1-methyl-4-phenoxy-1,2,3,6-tetrahydropyridine | 144466-71-7

• 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: 1-methyl-4-phenoxy-1,2,3,6-tetrahydropyridine
• 英文别名: 1-methyl-4-phenoxy-3,6-dihydro-2H-pyridine
• CAS: 144466-71-7
• 化学式: C₁₂H₁₅NO
• 分子量: 189.257
• InChiKey: FIUSLMSEWCUYCY-UHFFFAOYSA-N

物化性质

• 沸点：
  282.8±35.0 °C(Predicted)
• 密度：
  1.061±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-methyl-4-phenoxy-1,2,3,6-tetrahydropyridine 在 过氧化苯甲酸叔丁酯 、 copper(l) chloride 作用下， 以 乙腈 为溶剂， 反应 0.5h， 生成 1-methyl-4-phenoxy-2,3-dihydropyridinium perchlorate
  参考文献：
  名称：

  化学模型研究的单胺氧化酶B催化4-取代的1-甲基-1,2,3,6-四氢吡啶的氧化。

  摘要：

  已经提出了MAO-B催化的胺的α-碳氧化可通过单电子转移（SET）或氢原子转移（HAT）途径进行。为了试图区分这些途径，我们使用化学模型检查了一系列4-取代的1-甲基-1,2,3,6-四氢吡啶衍生物（为MAO-B底物的化合物）的α-碳氧化SET途径[使用Fe + 3（1,10-菲咯啉）3的PF-6盐作为电子受体]和HAT途径（使用叔丁氧基作为氢原子受体）。用这些化合物观察到的氧化和氘同位素速率与两个模型反应相似。因此，与它们在建模相关细胞色素P450催化的N，N-二甲基苯胺衍生物的α-碳氧化中的用途不同，

  DOI：

  10.1016/s0968-0896(97)00101-6
• 作为产物：
  描述：

  1-methyl-4-phenoxypyridinium iodide 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 0.25h， 生成 1-methyl-4-phenoxy-1,2,3,6-tetrahydropyridine
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of novel 4-substituted 1-methyl-1,2,3,6-tetrahydropyridine analogs of MPTP

  摘要：

  The exceptionally good MAO-B substrate properties of several 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) derivatives have prompted studies to evaluate the corresponding properties of tetrahydropyridines bearing heteroatom-linked groups at C-4. The 1-methyl-4-phenoxy-1,2,3,6-tetrahydropyridine analog proved to be an excellent MAO-B substrate. Unlike analogs bearing hydrocarbon substituents at C-4, the resulting dihydropyridinium metabolite did not undergo further oxidation to the pyridinium compound but rather underwent hydrolytic cleavage. This observation has led to studies designed to explore the possibility of developing novel, nontoxic derivatives of MPTP bearing potential pharmacologically active leaving groups at C-4. In this paper we report the results of synthetic and metabolic studies on a series of tetrahydropyridine analogs of MPTP with oxygen, sulfur, and carbamoyloxy derivatives on C-4 which serve as model compounds to evaluate the scope of this prodrug concept.

  DOI：

  10.1021/jm00101a026

文献信息

• <i>In Vivo</i> Metabolic Trapping Radiotracers for Imaging Monoamine Oxidase-A and -B Enzymatic Activity
  作者：Allen F. Brooks、Xia Shao、Carole A. Quesada、Phillip Sherman、Peter J. H. Scott、Michael R. Kilbourn

  DOI：10.1021/acschemneuro.5b00223

  日期：2015.12.16

  is trapped within brain tissues. Radiotracers with phenyl, biphenyl, and 7-coumarinyl ethers were evaluated using microPET imaging in rat and primate brains. No isozyme selectivity for radiotracer trapping was observed in the rat brain for any compound, but in the monkey brain, the phenyl ether demonstrated MAO-A selectivity and the coumarinyl ether showed MAO-B selectivity. These are lead compounds

