(1R,2S)-(-)-cis-(3,4-dichlorophenyl)-N-<2-(1-pyrrolidinyl)cyclohexyl>acetamide | 135093-10-6

• 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: (1R,2S)-(-)-cis-(3,4-dichlorophenyl)-N-<2-(1-pyrrolidinyl)cyclohexyl>acetamide
• 英文别名: 2-(3,4-Dichloro-phenyl)-N-(2-pyrrolidin-1-yl-cyclohexyl)-acetamide；2-(3,4-dichlorophenyl)-N-[(1R,2S)-2-pyrrolidin-1-ylcyclohexyl]acetamide
• CAS: 135093-10-6
• 化学式: C₁₈H₂₄Cl₂N₂O
• 分子量: 355.307
• InChiKey: KWSRPMWFUYDWFC-SJORKVTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (1R,2S)-(-)-cis-(3,4-dichlorophenyl)-N-<2-(1-pyrrolidinyl)cyclohexyl>acetamide 在 aluminium hydride 、 potassium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 0.08h， 生成
  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：

  3,4-二氯苯乙酸 、 (1R,2S)-2-(pyrrolidin-1-yl)cyclohexanamine 在 吡啶 、 N,N'-二环己基碳二亚胺 作用下， 生成 (1R,2S)-(-)-cis-(3,4-dichlorophenyl)-N-<2-(1-pyrrolidinyl)cyclohexyl>acetamide
  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

文献信息

• CIS-N-(2-AMINOCYCLOALIPHATIC)BENZENE ACETAMIDE AND -BENZAMIDE ANTICONVULSANTS
  申请人：THE UPJOHN COMPANY

  公开号：EP0248824A1

  公开（公告）日：1987-12-16
• Use of CIS-N-(2 Aminocycloaliphatic) benzene acetamide and Benzamide for the manufacture of anticonvulsants
  申请人：THE UPJOHN COMPANY

  公开号：EP0248824B1

  公开（公告）日：1990-01-17
• [EN] CIS-N-(2-AMINOCYCLOALIPHATIC)BENZENE ACETAMIDE AND -BENZAMIDE ANTICONVULSANTS
  申请人：THE UPJOHN COMPANY

  公开号：WO1987002584A1

  公开（公告）日：1987-05-07

  (EN) Certain cis-N-(2-amino-cycloaliphatic)benzeneacetamide and -benzamides of formula (I), where m is 0 or 1, n is 1 or 2, R is hydrogen or alkyl, R1 and R2 are separately alkyl, or, taken together with the nitrogen denote a pyrrolidine ring, and X and Y are hydrogen, fluorine, chlorine or bromine or one of X and Y is trifluoromethyl, e.g., cis-3,4-dichloro-N-methyl-N-¨AD2-(1-pyrrolidinyl)cyclohexyl¨BDbenzamide and salts thereof, have been found to have CNS seizure blocking or preventing drug action, e.g., anti-convulsant drug properties with little or no analgesic properties. Some of these compounds are new.(FR) Quelques acétamides et benzamides de Cis-N-(2-amino-cycloaliphatique)benzène ont la formule (I), dans laquelle m est égal à 0 ou 1, n est égal à 1 ou 2, R représente hydrogène ou alkyle, R1 et R2 sont séparément alkyle ou ensemble avec l'azote ils représentent une chaîne pyrrolidine fermée, X et Y sont hydrogène, fluor, chlore, ou brome ou X ou Y est du trifluorométhyle. Il s'est avéré que ces composés, par exemple CIS-3,4-dichloro-N-méthyle-N-¨AD2-(1-pyrrolidinyle)cyclohexyle¨BDbenzamide, et leurs sels, bloquent ou préviennent des attaques du système nerveux central, et ont, par exemple, des propriétés anti-convulsives accompagnées d'effets analgésiques minimes ou nuls. Certains de ces composés sont nouveaux.
• 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
  作者：Lilian Radesca、Wayne D. Bowen、Lisa Di Paolo、Brian R. De Costa

  DOI：10.1021/jm00114a015

  日期：1991.10

  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.