1-(2-O-acetyl-3,5-di-O-benzyl-4-C-triethylsilylethynyl-β-D-ribo-pentofuranosyl)thymine | 233266-85-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(2-O-acetyl-3,5-di-O-benzyl-4-C-triethylsilylethynyl-β-D-ribo-pentofuranosyl)thymine
• 英文别名: (2R,3R,4S,5R)-4-(benzyloxy)-5-((benzyloxy)methyl)-2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-5-((triethylsilyl)ethynyl)tetrahydrofuran-3-yl acetate；[(2R,3R,4S,5R)-2-(5-methyl-2,4-dioxopyrimidin-1-yl)-4-phenylmethoxy-5-(phenylmethoxymethyl)-5-(2-triethylsilylethynyl)oxolan-3-yl] acetate
• CAS: 233266-85-8
• 化学式: C₃₄H₄₂N₂O₇Si
• 分子量: 618.802
• InChiKey: KMKKUHDPULXFKL-IEDYJCJFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  44
• 可旋转键数：
  15
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(2-O-acetyl-3,5-di-O-benzyl-4-C-triethylsilylethynyl-β-D-ribo-pentofuranosyl)thymine 在 三氯化硼 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 1-(4-C-triethylsilylethynyl-β-D-ribo-pentofuranosyl)thymine
  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：

  1,2-O-(异丙亚基)-4-C-[(苯基甲氧基)甲基]-3-O-(苯基甲基)-beta-L-来苏呋喃糖 在 正丁基锂 、 草酰氯 、 三氟甲磺酸三甲基硅酯 、 溶剂黄146 、 二甲基亚砜 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 吡啶 、 二氯甲烷 、 水 、 1,2-二氯乙烷 为溶剂， 生成 1-(2-O-acetyl-3,5-di-O-benzyl-4-C-triethylsilylethynyl-β-D-ribo-pentofuranosyl)thymine
  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

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。
• Syntheses of 4<i>‘</i><i>-</i><i>C</i>-Ethynyl-β-<scp>d</scp>-<i>arabino- </i>and 4‘-<i>C-</i>Ethynyl-2<i>‘</i>-deoxy-β-<scp>d</scp>-<i>ribo-</i>pentofuranosylpyrimidines and -purines and Evaluation of Their Anti-HIV Activity
  作者：Hiroshi Ohrui、Satoru Kohgo、Kenji Kitano、Shinji Sakata、Eiichi Kodama、Kazuhisa Yoshimura、Masao Matsuoka、Shiro Shigeta、Hiroaki Mitsuya

  DOI：10.1021/jm000209n

  日期：2000.11.1

  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.