(1R,2S)-2-(pyrrolidin-1-yl)cyclohexanamine | 133575-74-3

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (1R,2S)-2-(pyrrolidin-1-yl)cyclohexanamine
• 英文别名: (-)-cis-2-(1-pyrrolidinyl)cyclohexylamine；(-)-cis-2-(1-pyrolidinyl)cyclohexylamine；(1R,2S)-2-pyrrolidin-1-yl-cyclohexanamine；(1R,2S)-2-(Pyrrolidin-1-yl)cyclohexan-1-amine；(1R,2S)-2-pyrrolidin-1-ylcyclohexan-1-amine
• CAS: 133575-74-3
• 化学式: C₁₀H₂₀N₂
• 分子量: 168.282
• InChiKey: FLEFKPPJPOWCSZ-ZJUUUORDSA-N

物化性质

• 沸点：
  86 °C(Press: 0.1 Torr)
• 密度：
  1.004±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  29.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (1R,2S)-2-(pyrrolidin-1-yl)cyclohexanamine 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 (1R,2S)-(-)-cis-N-<2-(3,4-dichlorophenyl)ethyl>-N-(cyclopropylmethyl)-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：

  trans-2-(N-phenylcarbonylamino)-1-cyclohexanol 在 palladium on activated charcoal 氢氧化钾 、 Jones reagent (CrO₃, conc. H₂SO₄, H₂O) 、 氢气 、 对甲苯磺酸 作用下， 以 乙二醇 、 丙酮 为溶剂， 反应 73.5h， 生成 (1R,2S)-2-(pyrrolidin-1-yl)cyclohexanamine
  参考文献：
  名称：

  Costa, Brian R. de; Radesca, Lilian, Heterocycles, 1990, vol. 31, # 10, p. 1837 - 1846

  摘要：

  DOI：

文献信息

• Kinetic Resolution of 5-Substituted Oxazinones with Bifunctional Chiral Base/Squaramide Organocatalysts
  作者：Albrecht Berkessel、Serap Eröksüz、Jörg Neudörfl

  DOI：10.1055/s-0036-1588852

  日期：2017.7

  5-Substituted oxazinones provide N-protected β2-amino acid esters upon alcoholytic ring opening. Thus far, this access to enantiopure β2-amino acids has been restricted to the use of enzymes (hydrolases) as catalysts for the kinetic resolution of racemic 5-substituted oxazinones, and branched alkyl or ortho-substituted aryl groups on the substrate oxazinone’s 5-position were typically not tolerated

  5-取代的恶嗪酮在醇解开环时提供 N-保护的 β2-氨基酸酯。迄今为止，对映体纯 β2-氨基酸的这种获取仅限于使用酶（水解酶）作为动力学拆分外消旋 5-取代恶嗪酮和底物恶嗪酮 5- 上的支链烷基或邻位取代芳基的催化剂。位置通常不被容忍。我们在此报告某些双功能手性碱/方酸酰胺有机催化剂，特别是衍生自 cis-1,2-diaminocyclohex 或 9-amino-9-epi-quinine 的那些，允许首次对这种“困难”类恶嗪酮底物进行有机催化动力学拆分，提供选择性因子高达 43 的 N 保护的 β2-氨基酸酯。
• Nitrogen-containing cyclohetero cycloalkylaminoaryl derivatives for CNS
  申请人：G. D. Searle & Co.

  公开号：US05130330A1

  公开（公告）日：1992-07-14

  Certain nitrogen-containing cyclohetero cycloalkylaminoaryl compounds are described for treatment of CNS disorders such as cerebral ischemia, psychotic disorders and convulsions. Compounds of particular interest are of the formula ##STR1## wherein R.sup.1 is selected from hydrido, loweralkyl, cycloalkylalkyl of four to six carbon atoms, and loweralkenylloweralkyl; wherein each of R.sup.2 and R.sup.3 is independently selected from hydrido and loweralkyl; wherein each of R.sup.4 through R.sup.7, R.sup.10 and R.sup.11 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.

