(1S,2R)-(+)-cis-2-pyrrolidinyl-N-methylcyclohexylamine | 121843-51-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (1S,2R)-(+)-cis-2-pyrrolidinyl-N-methylcyclohexylamine
• 英文别名: (1S,2R)-N-methyl-2-pyrrolidin-1-ylcyclohexan-1-amine
• CAS: 121843-51-4
• 化学式: C₁₁H₂₂N₂
• 分子量: 182.309
• InChiKey: MFOLKXSQEXMDIR-WDEREUQCSA-N

物化性质

• 沸点：
  240.6±8.0 °C(Predicted)
• 密度：
  0.96±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.61
• 重原子数：
  13.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  15.27
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  (1S,2R)-(+)-cis-2-pyrrolidinyl-N-methylcyclohexylamine 在 吡啶 、 lithium aluminium tetrahydride 、 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， 生成 (2-Benzo[1,3]dioxol-5-yl-ethyl)-methyl-((1S,2R)-2-pyrrolidin-1-yl-cyclohexyl)-amine
  参考文献：
  名称：

  高亲和力西格玛受体配体的N-取代的顺式-N-甲基-2-（1-吡咯烷基）环己胺的合成与评价。鉴定出新型的高效和选择性sigma受体探针。

  摘要：

  最近报道某些苯乙酰胺[（-）-和（+）-顺-3,4-二氯-N-甲基-N- [2-（1-吡咯烷基）环己基]苯乙酰胺]是有效的σ受体配体。为了确定是否可以提高对sigma受体的功效，合成了一系列与苯乙酰胺有关的化合物N-取代的顺式-2-（1-吡咯烷基）-N-甲基环己胺，并确定了其结构活性的要求。通过从先前报道的（+/-）-，1S，2R-（+）-和1R，2S-（-）-顺-2-（1-吡咯烷基）-N-甲基环己胺开始合成化合物。σ（[3H]（+）-3-PPP），kappa（[3H] bremazocine和[3H] U69,593），多巴胺-d2（[3H]（-）-舒必利）和苯环利定（PCP）的分析（[3H] TCP）受体在豚鼠脑中的结合揭示了许多高效和选择性的sigma受体配体。值得注意的是，1S，2R-顺-（-）-N-甲基-N- [2-（1-吡咯烷基）环己基]-（2-萘基）乙酰胺[（-）-29]（Ki

  DOI：

  10.1021/jm00173a030
• 作为产物：
  描述：

  (+/-)-2--N-methylamino>cyclohexanone 在 palladium on activated charcoal 盐酸 、 氢气 、 对甲苯磺酸 作用下， 反应 39.08h， 生成 (1S,2R)-(+)-cis-2-pyrrolidinyl-N-methylcyclohexylamine
  参考文献：
  名称：

  Alterations in the stereochemistry of the .kappa.-selective opioid agonist U50,488 result in high-affinity .sigma. ligands

  摘要：

  The synthesis and in vitro sigma receptor activity of the two diastereomers of U50,488 [(+/-)-2], namely, (1R,2S)-(+)- cis-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacet ami de [(+)-1] and (1S,2R)-(-)-cis-3,4-dichloro- N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide [(-)-1], are described. (+)-1 and (-)-1 were synthesized from (+/-)-trans-N-methyl-2-aminocyclohexanol [(+/-)-3]. Pyridinium chlorochromate (PCC) oxidation of the N-t-Boc-protected derivative of (+/-)-3 afforded (+/-)-2-[N- [(tert-butyloxy)carbonyl]-N-methylamino]cyclohexanone [(+/-)-5]. The sequence of enamine formation with pyrrolidine, catalytic reduction, N-deprotection, and optical resolution afforded (1R,2S)-(-)-cis-2-pyrrolidinyl-N-methylcyclohexylamine [(-)-10] and (1S,2R)-(+)-cis-2-pyrrolidinyl-N-methylcyclohexylamine [(+)-10]. The optical purity (greater than 99.5%) of (-)-10 and (+)-10 was determined by HPLC analysis of the diastereomeric ureas formed by reaction with optically pure (R)-alpha-methylbenzyl isocyanate. The absolute configuration of (-)-10 and (+)-10 was determined by single-crystal X-ray diffractometry of the bis-(R)-mandelate salt. Condensation of optically pure (-)-10 and (+)-10 with 3,4-dichlorophenylacetic acid furnished (+)-1 and (-)-1, respectively. Compounds (+)-1, (-)-1, (-)-2, and (+)-2 were compared for their binding affinities at kappa opioid, sigma, D2-dopamine, and phencyclidine (PCP) receptors in competitive binding assays using [3H]bremazocine ([3H]BREM) or [3H]U69,593, [3H]-(+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine [[3H]-(+)-3-PPP], or [3H]-1,3-di(o-tolyl)guanidine ([3H]DTG), [3H]-(-)-sulpiride [[3H]-(-)SULP], and [3H]-1- [1-(2-thienyl)cyclohexyl]piperidine ([3H]TCP), respectively. In the systems examined, (-)-2 exhibited the highest affinity for kappa receptors, with a Ki of 44 +/- 8 nM. However, (-)-2 also showed moderate affinity for sigma receptors, with a Ki of 594 +/- 3 nM [[3H]-(+)-3-PPP]. The (1R,2R)-(+)-enantiomer, (+)-2, had low affinity for both kappa and sigma receptors, exhibiting Ki values of 1298 +/- 49 nM at kappa ([3H]BREM) and 1270 +/- 168 nM at sigma [[3H]-(+)-3-PPP]. In contrast, the chiral cis compounds (+)-1 and (-)-1 showed high affinity for sigma receptors and negligible affinity for kappa opioid receptors in the [3H]BREM assay. Compound (-)-1 exhibited a Ki of 81 +/- 13 nM at sigma receptors [[3H]-(+)-3-PPP] and 250 +/- 8 nM ([3H]DTG).(ABSTRACT TRUNCATED AT 400 WORDS)

  DOI：

  10.1021/jm00128a050

文献信息

• A Study of the Effect of Catalyst on Stereochemistry in the Hydrogenation of N-(Menthyloxycarbonyl)-N-Methyl-2-(N-Pyrrolidinyl)-1-cyclohexenamine
  作者：Dorota Matecka、Brian R. de Costa

  DOI：10.1080/00397919408010153

  日期：1994.6

  Catalytic hydrogenation of N-(menthyloxycarbonyl)-N-methyl-2-(1-pyrrolidinyl)-1-cyclohexenamine (3) gave mainly 1R,2S-cis-N-(menthyloxycarbonyl)- and 1S,2R-cis-N-(menthyloxycarbonyl)-N-methyl-2-(1-pyrrolidinyl)cyclohexylamines 7 and 8 with diasterostereoselectivity favoring the 1S,2R-isomer 8.
• VONVOIGTLANDER, PHILIP F.;SZMUSZKOVICZ, JACOB
  作者：VONVOIGTLANDER, PHILIP F.、SZMUSZKOVICZ, JACOB

  DOI：——

  日期：——
• DE, COSTA BRIAN R.;RICE, KENNER C.;BOWEN, WAYNE D.;THURKAUF, ANDREW;ROTHM+, J. MED. CHEM., 33,(1990) N1, C. 3100-3110
  作者：DE, COSTA BRIAN R.、RICE, KENNER C.、BOWEN, WAYNE D.、THURKAUF, ANDREW、ROTHM+

  DOI：——

  日期：——
• HORWELL, DAVID C.
  作者：HORWELL, DAVID C.

  DOI：——

  日期：——