2-(3,4-二氯苯基)-N-甲基-N-[(1S,2S)-2-(1-吡咯烷基)环己基]乙酰胺盐酸盐(1:1) | 67198-19-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-(3,4-二氯苯基)-N-甲基-N-[(1S,2S)-2-(1-吡咯烷基)环己基]乙酰胺盐酸盐(1:1)
• 英文名称: (-)-trans-(1S,2S)-U-50488
• 英文别名: (-)-U 50488；trans-(1S,2S)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide；(1S,2S)-N-methyl-N-[2-(pyrrolidin-1-yl)cyclohexyl]-2-(3,4-dichlorophenyl)acetamide；2-(3,4-dichlorophenyl)-N-methyl-N-[(1S,2S)-2-pyrrolidinocyclohexyl]acetamide；(-)-(trans)-(1S,2S)-U50,488；U-(-)-50488；2-(3,4-dichlorophenyl)-N-methyl-N-[(1S,2S)-2-(1-pyrrolidinyl)cyclohexyl]acetamide；2-(3,4-dichlorophenyl)-N-methyl-N-[(1S,2S)-2-pyrrolidin-1-ylcyclohexyl]acetamide
• CAS: 67198-19-0
• 化学式: C₁₉H₂₆Cl₂N₂O
• 分子量: 369.334
• InChiKey: VQLPLYSROCPWFF-ROUUACIJSA-N

物化性质

• 沸点：
  496.6±45.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(3,4-二氯苯基)-N-甲基-N-[(1S,2S)-2-(1-吡咯烷基)环己基]乙酰胺盐酸盐(1:1) 在 aluminium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 0.08h， 生成 (1S,2S)-(+)-trans-N-<2-(3,4-dichlorophenyl)ethyl>-N-methyl-2-(1-pyrrolidinyl)cyclohexylamine
  参考文献：
  名称：

  Synthesis and receptor binding of enantiomeric N-substituted cis-N-[2-(3,4-dichlorophenyl)ethyl]-2-(1-pyrrolidinyl)cyclohexylamines as high-affinity .sigma. receptor ligands

  摘要：

  N-Alkyl-substituted derivatives of (+)- and (-)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-2-(1-pyrrolidinyl)cyclohexylamine have been synthesized in nine steps in a stereospecific manner starting from cyclohexene oxide. The key step in the reaction sequence involved catalytic hydrogenation of oxime 8 in the presence of PtO2 and AcOH to give the cis diamine (+/-)-7. Most of the compounds in this series exhibited very high affinity at sigma-receptors when tested against [H-3]-(+)-3-PPP, and in general it was observed that the 1R,2S enantiomers bound more potently to sigma-receptors than their corresponding 1S,2R enantiomers. The most potent sigma-ligand found in this class was the unsubstituted derivative (1R,2S)-(-)-4, which exhibited an affinity constant of 0.49 nM. This compound was also found to be very selective for sigma-receptors. It exhibited little or no affinity for kappa-opioid, PCP, and dopamine-D2 receptors. It was also demonstrated that the cis configuration as opposed to the trans configuration of (+)- and (-)-5 was necessary for a higher sigma-receptor affinity.

  DOI：

  10.1021/jm00114a015
• 作为产物：
  描述：

  氧化环己烯 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 乙醚 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.5h， 生成 2-(3,4-二氯苯基)-N-甲基-N-[(1S,2S)-2-(1-吡咯烷基)环己基]乙酰胺盐酸盐(1:1)
  参考文献：
  名称：

  阿片受体激动剂 U50488 抗布氏锥虫活性的优化

  摘要：

  针对培养的布氏锥虫（非洲昏睡病的病原体）筛选 Sigma-Aldrich 药理活性化合物库 (LOPAC) ，鉴定出许多对哺乳动物细胞具有选择性抗增殖活性的化合物。其中包括 (+)-(1 R ,2 R )-U50488，这是一种弱阿片类激动剂，EC 50值为 59 n M，如我们之前报道的布氏锥虫体外试验所测定。本文描述了对 U50488 关键结构元素的修饰，以研究结构-活性关系 (SAR) 并优化该化合物的抗增殖活性和药代动力学特性。

  DOI：

  10.1002/cmdc.201100278

文献信息

• Chemoenzymatic Preparation of Optically Active<i>trans</i>-Cyclohexane-1,2-diamine Derivatives: An Efficient Synthesis of the Analgesic U-(−)-50,488
  作者：Javier González-Sabín、Vicente Gotor、Francisca Rebolledo

