4-(3-甲氧基苯基)-1,5-二甲基-3,6-二氢-2H-吡啶 | 123004-53-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 4-(3-甲氧基苯基)-1,5-二甲基-3,6-二氢-2H-吡啶
• 英文名称: 1,3-dimethyl-4-(3-methoxyphenyl)-1,2,5,6-tetrahydropyridine
• 英文别名: 1,2,6-trihydro-1,3-dimethyl-4-(3-methoxyphenyl)pyridine；1,5-dimethyl-4-(3-methoxyphenyl)-1,2,3,6-tetrahydropyridine；Pyridine, 1,2,3,6-tetrahydro-4-(3-methoxyphenyl)-1,5-dimethyl-；4-(3-methoxyphenyl)-1,5-dimethyl-3,6-dihydro-2H-pyridine
• CAS: 123004-53-5
• 化学式: C₁₄H₁₉NO
• 分子量: 217.311
• InChiKey: FAXSYIMYVUFDIN-UHFFFAOYSA-N

物化性质

• 沸点：
  327.7±42.0 °C(Predicted)
• 密度：
  1.010±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(3-甲氧基苯基)-1,5-二甲基-3,6-二氢-2H-吡啶 在 氢氧化钾 、 sodium hydroxide 、 甲酸 、 磷酸 、 氢溴酸 、 仲丁基锂 、 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 187.25h， 生成 5-(3-hydroxyphenyl)-9β-methyl-2-azabicyclo<3.3.1>nonane
  参考文献：
  名称：

  N-Substituted 9β-Methyl-5-(3-hydroxyphenyl)morphans Are Opioid Receptor Pure Antagonists

  摘要：

  The inhibition of radioligand binding and [S-35]GTP gamma S functional assay data for N-methyl- and N-phenethyl-9 beta-methyl-5-(3-hydroxyphenyl (5b and 5c) show that these compounds are pure antagonists at the mu, delta, and kappa opioid receptors. Since 5b and 5c have the 5-(3-hydroxyphenyl) group locked in a conformation comparable to an equatorial group of a piperidine chair conformation, this information provides very strong evidence that opioid antagonists can interact with opioid receptors in this conformation. In addition, it suggests that the trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine class of antagonist operates via a phenyl equatorial piperidine chair conformation. Importantly, the close relationship between the 4-(3-hydroxyphenyl)piperidines and 5-(3-hydroxyphenyl)morph an antagonists shows that the latter class of compound provides a rigid platform on which to build a novel series of opioid antagonists.

  DOI：

  10.1021/jm980290i
• 作为产物：
  描述：

  1,3-二甲基-4-哌啶酮 在 磷酸 、 仲丁基锂 、 phosphorus pentoxide 作用下， 反应 7.25h， 生成 4-(3-甲氧基苯基)-1,5-二甲基-3,6-二氢-2H-吡啶
  参考文献：
  名称：

  Synthesis of picenadol via metallo enamine alkylation methodology

  摘要：

  DOI：

  10.1021/jo00281a019

文献信息

• A stereoselective synthetic approach to N-alkyl-4β-methyl-5-phenylmorphans
  作者：James B. Thomas、Kenneth M. Gigstad、Scott E. Fix、Jason P. Burgess、Julie B. Cooper、S.Wayne Mascarella、Buddy E. Cantrell、Dennis M. Zimmerman、F.Ivy Carroll

  DOI：10.1016/s0040-4039(98)02402-2

  日期：1999.1

  stereoselective synthetic approach to N-alkyl-4β-methyl-5-phenylmorphans has been developed utilizing alkylation of the metalloenamine of N-alkyl-1,2,3,6-tetrahydro-4-phenylpyridines with 2-(chloromethyl)-3,5-dioxahex-1-ene (Okahara's reagent) followed by Clemmensen reduction.

  利用N-烷基-1,2,3,6-四氢-4-苯基吡啶的金属烯胺与2-（氯甲基）-3,5-dioxahex-1-ene（冈原试剂），然后进行Clemmensen还原。
• Octahydroisoquinoline compounds as opioid receptor modulators
  申请人：Carroll Ivy Frank

  公开号：US20070027182A1

  公开（公告）日：2007-02-01

  Compounds which bind to opioid receptors are provided. In a preferred embodiment of the invention, the compounds are opioid receptor antagonists. The present invention also provides methods of treating conditions which are mediated by an opioid receptor.

