(1S,2R)-(+)-cis-N-ethyl-N-<2-(3,4-dichlorophenyl)ethyl>-2-(1-pyrrolidinyl)cyclohexylamine | 135093-16-2

• 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-ethyl-N-<2-(3,4-dichlorophenyl)ethyl>-2-(1-pyrrolidinyl)cyclohexylamine
• 英文别名: 1S,2R-(-)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-N-ethyl-2-(1-pyrrolidinyl)cyclohexylamine；(1S,2R)-N-[2-(3,4-dichlorophenyl)ethyl]-N-ethyl-2-pyrrolidin-1-ylcyclohexan-1-amine
• CAS: 135093-16-2
• 化学式: C₂₀H₃₀Cl₂N₂
• 分子量: 369.378
• InChiKey: FBINLPWZDBDJAV-VQTJNVASSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  6.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  3,4-二氯苯乙酸 在 吡啶 、 aluminium hydride 、 potassium carbonate 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 0.74h， 生成 (1S,2R)-(+)-cis-N-ethyl-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
• US5739158A
  申请人：——

  公开号：US5739158A

  公开（公告）日：1998-04-14
• [EN] NITROGEN-CONTAINING CYCLOHETERO CYCLOALKYLAMINOARYL DERIVATIVES FOR CNS DISORDERS
  申请人：G.D. SEARLE & CO.

  公开号：WO1991012247A1

  公开（公告）日：1991-08-22

  (EN) Certain nitrogen-containing cyclohetero cycloalkylaminoaryl compounds are described for treatment of CNS disorders such as cerebral ischemia, psychotic disorders, convulsions and parkinsonism. Compounds of particular interest are of formula (I), wherein R1 is selected from hydrido, loweralkyl, cycloalkylalkyl of four to six carbon atoms and loweralkenylloweralkyl; wherein each of R2 and R3 is independently selected from hydrido and loweralkyl; wherein each of R4 through R7, R10 and R11 is independently selected from hydrido, hydroxy, loweralkyl, benzyl, phenoxy, benzyloxy and haloloweralkyl; wherein n is a number selected from four through six; wherein p is a number selected from zero through four; wherein q is a number selected from three through five; wherein A is selected from phenyl, naphthyl and thienyl; wherein any of the foregoing A groups can be further substituted with one or more substituents independently selected from hydrido, hydroxy, loweralkyl, loweralkoxy, halo, haloloweralkyl, amino, monoloweralkylamino and diloweralkylamino; or a pharmaceutically acceptable salt thereof.(FR) L'invention concerne certains composés cyclohétéro cycloalkylaminoaryle contenant de l'azote, permettant le traitement de troubles du système nerveux central tels que l'ischémie cérébrale, des troubles psychotiques, des convulsions et le parkinsonisme. Les composés présentant un intérêt particulier ont la formule (I), dans laquelle R1 est choisi entre hydrido, alkyle inférieur, cycloalkylalkyle contenant 4 à 6 atomes de carbone et alkyle inférieur d'alcényle inférieur; dans la formule, chaque R2 et R3 est choisi indépendamment entre hydrido et alkyle inférieur; R4 à R7, R10 et R11 sont sélectionnés indépendamment entre hydrido, hydroxy, alkyle inférieur, benzyle, phénoxy, benzyloxy et haloalkyls inférieur; n représente un nombre choisi entre 4 et 6; p représente un nombre choisi entre 0 et 4; q représente un nombre choisi entre 3 et 5; A est choisi entre phényle, naphtyle et thiényle; n'importe lequel des groupes A précités peut être également remplacé par un ou plusieurs substituants sélectionnés indépendamment parmi hydrido, hydroxy, alkyle inférieur, alcoxy inférieur, halo, haloalkyle inférieur, amino, monoalkylamino inférieur et dialkylamino inférieur. L'invention se rapporte également à un de ses sels pharmaceutiquement acceptable.