[1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzimidazol-2-yl]methanol | 183161-82-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: [1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzimidazol-2-yl]methanol
• 英文别名: (1-((2-trimethylsilylethoxy)methyl)-1H-benzo[d]imidazol-2-yl)methanol；1-(2-trimethylsilylethoxymethyl)-2-hydroxymethylbenzimidazole；[1-(2-trimethylsilylethoxymethyl)benzimidazol-2-yl]methanol
• CAS: 183161-82-2
• 化学式: C₁₄H₂₂N₂O₂Si
• 分子量: 278.426
• InChiKey: AZUUKOITFSPFBH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.84
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  47.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzimidazol-2-yl]methanol 在 二氧化锰 二氯甲烷 、 resultant residue 、 silica gel 、 methanol-dichloromethane 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以to provide the title aldehyde (14.41 g, 55%) as a pale yellow oil的产率得到1-(2-trimethylsilylethoxymethyl)-1H-benzoimidazole-2-carbaldehyde
  参考文献：
  名称：

  CHEMOKINE RECEPTOR BINDING HETEROCYCLIC COMPOUNDS WITH ENHANCED EFFICACY

  摘要：

  该发明涉及由一个核心氮原子和三个侧基团组成的杂环化合物，其中三个侧基团中的两个优选为苯并咪唑甲基和四氢喹啉基，第三个侧基团含有N并且可以包含额外的环。这些化合物与趋化因子受体结合，包括CXCR4和CCR5，并且对人类免疫缺陷病毒（HW）感染目标细胞具有保护作用。

  公开号：

  US20120301427A1
• 作为产物：
  描述：

  2-羟甲基苯并咪唑 、 2-(三甲基硅烷基)乙氧甲基氯 在 N,N-二异丙基乙胺 作用下， 以 DMF (N,N-dimethyl-formamide) 、 正戊烷 为溶剂， 反应 2.0h， 以44%的产率得到[1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzimidazol-2-yl]methanol
  参考文献：
  名称：

  Chemokine receptor binding heterocyclic compounds with enhanced efficacy

  摘要：

  这项发明涉及由一个核心氮原子环绕着三个侧链基团的杂环化合物，其中三个侧链基团中的两个最好是苯并咪唑甲基和四氢喹啉基，第三个侧链基团含有N，并且可选地含有额外的环。这些化合物与趋化因子受体结合，包括CXCR4和CCR5，并且表现出对人类免疫缺陷病毒（HIV）感染靶细胞的保护作用。

  公开号：

  US20030220341A1

文献信息

• Chemokine receptor binding heterocyclic compounds with enhanced efficacy
  申请人：——

  公开号：US20030220341A1

  公开（公告）日：2003-11-27

  The invention relates to heterocyclic compounds consisting of a core nitrogen atom surrounded by three pendant groups, wherein two of the three pendant groups are preferably benzimidazolyl methyl and tetrahydroquinolyl, and the third pendant group contains N and optionally contains additional rings. The compounds bind to chemokine receptors, including CXCR4 and CCR5, and demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).

  这项发明涉及由一个核心氮原子环绕着三个侧链基团的杂环化合物，其中三个侧链基团中的两个最好是苯并咪唑甲基和四氢喹啉基，第三个侧链基团含有N，并且可选地含有额外的环。这些化合物与趋化因子受体结合，包括CXCR4和CCR5，并且表现出对人类免疫缺陷病毒（HIV）感染靶细胞的保护作用。
• CHEMOKINE RECEPTOR BINDING HETEROCYCLIC COMPOUNDS WITH ENHANCED EFFICACY
  申请人：BRIDGER Gary

  公开号：US20080167341A1

  公开（公告）日：2008-07-10

  The invention relates to heterocyclic compounds consisting of a core nitrogen atom surrounded by three pendant groups, wherein two of the three pendant groups are preferably benzimidazolyl methyl and tetrahydroquinolyl, and the third pendant group contains N and optionally contains additional rings. The compounds bind to chemokine receptors, including CXCR4 and CCR5, and demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).

  该发明涉及由一个核心氮原子和三个侧链基团组成的杂环化合物，其中三个侧链基团中有两个是苯并咪唑甲基和四氢喹啉基，第三个侧链基团含有N，并且可以含有额外的环。这些化合物结合趋化因子受体，包括CXCR4和CCR5，并且表现出对人类免疫缺陷病毒（HIV）感染靶细胞的保护效果。
• Chemokine Receptor Binding Heterocyclic Compounds With Enhanced Efficacy
  申请人：Genzyme Corporation

  公开号：US20150038509A1

  公开（公告）日：2015-02-05

  The invention relates to heterocyclic compounds consisting of a core nitrogen atom surrounded by three pendant groups, wherein two of the three pendant groups are preferably benzimidazolyl methyl and tetrahydroquinolyl, and the third pendant group contains N and optionally contains additional rings. The compounds bind to chemokine receptors, including CXCR4 and CCR5, and demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).

  该发明涉及杂环化合物，其由一个核心氮原子和三个下垂基团组成，其中三个下垂基团中的两个优选为苯并咪唑甲基和四氢喹啉基，第三个下垂基团含有N，并且可以包含其他环。这些化合物结合趋化因子受体，包括CXCR4和CCR5，并且对人类免疫缺陷病毒（HIV）感染目标细胞具有保护作用。
• Discovery of Novel Small Molecule Orally Bioavailable C−X−C Chemokine Receptor 4 Antagonists That Are Potent Inhibitors of T-Tropic (X4) HIV-1 Replication
  作者：Renato T. Skerlj、Gary J. Bridger、Al Kaller、Ernest J. McEachern、Jason B. Crawford、Yuanxi Zhou、Bem Atsma、Jonathon Langille、Susan Nan、Duane Veale、Trevor Wilson、Curtis Harwig、Sigrid Hatse、Katrien Princen、Erik De Clercq、Dominique Schols

  DOI：10.1021/jm100073m

  日期：2010.4.22

  The redesign of azamacrocyclic CXCR4 chemokine receptor antagonists resulted in the discovery of novel, small molecule, orally bioavailable compounds that retained T-tropic (CXCR4 using, X4) anti-HIV-1 activity. A structure activity relationship (SA R) was determined on the basis of the inhibition of replication of X4 HIV-1 NL4.3 in MT-4 cells. As a result of lead optimization, we identified (S)-N'-((1H-benzo[d]imidazol-2-Amethyl)-N'-(5,6,7,8-tetrahydroquinolin-8-yl)butane-1,4-diamine (AMD070) 2 as a potent and selective antagonist of CXCR4 with an IC(50) value of 13 nM in a CXCR4 (125)I-SDF inhibition binding assay. Compound 2 inhibited the replication of T-tropic HIV-1 (NL4.3 strain) in MT-4 cells and PBMCs with an IC(50) of 2 and 26 nM, respectively, while remaining noncytotoxic to cells at concentrations exceeding 23 mu M. The pharmacokinetics of 2 was evaluated in rat and dog, and good oral bioavailability was observed in both species. This compound represents the first small molecule orally bioavailable CXCR4 antagonist that was developed for the treatment of HIV-1 infection.