4-hydroxypiperidinocyclohexyl carbonitrile | 60756-86-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 4-hydroxypiperidinocyclohexyl carbonitrile
• 英文别名: 4-hydroxypiperidinocyclohexylcarbonitrile；1-(1-Cyanocyclohexyl)-4-hydroxyl piperidine；1-(1-cyanocyclohexyl)-4-hydroxypiperidine；1-(4-hydroxypiperidin-1-yl)cyclohexane-1-carbonitrile
• CAS: 60756-86-7
• 化学式: C₁₂H₂₀N₂O
• 分子量: 208.304
• InChiKey: XMLRSCCKOPHXDT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  47.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-hydroxypiperidinocyclohexyl carbonitrile 在 吡啶 、 aluminum isopropoxide 、 magnesium 、 六甲基二硅氮烷 作用下， 以 丙酮 、 苯 为溶剂， 反应 13.0h， 生成 1-(1-phenylcyclohexyl)-4-piperidone
  参考文献：
  名称：

  衍生自苯环利定的新型止痛药。

  摘要：

  1-（1-苯基环己基）-4-哌啶醇（3），1-（1-苯基环己基）-4-苯基-4-哌啶醇（10）及其丙酸酯（11）和1-（1-苯基环己基）的几种酯制备并表征了）-4-苯基哌啶（13）。衍生自苯环利定的新化合物在小鼠中发挥镇痛作用。最有效的是10，活性是吗啡的两倍。10、11和13的抗伤害感受活性可能与它们在小鼠输精管生物测定中的功效密切相关，并且纳洛酮可完全逆转两者。

  DOI：

  10.1021/jm00137a004
• 作为产物：
  描述：

  4-羟基哌啶 、 环己酮 、 丙酮氰醇 在 magnesium sulfate 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 48.0h， 以85%的产率得到4-hydroxypiperidinocyclohexyl carbonitrile
  参考文献：
  名称：

  1- [1-2-苯并[b]噻吩基）环己基]哌啶盐酸盐（BTCP）在体外产生两种活性初级代谢产物：合成，从大鼠肝微粒体提取物中鉴定以及对神经元多巴胺转运蛋白的亲和力。

  摘要：

  1- [1-（2-苯并[b]噻吩基）环己基]哌啶盐酸盐（BTCP，1）和可卡因与神经元多巴胺转运蛋白结合，以抑制多巴胺（DA）的再摄取。但是，在长期给药时，可卡因会产生致敏作用，但1会产生耐受性。因为1的代谢物可能是其某些药理特性的原因，所以我们确定了大鼠肝微粒体产生的1的主要代谢物，并确定了它们对DA转运蛋白的亲和力。通过与HPLC和GC系统中的合成标准品进行比较，鉴定出五种单羟基化衍生物（3、5、9、10、14）和两种降解化合物（15、16）为代谢物。使用先前用于合成苯环利定代谢物的合成方案获得标准品。在体外，有两种化合物（3，5）显示出对DA转运蛋白的高亲和力。这些活性代谢物可能在1.的药理学中很重要。

  DOI：

  10.1021/jm970078z

文献信息

• Application of chemical P450 model systems to studies on drug metabolism. I. Phencyclidine. A multi-functional model substrate.
  作者：Hiroshi MASUMOTO、Kaoru TAKEUCHI、Shigeru OHTA、Masaaki HIROBE

  DOI：10.1248/cpb.37.1788

  日期：——

  Cytochrome P450 model and liver microsomal oxidations of drugs were compared using phencyclidine. In general, the chemical reaction systems produced many oxidation products. Besides the formation of the cyclohexane-4-hydroxyl compound (2), hydroxylation of the aromatic ring was favored in the Fenton reaction system (Fe2++H2O2). Formation of an m-hydroxylated product (m-5) was the main aromatic oxidation pathway in the Udenfriend reaction (Fe2+-ascorbic acid-O2), and 2, the piperidine-3-hydroxyl compound (3), and the piperidine-4-hydroxyl compound (4) were also formed. In the system using meso-tetraphenylporphinatoiron chloride (Fe(III)TPPC1) with an oxidant, the main product was the piperidine-3-oxo compound (8). In the liver microsomes system, 2, 4, 8, and m-5, which were all generated by the chemical oxidation reactions, were detected as metabolites of phencyclidine. They were formed by cytochrome P450-dependent reactions. Chemical oxidation systems can be used to study drug metabolism; they can reveal some tendencies of the real metabolis reactions, are easy to operate, and yield sufficient amounts of product.

