1-[4-[2-[2-[2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-[(2R)-4-benzoyl-2-methylpiperazin-1-yl]ethane-1,2-dione | 1196449-88-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: 1-[4-[2-[2-[2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-[(2R)-4-benzoyl-2-methylpiperazin-1-yl]ethane-1,2-dione
• CAS: 1196449-88-3
• 化学式: C₃₃H₄₃N₇O₉
• 分子量: 681.746
• InChiKey: SIINNOUAZQUBQP-RUZDIDTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  49
• 可旋转键数：
  22
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  156
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  N-(2,4-dinitrophenyl)-3,6,9,12-tetraoxapentadec-14-yn-1-amine 、 1-[4-[2-[2-[2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-[(2R)-4-benzoyl-2-methylpiperazin-1-yl]ethane-1,2-dione 在 copper(ll) sulfate pentahydrate 、 sodium ascorbate 作用下， 以 水 、 叔丁醇 为溶剂， 反应 0.33h， 以80%的产率得到ARM-H
  参考文献：
  名称：

  BIFUNCTIONAL MOLECULES WITH ANTIBODY-RECRUITING AND ENTRY INHIBITORY ACTIVITY AGAINST THE HUMAN IMMUNODEFICIENCY VIRUS

  摘要：

  本发明涉及新的双功能化合物和治疗HIV感染的方法。这些双功能小分子通常被称为ARM-H'，通过抑制gp120-CD4相互作用和招募抗DNP抗体到gp120表达细胞上，从而通过正交途径发挥作用，防止细胞感染和HIV的传播。已经证明ARM-H与gp120和gp-120表达的细胞竞争性地结合CD4，从而通过MT-2细胞测定减少病毒的感染性，结合导致三元复合物的形成，招募抗DNP抗体结合到其中，三元复合物中的抗体促进gp120表达细胞的补体依赖性破坏。本文描述了化合物和方法。

  公开号：

  US20120269766A1
• 作为产物：
  描述：

  4-benzoyl-2-(R)-methyl-1-[(4-nitro-7-oxido-1H-pyrrolo[2,3-b]pyridin-3-yl)oxoacetyl]piperazine 在 sodium hydride 、 三氯化磷 作用下， 以 乙二醇二甲醚 、 乙酸乙酯 为溶剂， 反应 6.0h， 生成 1-[4-[2-[2-[2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]-1H-pyrrolo[2,3-b]pyridin-3-yl]-2-[(2R)-4-benzoyl-2-methylpiperazin-1-yl]ethane-1,2-dione
  参考文献：
  名称：

  BIFUNCTIONAL MOLECULES WITH ANTIBODY-RECRUITING AND ENTRY INHIBITORY ACTIVITY AGAINST THE HUMAN IMMUNODEFICIENCY VIRUS

  摘要：

  本发明涉及新的双功能化合物和治疗HIV感染的方法。这些双功能小分子通常被称为ARM-H'，通过抑制gp120-CD4相互作用和招募抗DNP抗体到gp120表达细胞上，从而通过正交途径发挥作用，防止细胞感染和HIV的传播。已经证明ARM-H与gp120和gp-120表达的细胞竞争性地结合CD4，从而通过MT-2细胞测定减少病毒的感染性，结合导致三元复合物的形成，招募抗DNP抗体结合到其中，三元复合物中的抗体促进gp120表达细胞的补体依赖性破坏。本文描述了化合物和方法。

  公开号：

  US20120269766A1

文献信息

• Bifunctional molecules with antibody-recruiting and entry inhibitory activity against the human immunodeficiency virus
  申请人：YALE UNIVERSITY

  公开号：US10030008B2

  公开（公告）日：2018-07-24

  The present invention is directed to new bifunctional compounds and methods for treating HIV infections. The bifunctional small molecules, generally referred to as ARM-HI's, function through orthogonal pathways, by inhibiting the gp120-CD4 interaction, and by recruiting anti-DNP antibodies to gp120-expressing cells, thereby preventing cell infection and spread of HIV. It has been shown that ARM-HI's bind to gp120 and gp-120 expressing cells competitively with CD4, thereby decreasing viral infectivity as shown by an MT-2 cell assay, the binding leading to formation of a ternary complex by recruiting anti-DNP antibodies to bind thereto, the antibodies present in the ternary complex promoting the complement-dependent destruction of the gp120-expressing cells. Compounds and methods are described herein.

