1-(1-氰基-环己基)-4-甲基-哌嗪 | 22912-29-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 1-(1-氰基-环己基)-4-甲基-哌嗪
• 英文名称: 1-(1-cyano-cyclohexyl)-4-methyl-piperazine
• 英文别名: 1-(4-methylpiperazin-1-yl)cyclohexanecarbonitrile；1-(1-Cyano-cyclohexyl)-4-methyl-piperazin, 1-(4-Methyl-piperazino)-cyclohexancarbonsaeurenit；1-(1-Cyano-cyclohexyl)-4-methyl-piperazin；1-(4-methylpiperazin-1-yl)cyclohexane-1-carbonitrile
• CAS: 22912-29-4
• 化学式: C₁₂H₂₁N₃
• 分子量: 207.319
• InChiKey: IGSKSRTXNRBWJT-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：
  30.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(1-氰基-环己基)-4-甲基-哌嗪 在 吡啶 、 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 反应 24.0h， 生成 2-chloro-N-[[1-(4-methylpiperazin-1-yl)cyclohexyl]methyl]benzamide
  参考文献：
  名称：

  Discovery of a novel series of selective HCN1 blockers

  摘要：

  The discovery of a series of novel, potent, and selective blockers of the cyclic nucleotide-modulated channel HCN1 is disclosed. Here we report an SAR study around a series of selective blockers of the HCN1 channel. Utilization of a high-throughput VIPR assay led to the identification of a novel series of 2,2-disubstituted indane derivatives, which had moderate selectivity and potency at HCN1. Optimization of this hit led to the identification of the potent, 1,1-disubstituted cyclohexane HCN1 blocker, 2-ethoxy- N-(( 1-(4-isopropylpiperazin-1-yl) cyclohexyl) methyl) benzamide. The work leading to the discovery of this compound is described herein. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.051
• 作为产物：
  描述：

  N-甲基哌嗪 、 三甲基氰硅烷 、 环己酮 在 zinc(II) iodide 作用下， 以 甲醇 、 乙醚 为溶剂， 反应 8.0h， 生成 1-(1-氰基-环己基)-4-甲基-哌嗪
  参考文献：
  名称：

  Discovery of a novel series of selective HCN1 blockers

  摘要：

  The discovery of a series of novel, potent, and selective blockers of the cyclic nucleotide-modulated channel HCN1 is disclosed. Here we report an SAR study around a series of selective blockers of the HCN1 channel. Utilization of a high-throughput VIPR assay led to the identification of a novel series of 2,2-disubstituted indane derivatives, which had moderate selectivity and potency at HCN1. Optimization of this hit led to the identification of the potent, 1,1-disubstituted cyclohexane HCN1 blocker, 2-ethoxy- N-(( 1-(4-isopropylpiperazin-1-yl) cyclohexyl) methyl) benzamide. The work leading to the discovery of this compound is described herein. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.051

文献信息

• Propionamide Derivatives as Dual μ-Opioid Receptor Agonists and σ₁ Receptor Antagonists for the Treatment of Pain
  作者：Mónica García、Virginia Llorente、Lourdes Garriga、Ute Christmann、Sergi Rodríguez-Escrich、Marina Virgili、Begoña Fernández、Magda Bordas、Eva Ayet、Javier Burgueño、Marta Pujol、Albert Dordal、Enrique Portillo-Salido、Georgia Gris、José Miguel Vela、Carmen Almansa

  DOI：10.1021/acs.jmedchem.1c00417

  日期：2021.7.22

  A new series of propionamide derivatives was developed as dual μ-opioid receptor agonists and σ1 receptor antagonists. Modification of a high-throughput screening hit originated a series of piperazinylcycloalkylmethyl propionamides, which were explored to overcome the challenge of achieving balanced dual activity and convenient drug-like properties. The lead compound identified, 18g, showed good analgesic

  开发了一系列新的丙酰胺衍生物作为μ阿片受体双重激动剂和σ1受体拮抗剂。对高通量筛选命中的修饰产生了一系列哌嗪基环烷基甲基丙酰胺，其被探索以克服实现平衡的双重活性和方便的类药特性的挑战。鉴定出的先导化合物18g在多种急性（爪压）和慢性（部分坐骨神经结扎）疼痛动物模型中显示出良好的镇痛效果，与羟考酮相比，胃肠道影响减轻。
• 1-(3,4-DICHLOROBENZAMIDOMETHYL)-CYCLOHEXYLDIMETHYLAMINE
  申请人：Allen & Hanburys Limited