  使用苯环利定比较了细胞色素P450模型和肝微粒体的药物氧化。一般来说，化学反应系统产生了许多氧化产物。除了形成环己烷-4-羟基化合物（2）外，在芬顿反应体系（Fe2++H2O2）中芳香环的羟基化反应被优先生成。在尤登友反应（Fe2+-抗坏血酸-O2）中，形成m-羟基化产物（m-5）是主要的芳香氧化途径，同时也形成了化合物2、哌啶-3-羟基化合物（3）和哌啶-4-羟基化合物（4）。在使用含氧化剂的美索-四苯基卟啉铁氯化物（Fe(III)TPPC1）体系中，主要产物是哌啶-3-氧化物（8）。在肝微粒体系统中，2、4、8和m-5都是通过化学氧化反应生成的苯环利定代谢物，它们是通过细胞色素P450依赖的反应形成的。化学氧化系统可用于研究药物代谢；它们能够揭示一些真实代谢反应的趋势，操作简单，并能产生足够的产物。
• Synthesis and Antinociceptive Behaviors of New Methyl and Hydroxyl Derivatives of Phencyclidine
  作者：A. Ahmadi、M. Kermani、N. Naderi、R. Hajikhani、N.M. Rezaee、M. Javadi、B.N. Niknafs

  DOI：10.2174/092986712798992057

  日期：2012.2.1

  Phencyclidine (I) and its derivatives show such pharmacological behaviors as analgesic, anticonsulvant, anti-anxiety and antidepressant, while interacting with central nervous system. In this study, new methyl and hydroxyl derivatives of PCP were synthesized and their antinociceptive behaviors in animals were examined by measuring the number of writhing in a writhing test of visceral pain and the pain

  苯环利定（I）及其衍生物在与中枢神经系统相互作用时表现出诸如止痛，抗惊厥，抗焦虑和抗抑郁等药理行为。在这项研究中，合成了五氯苯酚的新的甲基和羟基衍生物，并通过测量内脏疼痛扭结试验中的扭结次数和福尔马林试验中的疼痛评分来检查它们在动物中的抗伤害感受行为。与对照组和PCP组相比，实验组的发现表明，新合成的PCP类似物（化合物II，III和V，10 mg / kg）能够在福尔马林和扭体试验中产生更多的镇痛作用，尤其是对于化合物V。结论是，新合成的五氯苯酚衍生物可以大大减轻急性和慢性疼痛。
• Phencyclidine and phencyclidine metabolites assay, tracers, immunogens
  申请人：Abbott Laboratories

  公开号：US05124457A1

  公开（公告）日：1992-06-23

  The present invention is directed to a fluorescence polarization assay for phencyclidine and phencyclidine derivatives, to the various components needed for preparing and carrying out such an assay, and to methods of making these components. Specifically, tracers, immunogens and antibodies are disclosed, as well as methods for making them. The tracers and the immunogens are made from substituted phencyclidine compounds. A fluorescein moiety is included in the tracer, while a poly(amino acid) forms a part of the immunogen. The assay is conducted by measuring the degree of polarization retention of plane polarized light that has been passed through a sample containing antiserum and tracer.

