oxasine 5'-monophosphate

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: oxasine 5'-monophosphate
• 英文别名: Oxanosine 5'-monophosphate；[(2R,3S,4R,5R)-5-(5-amino-7-oxo-imidazo[4,5-d][1,3]oxazin-3-yl)-3,4-dihydroxy-tetrahydrofuran-2-yl]methyl dihydrogen phosphate；[(2R,3S,4R,5R)-5-(5-amino-7-oxoimidazo[4,5-d][1,3]oxazin-3-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate
• 化学式: C₁₀H₁₃N₄O₉P
• 分子量: 364.208
• InChiKey: FUZZUJLIYORYBU-ZIYNGMLESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  199
• 氢给体数：
  5
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  鸟苷酸 在 sodium nitrite 作用下， 以 aq. acetate buffer 为溶剂， 反应 18.0h， 以20%的产率得到oxasine 5'-monophosphate
  参考文献：
  名称：

  Oxanosine Monophosphate Is a Covalent Inhibitor of Inosine 5′-Monophosphate Dehydrogenase

  摘要：

  活性氮物质（RNS）在感染和炎症过程中产生，这些物质对蛋白质、DNA和脂质的影响已被广泛认可。相对而言，RNS 损伤代谢物的影响则较少被关注。5-氨基-3-β-(d-核糖呋喃糖基)-3H-咪唑-[4,5-d][1,3]氧噻唑-7-酮（oxanosine）及其核苷酸是鸟苷进行亚硝化反应的产物。在这里我们证明，oxanosine 单磷酸（OxMP）是 IMPDH 的一种有效可逆竞争抑制剂。对于来自五种不同生物的 IMPDH，Ki 值从 50 到 340 nM 不等。UV 光谱和 X 射线晶体学表明，OxMP 与活性位点的半胱氨酸形成环打开的共价加合物（E-OxMP*）。不同于正常催化反应的共价中间体，E-OxMP* 不会水解，而是重新环化回 OxMP。IMPDH 抑制剂可以阻止细胞增殖并诱导细胞凋亡，因此 OxMP 对 IMPDH 的抑制提供了 RNS 毒性的另一种潜在机制。

  DOI：

  10.1021/acs.chemrestox.8b00342

文献信息

• Synthesis of sugar-modified derivatives of the unusual nucleoside oxanosine and its carbocyclic analogs as potential inhibitors of HIV
  作者：Yoshio Saito、Mariko Nakamura、Tsuneya Ohno、Chanya Chaicharoenpong、Eiko Ichikawa、Shosuke Yamamura、Kuniki Kato、Kazuo Umezawa

  DOI：10.1039/b006763f

  日期：——

  A series of sugar-modified derivatives of oxanosine and its carbocyclic analogs were synthesized from natural oxanosine and (−)-2-azabicyclo[2.2.1]hept-5-en-3-one, respectively. Among nucleosides tested for anti-HIV activities in vitro, oxanosine 1, its 5′-monophosphate 9, and 2′-deoxyoxanosine 8 reduced the number of HIV particles in CEM cells to almost the same level as ddI.

  研究人员分别从天然草苷和(-)-2-氮杂双环[2.2.1]庚-5-烯-3-酮合成了一系列草苷及其碳环类似物的糖修饰衍生物。在体外抗艾滋病毒活性测试的核苷中，草苷 1、其 5′-单磷酸 9 和 2′-脱氧草苷 8 可将 CEM 细胞中的艾滋病毒颗粒数量减少到与 ddI 几乎相同的水平。
• Formation of 2-chloroinosine from guanosine by treatment of HNO2 in the presence of NaCl
  作者：Toshinori Suzuki、Hiroshi Ide、Masaki Yamada、Takashi Morii、Keisuke Makino

  DOI：10.1016/s0968-0896(01)00173-0

  日期：2001.11

  We investigated the reaction of Guo with nitrous acid in the presence of NaCl. When 1 mM Guo was incubated with 100 mM NaNO2 and 2 M NaCl in sodium acetate buffer at pH 3.2 and 37 degreesC, 2-chloroinosine (2-Cl-Ino) was produced in addition to oxanosine (Oxo) and xanthosine (Xao). The yield of 2-Cl-Ino was 0.033 mM at an incubation time of 2 h. Under the same reaction conditions, GMP and dGuo gave rise to the corresponding 2-chloro derivatives with comparable yields. All the 2-chloro derivatives were fairly stable (t(1/2) > 360 h) at physiological pH and temperature. To elucidate the reaction mechanism of the chlorination, the diazoate derivative of Guo, a reaction intermediate of the Guo-HNO2 system, was employed as a starting compound. When the diazoate was incubated with 2M NaCl in a neutral solution, 2-Cl-Ino was produced in addition to Oxo and Xao. These results suggest that the 2-chloro derivatives can be produced from foodstuffs in the human stomach and may have potential importance as a carcinogen causing gastric cancer. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Syntheses of Oxanosine and Carbocyclic Oxanosine Derivatives as Anti-HIV Agents.
  作者：YOSHIO SAITO、MARIKO NAKAMURA、TSUNEYA OHNO、CHANYA CHAICHAROENPONG、EIKO ICHIKAWA、SHOSUKE YAMAMURA、KUNIKI KATO、KAZUO UMEZAWA

  DOI：10.7164/antibiotics.53.309

  日期：——
• Pre-Activated Nucleoside IMPDH Inhibitors As Anti-Infective Drugs
  申请人：Octagon Therapeutics Inc.

  公开号：US20210353660A1

  公开（公告）日：2021-11-18

  The present disclosure provides inosine-5′-monophosphate dehydrogenase (IMPDH)-inhibiting nucleoside derivatives having anti-infective activities, and methods of their synthesis and use.