(2R,6R,11R)-8-Methoxy-6,11-dimethyl-1,2,3,4,5,6,7,10-octahydro-2,6-methano-benzo[d]azocine | 60332-50-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (2R,6R,11R)-8-Methoxy-6,11-dimethyl-1,2,3,4,5,6,7,10-octahydro-2,6-methano-benzo[d]azocine
• 英文别名: (1R,9R,13R)-4-methoxy-1,13-dimethyl-10-azatricyclo[7.3.1.02,7]trideca-2(7),4-diene
• CAS: 60332-50-5
• 化学式: C₁₅H₂₃NO
• 分子量: 233.354
• InChiKey: JCGTZLUDVMKKIC-COLVAYQJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (2R,6R,11R)-8-Methoxy-6,11-dimethyl-1,2,3,4,5,6,7,10-octahydro-2,6-methano-benzo[d]azocine 在 palladium on activated charcoal 盐酸 、 盐酸肼 、 氢气 、 sodium cyanoborohydride 、 potassium hydrogencarbonate 、 氟化氢吡啶 、 溶剂黄146 、 sodium nitrite 作用下， 以 吡啶 、 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 (-)-cis-2-(3,3-dimethylallyl)-5,9α-dimethyl-2'-fluoro-6,7-benzomorphan
  参考文献：
  名称：

  Synthesis and .sigma. Binding Properties of 2'-Substituted 5,9.alpha.-Dimethyl-6,7-benzomorphans

  摘要：

  The synthesis and sigma 1 and sigma 2 binding properties of several (+)- and (-)-2-benzyl- and 2-dimethylallyl-2'-substituted-5,9 alpha-dimethyl-6,7-benzomorphans (3 and 4) are presented. In agreement with previously reported binding data for 2-substituted 5,9 alpha-dimethyl-2'-hydroxy-6,7-benzomorphans (N-substituted-N-normetazocine), all (1S,5S,SS)-(+)-isomers showed higher affinity for the sigma 1 site than the corresponding (1R,5R,9R)-(-)-isomers. Replacement of the 2'-hydroxy group of (+)-2-benzyl-5,9 alpha-dimethyl-2'-hydroxy-6,7-benzomorphan [(+)-1f] with a 2'-NH2 and 2'-N(CH3)(2) [(+)-3b and (+)-3c, respectively] had only a small effect on the sigma 1 K-i values. Changing the 2'-hydroxy group of (+)-1f to an H, F, Cl, Br, I, NHAc, or NHSO2CH3 resulted in a 5-fold or greater loss in potency. In contrast, replacement of the 2'-hydroxy group of (+)-2-(dimethylallyl)-5,9 alpha-dimethyl-2'-hydroxy-6,7-benzomorphan [(+)-1b, (+)-pentazocine] with a 2'-H or 2'-F group resulted in a 2-fold increase in potency. Conversion of (+)-1f to its 2'-desoxy analogue (+)-2d resulted in a 27.5-fold loss in affinity. This suggests that (+)-1f and other N-substituted benzomorphan analogues may be binding to single al receptors in a different way or to different sigma 1 receptors. (-)-Pentazocine [(-)-1b] and its 2'-fluoro analogue, (-)-2-(dimethylallyl)-5,9 alpha-dimethyl-2'-fluoro-6,7-benzomorphan [(-)-4a] showed the highest potency for the sigma 2 binding site.

  DOI：

  10.1021/jm00015a022
• 作为产物：
  描述：

  (-)-N-benzyl-N-normetazocine 在 palladium on activated charcoal 氨 、 氢气 、 sodium 、 四丁基碘化铵 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 异丙醇 为溶剂， 生成 (2R,6R,11R)-8-Methoxy-6,11-dimethyl-1,2,3,4,5,6,7,10-octahydro-2,6-methano-benzo[d]azocine
  参考文献：
  名称：

  Synthesis and .sigma. Binding Properties of 2'-Substituted 5,9.alpha.-Dimethyl-6,7-benzomorphans

