2,5,6-Trichloro-1-(5deoxy-α-D-lyxofuranosyl)benzimidazole | 202119-79-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2,5,6-Trichloro-1-(5deoxy-α-D-lyxofuranosyl)benzimidazole
• 英文别名: 2,5,6-Trichloro-1-(5-deoxy-α-D-lyxofuranosyl)1H-benzimidazole；(2R,3R,4S,5S)-2-methyl-5-(2,5,6-trichlorobenzimidazol-1-yl)tetrahydrofuran-3,4-diol；(2R,3R,4S,5S)-2-methyl-5-(2,5,6-trichlorobenzimidazol-1-yl)oxolane-3,4-diol
• CAS: 202119-79-7
• 化学式: C₁₂H₁₁Cl₃N₂O₃
• 分子量: 337.59
• InChiKey: FHBOHRZOOVSDLE-GYXCMCCDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  67.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  异丙胺 、 2,5,6-Trichloro-1-(5deoxy-α-D-lyxofuranosyl)benzimidazole 以 乙醇 为溶剂， 反应 48.0h， 以79%的产率得到(2S,3S,4R,5R)-2-[5,6-dichloro-2-(isopropylamino)benzimidazol-1-yl]-5-methyl-tetrahydrofuran-3,4-diol
  参考文献：
  名称：

  Design, Synthesis, and Antiviral Activity of α-Nucleosides:  d- and l-Isomers of Lyxofuranosyl- and (5-Deoxylyxofuranosyl)benzimidazoles

  摘要：

  Several 2-substituted alpha-D- and alpha-L-lyxofuranosyl and 5-deoxylyxofuranosyl derivatives of 5,6-dichloro-2-(isopropylamino)-1- -(beta-L-ribofuranosyl)benzimidazole (1263W94) and 2,5,6-trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) were synthesized and evaluated for activity against two herpesviruses (HSV-1 and HCMV) and for their cytotoxicity against HFF and KB cells. Condensation of 1,2,3,5-tetra-O-acetyl-L-lyxofuranose (2a) with 2,5,6-trichlorobenzimidazole (1) yielded the or-nucleoside 3a. The 2-bromo derivative and 2-methylamino derivative were prepared by treatment of 3a with HBr followed by deprotection or from methylamine, respectively. Compound 3a was deprotected and the resultant nucleoside used to prepare the 2-cyclopropylamino and 2-isopropylamino derivatives. The 2-alkylthio nucleosides were prepared by condensing 2a with 5,6-dichlorobenzimidazole-2-thione followed by deprotection. Alkylation of this adduct gave the 2-methylthio and 2-benzylthio derivatives. Condensation of 5-deoxy-1,2,3-tri-O-acetyl-L-lyxofuranosyl, prepared from L-lyxose, with 1 or 2-bromo-5,6-dichlorobenzimidazole (15), followed by deprotection, gave the 2-chloro or 2-bromo-5'-deoxylyxofuranosyl derivative, respectively. The cyclopropylamino derivative was prepared from the 2-chloro derivative. All D-isomers were prepared in an analogous fashion from D-lyxose. Either compounds were inactive against HSV-1 or weak activity was poorly separated from cytoxicity. In contrast, the 2-halogen derivatives in both the alpha-lyxose and 5-deoxy-alpha-lyxose series were active against the Towne strain of HCMV. The 5-deoxy alpha-L analogues were the most active, IC50's = 0.2-0.4 mu M, plaque assay; IC90's = 0.2-2 mu M, yield reduction assay. All of the 2-isopropylamino or 2-cyclopropylamino derivatives were less active (IC50's = 60-100 mu M, plaque assay; IC90's = 17-100 mu M, yield reduction assay) and were not cytotoxic. The methylamino, thio, and methylthio derivatives were neither active nor cytotoxic. The benzylthio derivatives were weakly active, but this activity was poorly separated from cytotoxicity. The alpha-lyxose L-isomers were more active in a plaque assay against the AD169 strain of HCMV compared to the Towne strain, thereby providing additional evidence of antiviral specificity.