  单胺氧化酶（MAO-A和MAO-B）的同工酶是参与许多生物胺代谢的重要酶，包括神经递质5-羟色胺，多巴胺和去甲肾上腺素。近来，已经提出MAO-B浓度的变化是与阿尔茨海默氏病有关的神经炎症的体内标志物。用于对MAO酶表达或活性变化进行成像的体内放射性示踪剂的先前开发已经利用了不可逆的基于炔丙基胺的自杀抑制剂或高亲和力可逆结合抑制剂。作为替代方法，我们研究了1- [ 11C]甲基-4-芳氧基-1,2,3,6-四氢吡啶类作为单胺氧化酶的代谢捕获剂。MAO介导的氧化和自发水解产生1- [ 11 C]甲基-2,3-二氢-4-吡啶酮作为一种亲水性代谢产物，被捕集在脑组织中。使用microPET成像在大鼠和灵长类动物大脑中评估了具有苯基，联苯和7-香豆素醚的放射性示踪剂。在大鼠脑中没有观察到任何化合物对放射性示踪剂捕获的同工酶选择性，但是在猴脑中，苯醚显示出MAO-A选择性，香豆素醚显示出MAO-B选择
• [EN] COMPOUND COMPRISING A MAO TARGETING/ SEEKER MOIETY FOR TREATING HUMAN GLIOMAS<br/>[FR] COMPOSÉ COMPRENANT UN FRAGMENT DE CIBLAGE/RECHERCHE DE MAO POUR LE TRAITEMENT DE GLIOMES HUMAINS
  申请人：METHODIST HOSPITAL RES INST

  公开号：WO2013151584A1

  公开（公告）日：2013-10-10

  Disclosed are compound for targeting chemotherapeutic agents to mammalian mitochondria. Also disclosed are monoamine oxidase compositions, and methods of using them for the selective therapy of mammalian cancers, and in particular, in the treatment of human gliomas. Also disclosed are methods employing the novel targeted chemotherapeutics with one or more conventional anti-cancer therapies, including, for example, radiotherapy.

  本发明涉及用于靶向化学治疗药物到哺乳动物线粒体的化合物。还揭示了单胺氧化酶组成物，并使用它们进行哺乳动物癌症的选择性治疗，特别是在人类胶质瘤的治疗中。还揭示了使用新型靶向化疗药物与一种或多种传统抗癌疗法（例如放疗）的方法。
• Chemotherapeutic Compositions and Methods for Treating Human Gliomas
  申请人：The Methodist Hospital Research Institute

  公开号：US20140323513A1

  公开（公告）日：2014-10-30

  Disclosed are compound for targeting chemotherapeutic agents to mammalian mitochondria. Also disclosed are monoamine oxidase-specific compositions, and methods of using them for the selective therapy of mammalian cancers, and in particular, in the treatment of human gliomas. Also disclosed are methods employing the novel targeted chemotherapeutics with one or more conventional anti-cancer therapies, including, for example, radiotherapy, or multi-drug regimens.

  本发明涉及用于靶向化疗药物作用于哺乳动物线粒体的化合物。还公开了单胺氧化酶特异性组合物，以及使用它们进行哺乳动物癌症的选择性治疗的方法，特别是在人类胶质瘤的治疗中。还公开了使用新型靶向化疗药物与一种或多种常规抗癌疗法，包括放射治疗或多药物方案的方法。
• COMPOUND COMPRISING A MAO TARGETING/SEEKER MOIETY FOR TREATING HUMAN GLIOMAS
  申请人：The Methodist Hospital Research Institute

  公开号：EP3815685A2

  公开（公告）日：2021-05-05

  Disclosed are compound for targeting chemotherapeutic agents to mammalian mitochondria. Also disclosed are monoamine oxidase compositions, and methods of using them for the selective therapy of mammalian cancers, and in particular, in the treatment of human gliomas. Also disclosed are methods employing the novel targeted chemotherapeutics with one or more conventional anti-cancer therapies, including, for example, radiotherapy.

  本发明公开了将化疗药物靶向哺乳动物线粒体的化合物。还公开了单胺氧化酶组合物，以及使用它们选择性治疗哺乳动物癌症，特别是治疗人类胶质瘤的方法。还公开了将新型靶向化疗药物与一种或多种常规抗癌疗法（包括放疗等）结合使用的方法。
• Chemotherapeutic compositions and methods for treating human gliomas
  申请人：The Methodist Hospital

  公开号：US10555936B2

  公开（公告）日：2020-02-11

  Disclosed are compound for targeting chemotherapeutic agents to mammalian mitochondria. Also disclosed are monoamine oxidase-specific compositions, and methods of using them for the selective therapy of mammalian cancers, and in particular, in the treatment of human gliomas. Also disclosed are methods employing the novel targeted chemotherapeutics with one or more conventional anti-cancer therapies, including, for example, radiotherapy, or multi-drug regimens.

  所公开的是将化疗药物靶向哺乳动物线粒体的化合物。还公开了单胺氧化酶特异性组合物，以及用它们选择性治疗哺乳动物癌症，特别是治疗人类胶质瘤的方法。还公开了将新型靶向化疗药物与一种或多种常规抗癌疗法（包括放疗等）或多种药物疗法结合使用的方法。