6-methoxycarbonyluridine-5’-O-monophosphate | 934014-53-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: 6-methoxycarbonyluridine-5’-O-monophosphate
• 英文别名: 6-methoxycarbonyl-uridine-5'-O-monophosphate；6-(Methoxycarbonyl)uridine 5'-(Dihydrogen Phosphate)；methyl 3-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(phosphonooxymethyl)oxolan-2-yl]-2,6-dioxopyrimidine-4-carboxylate
• CAS: 934014-53-6
• 化学式: C₁₁H₁₅N₂O₁₁P
• 分子量: 382.221
• InChiKey: VOHILSGGFMXAFJ-ZOQUXTDFSA-N

物化性质

• 密度：
  1.825±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -3.9
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  192
• 氢给体数：
  5
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  6-methoxycarbonyluridine-5’-O-monophosphate 在 氨 作用下， 以 水 为溶剂， 生成 6-methoxycarbonyl-uridine-5'-O-monophosphate di-ammonium salt
  参考文献：
  名称：

  WO2008/83465

  摘要：

  公开号：
• 作为产物：
  描述：

  尿嘧啶核苷 在 吡啶 、 咪唑 、 硫酸 、 水 、 三氟乙酸 、 lithium diisopropyl amide 、 三氯氧磷 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 15.0h， 生成 6-methoxycarbonyluridine-5’-O-monophosphate
  参考文献：
  名称：

  Substrate Distortion Contributes to the Catalysis of Orotidine 5′-Monophosphate Decarboxylase

  摘要：

  Orotidine 5'-monophosphate decarboxylase (OD-Case) accelerates the decarboxylation of orotidine 5'-monophosphate (OMP) to uridine 5'-monophosphate (UMP) by 17 orders of magnitude. Eight new crystal structures with ligand analogues combined with computational analyses of the enzyme's short-lived intermediates and the intrinsic electronic energies to distort the substrate and other ligands improve our understanding of the still controversially discussed reaction mechanism. In their respective complexes, 6-methyl-UMP displays significant distortion of its methyl substituent bond, 6-amino-UMP shows the competition between the K72 and C6 substituents for a position close to D70, and the methyl and ethyl esters of OMP both induce rotation of the carboxylate group substituent out of the plane of the pyrimidine ring. Molecular dynamics and quantum mechanics/molecular mechanics computations of the enzyme-substrate complex also show the bond between the carboxylate group and the pyrimidine ring to be distorted, with the distortion contributing a 10-15% decrease of the Delta Delta G(double dagger) value. These results are consistent with ODCase using both substrate distortion and transition-state stabilization, primarily exerted by K72, in its catalysis of the OMP decarboxylation reaction.

  DOI：

  10.1021/ja408197k

文献信息

• ODCASE INHIBITORS FOR THE TREATMENT OF MALARIA
  申请人：Kotra Lakshmi P.

  公开号：US20090221524A1

  公开（公告）日：2009-09-03

  The present invention includes methods of treating or preventing malaria by administering an anti-malarial effective amount of 6-substituted uridine derivatives to a subject need thereof. The invention also includes new 6-substituted uridine derivatives for use as therapeutics, in particular to treat malaria.

  本发明涉及通过向需要治疗或预防疟疾的受体施用抗疟疾有效量的6-取代尿嘧啶衍生物来治疗或预防疟疾的方法。本发明还包括新的6-取代尿嘧啶衍生物，用于作为治疗剂，特别是用于治疗疟疾。
• Pyrimidine Derivatives As Anticancer Agents
  申请人：Kotra Lakshmi P.

  公开号：US20100056468A1

  公开（公告）日：2010-03-04

  The present invention includes methods of treating or preventing cancer by administering an effective amount of 6-substituted pyrimidine derivatives of the Formula I to a subject need thereof:

  本发明涉及通过向需要该治疗的受体施用公式I的6-取代嘧啶衍生物的有效量来治疗或预防癌症的方法：
• WO2007/38859
  申请人：——

  公开号：——

  公开（公告）日：——
• US8067391B2
  申请人：——

  公开号：US8067391B2

  公开（公告）日：2011-11-29
• Substrate Distortion Contributes to the Catalysis of Orotidine 5′-Monophosphate Decarboxylase
  作者：Masahiro Fujihashi、Toyokazu Ishida、Shingo Kuroda、Lakshmi P. Kotra、Emil F. Pai、Kunio Miki

  DOI：10.1021/ja408197k

  日期：2013.11.20

  Orotidine 5'-monophosphate decarboxylase (OD-Case) accelerates the decarboxylation of orotidine 5'-monophosphate (OMP) to uridine 5'-monophosphate (UMP) by 17 orders of magnitude. Eight new crystal structures with ligand analogues combined with computational analyses of the enzyme's short-lived intermediates and the intrinsic electronic energies to distort the substrate and other ligands improve our understanding of the still controversially discussed reaction mechanism. In their respective complexes, 6-methyl-UMP displays significant distortion of its methyl substituent bond, 6-amino-UMP shows the competition between the K72 and C6 substituents for a position close to D70, and the methyl and ethyl esters of OMP both induce rotation of the carboxylate group substituent out of the plane of the pyrimidine ring. Molecular dynamics and quantum mechanics/molecular mechanics computations of the enzyme-substrate complex also show the bond between the carboxylate group and the pyrimidine ring to be distorted, with the distortion contributing a 10-15% decrease of the Delta Delta G(double dagger) value. These results are consistent with ODCase using both substrate distortion and transition-state stabilization, primarily exerted by K72, in its catalysis of the OMP decarboxylation reaction.