  DOI：

  10.1021/jm970545c
• 作为产物：
  描述：

  2,5,6-三氯苯并咪唑 在 苯磺酰胺 、 三氟甲磺酸三甲基硅酯 、 水 、 sodium carbonate 作用下， 以 乙醇 为溶剂， 反应 32.25h， 生成 2,5,6-Trichloro-1-(5deoxy-α-D-lyxofuranosyl)benzimidazole
  参考文献：
  名称：

  Design, Synthesis, and Antiviral Activity of α-Nucleosides:  d- and l-Isomers of Lyxofuranosyl- and (5-Deoxylyxofuranosyl)benzimidazoles

  摘要：

  Several 2-substituted alpha-D- and alpha-L-lyxofuranosyl and 5-deoxylyxofuranosyl derivatives of 5,6-dichloro-2-(isopropylamino)-1- -(beta-L-ribofuranosyl)benzimidazole (1263W94) and 2,5,6-trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) were synthesized and evaluated for activity against two herpesviruses (HSV-1 and HCMV) and for their cytotoxicity against HFF and KB cells. Condensation of 1,2,3,5-tetra-O-acetyl-L-lyxofuranose (2a) with 2,5,6-trichlorobenzimidazole (1) yielded the or-nucleoside 3a. The 2-bromo derivative and 2-methylamino derivative were prepared by treatment of 3a with HBr followed by deprotection or from methylamine, respectively. Compound 3a was deprotected and the resultant nucleoside used to prepare the 2-cyclopropylamino and 2-isopropylamino derivatives. The 2-alkylthio nucleosides were prepared by condensing 2a with 5,6-dichlorobenzimidazole-2-thione followed by deprotection. Alkylation of this adduct gave the 2-methylthio and 2-benzylthio derivatives. Condensation of 5-deoxy-1,2,3-tri-O-acetyl-L-lyxofuranosyl, prepared from L-lyxose, with 1 or 2-bromo-5,6-dichlorobenzimidazole (15), followed by deprotection, gave the 2-chloro or 2-bromo-5'-deoxylyxofuranosyl derivative, respectively. The cyclopropylamino derivative was prepared from the 2-chloro derivative. All D-isomers were prepared in an analogous fashion from D-lyxose. Either compounds were inactive against HSV-1 or weak activity was poorly separated from cytoxicity. In contrast, the 2-halogen derivatives in both the alpha-lyxose and 5-deoxy-alpha-lyxose series were active against the Towne strain of HCMV. The 5-deoxy alpha-L analogues were the most active, IC50's = 0.2-0.4 mu M, plaque assay; IC90's = 0.2-2 mu M, yield reduction assay. All of the 2-isopropylamino or 2-cyclopropylamino derivatives were less active (IC50's = 60-100 mu M, plaque assay; IC90's = 17-100 mu M, yield reduction assay) and were not cytotoxic. The methylamino, thio, and methylthio derivatives were neither active nor cytotoxic. The benzylthio derivatives were weakly active, but this activity was poorly separated from cytotoxicity. The alpha-lyxose L-isomers were more active in a plaque assay against the AD169 strain of HCMV compared to the Towne strain, thereby providing additional evidence of antiviral specificity.

  DOI：

  10.1021/jm970545c
• 作为试剂：
  描述：

  2,5,6-三氯苯并咪唑 、 tri-O-acetyl-5-deoxy-D-ribofuranose 、 三氟甲磺酸三甲基硅酯 、 disodium;carbonate 在 二氯甲烷 、 碳酸氢钠 、 水 、 Sodium sulfate-III 、 silica gel 、 甲醇 、 乙醇 、 乙酸乙酯 、 2,5,6-Trichloro-1-(5deoxy-α-D-lyxofuranosyl)benzimidazole 、 methanolic solution 作用下， 以 乙腈 为溶剂， 反应 34.25h， 生成 2,5,6-Trichloro-1-(5deoxy-α-D-lyxofuranosyl)benzimidazole
  参考文献：
  名称：

