1-(4-benzoylpiperazin-1-yl)-2-(7-bromo-4-methoxy-1H-indol-3-yl)ethane-1,2-dione | 313335-01-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1-(4-benzoylpiperazin-1-yl)-2-(7-bromo-4-methoxy-1H-indol-3-yl)ethane-1,2-dione
• CAS: 313335-01-2
• 化学式: C₂₂H₂₀BrN₃O₄
• 分子量: 470.322
• InChiKey: NLJKWZBNIWOQAT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  82.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(4-benzoylpiperazin-1-yl)-2-(7-bromo-4-methoxy-1H-indol-3-yl)ethane-1,2-dione 在 四(三苯基膦)钯 碳酸氢钠 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.2h， 生成 1-(7-(5-(aminomethyl)furan-2-yl)-4-methoxy-1H-indol-3-yl)-2-(4-benzoylpiperazin-1-yl)ethane-1,2-dione 2,2,2-trifluoroacetate
  参考文献：
  名称：

  [EN] BIFUNCTIONAL MOLECULES WITH ANTIBODY-RECRUITING AND ENTRY INHIBITORY ACTIVITY AGAINST THE HUMAN IMMUNODEFICIENCY VIRUS
  [FR] MOLÉCULES BIFONCTIONNELLES DOTÉES D'UNE ACTIVITÉ DE RECRUTEMENT D'ANTICORPS ET D'INHIBITION DE L'ENTRÉE DU VIRUS DIRIGÉES CONTRE LE VIRUS DE L'IMMUNODÉFICIENCE HUMAINE

  摘要：

  公开号：

  WO2012068366A9
• 作为产物：
  描述：

  tert-butyl 4-[2-(7-bromo-4-methoxy-1H-indol-3-yl)-2-oxoacetyl]piperazine-1-carboxylate 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 1-(4-benzoylpiperazin-1-yl)-2-(7-bromo-4-methoxy-1H-indol-3-yl)ethane-1,2-dione
  参考文献：
  名称：

  [EN] TARGETED BIFUNCTIONAL DEGRADERS
  [FR] AGENTS DE DÉGRADATION BIFONCTIONNELS CIBLÉS

  摘要：

  本发明在一个方面提供了可以用来促进或增强降解某些循环蛋白的双功能化合物。在另一个方面，本发明提供了可以用来促进或增强降解某些自身抗体的双功能化合物。在某些实施方式中，治疗或管理疾病和/或疾病需要降解、去除或减少受试者体内循环蛋白或自身抗体的浓度。因此，在某些实施方式中，将本发明的化合物给予受试者可去除或减少循环蛋白或自身抗体的循环浓度，从而治疗、改善或预防疾病和/或疾病。在某些实施方式中，循环蛋白是TNF。

  公开号：

  WO2021072269A1

文献信息

• [EN] CYTOTOXIC-DRUG DELIVERING MOLECULES TARGETING HIV (CDM-HS), CYTOTOXIC ACTIVITY AGAINST THE HUMAN IMMUNODEFICIENCY VIRUS AND METHODS OF USE<br/>[FR] MOLÉCULE DE DÉLIVRANCE DE MÉDICAMENT SOUS FORME CYTOTOXIQUE CIBLANT LE VIH (CDM-H), ACTIVITÉ CYTOTOXIQUE CONTRE LE VIRUS DE L'IMMUNODÉFICIENCE HUMAINE ET LEURS MÉTHODES D'UTILISATION
  申请人：UNIV YALE

  公开号：WO2013162757A1

  公开（公告）日：2013-10-31

  The present invention is directed to new bifunctional compounds and methods for treating HIV infections. The bifunctional small molecules, generally referred to as CDM-Hs, function through orthogonal pathways, by inhibiting the gp120-CD4 interaction, and by introducing cytotoxic moieties to gp120-expressing cells, thereby causing cell death and preventing cell infection and spread of HIV. It is shown that CDM-Hs bind to gp120 and gp-120 expressing cells competitively with CD4, and these compounds cause cell death of HIV-infected cells, thereby decreasing viral infectivity. 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CDM-Hs，通过抑制gp120-CD4相互作用和向gp120表达细胞引入细胞毒性基团的正交途径发挥作用，从而导致细胞死亡，防止细胞感染和HIV传播。已经证明CDM-Hs与gp120和表达gp120的细胞竞争性结合CD4，这些化合物导致HIV感染细胞死亡，从而降低病毒的传染性。本文描述了化合物和方法。
• 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。
• 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。
• [EN] BIFUNCTIONAL SMALL MOLECULES TO TARGET THE SELECTIVE DEGRADATION OF CIRCULATING PROTEINS<br/>[FR] PETITES MOLÉCULES BIFONCTIONNELLES POUR CIBLER LA DÉGRADATION SÉLECTIVE DE PROTÉINES CIRCULANTES
  申请人：UNIV YALE

  公开号：WO2019199634A4

  公开（公告）日：2019-12-05
• BIFUNCTIONAL MOLECULES WITH ANTIBODY-RECRUITING AND ENTRY INHIBITORY ACTIVITY AGAINST THE HUMAN IMMUNODEFICIENCY VIRUS
  申请人：YALE UNIVERSITY

  公开号：US20190002447A1

  公开（公告）日：2019-01-03

  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.