  本发明涉及治疗艾滋病毒感染的新型双功能化合物和方法。这种双功能小分子一般称为 ARM-HI，通过正交途径发挥作用，抑制 gp120 与 CD4 的相互作用，并将抗 DNP 抗体募集到表达 gp120 的细胞，从而防止细胞感染和 HIV 的传播。研究表明，ARM-HI 与 CD4 竞争性地结合到 gp120 和表达 gp-120 的细胞上，从而降低病毒的感染性，如 MT-2 细胞试验所示，这种结合通过招募抗 DNP 抗体与之结合而形成三元复合物，存在于三元复合物中的抗体可促进依赖补体的 gp120 表达细胞的破坏。本文描述了化合物和方法。
• US9181224B2
  申请人：——

  公开号：US9181224B2

  公开（公告）日：2015-11-10
• US9562038B2
  申请人：——

  公开号：US9562038B2

  公开（公告）日：2017-02-07
• BIFUNCTIONAL MOLECULES WITH ANTIBODY-RECRUITING AND ENTRY INHIBITORY ACTIVITY AGAINST THE HUMAN IMMUNODEFICIENCY VIRUS
  申请人：Spiegel David

  公开号：US20120269766A1

  公开（公告）日：2012-10-25

  The present invention is directed to new bifunctional compounds and methods for treating HIV infections. The bifunctional small molecules, generally referred to as ARM-H′ function through orthogonal pathways, by inhibiting the gp120-CD4 interaction, and by recruiting anti-DNP antibodies to gp120-expressing cells, thereby preventing cell infection and spread of HIV. It has been shown that ARM-H's bind to gp120 and gp-120 expressing cells competitively with CD4, thereby decreasing viral infectivity as shown by an MT-2 cell assay, the binding leading to formation of a ternary complex by recruiting anti-DNP antibodies to bind thereto, the antibodies present in the ternary complex promoting the complement-dependent destruction of the gp120-expressing cells. Compounds and methods are described herein.

  本发明涉及新的双功能化合物和治疗HIV感染的方法。这些双功能小分子通常被称为ARM-H'，通过抑制gp120-CD4相互作用和招募抗DNP抗体到gp120表达细胞上，从而通过正交途径发挥作用，防止细胞感染和HIV的传播。已经证明ARM-H与gp120和gp-120表达的细胞竞争性地结合CD4，从而通过MT-2细胞测定减少病毒的感染性，结合导致三元复合物的形成，招募抗DNP抗体结合到其中，三元复合物中的抗体促进gp120表达细胞的补体依赖性破坏。本文描述了化合物和方法。
• An Antibody-Recruiting Small Molecule That Targets HIV gp120
  作者：Christopher G. Parker、Robert A. Domaoal、Karen S. Anderson、David A. Spiegel

  DOI：10.1021/ja9057647

  日期：2009.11.18

  HIV/AIDS is a global pandemic for which new treatment strategies are desperately needed. We have designed a novel small molecule, designated as ARM-H, that has the potential to interfere with HIV survival through two mechanisms: (1) by recruiting antibodies to gp120-expressing virus particles and infected human Celts, thus enhancing their uptake and destruction by the human immune system, and (2) by binding the viral glycoprotein gp120, inhibiting its interaction with the human protein CD4 and preventing virus entry. Here we demonstrate that ARM-H is capable of simultaneously binding gp120, a component of the Env surface viral glycoprotein (found on the surface of both HIV and virus-infected cells) and anti-2,4-dinitrophenyl antibodies (already present in the human bloodstream). The ternary complex formed between the antibody, ARM-H, and gp120 is immunologically active and leads to the complement-mediated destruction of Env-expressing cells. Furthermore, ARM-H prevents virus entry into human T-cells and should therefore be capable of inhibiting virus replication through two mutually reinforcing mechanisms (inhibition of virus entry and antibody-mediated killing). These studies demonstrate the viable anti-HIV activity of antibody-recruiting small molecules and have the potential to initiate novel paradigms in HIV treatment.