N-(2,4-dinitrophenyl)-3,6,9,12-tetraoxapentadec-14-yn-1-amine | 1196449-87-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(2,4-dinitrophenyl)-3,6,9,12-tetraoxapentadec-14-yn-1-amine
• 英文别名: DNP-PEG4-propargyl；2,4-dinitro-N-[2-[2-[2-(2-prop-2-ynoxyethoxy)ethoxy]ethoxy]ethyl]aniline
• CAS: 1196449-87-2
• 化学式: C₁₇H₂₃N₃O₈
• 分子量: 397.385
• InChiKey: TVRWKNZCQCLIJA-UHFFFAOYSA-N

物化性质

• 沸点：
  553.8±50.0 °C(Predicted)
• 密度：
  1.295±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  28
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  141
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N-(2,4-dinitrophenyl)-3,6,9,12-tetraoxapentadec-14-yn-1-amine 在 zinc dibromide 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 4.0h， 生成
  参考文献：
  名称：

  Preparation and Evaluation of Radiolabeled Antibody Recruiting Small Molecules That Target Prostate-Specific Membrane Antigen for Combined Radiotherapy and Immunotherapy

  摘要：

  The feasibility of developing a single agent that can deliver radioactive iodine and also direct cellular immune function by engaging endogenous antibodies as an antibody-recruiting small molecule (ARM) was determined. A library of new prostate-specific membrane antigen (PSMA)-binding ligands that contained antibody-recruiting 2,4-dinitrophenyl (DNP) groups and iodine were synthesized and screened in vitro and in vivo. A lead compound (9b) showed high affinity for PSMA and the ability to bind anti-DNP antibodies. Biodistribution studies of the iodine-125 analogue showed 3% ID/g in LNCaP xenograft tumors at 1 h postinjection with tumor-to-blood and tumor-to-muscle ratios of 10:1 and 44:1, respectively. The radiolabeled analogue was bound and internalized by LNCaP cells, with both functions blocked using a known PSMA inhibitor. A second candidate showed high tumor uptake (>10% ID/g) but had minimal binding to anti-DNP antibodies. The compounds reported represent the first examples of small molecules developed specifically for combination immunotherapy and radiotherapy for prostate cancer.

  DOI：

  10.1021/acs.jmedchem.5b01881
• 作为产物：
  描述：

  1-azido-3,6,9,12-tetraoxapentadec-14-yne 在 水 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 2.0h， 生成 N-(2,4-dinitrophenyl)-3,6,9,12-tetraoxapentadec-14-yn-1-amine
  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

• Chemical Control over Immune Recognition: A Class of Antibody-Recruiting Small Molecules That Target Prostate Cancer
  作者：Ryan P. Murelli、Andrew X. Zhang、Julien Michel、William L. Jorgensen、David A. Spiegel

  DOI：10.1021/ja906844e

  日期：2009.12.2

  Prostate cancer is the second leading cause of cancer-related death among the American male population, and society is in dire need of new approaches to treat this disease. Here we report the design, synthesis, and biological evaluation of a class of bifunctional small molecules called antibody-recruiting molecules targeting prostate cancer (ARM-Ps) that enhance the recognition of prostate cancer cells

  前列腺癌是美国男性人口中癌症相关死亡的第二大原因，社会迫切需要治疗这种疾病的新方法。在这里，我们报告了一类双功能小分子的设计、合成和生物学评估，称为靶向前列腺癌的抗体招募分子 (ARM-Ps)，可增强人类免疫系统对前列腺癌细胞的识别。ARM-P 衍生物是通过晶体学数据的计算分析合理设计的，我们在此证明这些材料能够 (1) 以高亲和力（从高 pM 到低 nM）结合前列腺特异性膜抗原 (PSMA)，（2 ) 以抗 DNP 抗体、ARM-P 和 LNCaP 人前列腺癌细胞三元复合物的形成为模板，(3) 在人效应细胞存在下介导 LNCaP 细胞的抗体依赖性杀伤。这份手稿描述了基本化学原理在设计一类具有高治疗潜力的新型分子中的应用。我们相信，这种基于小分子的通用策略可以为治疗癌症和其他疾病带来新的方向。
• Bifunctional molecules with antibody-recruiting and entry inhibitory activity against the human immunodeficiency virus
  申请人：Spiegel David

  公开号：US09181224B2

  公开（公告）日：2015-11-10

  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表达细胞中，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gp120表达的细胞竞争性地结合CD4，从而通过MT-2细胞测定显示降低病毒的感染性，结合导致三元复合物的形成，通过招募抗DNP抗体结合到其中，三元复合物中存在的抗体促进了gp120表达细胞的补体依赖性破坏。本文描述了化合物和方法。
• [EN] BIFUNCTIONAL MOLECULES WITH ANTIBODY-RECRUITING AND ENTRY INHIBITORY ACTIVITY AGAINST THE HUMAN IMMUNODEFICIENCY VIRUS<br/>[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
  申请人：UNIV YALE

  公开号：WO2012068366A9

  公开（公告）日：2013-07-18
• 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.
• US9181224B2
  申请人：——

  公开号：US9181224B2

  公开（公告）日：2015-11-10