  本文描述了一些含氮的环杂环烷基氨基芳基化合物，用于治疗中枢神经系统疾病，如脑缺血、精神障碍和癫痫。特别感兴趣的化合物为下式：##STR1##其中R1选自氢、低碳基、四至六个碳原子的环烷基烷基和低碳烯基烷基；其中R2和R3各自独立地选自氢和低碳基；其中R4至R7、R10和R11各自独立地选自氢、羟基、低碳基、苄基、苯氧基、苄氧基和卤代低碳基；其中n为4至6的数字；其中p为0至4之间的数字；其中q为3至5之间的数字；其中A选自苯基、萘基和噻吩基；其中上述任何A基团都可以进一步用一个或多个取代基独立地选自氢、羟基、低碳基、低碳氧基、卤素、卤代低碳基、氨基、单低碳基氨基和双低碳基氨基取代；或其药学上可接受的盐。
• 2-AMINOBENZAMIDE DERIVATIVE
  申请人：Kuramochi Takahiro

  公开号：US20090233900A1

  公开（公告）日：2009-09-17

  To provide a novel and excellent agent for treating or preventing nociceptive pain, neuropathic pain, cancer pain, headache, bladder function disorder and the like, based on the inhibitory action on the capsaicin receptor VR1 activation. The present invention was accomplished by confirming that a benzamide derivative characterized by the possession of a benzene ring in which a single ring is condensed on the nitrogen atom of amido group and possession of a lower alkylamino or an amino group substituted with a ring group at the neighboring position of said amido group has a strong inhibitory action on VR1 activation and excellent pharmacological actions based on this and by finding that it can become an excellent agent for treating or preventing VR1-involved diseases such as nociceptive pain, neuropathic pain, cancer pain, headache, bladder function disorder and the like.

  本发明提供了一种基于对辣椒素受体VR1激活的抑制作用的新型优良药剂，用于治疗或预防伤害性疼痛、神经病理性疼痛、癌症疼痛、头痛、膀胱功能障碍等疾病。本发明通过确认一种苯甲酰胺衍生物，其特征在于其苯环上的单环在酰胺基氮原子上被紧缩，其低烷基氨基或邻位于酰胺基的环基取代的氨基具有对VR1激活的强抑制作用和优良的药理作用，从而发现它可以成为治疗或预防伤害性疼痛、神经病理性疼痛、癌症疼痛、头痛、膀胱功能障碍等VR1相关疾病的优良药剂。
• <i>trans-</i> and <i>cis-</i>DACH-Based Bifunctional Squaramides Catalyzed Ring-Opening Polymerizations of Asymmetric Substituted Glycolides
  作者：Ayşenur Vardar、Özden Erdebil、Olcay Mert、Serap Mert

  DOI：10.1021/acs.macromol.3c00293

  日期：2023.6.27

  aromatic ring, and different sizes of cyclic tertiary amines from piperidine to pyrrolidine on the DACH ring. Then, the ring-opening polymerizations of asymmetrically substituted glycolides (ASGs) such as isobutyl glycolide (IBG), isobutyl methyl glycolide (IBMG), and isobutyl ethyl glycolide (IBEG) were achieved with bifunctional squaramide organocatalysts at ambient temperature (20 °C) in dichloromethane

  广泛的方酰胺有机催化剂库是从两种几何异构体（反式和顺式（1,2-二氨基环己烷）（DACH））开始制备的，在方酰胺核心和芳族基团之间具有不同数量的 -CH 2 - 连接，芳香环上有不同数量的吸电子-CF 3基团，以及DACH环上有不同大小的从哌啶到吡咯烷的环状叔胺。然后，不对称取代的乙交酯（ASG）如异丁基乙交酯（IBG）、异丁基甲基乙交酯（IBMG）和异丁基乙基乙交酯（IBEG ）的开环聚合）是使用双功能方酰胺有机催化剂在环境温度（20°C）下在二氯甲烷（DCM）或在50°C的1,2-二氯乙烷（DCE）中实现的。聚（取代乙交酯）（PSG）均聚物的分子量可根据单体/引发剂比例进行预测，转化率高达 100%，多分散性（PDI）值低至 1.04，产率高达 93%。与顺式 DACH衍生物相比， IBG、IBMG和IBEG单体在反式DACH 催化剂存在下表现出更好的聚合活性。结果表明， NH CH 2和NH
• Cis-N-[(2-aminocycloaliphatic)benzene acetamide and -benzamide anticonvulsants
  申请人：THE UPJOHN COMPANY

  公开号：EP0222533A1

  公开（公告）日：1987-05-20

  Certain cis-N-(2-amino-cycloaliphatic)benzeneacetamide and -benz­amides of the formula 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-[2-(1-pyrrolidinyl)cyclohexyl]benzamide 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.

  某些顺式-N-(2-氨基环脂族)苯乙酰胺和-苯甲酰胺，其式为 其中m为0或1，n为1或2，R为氢或烷基，R₁和R₂分别为烷基，或与氮一起表示吡咯烷环，X和Y为氢、氟、氯或溴，或X和Y之一为三氟甲基，例如已发现顺式-3,4-二氯-N-甲基-N-[2-(1-吡咯烷基)环己基]苯甲酰胺及其盐类具有中枢神经系统癫痫发作阻断或预防药物作用，例如抗惊厥药物特性，但几乎没有镇痛特性。其中一些化合物是新化合物。