  公开号：US03975443A1

  公开（公告）日：1976-08-17

  Compounds of the general formula I: ##EQU1## in which R.sup.1 - R.sup.4 which may be the same or different represent hydrogen atoms, or C.sub.1.sub.-6 straight or branched chain alkyl, alkenyl or alkynyl group or an alkyl group substituted by a cycloalkyl group, or represents a cycloalkyl, alkoxycarbonyl, aryl, arakyl, acyl (which includes anylsulphonyl) groups in which the alkyl group or the alkyl portion of the aralkyl group may be substituted with one or more hydroxy or esterified hydroxy groups and in which the aryl groups or the aryl portion of the acyl or aralkyl group may be substituted by one or more halogen atoms, alkyl groups, hydroxy groups, alkoxy groups, trifluoromethyl, nitro, amino or dialkylamino groups, and in which R.sup.5 - R.sup.8 which may be the same or different represent hydrogen atoms or alkyl groups except that not all groups may be hydrogen, or R.sup.5 and R.sup.6 or R.sup.7 and R.sup.8 together represent a carbonyl (=O) oxygen and in any of the pairs of groups R.sup.1 /R.sup.2, R.sup.3 /R.sup.4, R.sup.5 /R.sup.6 and R.sup.7 /R.sup.8 may represent a carbocyclic or heterocyclic ring system optionally substituted by lower alkyl or aryl groups, said ring being saturated or unsaturated. These compounds have utility as oral analgesics.

  通式I的化合物：##EQU1##其中R.sup.1 - R.sup.4可能相同也可能不同，代表氢原子，或C.sub.1-6直链或支链烷基，烯基或炔基或被环烷基取代的烷基，或代表环烷基，烷氧羰基，芳基，芳基烷基，酰基（包括任何磺酰基）基团，其中烷基或芳基烷基的烷基部分可以被一个或多个羟基或酯化羟基基团取代，芳基或酰基或芳基烷基的芳基部分可以被一个或多个卤素原子，烷基基团，羟基基团，烷氧基团，三氟甲基，硝基，氨基或二烷基氨基基团取代，且R.sup.5 - R.sup.8可能相同也可能不同，代表氢原子或烷基基团，除非所有基团都是氢原子，或R.sup.5和R.sup.6或R.sup.7和R.sup.8一起代表一个羰基（=O）氧原子，在R.sup.1 /R.sup.2，R.sup.3 /R.sup.4，R.sup.5 /R.sup.6和R.sup.7 /R.sup.8中的任何一对基团中，可能代表一个由较低烷基或芳基基团取代的脂环或杂环系统，所述环饱和或不饱和。这些化合物在口服止痛剂中具有应用价值。
• Synthesis and Antinociceptive Activity of Newly Modified Amine Analogs of Phencyclidine in Mice
  作者：Seyed Ali Sobhanian、Maryam Shokrollahi、Marjaneh Samadizadeh、Mohsen Khalili、Abbas Ahmadi

  DOI：10.2174/1386207325666211005155128

  日期：2022.9

  compared. RESULTS The outcomes indicated that some new compounds have more antinociceptive effects than PCP in tail immersion and formalin tests. In the tail immersion test, the methyl piperazine analog (III) shows more efficacy than others. In the formalin test, none of the compounds are as effective as phencyclidine at the earliest time-point, but compounds IV and V show effectiveness during the second stage

  背景苯环利定（PCP，I）及其替代类似物是影响中枢神经系统的重要且广泛滥用的拟精神病药物。由于大脑中存在特定的受体，它们具有许多药理特性。目的和目的 甲基虽然具有强给电子性和偶极矩的特性，但仍被置于苯环利定的苯基和胺部分的不同位置，同时取代苄胺、哌嗪和苯胺衍生物代替苯环利定的哌啶环，形成具有镇痛特性的新型核心化合物。材料和方法 为了评价新合成的化合物的镇痛活性，它们通过尾浸（热）和福尔马林（化学）疼痛试验进行筛选。还比较了与对照组和 PCP 组获得的数据。结果 结果表明，在尾浸和福尔马林试验中，一些新化合物比五氯苯酚具有更强的镇痛作用。在尾浸试验中，甲基哌嗪类似物 (III) 显示出比其他药物更有效的效果。在福尔马林试验中，没有一种化合物在最早的时间点与苯环利定一样有效，但化合物 IV 和 V 在福尔马林疼痛的第二阶段显示出有效性。结论 可以得出结论，苯环利定的甲基哌嗪类似物是减轻急性热痛
• New compounds resulting from structural and biochemical similarities between GBR 1278 and BTCP, two potent inhibitors of dopamine uptake
  作者：E Coderc、R Martin-Fardon、J Vignon、JM Kamenka

  DOI：10.1016/0223-5234(93)90042-d

  日期：1993.1
• US7314879B2
  申请人：——

  公开号：US7314879B2

  公开（公告）日：2008-01-01