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N4-phenyl modifications of N2-(2-hydroxyl)ethyl-6-(pyrrolidin-1-yl)-1,3,5-triazine-2,4-diamines enhance glucocerebrosidase inhibition by small molecules with potential as chemical chaperones for Gaucher disease.N2-(2-羟乙基)-6-(吡咯烷-1-基)-1,3,5-三嗪-2,4-二胺的N4-苯基修饰增强了小分子对葡糖脑苷脂酶的抑制作用，这些小分子具有作为戈谢病化学伴侣的潜力。
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Glucocerebrosidase inhibitors: future drugs for the treatment of Gaucher disease?葡萄糖脑苷脂酶抑制剂：治疗戈谢病的未来药物？
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本文引用的文献

1
Three classes of glucocerebrosidase inhibitors identified by quantitative high-throughput screening are chaperone leads for Gaucher disease.通过定量高通量筛选鉴定出的三类葡萄糖脑苷脂酶抑制剂是戈谢病的伴侣型先导化合物。
Proc Natl Acad Sci U S A. 2007 Aug 7;104(32):13192-7. doi: 10.1073/pnas.0705637104. Epub 2007 Aug 1.
2
Pharmacotherapeutic strategies using small molecules for the treatment of glycolipid lysosomal storage disorders.使用小分子治疗糖脂溶酶体贮积症的药物治疗策略。
Expert Opin Pharmacother. 2007 Mar;8(4):427-35. doi: 10.1517/14656566.8.4.427.
3
Development of adamantan-1-yl-methoxy-functionalized 1-deoxynojirimycin derivatives as selective inhibitors of glucosylceramide metabolism in man.金刚烷-1-基甲氧基官能化的1-脱氧野尻霉素衍生物作为人葡萄糖神经酰胺代谢选择性抑制剂的研发。
J Org Chem. 2007 Feb 16;72(4):1088-97. doi: 10.1021/jo061280p. Epub 2007 Jan 23.
4
Isofagomine- and 2,5-anhydro-2,5-imino-D-glucitol-based glucocerebrosidase pharmacological chaperones for Gaucher disease intervention.用于戈谢病干预的基于异法戈明和2,5-脱水-2,5-亚氨基-D-葡萄糖醇的葡萄糖脑苷脂酶药理学伴侣分子。
J Med Chem. 2007 Jan 11;50(1):94-100. doi: 10.1021/jm060677i.
5
Chemical chaperones and permissive temperatures alter localization of Gaucher disease associated glucocerebrosidase variants.化学伴侣和允许温度改变了与戈谢病相关的葡萄糖脑苷脂酶变体的定位。
ACS Chem Biol. 2006 May 23;1(4):235-51. doi: 10.1021/cb600187q.
6
Therapeutic strategies to ameliorate lysosomal storage disorders--a focus on Gaucher disease.改善溶酶体贮积症的治疗策略——聚焦戈谢病
Cell Mol Life Sci. 2006 May;63(10):1179-92. doi: 10.1007/s00018-005-5437-0.
7
Gaucher disease-associated glucocerebrosidases show mutation-dependent chemical chaperoning profiles.戈谢病相关的葡萄糖脑苷脂酶表现出突变依赖性化学伴侣谱。
Chem Biol. 2005 Nov;12(11):1235-44. doi: 10.1016/j.chembiol.2005.09.007.
8
Rational design and synthesis of highly potent beta-glucocerebrosidase inhibitors.高效β-葡萄糖脑苷脂酶抑制剂的合理设计与合成
Angew Chem Int Ed Engl. 2005 Dec 1;44(45):7450-3. doi: 10.1002/anie.200502662.
9
Synthesis of 2-[3,5-substituted pyrazol-1-yl]-4,6-trisubstituted triazine derivatives as antimalarial agents.2-[3,5-取代吡唑-1-基]-4,6-三取代三嗪衍生物作为抗疟剂的合成
Bioorg Med Chem Lett. 2005 Nov 15;15(22):4957-60. doi: 10.1016/j.bmcl.2005.08.023.
10
The discovery of orally active triaminotriazine aniline amides as inhibitors of p38 MAP kinase.口服活性三氨基三嗪苯胺酰胺作为p38丝裂原活化蛋白激酶抑制剂的发现。
J Med Chem. 2004 Dec 2;47(25):6283-91. doi: 10.1021/jm049521d.

N2-(2-羟乙基)-6-(吡咯烷-1-基)-1,3,5-三嗪-2,4-二胺的N4-苯基修饰增强了小分子对葡糖脑苷脂酶的抑制作用，这些小分子具有作为戈谢病化学伴侣的潜力。

N4-phenyl modifications of N2-(2-hydroxyl)ethyl-6-(pyrrolidin-1-yl)-1,3,5-triazine-2,4-diamines enhance glucocerebrosidase inhibition by small molecules with potential as chemical chaperones for Gaucher disease.

作者信息

Huang Wenwei, Zheng Wei, Urban Daniel J, Inglese James, Sidransky Ellen, Austin Christopher P, Thomas Craig J

机构信息

NIH Chemical Genomics Center, National Human Genome Research Institute, NIH, 9800 Medical Center Drive, MSC 3370, Bethesda, MD 20892-3370, USA.

出版信息

Bioorg Med Chem Lett. 2007 Nov 1;17(21):5783-9. doi: 10.1016/j.bmcl.2007.08.050. Epub 2007 Aug 28.

DOI:10.1016/j.bmcl.2007.08.050
PMID:17827006
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2083578/
Abstract

A series of 1,3,5-triazine-2,4,6-triamines were prepared and analyzed as inhibitors of glucocerebrosidase. Synthesis, structure activity relationships and the selectivity of chosen analogues against related sugar hydrolases enzymes are described.

摘要

制备了一系列1,3,5-三嗪-2,4,6-三胺，并将其作为葡萄糖脑苷脂酶抑制剂进行分析。描述了所选类似物的合成、构效关系及其对相关糖水解酶的选择性。