trans-N-<2-(dimethylamino)cyclohexyl>-p-methoxy-N-methylbenzamide | 67579-70-8

• 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: trans-N-<2-(dimethylamino)cyclohexyl>-p-methoxy-N-methylbenzamide
• 英文别名: trans-N-[2-(dimethylamino)cyclohexyl]-p-methoxy-N-methylbenzamide；N-[(1R,2R)-2-(Dimethylamino)cyclohexyl]-4-methoxy-N-methylbenzamide
• CAS: 67579-70-8
• 化学式: C₁₇H₂₆N₂O₂
• 分子量: 290.406
• InChiKey: FUPLXXJNTCSEIW-HZPDHXFCSA-N

物化性质

• 沸点：
  439.1±40.0 °C(Predicted)
• 密度：
  1.08±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  trans-N-<2-(dimethylamino)cyclohexyl>-p-methoxy-N-methylbenzamide 在 sodium hydride 、 乙硫醇 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以0.187 g的产率得到trans-N-<2-(dimethylamino)cyclohexyl>-p-hydroxy-N-methylbenzamide
  参考文献：
  名称：

  Factors affecting binding of trans-N-[2-(methylamino)cyclohexyl]benzamides at the primary morphine receptor

  摘要：

  In this paper, we describe the synthesis of a series of trans-N-[2-(methylamino)cyclohexyl]benzamides possessing morphine-like pharmacological properties. The affinity of the compounds for the agonist and antagonist states of the mu opioid receptor has been established by means of an in vitro binding assay. We have investigated the geometry and electronic structure of the molecules using molecular mechanics and an ab initio SCF-MO procedure with FSGO basis sets. Comparison to naloxone reveals properties of possible importance in receptor association. We have considered both the S,S and R,R isomers in the binding model. Statistical analyses imply that three factors play a significant role in binding: (1) membrane-water partitioning, (2) the capacity of the aromatic ring and amine N-substituent to act as electron acceptors, (3) the conformational energy required to attain the binding configuration.

  DOI：

  10.1021/jm00150a017
• 作为产物：
  描述：

  (±)-N,N-dimethyl-trans-1,2-diaminocyclohexane 在 lithium aluminium tetrahydride 、 三乙胺 作用下， 以 乙醚 为溶剂， 反应 51.0h， 生成 trans-N-<2-(dimethylamino)cyclohexyl>-p-methoxy-N-methylbenzamide
  参考文献：
  名称：

  Factors affecting binding of trans-N-[2-(methylamino)cyclohexyl]benzamides at the primary morphine receptor

  摘要：

  In this paper, we describe the synthesis of a series of trans-N-[2-(methylamino)cyclohexyl]benzamides possessing morphine-like pharmacological properties. The affinity of the compounds for the agonist and antagonist states of the mu opioid receptor has been established by means of an in vitro binding assay. We have investigated the geometry and electronic structure of the molecules using molecular mechanics and an ab initio SCF-MO procedure with FSGO basis sets. Comparison to naloxone reveals properties of possible importance in receptor association. We have considered both the S,S and R,R isomers in the binding model. Statistical analyses imply that three factors play a significant role in binding: (1) membrane-water partitioning, (2) the capacity of the aromatic ring and amine N-substituent to act as electron acceptors, (3) the conformational energy required to attain the binding configuration.

  DOI：

  10.1021/jm00150a017

文献信息

• Synthesis and pharmacological characterization of ethylenediamine synthetic opioids in human μ‐opiate receptor 1 (OPRM1) expressing cells
  作者：Tom Hsu、Jayapal R. Mallareddy、Kayla Yoshida、Vincent Bustamante、Tim Lee、John L. Krstenansky、Alexander C. Zambon

  DOI：10.1002/prp2.511

  日期：2019.10

  substituents were the most potent with comparable EC50 values for inhibition of cAMP accumulation; 26.49 ± 11.2 nmol L-1 and 8.8 ± 4.9 nmol L-1, respectively. Despite similar potencies for Gαi coupling, these two compounds had strikingly different hMOR internalization efficacies: U-47700 (10 μmol L-1) induced ~25% hMOR internalization similar to DAMGO while AH-7921 (10 μmol L-1) induced ~5% hMOR internalization

  阿片类药物是强效镇痛药，通过人类 μ-阿片受体 (hMOR) 发挥作用。阿片类药物的使用与耐受、成瘾、呼吸抑制和便秘等不良反应有关。两种合成阿片类药物 AH-7921 和 U-47700 于 20 世纪 70 年代开发，但从未上市，最近出现在非法药物市场和法医毒理学报告中。这些药物最初的特点是在啮齿类动物中具有镇痛活性；然而，它们在 hMOR 上的药理学尚未描述。因此，我们基于核心 AH-7921 和 U-47700 结构合成了 50 多种化学类似物，以评估它们与 Gαi 信号传导偶联并诱导 hMOR 内化的能力。对于 AH-7921 和 U-47700 类似物，3,4-二氯苯甲酰取代基是最有效的，具有可比的 EC50 值来抑制 cAMP 积累；分别为 26.49 ± 11.2 nMOl L-1 和 8.8 ± 4.9 nMOl L-1。尽管 Gαi 偶联的效力相似，但这两种化合物具有显着不同的
• CHENEY, B. V.;SZMUSZKOVICZ, J.;LAHTI, R. A.;ZICHI, D. A., J. MED. CHEM., 1985, 28, N 12, 1853-1864
  作者：CHENEY, B. V.、SZMUSZKOVICZ, J.、LAHTI, R. A.、ZICHI, D. A.

  DOI：——

  日期：——