  摘要：

  The synthesis and sigma 1 and sigma 2 binding properties of several (+)- and (-)-2-benzyl- and 2-dimethylallyl-2'-substituted-5,9 alpha-dimethyl-6,7-benzomorphans (3 and 4) are presented. In agreement with previously reported binding data for 2-substituted 5,9 alpha-dimethyl-2'-hydroxy-6,7-benzomorphans (N-substituted-N-normetazocine), all (1S,5S,SS)-(+)-isomers showed higher affinity for the sigma 1 site than the corresponding (1R,5R,9R)-(-)-isomers. Replacement of the 2'-hydroxy group of (+)-2-benzyl-5,9 alpha-dimethyl-2'-hydroxy-6,7-benzomorphan [(+)-1f] with a 2'-NH2 and 2'-N(CH3)(2) [(+)-3b and (+)-3c, respectively] had only a small effect on the sigma 1 K-i values. Changing the 2'-hydroxy group of (+)-1f to an H, F, Cl, Br, I, NHAc, or NHSO2CH3 resulted in a 5-fold or greater loss in potency. In contrast, replacement of the 2'-hydroxy group of (+)-2-(dimethylallyl)-5,9 alpha-dimethyl-2'-hydroxy-6,7-benzomorphan [(+)-1b, (+)-pentazocine] with a 2'-H or 2'-F group resulted in a 2-fold increase in potency. Conversion of (+)-1f to its 2'-desoxy analogue (+)-2d resulted in a 27.5-fold loss in affinity. This suggests that (+)-1f and other N-substituted benzomorphan analogues may be binding to single al receptors in a different way or to different sigma 1 receptors. (-)-Pentazocine [(-)-1b] and its 2'-fluoro analogue, (-)-2-(dimethylallyl)-5,9 alpha-dimethyl-2'-fluoro-6,7-benzomorphan [(-)-4a] showed the highest potency for the sigma 2 binding site.

  DOI：

  10.1021/jm00015a022

文献信息

• Synthesis and pharmacology of 8-amino-3-(cyclopropylmethyl)-1,2,3,4,5,6-hexahydro-cis-6,11-dimethyl-2,6-methano-3-benzazocine and related compounds
  作者：Mark P. Wentland、Noel F. Albertson、Anne K. Pierson

  DOI：10.1021/jm00175a013

  日期：1980.1

  The little compound 1a has been prepared and was found to be a strong, orally active agonist with narcotic--antagonist properties. 1a was prepared by two independent routes: (1) nitration of volazocine and subsequent reduction and (b) a sequence involving dissolving metal reduction of cyclazocine methyl ether, followed by oximination and Semmler--Wolff rearrangement. Several analogues were prepared

  已制备了少量化合物1a，发现该化合物是一种具有麻醉-拮抗剂特性的强口服活性激动剂。1a是通过两种独立的途径制备的：（1）硝唑啉的硝化反应和随后的还原反应;（b）涉及将金属溶解的环唑嘌呤甲醚还原的顺序，然后进行氧化和Semmler-Wolff重排。制备并测试了几种类似物。
• Synthesis and .sigma. Binding Properties of 2'-Substituted 5,9.alpha.-Dimethyl-6,7-benzomorphans
  作者：Richmond Danso-Danquah、Xu Bai、X. Zhang、S. Wayne Mascarella、Wanda Williams、Bethel Sine、Wayne D. Bowen、F. Ivy Carroll

  DOI：10.1021/jm00015a022

  日期：1995.7

  The synthesis and sigma 1 and sigma 2 binding properties of several (+)- and (-)-2-benzyl- and 2-dimethylallyl-2'-substituted-5,9 alpha-dimethyl-6,7-benzomorphans (3 and 4) are presented. In agreement with previously reported binding data for 2-substituted 5,9 alpha-dimethyl-2'-hydroxy-6,7-benzomorphans (N-substituted-N-normetazocine), all (1S,5S,SS)-(+)-isomers showed higher affinity for the sigma 1 site than the corresponding (1R,5R,9R)-(-)-isomers. Replacement of the 2'-hydroxy group of (+)-2-benzyl-5,9 alpha-dimethyl-2'-hydroxy-6,7-benzomorphan [(+)-1f] with a 2'-NH2 and 2'-N(CH3)(2) [(+)-3b and (+)-3c, respectively] had only a small effect on the sigma 1 K-i values. Changing the 2'-hydroxy group of (+)-1f to an H, F, Cl, Br, I, NHAc, or NHSO2CH3 resulted in a 5-fold or greater loss in potency. In contrast, replacement of the 2'-hydroxy group of (+)-2-(dimethylallyl)-5,9 alpha-dimethyl-2'-hydroxy-6,7-benzomorphan [(+)-1b, (+)-pentazocine] with a 2'-H or 2'-F group resulted in a 2-fold increase in potency. Conversion of (+)-1f to its 2'-desoxy analogue (+)-2d resulted in a 27.5-fold loss in affinity. This suggests that (+)-1f and other N-substituted benzomorphan analogues may be binding to single al receptors in a different way or to different sigma 1 receptors. (-)-Pentazocine [(-)-1b] and its 2'-fluoro analogue, (-)-2-(dimethylallyl)-5,9 alpha-dimethyl-2'-fluoro-6,7-benzomorphan [(-)-4a] showed the highest potency for the sigma 2 binding site.