ethyl (chloro(4-methoxyphenoxy)phosphoryl)-L-leucinate | 926309-44-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ethyl (chloro(4-methoxyphenoxy)phosphoryl)-L-leucinate
• CAS: 926309-44-6
• 化学式: C₁₅H₂₃ClNO₅P
• 分子量: 363.778
• InChiKey: SZAWLYDXIPALFF-JRQMZCAUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.99
• 重原子数：
  23.0
• 可旋转键数：
  9.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  73.86
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  ethyl (chloro(4-methoxyphenoxy)phosphoryl)-L-leucinate 、 盐酸茚罗西生 在 叔丁基氯化镁 作用下， 以 四氢呋喃 为溶剂， 反应 17.0h， 生成 (S)-2-[[(2R,3S,4R,5R)-5-(4-amino-2-oxo-2H-pyrimidin-1-yl)-2-azido-3,4-dihydroxy-tetrahydro-furan-2-ylmethoxy]-(4-methoxy-phenoxy)-phosphorylamino]-4-methyl-pentanoic acid ethyl ester
  参考文献：
  名称：

  The application of phosphoramidate ProTide technology to the potent anti-HCV compound 4′-azidocytidine (R1479)

  摘要：

  We report the design, synthesis and evaluation of a family of ca 50 phosphoramidate ProTides of the potent anti-HCV compound 4 '-azidocytidine (R1479), with variation on the ester, amino acid and aryl moiety of the ProTide. Sub-mu M inhibitors of HCV emerge. The compounds are all non-cytotoxic in the replicon assay. We herein report detailed SARs for each of the regions of the ProTide. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.05.099
• 作为产物：
  描述：

  L-亮氨酸乙酯 、 4-methoxyphenyl phosphorodichloridate 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.25h， 以99%的产率得到ethyl (chloro(4-methoxyphenoxy)phosphoryl)-L-leucinate
  参考文献：
  名称：

  Targeting GNE Myopathy: A Dual Prodrug Approach for the Delivery of N-Acetylmannosamine 6-Phosphate

  摘要：

  ProTides comprise an important class of prodrugs currently marketed and developed as antiviral and anticancer therapies. The ProTide technology employs phosphate masking groups capable of providing more favorable druglike properties and an intracellular activation mechanism for enzyme-mediated release of a nucleoside monophosphate. Herein, we describe the application of phosphoramidate chemistry to 1,3,4-O-acetylated N-acetylmannosamine (Ac(3)ManNAc) to deliver ManNAc-6-phosphate (ManNAc-6-P), a critical intermediate in sialic acid biosynthesis. Sialic acid deficiency is a hallmark of GNE myopathy, a rare congenital disorder of glycosylation (CDG) caused by mutations in GNE that limit the production of ManNAc-6-P. Synthetic methods were developed to provide a library of Ac(3)ManNAc-6-phosphoramidates that were evaluated in a series of studies for their potential as a treatment for GNE myopathy. Prodrug 12b showed rapid activation in a carboxylesterase (CPY) enzymatic assay and favorable ADME properties, while also being more effective than ManNAc at increasing sialic acid levels in GNE-deficient cell lines. These results provide a potential platform to address substrate deficiencies in GNE myopathy and other CDGs.

  DOI：

  10.1021/acs.jmedchem.9b00833