(1S,2R)-(+)-cis-N-<2-(3,4-dichlorophenyl)ethyl>-2-(1-pyrrolidinyl)cyclohexylamine | 135211-15-3

• 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: (1S,2R)-(+)-cis-N-<2-(3,4-dichlorophenyl)ethyl>-2-(1-pyrrolidinyl)cyclohexylamine
• 英文别名: 1S,2R-(+)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-2-(1-pyrrolidinyl)cyclohexylamine；K7C7Xkk3P3；(1S,2R)-N-[2-(3,4-dichlorophenyl)ethyl]-2-pyrrolidin-1-ylcyclohexan-1-amine
• CAS: 135211-15-3
• 化学式: C₁₈H₂₆Cl₂N₂
• 分子量: 341.324
• InChiKey: NREHOBGKKWFKES-ZWKOTPCHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (1S,2R)-(+)-cis-N-<2-(3,4-dichlorophenyl)ethyl>-2-(1-pyrrolidinyl)cyclohexylamine 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 (1S,2R)-(+)-cis-N-<2-(3,4-dichlorophenyl)ethyl>-N-(n-propyl)-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：

  3,4-二氯苯乙酸 在 吡啶 、 aluminium hydride 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 0.66h， 生成 (1S,2R)-(+)-cis-N-<2-(3,4-dichlorophenyl)ethyl>-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

文献信息

• Sigma-2 receptor agonists and their use in the treatment of HIV infection
  申请人：Bowen D. Wayne

  公开号：US20060004036A1

  公开（公告）日：2006-01-05

  The present invention relates to sigma-2 receptor agonists and their use in the treatment of immunodeficiency virus infections, especially human immunodeficiency virus (HIV) infections. The invention particularly relates to sigma-2 agonists, especially CB-184 and its analogues, that decrease cellular production of sphingomyelin when provided to recipient cells, and inhibit HIV replication.

  本发明涉及sigma-2受体激动剂及其在治疗免疫缺陷病毒感染，特别是人类免疫缺陷病毒（HIV）感染中的用途。本发明尤其涉及σ-2激动剂，特别是CB-184及其类似物，当提供给受体细胞时，它们能减少细胞产生鞘磷脂，并抑制HIV的复制。
• NITROGEN-CONTAINING CYCLOHETERO CYCLOALKYLAMINOARYL DERIVATIVES FOR CNS DISORDERS
  申请人：G.D. Searle & Co.

  公开号：EP0594597A1

  公开（公告）日：1994-05-04
• EP0594597A4
  申请人：——

  公开号：EP0594597A4

  公开（公告）日：1993-04-30
• THERAPEUTICS AND METHODS OF TREATMENT OF ANGIOTENSIN-CONVERTING ENZYME 2 ASSOCIATED CONDITIONS
  申请人：Board of Supervisors of Louisiana State University and Agricultural and Mechanical College

  公开号：US20210379016A1

  公开（公告）日：2021-12-09

  Therapeutics and methods of treating one of an angiotensin-converting enzyme 2 (ACE2) associated condition and an ACE2 associated pre-condition patient comprising administering to the patient a pharmaceutically therapeutic dose of a therapeutic, wherein the therapeutic includes either a Sigmar1 antagonist or any pharmaceutically acceptable salt, solvate, or prodrug thereof, or a Sigmar1 enhancer, or any pharmaceutically acceptable salt, solvate, or prodrug thereof. A method of treating coronavirus disease 2019 (COVID-19) patient comprising administering to the patient a pharmaceutically therapeutic dose of a therapeutic, wherein the therapeutic includes a Sigmar1 enhancer, or any pharmaceutically acceptable salt, solvate, or prodrug thereof.
• US5130330A
  申请人：——

  公开号：US5130330A

  公开（公告）日：1992-07-14