  DOI：10.1002/chem.200400607

  日期：2004.11.19

  Stereoespecific syntheses of (+/-)-trans-N,N-cyclohexane-1,2-diamines ((+/-)-4 a-g) were carried out from the corresponding (+/-)-trans-N,N-dialkylaminocyclohexanols by successive treatment with mesyl chloride and aqueous ammonia. The stereochemical outcome indicates the formation of a meso-aziridinium ion intermediate. Kinetic resolutions of diamines (+/-)-4 were efficiently accomplished in aminolysis

  （+/-）-反-N，N-环己烷-1,2-二胺（（+/-）-4 ag）的立体定向合成是从相应的（+/-）-反-N，N-通过连续用甲磺酰氯和氨水处理二烷基氨基环己醇。立体化学结果表明形成了中叠氮鎓离子中间体。二胺（+/-）-4的动力学拆分可有效地完成南极假丝酵母脂肪酶B催化的氨解反应，其中乙酸乙酯为溶剂和酰基供体。分离出的乙酰胺和其余的二胺作为苄氧羰基衍生物，具有很高的ee值（92-99％）。一种氨基甲酸酯用作镇痛剂U-（-）-50,488的前体。
• OPIOID RECEPTOR LIGANDS
  申请人：Bohn Laura M.

  公开号：US20090088466A1

  公开（公告）日：2009-04-02

  The invention provides novel compounds of formula (I), (II), (III), and (IV). The invention also provides pharmaceutical compositions comprising such compounds as well as methods for treating diseases associated with opioid receptor function by administering such compounds to an animal in need of treatment. The invention also provides therapeutic methods for the use of compounds of formula (V), as well as methods for treating diseases by administering such compounds.

  本发明提供了化合物(I)、(II)、(III)和(IV)的新型化合物。本发明还提供了包含这些化合物的药物组合物，以及通过向需要治疗的动物施用这些化合物来治疗与阿片受体功能相关的疾病的方法。本发明还提供了化合物(V)的治疗方法，以及通过施用这些化合物来治疗疾病的方法。
• Capture compounds, collections thereof and methods for analyzing the proteome and complex compositions
  申请人：Kõster Hubert

  公开号：US20100248264A1

  公开（公告）日：2010-09-30

  Capture compounds and collections thereof and methods using the compounds for the analysis of biomolecules are provided. In particular, collections, compounds and methods are provided for analyzing complex protein mixtures, such as the proteome. The compounds are multifunctional reagents that provide for the separation and isolation of complex protein mixtures. Automated systems for performing the methods also are provided.

  提供了捕获化合物及其集合以及使用这些化合物进行生物分子分析的方法。特别地，提供了用于分析复杂蛋白质混合物（如蛋白质组）的集合、化合物和方法。这些化合物是多功能试剂，可用于分离和分离复杂的蛋白质混合物。还提供了执行这些方法的自动化系统。
• 2-Aminocycloalkenyl carboxamides and their tritiated 2-aminocycloalkyl carboxamide derivatives
  申请人：THE UPJOHN COMPANY

  公开号：EP0129991A1

  公开（公告）日：1985-01-02

  2-Aminocycloalkenyl benzamides and phenylacet- amides, e.g. 3,4-dichloro-N-methyl-N-[6-(1- pyrrolidinyl) -3-cyclohexenyl]benzeneacetamide, and their salts, are of potential value as analgesics. The corresponding tritiated, saturated compounds are also new, and of utility as radio-labelled compounds for pharmacological and metabolic studies in animals.

  2-Aminocycloalkenyl benzamides and phenylacet- amides, e.g. 3,4-dichloro-N-methyl-N-[6-(1- pyrrolidinyl) -3-cyclohexenyl]benzeneacetamide, and their salts, are of potential value as analgesics.相应的三价饱和化合物也是一种新化合物，可作为放射性标记化合物用于动物药理和代谢研究。
• 3,4-Dichloro-N-[2-(2,5-dihydro-1H-pyrrol-1-yl)cyclohexyl]-N-methylbenzeneacetamide
  申请人：THE UPJOHN COMPANY

  公开号：EP0126612A1

  公开（公告）日：1984-11-28

  N-[2-(2,5-dihydro-1H-pyrrol-1-yl)cycloaliphatic]benzeneacetamide and -benzamide compounds, e.g. (1α,2β)-(±)-3,4--dichloro-N-(2-(2,5-dihydro-1 H-pyrrol-1-yl)cyclohexyl]-N-me- thylbenzeneacetamide, and salts thereof, which can have useful analgesic activity, low abuse or physical dependence liability properties.

  N-[2-(2,5-二氢-1H-吡咯-1-基)环脂族]苯乙酰胺和-苯甲酰胺化合物，例如(1α,2β)-(±)-3,4-二氯-N-(2-(2,5-二氢-1H-吡咯-1-基)环己基]-N-甲基-苯乙酰胺及其盐，它们具有有用的镇痛活性、低滥用或身体依赖性。