5'-deoxy-5'-N-morpholinouridine | 1119504-21-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 5'-脱氧核糖核苷
• 英文名称: 5'-deoxy-5'-N-morpholinouridine
• 英文别名: 5''-deoxy-5''-N-morpholinouridine；1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(morpholin-4-ylmethyl)oxolan-2-yl]pyrimidine-2,4-dione
• CAS: 1119504-21-0
• 化学式: C₁₃H₁₉N₃O₆
• 分子量: 313.31
• InChiKey: LZYQLCIKQTYBER-HJQYOEGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.2
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  112
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1-[(3aR,4R,6R,6aR)-2,2-dimethyl-6-(morpholin-4-ylmethyl)-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]pyrimidine-2,4-dione 在 三氟乙酸 作用下， 以 水 为溶剂， 反应 0.5h， 以65%的产率得到5'-deoxy-5'-N-morpholinouridine
  参考文献：
  名称：

  Morpholino, Piperidino, and Pyrrolidino Derivatives of Pyrimidine Nucleosides as Inhibitors of Ribonuclease A: Synthesis, Biochemical, and Crystallographic Evaluation^,

  摘要：

  Six 5'-deoxy-5'-morpholine, piperidine, and pyrrolidine of pyrimidine nucleosides have been synthesized and characterized. Their inhibitory action to ribonuclease A has been studied by biochemical analysis and X-ray crystallography. These compounds are moderate inhibitors of RNase A with mid-to-upper micromolar inhibition constants (K(i)). The high resolution X-ray crystal structures of the RNase A-inhibitor complexes have shown that all inhibitors bind at the enzyme catalytic cleft with the pyrimidine nucleobase at the B(1)R(2) subsites while the 5' group binds away from the main subsite P(1), where P-O(5') bond cleavage occurs, toward the solvent close to subsite P(0). Structure-activity relationship analysis has demonstrated that the compounds with the larger group in the 5' position are more potent. Comparative structural analysis of these RNase A complexes with other similar RNase A-ligand complexes provides a structural explanation of their potency and suggests ways to improve their efficiency and selectivity. These inhibitors can be the starting point for the development of compounds that can be used as pharmaceuticals against pathologies associated with RNase A homologues such as human angiogenin, which is implicated in tumor induced neovascularization.

  DOI：

  10.1021/jm800724t

文献信息

• MODIFIED RNA AGENTS WITH REDUCED OFF-TARGET EFFECT
  申请人：Alnylam Pharmaceuticals, Inc.

  公开号：EP3544617A1

  公开（公告）日：2019-10-02
• [EN] MODIFIED RNA AGENTS WITH REDUCED OFF-TARGET EFFECT<br/>[FR] AGENTS ARN MODIFIÉS À EFFET HORS CIBLE RÉDUIT
  申请人：ALNYLAM PHARMACEUTICALS INC

  公开号：WO2018098328A1

  公开（公告）日：2018-05-31

  One aspect of the present invention relates to double-stranded RNA (dsRNA) agent capable of inhibiting the expression of a target gene. The antisense strand of the dsRNA molecule comprises at least one thermally destabilizing nucleotide occurring at a seed region; the dsRNA comprises at least four 2'-fluoro modifications, and the sense strand of the dsRNA molecule comprises ligand, wherein the ligand is an ASGPR ligand. Other aspects of the invention relates to pharmaceutical compositions comprising these dsRNA molecules suitable for therapeutic use, and methods of inhibiting the expression of a target gene by administering these dsRNA molecules, e.g., for the treatment of various disease conditions.
• Morpholino, Piperidino, and Pyrrolidino Derivatives of Pyrimidine Nucleosides as Inhibitors of Ribonuclease A: Synthesis, Biochemical, and Crystallographic Evaluation^,
  作者：Anirban Samanta、Demetres D. Leonidas、Swagata Dasgupta、Tanmaya Pathak、Spyros E. Zographos、Nikos G. Oikonomakos

  DOI：10.1021/jm800724t

  日期：2009.2.26

  Six 5'-deoxy-5'-morpholine, piperidine, and pyrrolidine of pyrimidine nucleosides have been synthesized and characterized. Their inhibitory action to ribonuclease A has been studied by biochemical analysis and X-ray crystallography. These compounds are moderate inhibitors of RNase A with mid-to-upper micromolar inhibition constants (K(i)). The high resolution X-ray crystal structures of the RNase A-inhibitor complexes have shown that all inhibitors bind at the enzyme catalytic cleft with the pyrimidine nucleobase at the B(1)R(2) subsites while the 5' group binds away from the main subsite P(1), where P-O(5') bond cleavage occurs, toward the solvent close to subsite P(0). Structure-activity relationship analysis has demonstrated that the compounds with the larger group in the 5' position are more potent. Comparative structural analysis of these RNase A complexes with other similar RNase A-ligand complexes provides a structural explanation of their potency and suggests ways to improve their efficiency and selectivity. These inhibitors can be the starting point for the development of compounds that can be used as pharmaceuticals against pathologies associated with RNase A homologues such as human angiogenin, which is implicated in tumor induced neovascularization.