tert-butyl 3-(2,4-dichlorophenoxy)propylcarbamate | 1421333-90-5

• 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: tert-butyl 3-(2,4-dichlorophenoxy)propylcarbamate
• 英文别名: Tert-butyl 3-(2,4-dichlorophenoxy)propylcarbamate；tert-butyl N-[3-(2,4-dichlorophenoxy)propyl]carbamate
• CAS: 1421333-90-5
• 化学式: C₁₄H₁₉Cl₂NO₃
• 分子量: 320.216
• InChiKey: GNGXIXMEDGUCOH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-(2,4-dichlorophenoxy)propylcarbamate 在 盐酸 、 4-二甲氨基吡啶 、 sodium hydride 、 potassium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 13.38h， 生成 6-((Z)-2-((E)-2-(2-chloro-3-((E)-2-(1-(6-((3-((3-(2,4-dichlorophenoxy)propyl)(prop-2-yn-1-yl)amino)propyl)thio)-6-oxohexyl)-3,3-dimethyl-3H-indol-1-ium-2-yl)vinyl)cyclohex-2-en-1-ylidene)ethylidene)-3,3-dimethylindolin-1-yl)hexanoate
  参考文献：
  名称：

  Monoamine Oxidase A Inhibitor–Near-Infrared Dye Conjugate Reduces Prostate Tumor Growth

  摘要：

  Development of anti-cancer agents with high tumor-targeting specificity and efficacy is critical for modern multidisciplinary cancer research. Monoamine oxidase A (MAOA), a mitochondria-bound enzyme, degrades monoamine neurotransmitters and dietary monoamines. Recent evidence suggests a correlation between increased MAOA expression and prostate cancer (PCa) progression with poor outcomes for patients. MAOA induces epithelialmesenchymal transition (EMT) and augments hypoxic effects by producing excess reactive oxygen species. Thus, development of MAOA inhibitors which selectively target tumors becomes an important goal in cancer pharmacology. Here we describe the design, synthesis, and in vitro and in vivo evaluation of NMI, a conjugate that combines a near-infrared dye for tumor targeting with the moiety derived from the MAOA inhibitor clorgyline. NMI inhibits MAOA with low micromolar IC50, suppresses PCa cell proliferation and colony formation, and reduces migration and invasion. In mouse PCa xenografts, NMI targets tumors with no detectable accumulation in normal tissues, providing effective reduction of the tumor burden. Analysis of tumor specimens shows reduction in Ki-67(+) and CD31(+) cells, suggesting a decrease of cell proliferation and angiogenesis and an increase in M30+ cells, indicating increased apoptosis. Gene expression profiles of tumors treated with NMI demonstrate reduced expression of oncogenes FOS, JUN, NFKB, and MYC and cell cycle regulators CCND1, CCNE1, and CDK4/6, along with increases in the levels of tumor suppressor gene TP53, cell cycle inhibitors CDKN1A and CDKN2A, and MAOA-downstream genes that promote EMT, tumor hypoxia, cancer cell migration, and invasion. These data suggest that NMI exerts its effect through tumor-targeted delivery of a MAOA-inactivating group, making NMI a valuable anti-tumor agent.

  DOI：

  10.1021/ja512613j
• 作为产物：
  描述：

  1-(3-溴丙氧基)-2,4-二氯苯 在 sodium azide 、 palladium on activated charcoal 、 氢气 作用下， 以 甲基叔丁基醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 tert-butyl 3-(2,4-dichlorophenoxy)propylcarbamate
  参考文献：
  名称：

  [EN] MONOAMINE OXIDASE INHIBITORS AND METHODS FOR TREATMENT AND DIAGNOSIS OF PROSTATE CANCER
  [FR] INHIBITEURS DE MONOAMINE OXYDASE ET PROCÉDÉS POUR LE TRAITEMENT ET LE DIAGNOSTIC DU CANCER DE LA PROSTATE

  摘要：

  公开号：

  WO2013016580A3

文献信息

• MONOAMINE OXIDASE INHIBITORS AND METHODS FOR TREATMENT AND DIAGNOSIS OF PROSTATE CANCER
  申请人：SHIH Jean C.

