioorg Med Chem Lett. 2009 Sep 15;19(18):5392-6. doi: 10.1016/j.bmcl.2009.07.114. Epub 2009 Jul 28.
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7
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10
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