  提供结合到阿片受体的化合物。在发明的首选实施例中，这些化合物是阿片受体拮抗剂。本发明还提供了治疗由阿片受体介导的疾病的方法。
• Synthesis of 9β-methyl-2-alkyl-7-oxo-5-arylmorphans
  作者：James B. Thomas、Xiaoling Zheng、Lawrence E. Brieaddy、Jason P. Burgess、S. Wayne Mascarella、Scott E. Fix、Buddy E. Cantrell、Dennis M. Zimmerman、F. Ivy Carroll

  DOI：10.1016/s0040-4039(98)01549-4

  日期：1998.9

  synthetic approach to 9β-methyl-2-alkyl-7-oxo-5-arylmorphans has been developed utilizing alkylation of the metalloenamine of 1,2,3,6-tetrahydro-4-aryl-1-alkylpyridines with 2-(chloromethyl)-3,5-dioxahex-1-ene (Okahara's reagent).

  利用1,2,3,6-四氢-4-芳基-1-烷基吡啶的金属烯胺与2-（-氯甲基）-3,5-二恶己基-1-烯（冈原试剂）。
• N-Substituted <i>cis-</i>4a-(3-Hydroxyphenyl)-8a-methyloctahydroisoquinolines Are Opioid Receptor Pure Antagonists
  作者：F. Ivy Carroll、Sachin Chaudhari、James B. Thomas、S. Wayne Mascarella、Kenneth M. Gigstad、Jeffrey Deschamps、Hernán A. Navarro

  DOI：10.1021/jm058261c

  日期：2005.12.1

  N-Substituted cis-4a-(3-hydroxyphenyl)-8a-methyloctahydroisoquinolines (6a-g) were designed and synthesized as conformationally constrained analogues of the trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine (4) class of opioid receptor pure antagonists. The methyloctabydroisoquinolines 6a-g can exist in conformations where the 3-hydroxyphenyl substituent is either axial or equatorial, similar to the (3-hydroxyphenyl)piperidines 4. The 3-hydroxyphenyl equatorial conformation is responsible for the antagonist activity observed in the (3-hydroxyphenyl)piperidine antagonists. Single-crystal X-ray analysis of 6a shows that the 3-hydroxyphenyl equatorial conformation is favored in the solid state. Molecular modeling studies also suggest that the equatorial conformation has lower potential energy relative to that of the axial conformation. Evaluation of 6a-g in the [S-35]GTP-gamma-S in vitro functional assay showed that they were opioid receptor pure antagonists. N-[4a-(3-Hydroxyphenyl)-8a-methyl-2-(3-phenylpropyl)octahydroisoquinoline-6-yl]-3-(piperidin-1-yl)propionamide (6d) with a K-e of 0.27 nM at the kappa opioid receptor with 154- and 46-fold selectivity relative to those of the mu and 6 receptors, respectively, possessed the best combination Of K potency and selectivity.
• N-substituted octahydro-4a-(3-hydroxyphenyl)-10a-methyl-benzo[g]isoquinolines are opioid receptor pure antagonists
  作者：James B. Thomas、S.Wayne Mascarella、Jason P. Burgess、Heng Xu、Karen B. McCullough、Richard B. Rothman、Judith L. Flippen-Anderson、Clifford F. George、Buddy E. Cantrell、Dennis M. Zimmerman、F.Ivy Carroll

  DOI：10.1016/s0960-894x(98)00576-9

  日期：1998.11

  N-Methyl- and N-phenylethyl-(+/-)-1,2,3,4,4a,5,10,10a-octahydro-4a-(3-hydroxyphenyl)-10a-methyl- benzo[g]isoquinolines (4 and 5, respectively) were found to be pure opioid antagonists. These compounds were shown to share many of the characteristics identified with the N-methyl- and N-phenylethyl trans-3,4-dimethyl-4(3-hydroxyphenyl)piperidine (1 and 2, respectively) including N-substituent mediated potency and a lack of N-substituent mediated antagonism. These data suggest that compounds 4 and 5 and the N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines (1 and 2) may interact with opioid receptors similarly. (C) 1998 Elsevier Science Ltd. All rights reserved.