  公开号：US20130039854A1

  公开（公告）日：2013-02-14

  A mechanism of monoamine oxidases (MAOs) driven epithelium-to-mesenchymal transition (EMT) is disclosed. Also disclosed are methods for treating cancer by inhibiting or suppressing MAOs in cancer cells. Novel MAOs inhibitors, such as small molecules, siRNA, shRNA, antisense oligonucleotides, aptamers, decoys, and pharmaceutical compositions useful for treating cancer by disrupting the workings of MAOs are provided. In particular, a class of conjugates formed by covalently conjugating near infrared dye 783, IR-780, and MHI-148 to a MAO inhibitor, such as clorgyline, with and without encapsulation it in a nanoparticle is provided. Other aspects of the invention include methods for forming the nano-conjugates, method for monitoring treatment progress in a cancer patient by monitoring the changes in MAO activity, methods for screening patients who are at risk of cancer or differentiating different forms of cancer by assaying the level and location of MAO activity.

  本发明揭示了一种单胺氧化酶(MAOs)驱动的上皮-间质转化(EMT)机制。同时，本发明还揭示了通过抑制或抑制癌细胞中的MAOs来治疗癌症的方法。本发明提供了新型的MAOs抑制剂，例如小分子、siRNA、shRNA、反义寡核苷酸、aptamer、诱饵和制药组合物，用于通过破坏MAOs的作用来治疗癌症。特别地，本发明提供了一类共价结合近红外染料783、IR-780和MHI-148与MAO抑制剂（例如克洛吉林）形成的共轭物，有或没有包封在纳米粒子中。本发明的其他方面包括形成纳米共轭物的方法，通过监测MAO活性的变化来监测癌症患者的治疗进展的方法，通过测定MAO活性水平和位置来筛选癌症风险患者或区分不同类型的癌症的方法。
• MAO Inhibitors and Their Conjugates as Therapeutics For The Treatment of Brain Cancer
  申请人：University of Southern California

  公开号：US20150209361A1

  公开（公告）日：2015-07-30

  A pharmaceutical composition and method for treating brain cancer are provided. The method includes administering to a patient in need thereof an effective amount of one or more compounds that include moclobemide, clorgyline, clorgyline's Near-infra-red dye Monoamine Oxidase Inhibitor (NMI), and MHI 148-clorgyline, and their salt thereof. The composition and method are particularly effective in reducing the size of glioblastomas that are temozolomide (TMZ) resistant.

  提供了一种用于治疗脑癌的药物组合物和方法。该方法包括向需要治疗的患者施用一种或多种化合物的有效量，其中包括莫克洛贝胺、克洛吉林、克洛吉林的近红外染料单胺氧化酶抑制剂(NMI)和MHI 148-克洛吉林及其盐。该组合物和方法特别有效于减小对替莫唑胺（TMZ）具有抵抗力的胶质母细胞瘤的大小。
• MAO inhibitors and their conjugates as therapeutics for the treatment of brain cancer
  申请人：University of Southern California

  公开号：US10561663B2

  公开（公告）日：2020-02-18

  A pharmaceutical composition and method for treating brain cancer are provided. The method includes administering to a patient in need thereof an effective amount of one or more compounds that include moclobemide, clorgyline, clorgyline's Near-infra-red dye Monoamine Oxidase Inhibitor (NMI), and MHI 148-clorgyline, and their salt thereof. The composition and method are particularly effective in reducing the size of glioblastomas that are temozolomide (TMZ) resistant.

  提供了一种治疗脑癌的药物组合物和方法。该方法包括向有需要的患者施用有效量的一种或多种化合物，这些化合物包括吗氯贝胺、氯吉林、氯吉林的近红染料单胺氧化酶抑制剂（NMI）和MHI 148-氯吉林，以及它们的盐。该组合物和方法对减小对替莫唑胺（TMZ）耐药的胶质母细胞瘤的体积特别有效。
• MAO INHIBITORS AND THEIR CONJUGATES AS THERAPEUTICS FOR THE TREATMENT OF BRAIN CANCER
  申请人：University Of Southern California

  公开号：EP3104846B1

  公开（公告）日：2020-10-14
• US9675620B2
  申请人：——

  公开号：US9675620B2

  公开（公告）日：2017-06-13