  Benzimidazole derivatives for the treatment of viral infections

  摘要：

  根据本发明的第一个方面，提供了以下式子(I)的化合物：其中：R1是羟基；O-乙酰基；或卤素原子；R2是羟基；O-乙酰基；或卤素原子；R3是氢；卤素原子；叠氮基；C2-6烯基；C2-6炔基；C6-14芳基C2-6烯基；C6-14芳基C2-6炔基—NR8R9（其中R8和R9可以相同或不同，并且是氢，C1-8烷基，氰基C1-8烷基，羟基C1-8烷基，卤素C1-8烷基，C3-7环烷基，C1-8烷基C3-7环烷基，C2-6烯基，C3-7环烷基C1-8烷基，C2-6炔基，C6-14芳基，C6-14芳基C1-8烷基，杂环C1-8烷基，C1-8烷基羰基，C6-14芳基磺酰基，C1-8烷基磺酰基或R8R9与它们连接的N原子形成3,4,5或6成员杂环环）；—OR10（其中R10是氢，C1-8烷基，C6-14芳基或C6-14芳基C1-8烷基，C2-6烯基，C2-6炔基，C6-14芳基C2-6烯基或C6-14芳基C2-6炔基）；或—SR11（其中R11是氢，C1-8烷基，C6-14芳基或C6-14芳基C1-8烷基）。

  公开号：

  US06413938B1

文献信息

• [EN] BENZIMIDAZOLE DERIVATIVES<br/>[FR] DERIVES DE BENZIMIDAZOLE
  申请人：GLAXO GROUP LIMITED

  公开号：WO1998035977A1

  公开（公告）日：1998-08-20

  (EN) The present invention relates to certain benzimidazole derivatives and their use in medical therapy particularly for the treatment or prophylaxis of virus infections such as those caused by herpes viruses.(FR) La présente invention concerne certains dérivés de benzimidazole, ainsi que leur utilisation en thérapie médicale, particulièrement dans le traitement ou la prophylaxie d'infections virales telles que les infections aux herpèsvirus.

  (中) 本发明涉及某些苯并咪唑衍生物及其在医疗治疗中的应用，特别是用于治疗或预防病毒感染，如由疱疹病毒引起的感染。(FR) 本发明涉及某些苯并咪唑衍生物及其在医疗治疗中的应用，特别是用于治疗或预防病毒感染，如由疱疹病毒引起的感染。
• BENZIMIDAZOLE DERIVATIVES
  申请人：GLAXO GROUP LIMITED

  公开号：EP0970100A1

  公开（公告）日：2000-01-12
• US6413938B1
  申请人：——

  公开号：US6413938B1

  公开（公告）日：2002-07-02
• Design, Synthesis, and Antiviral Activity of α-Nucleosides:  <scp>d</scp>- and <scp>l</scp>-Isomers of Lyxofuranosyl- and (5-Deoxylyxofuranosyl)benzimidazoles
  作者：Michael T. Migawa、Jean-Luc Girardet、John A. Walker、George W. Koszalka、Stanley D. Chamberlain、John C. Drach、Leroy B. Townsend

