2'-desoxyguanosine methylphosphonate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 2'-desoxyguanosine methylphosphonate
• 英文别名: 2'-deoxyguanosine methylphosphonate；[(2R,3S,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxy-tetrahydrofuran-2-yl]methoxy-methyl-phosphinic acid；[(2R,3S,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-methylphosphinic acid
• 化学式: C₁₁H₁₆N₅O₆P
• 分子量: 345.252
• InChiKey: ZFTJSJHHWJGKBU-RRKCRQDMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  166
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  在 氢氧化钾 作用下， 生成 2'-desoxyguanosine methylphosphonate
  参考文献：
  名称：

  5′-Phosphonates of Ribonucleosides and 2′-Deoxyribonucleosides: Synthesis and Antiviral Activity

  摘要：

  5'-Phosphonates of natural 2'-deoxynucleosides and ribonucleosides were synthesized by condensation of 3'-O-acylated 2'-deoxynucleosides or 2',3'-substituted (2',3'-O-isopropylidene, 2',3'-O-methoxymethylene or 2',3'-O-ethoxymethylene) ribonucleosides. As condensing agents, either N,N'-dicyclohexylcarbodiimide or 2,4,6-triisopropylbenzenesulphonyl chloride were used. Nucleoside 5'-ethoxycarbonylphosphonates were converted into corresponding nucleoside 5'-aminocarbonylphosphonates by action of ammonia in methanol or aqueous ammonia. 5'-Hydrogenphosphonothioates of thymidine and 3'-deoxythymidine were obtained by reaction of phosphinic acid in the presence of pivaloyl chloride with 3'-O-acetylthymidine or 3'-deoxythymidine, respectively, followed by addition of powedered sulfur. 5'-O-methylenephosphonates of thymidine and 2'-deoxyadenosine were prepared by intramolecular reaction of corresponding 3'-O-iodomethylphosphonates under basic conditions. All compounds were tested for inhibition of several viruses, including HSV-2 and CMV, but showed no activity. A few compounds insignificantly inhibited HIV-1 reproduction. Thymidine 5'-hydrogenphosphonate neutralized anti-HIV action of 3'-azido-3'-deoxythymidine (AZT) and it indirectly showed that even some nucleoside 5'-phosphonates could be partly hydrolyzed in cell culture to corresponding nucleosides.

  DOI：

  10.1080/07328319308018558

文献信息

• Methods of treating colorectal cancer
  申请人：Nogra Pharma Limited

  公开号：US10006029B2

  公开（公告）日：2018-06-26

  Disclosed herein are methods for treating/and or preventing colorectal cancer using a specific inhibitor of SMAD7 expression or function. Also disclosed are pharmaceutical compositions containing an inhibitor of SMAD7 for treating and/or preventing colorectal cancer and manufacture of medicaments containing an inhibitor of SMAD7 to be used in treating and/or preventing colorectal cancer.

  本文公开了使用SMAD7表达或功能的特异性抑制剂治疗/和或预防结直肠癌的方法。还公开了含有SMAD7抑制剂的治疗和/或预防结直肠癌的药物组合物，以及含有SMAD7抑制剂的用于治疗和/或预防结直肠癌的药物的制造。
• Antisense oligonucleotides (ODN) against Smad7 and uses thereof in medical field
  申请人：Nogra Pharma Limited

  公开号：US10036022B2

  公开（公告）日：2018-07-31

  The invention relates to antisense oligonucleotidic sequences (ODN) against Smad7 suitably modified, and their uses in medical field as therapeutic biological agents, in particular in the treatment of chronic inflammatory bowel disease, such as Crohn's disease and ulcerative colitis.

  本发明涉及经适当修饰的针对 Smad7 的反义寡核苷酸序列（ODN）及其在医疗领域作为治疗生物制剂的用途，特别是在治疗慢性炎症性肠病（如克罗恩病和溃疡性结肠炎）方面的用途。
• Methods of treating diabetes and/or promoting survival of pancreatic islets after transplantation
  申请人：Nogra Pharma Limited

  公开号：US10081809B2

  公开（公告）日：2018-09-25

  Disclosed herein are methods for treating/and or preventing diabetes using a specific inhibitor of SMAD7 expression or function. Also disclosed are methods of promoting organ and/or cell, e.g., pancreatic islet cell, survival after transplantation using a specific inhibitor of SMAD7 expression or function.

  本文公开了使用 SMAD7 表达或功能的特异性抑制剂治疗/和或预防糖尿病的方法。还公开了使用 SMAD7 表达或功能特异性抑制剂促进器官和/或细胞（如胰岛细胞）移植后存活的方法。
• Methods and compositions for treating a subject with a SMAD7 antisense oligonucleotide
  申请人：Nogra Pharma Limited

  公开号：US10337004B2

  公开（公告）日：2019-07-02

  The present invention relates to treatment of inflammatory bowel disease (e.g., Crohn's disease and ulcerative colitis) using antisense nucleotides that are directed against polymorphic forms (e.g., those containing single nucleotide polymorphisms) of the SMAD7 mRNA. The invention thus relates to treatment methods for subjects having polymorphic forms of SMAD7 and antisense oligonucleotides that specifically target SMAD7 mRNA transcripts containing polymorphisms.

  本发明涉及使用反义核苷酸治疗炎症性肠病（如克罗恩病和溃疡性结肠炎），反义核苷酸针对SMAD7 mRNA的多态形式（如含有单核苷酸多态性的形式）。因此，本发明涉及针对具有 SMAD7 多态形式的受试者的治疗方法，以及特异性靶向含有多态性的 SMAD7 mRNA 转录本的反义寡核苷酸。
• Methods for treating inflammatory bowel disease
  申请人：Nogra Pharma Limited

  公开号：US10473669B2

  公开（公告）日：2019-11-12

  Methods of treating a subject with IBD with an anti-SMAD7 therapy, such as a SMAD7 antisense oligonucleotide, to reduce CRP levels are disclosed. Methods of treating and managing IBD in a subject using an anti-SMAD7 therapy, such as a SMAD7 antisense oligonucleotide, based on CRP levels are also disclosed. Also disclosed are methods of determining whether a subject with IBD is responsive or likely to be responsive to treatment an anti-SMAD7 therapy. Reduction of CRP levels may correlated with IBD remission or decreases in CDAI score. The present invention also relates to treatment of IBD using an anti-SMAD7 therapy (e.g., an antisense oligonucleotide) in combination with an additional agent. The invention also features related pharmaceutical compositions and kits.

  公开了用抗SMAD7疗法（如SMAD7反义寡核苷酸）治疗IBD患者以降低CRP水平的方法。还公开了基于CRP水平使用抗SMAD7疗法（如SMAD7反义寡核苷酸）治疗和管理受试者IBD的方法。还公开了确定IBD患者是否对抗SMAD7疗法有反应或可能有反应的方法。CRP水平的降低可能与IBD缓解或CDAI评分的降低相关。本发明还涉及使用抗SMAD7疗法（如反义寡核苷酸）与附加药剂联合治疗IBD。本发明还涉及相关药物组合物和试剂盒。