2-bromo-5,6-dichloro-1-(α-D-lyxofuranosyl)benzimidazole | 202119-38-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 苯并咪唑核糖核苷和核糖核苷酸
• 英文名称: 2-bromo-5,6-dichloro-1-(α-D-lyxofuranosyl)benzimidazole
• 英文别名: (2S,3S,4R,5R)-2-(2-bromo-5,6-dichloro-benzimidazol-1-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol；(2S,3S,4R,5R)-2-(2-bromo-5,6-dichlorobenzimidazol-1-yl)-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 202119-38-8
• 化学式: C₁₂H₁₁BrCl₂N₂O₄
• 分子量: 398.04
• InChiKey: NMAMPJIAXSGTLN-RCWTZXSCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  87.7
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  甲胺 、 2-bromo-5,6-dichloro-1-(α-D-lyxofuranosyl)benzimidazole 以 乙醇 为溶剂， 反应 16.0h， 以62%的产率得到1-(α-D-lyxofuranosyl)-2-methylamino-5,6-dichloro-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 、 氢溴酸 、 sodium carbonate 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 29.08h， 生成 2-bromo-5,6-dichloro-1-(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

文献信息

• LYXOFURANOSYL BENZIMIDAZOLES AS ANTIVIRAL AGENTS
  申请人：THE REGENTS OF THE UNIVERSITY OF MICHIGAN

  公开号：EP1000080A1

  公开（公告）日：2000-05-17
• US6455506B1
  申请人：——

  公开号：US6455506B1

  公开（公告）日：2002-09-24
• [EN] LYXOFURANOSYL BENZIMIDAZOLES AS ANTIVIRAL AGENTS<br/>[FR] BENZIMIDAZOLES DE LYXOFURANOSYLE EN TANT QU'AGENTS ANTIVIRAUX
  申请人：THE REGENTS OF THE UNIVERSITY OF MICHIGAN

  公开号：WO1999006424A1

  公开（公告）日：1999-02-11

  (EN) The present invention pertains to D- and L-lyxofuranosyl benzimidazole compounds. In one embodiment, the present invention pertains to D- and L-lyxofuranosyl benzimidazole compounds selected from the group consisting of compounds having a formula selected from the following: (beta-D), (beta-L), (alpha-L) and (alpha-D) wherein R2, R4, R5, R6, and R7 are independently the same or different and independently selected from the group consisting of: -H, -F, -Cl, -Br, -I, -NO2, -N(R8)2, -OR8, -SR12, and -CF3, wherein R8 is independently -H or an alkyl group having 1-6 carbon atoms and wherein R12 is independently -H or a hydrocarbyl group having 1-10 carbon atoms; and R9, R10 and R11 are independently the same or different and are H or a hydroxyl protecting group; anomeric and optical isomers thereof; and pharmaceutically acceptable salts and prodrug derivatives thereof. The present invention also pertains to antiviral compositions using these compounds, methods of treating a viral infection using these compounds, and the use of these compounds in the preparation of a medicament for use in the treatment of a viral infection.(FR) L'invention concerne des composés de benzimidazole de D-et L-lyxofuranosyle. Dans un mode de réalisation, elle concerne des composés de benzimidazole de D- et L-lyxofuranosyle sélectionnés dans le groupe constitué par des composés dont la formule est sélectionnée dans les suivantes: (bêta-D) (bêta-L) (alpha-L) (alpha-D) dans lesquelles R2, R4, R5, R6 et R7 sont indépendamment semblables ou différents et sélectionnés indépendamment dans le groupe constitué par: -H, -F, -Cl, -Br, -I, -NO2, -N(R8)2, -OR8, -SR12 et -CF3, dans lesquelles R8 représente indépendamment -H ou un groupe alkyle possédant 1-6 atomes de carbone et R12 représente indépendamment -H ou un groupe hydrocarbyle possédant 1-10 atomes de carbone; R9, R10 et R11 sont indépendamment semblables ou différents et représentent H ou un groupe de protection hydroxyle; leurs isomères anomères et optiques; leurs sels et leurs dérivés de promédicaments acceptables sur le plan pharmaceutique. Elle concerne également des compositions antivirales mettant ces composés en application, des procédés servant à traiter l'infection virale au moyen de ces composés et l'utilisation de ces composés dans la préparation d'un médicament conçu pour être utilisé afin de traiter une infection virale.
• 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.