1-((2R,3R,4S,5R)-4-(benzyloxy)-5-((benzyloxy)methyl)-5-ethynyl-3-hydroxytetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione | 1048374-27-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-((2R,3R,4S,5R)-4-(benzyloxy)-5-((benzyloxy)methyl)-5-ethynyl-3-hydroxytetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione
• 英文别名: 1-[(2R,3R,4S,5R)-5-ethynyl-3-hydroxy-4-phenylmethoxy-5-(phenylmethoxymethyl)oxolan-2-yl]pyrimidine-2,4-dione
• CAS: 1048374-27-1
• 化学式: C₂₅H₂₄N₂O₆
• 分子量: 448.475
• InChiKey: QLHXOTWXEYLGTH-STAYPELNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  97.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-((2R,3R,4S,5R)-4-(benzyloxy)-5-((benzyloxy)methyl)-5-ethynyl-3-hydroxytetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione 在 ammonium hydroxide 、 sodium hydroxide 、 Cl₂P(O)OC₆H₄Cl 、 三溴化硼 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 吡啶 、 二氯甲烷 、 水 为溶剂， 生成 4'-C-ethynyl-β-D-arabino-pentofuranosyl cytosine
  参考文献：
  名称：

  Synthesis of 4′-C-Ethynyl-β-D-arabino- and 4′-C-Ethynyl-2′-deoxy-β-D-ribo- pentofuranosyl Pyrimidines, and Their Biological Evaluation

  摘要：

  4′-C-乙炔基-β-D-阿拉伯五碳呋喃糖胸腺嘧啶（14）和细胞嘧啶（16），以及4′-C-乙炔基-2′-脱氧-β-D-核糖五碳呋喃糖胸腺嘧啶（25）和细胞嘧啶（27）是通过适当保护的4′-C-羟甲基-3,5-二-O-苄基-α-D-核糖五碳呋喃糖（1）从D-葡萄糖合成的。其中，2′-脱氧衍生物25和27表现出了抗病毒活性，而胞苷衍生物16和27抑制了肿瘤细胞的生长。

  DOI：

  10.1271/bbb.63.1146
• 作为产物：
  描述：

  4-C-ethynyl-3,5-di-O-benzyl-1,2-di-O-acetyl-D-ribo-pentofuranose 在 sodium hydroxide 、 N,O-双三甲硅基乙酰胺 、 三氟甲磺酸三甲基硅酯 作用下， 以 甲醇 、 1,2-二氯乙烷 为溶剂， 反应 14.0h， 生成 1-((2R,3R,4S,5R)-4-(benzyloxy)-5-((benzyloxy)methyl)-5-ethynyl-3-hydroxytetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  Syntheses of 4‘-C-Ethynyl-β-d-arabino- and 4‘-C-Ethynyl-2‘-deoxy-β-d-ribo-pentofuranosylpyrimidines and -purines and Evaluation of Their Anti-HIV Activity

  摘要：

  4'-C-Ethynyl-beta -D-arabino- and 4'-C-ethynyl-2'-deoxy-beta -D-ribo-pentofuranosylpyrine and -purine nucleosides were synthesized and evaluated for their in vitro anti-HIV activity. The key intermediate, 4-C-ethynyl- or 4-C-triethylsilylethynyl-D-ribo-pentofuranose, was prepared from D-glucose and glycosidated with various pyrimidine or purine bases. The arabino pyrimidine derivatives were prepared from the corresponding ribo derivatives via O-2,2'-anhydro nucleosides. The 2'-deoxy-ribo derivatives were synthesized by radical reduction of 2'-bromo or 2'- phenoxythiocarbonyloxy nucleosides. Among these 4'-C-ethynyl nucleosides, seven analogues proved to be potent against HIV-1 in vitro with EC50 values ranging from 0.0003 to 0.03 muM. These compounds also exerted activity against clinical and multi-dideoxy-nucleoside-resistant HIV-1 strains with comparable EC50 values. Three such 4'-C-ethynyl-2'-deoxypurine analogues including 4'-C-ethynyl-2'-deoxyadenosine and 4'-C-ethynyl-2,6-diamino-2'-deoxy-purine were less cytotoxic [selectivity indices (SIs): 975-2733] than three 4'-C-ethynyl-2-deoxycytidine analogues (SIs: 63-363). 4'-C-Ethynyl-5-fluoro-2'-deoxycytidine was least toxic (SI: >3333) and potent against all HIV strains tested.

  DOI：

  10.1021/jm000209n

文献信息

• [EN] COMBINED MODALITIES FOR NUCLEOSIDES AND/OR NADPH OXIDASE (NOX) INHIBITORS AS MYELOID-SPECIFIC ANTIVIRAL AGENTS<br/>[FR] MODALITÉS COMBINÉES POUR DES NUCLÉOSIDES ET/OU DES INHIBITEURS DE LA NADPH OXYDASE (NOX) EN TANT QU'AGENTS ANTIVIRAUX SPÉCIFIQUES DE CELLULES MYÉLOÏDES
  申请人：SCHINAZI RAYMOND F

  公开号：WO2019133712A1

  公开（公告）日：2019-07-04

  The present invention is directed to compounds, compositions and methods for treating or preventing HIV and other viral infections, particularly where the virus is present in macrophages, microglia, and primary myeloid cells, and eliminating and/or treating infection in patients infected by these viruses.

  本发明涉及治疗或预防HIV和其他病毒感染的化合物、组合物和方法，特别是针对病毒存在于巨噬细胞、微胶质细胞和原始髓样细胞中的情况，并消除和/或治疗感染了这些病毒的患者的感染。
• COMBINED MODALITIES FOR NUCLEOSIDES AND/OR NADPH OXIDASE (NOX) INHIBITORS AS MYELOID-SPECIFIC ANTIVIRAL AGENTS
  申请人：Emory University

  公开号：EP3732180A1

  公开（公告）日：2020-11-04