  DOI：10.1021/jm970545c

  日期：1998.4.1

  Several 2-substituted alpha-D- and alpha-L-lyxofuranosyl and 5-deoxylyxofuranosyl derivatives of 5,6-dichloro-2-(isopropylamino)-1- -(beta-L-ribofuranosyl)benzimidazole (1263W94) and 2,5,6-trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) were synthesized and evaluated for activity against two herpesviruses (HSV-1 and HCMV) and for their cytotoxicity against HFF and KB cells. Condensation of 1,2,3,5-tetra-O-acetyl-L-lyxofuranose (2a) with 2,5,6-trichlorobenzimidazole (1) yielded the or-nucleoside 3a. The 2-bromo derivative and 2-methylamino derivative were prepared by treatment of 3a with HBr followed by deprotection or from methylamine, respectively. Compound 3a was deprotected and the resultant nucleoside used to prepare the 2-cyclopropylamino and 2-isopropylamino derivatives. The 2-alkylthio nucleosides were prepared by condensing 2a with 5,6-dichlorobenzimidazole-2-thione followed by deprotection. Alkylation of this adduct gave the 2-methylthio and 2-benzylthio derivatives. Condensation of 5-deoxy-1,2,3-tri-O-acetyl-L-lyxofuranosyl, prepared from L-lyxose, with 1 or 2-bromo-5,6-dichlorobenzimidazole (15), followed by deprotection, gave the 2-chloro or 2-bromo-5'-deoxylyxofuranosyl derivative, respectively. The cyclopropylamino derivative was prepared from the 2-chloro derivative. All D-isomers were prepared in an analogous fashion from D-lyxose. Either compounds were inactive against HSV-1 or weak activity was poorly separated from cytoxicity. In contrast, the 2-halogen derivatives in both the alpha-lyxose and 5-deoxy-alpha-lyxose series were active against the Towne strain of HCMV. The 5-deoxy alpha-L analogues were the most active, IC50's = 0.2-0.4 mu M, plaque assay; IC90's = 0.2-2 mu M, yield reduction assay. All of the 2-isopropylamino or 2-cyclopropylamino derivatives were less active (IC50's = 60-100 mu M, plaque assay; IC90's = 17-100 mu M, yield reduction assay) and were not cytotoxic. The methylamino, thio, and methylthio derivatives were neither active nor cytotoxic. The benzylthio derivatives were weakly active, but this activity was poorly separated from cytotoxicity. The alpha-lyxose L-isomers were more active in a plaque assay against the AD169 strain of HCMV compared to the Towne strain, thereby providing additional evidence of antiviral specificity.
• Benzimidazole derivatives for the treatment of viral infections
  申请人：The Regents of the University of Michigan

  公开号：US06413938B1

  公开（公告）日：2002-07-02

  According to a first aspect of the invention there is provided compounds of formula (I): wherein: R1 is hydroxy; O-acetyl; or a halo atom; R2 is hydroxy; O-acetyl; or a halo atom; R3 is hydrogen; a halo atom; azido; C2-6alkenyl; C2-6alkynyl; C6-14aryl C2-6alkenyl; C6-14arylC2-6alkynyl —NR8R9 (where R8 and R9 may be the same or different and are hydrogen, C1-8alkyl, cyanoC1-8alkyl, hydroxyC1-8alkyl, haloC1-8alkyl, C3-7cycloalkyl, C1-8alkylC3-7cycloalkyl, C2-6alkenyl, C3-7cycloalkylC1-8alkyl, C2-6alkynyl, C6-14aryl, C6-14arylC1-8alkyl, heterocycleC1-8alkyl, C1-8alkylcarbonyl, C6-14arylsulfonyl, C1-8alkysulfonyl, or R8R9 together with the N atom to which they are attached form a 3,4,5 or 6 membered heterocyclic ring); —OR10 (where R10 is hydrogen, C1-8alkyl, C6-14aryl, or C6-14arylC1-8alkyl, C2-6alkenyl, C2-6alkynyl, C6-14aryl C2-6alkenyl or C6-14arylC2-6alkynyl); or —SR11 (where R11 is hydrogen, C1-8alkyl, C6-14aryl, or C6-14arylC1-8alkyl).

  根据本发明的第一个方面，提供了以下式（I）的化合物：其中：R1是羟基；O-乙酰基；或卤原子；R2是羟基；O-乙酰基；或卤原子；R3是氢原子；卤原子；叠氮基；C2-6烯基；C2-6炔基；C6-14芳基C2-6烯基；C6-14芳基C2-6炔基-NR8R9（其中R8和R9可能相同也可能不同，为氢原子，C1-8烷基，氰基C1-8烷基，羟基C1-8烷基，卤基C1-8烷基，C3-7环烷基，C1-8烷基C3-7环烷基，C2-6烯基，C3-7环烷基C1-8烷基，C2-6炔基，C6-14芳基，C6-14芳基C1-8烷基，杂环C1-8烷基，C1-8烷基羰基，C6-14芳基磺酰基，C1-8烷基磺酰基，或R8R9与它们连接的N原子一起形成3,4,5或6个成员的杂环环）；-OR10（其中R10是氢原子，C1-8烷基，C6-14芳基，或C6-14芳基C1-8烷基，C2-6烯基，C2-6炔基，C6-14芳基C2-6烯基或C6-14芳基C2-6炔基）；或-SR11（其中R11是氢原子，C1-8烷基，C6-14芳基，或C6-14芳基C1-8烷基）。