  本发明涉及一种用于苯环丙胺和苯环丙胺衍生物的荧光偏振测定的方法，涉及用于准备和执行此类测定所需的各种组分，以及制备这些组分的方法。具体地，公开了示踪剂、免疫原和抗体，以及制备它们的方法。示踪剂和免疫原由取代苯环丙胺化合物制成。示踪剂中包含荧光基团，而多肽（氨基酸）构成免疫原的一部分。该测定通过测量已通过含有抗血清和示踪剂的样品的偏振保留度的平面偏振光的程度来进行。
• Phencyclidine and phencyclidine metabolites assay, tracers, immunogens,
  申请人：Abbott Laboratories

  公开号：US05155212A1

  公开（公告）日：1992-10-13

  The present invention is directed to a fluorescence polarization assay for phencyclidine and phencyclidine derivatives, to the various components needed for preparting and carrying out such an assay, and to methods of making these components. Specifically, tracers, immunogens and antibodies are disclosed, as well as methods for making them, and a reagent kit containing them. The tracers and the immunogens are made from substituted phencyclidine compounds. A fluorescein moiety is included in the tracer, while a poly(amino acid) forms a part of the immunogen. The assay is conducted by measuring the degree of polarization retention of plane polarized light that has been passed through a sample containing antiserum and tracer.

  本发明涉及一种用于苯环丙胺和苯环丙胺衍生物的荧光偏振测定法，以及制备和执行此类测定所需的各种组分和制备这些组分的方法。具体而言，本发明揭示了示踪剂、免疫原和抗体，以及制备它们的方法和包含它们的试剂盒。示踪剂和免疫原是由取代苯环丙胺化合物制备而成。示踪剂中包含荧光素基团，而免疫原中包含一种聚（氨基酸）。该测定方法是通过测量通过含有抗血清和示踪剂的样品的偏振平面光的偏振保留度来进行的。
• N-(1-thienylcycloalkyl)alkenylamines for treatment of neurotoxic injury
  申请人：G.D. Searle & Co.

  公开号：EP0317953A2

  公开（公告）日：1989-05-31

  Compounds, compositions and methods of treatment are described to control brain damage associated with anoxia or ischemia which typically follows stroke, cardiac arrest or perinatal asphyxia. The treatment includes administration of an N-(1-thienylcycloalkyl)alkenylamine compound as an antagonist to inhibit excitotoxic actions at major neuronal excitatory amino acid receptor sites. Compounds of most interest are those of the formula wherein R¹ is one or more groups selected from hydrido, alkyl of one to about five carbon atoms, cycloalkyl of three to about five carbon atoms, alkenyl of two to about five carbon atoms, hydroxyl and alkoxy; wherein each of R² is one or more groups selected from hydrido, alkyl of one to about five carbon atoms, cycloalkyl of three to about five carbon atoms, alkenyl of two to about five carbon atoms, hydroxyl, oxo and alkoxy; wherein R⁵ is one or more groups selected from hydrido, alkyl of one to about five carbon atoms, cycloalkyl of three to about five carbon atoms, alkenyl of two to about five carbon atoms, hydroxyl and alkoxy; and wherein the broken line within the N-containing ring represents a double bond between any two adjacent carbon atoms involving the 3-, 4- and 5-positions of the N-containing ring.

  所述化合物、组合物和治疗方法可控制与缺氧或缺血有关的脑损伤，缺氧或缺血通常是中风、心脏骤停或围产期窒息之后的症状。治疗方法包括施用 N-（1-噻吩基环烷基）烯胺化合物作为拮抗剂，以抑制主要神经元兴奋性氨基酸受体位点的兴奋毒性作用。最令人感兴趣的化合物是那些式中 其中 R¹ 是一个或多个基团，选自氢基、一至约五个碳原子的烷基、三至约五个碳原子的环烷基、二至约五个碳原子的烯基、羟基和烷氧基；其中每个 R² 是一个或多个基团，选自氢基、一至约五个碳原子的烷基、三至约五个碳原子的环烷基、二至约五个碳原子的烯基、羟基、氧代和烷氧基；其中 R⁵是一个或多个基团，选自水rido、1 至 5 个碳原子的烷基、3 至 5 个碳原子的环烷基、2 至 5 个碳原子的烯基、羟基和烷氧基；且其中含 N 环内的断线代表涉及含 N 环的 3、4 和 5 位的任意两个相邻碳原子之间的双键。