(+)-N-Benzylnormetazocine | 57573-46-3

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 6,7-苯并吗啡烷
• 英文名称: (+)-N-Benzylnormetazocine
• 英文别名: (+)-N-benzyl-N-normetazocine；(2S,6S,11S)-3-Benzyl-6,11-dimethyl-1,2,3,4,5,6-hexahydro-2,6-methano-benzo[d]azocin-8-ol；(1S,9S,13S)-10-benzyl-1,13-dimethyl-10-azatricyclo[7.3.1.02,7]trideca-2(7),3,5-trien-4-ol
• CAS: 57573-46-3
• 化学式: C₂₁H₂₅NO
• 分子量: 307.436
• InChiKey: RPMPAQXGZYLEST-NQERJWCQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (+)-N-Benzylnormetazocine 在 palladium on activated charcoal 盐酸 、 盐酸肼 、 氨 、 氢气 、 sodium 、 四丁基碘化铵 、 sodium hydride 、 potassium hydrogencarbonate 、 溶剂黄146 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 60.5h， 生成 (+)-2'-amino-2-benzyl-5,9α-dimethyl-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：

  (2alpha,6alpha,11R*)-1,2,3,4,5,6-六氢-6,11-二甲基-2,6-甲桥-3-苯并氮杂环辛四烯-8-醇 、 alkaline earth salt of/the/ methylsulfuric acid 在 碳酸氢钠 作用下， 以 乙醇 为溶剂， 反应 5.0h， 以67%的产率得到(+)-N-Benzylnormetazocine
  参考文献：
  名称：

  对映体N-取代的N-去甲偶氮胺：对sigma，PCP和mu阿片受体的亲和力的比较研究。

  摘要：

  N-烯丙基-N-去甲甲氮嗪的光学对映体（2; SKF 10047，NANM）是用于σ受体分类的原始化合物，与其他受体（例如PCP（NMDA），阿片类和多巴胺受体）不同。后来的研究表明（+）-N-（二甲基烯丙基）-N-去甲偶氮辛[（+）-4，（+）-戊三嗪]对sigma受体更有效且更具选择性。为了获得更多的结构-活性关系信息，制备了几种N-取代的N-正甲氮嗪类似物，并对其σ-1（[3H]-（+）-3-PPP或[3H]-（+）-戊唑嗪进行了评估），PCP（[3H] TCP）和mu阿片类药物（[3H] DAMGO）受体结合亲和力。（+）-N-苄基-N-去甲偶氮辛[（+）-10）对sigma位点具有亚纳摩尔亲和力，Ki = 0.67。类似物（+）-10的选择性分别超过14,000和2400倍，相对于PCP和mu阿片类药物受体来说是σ受体。N-取代的N-去甲氮嗪对sigma位点是对映选择性的。（+）

  DOI：

  10.1021/jm00093a014

文献信息

• 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.
• Enantiomeric N-substituted N-normetazocines: a comparative study of affinities at .sigma., PCP, and .mu. opioid receptors
  作者：F. I. Carroll、P. Abraham、K. Parham、X. Bai、X. Zhang、G. A. Brine、S. W. Mascarella、B. R. Martin、E. L. May、C Sauss、L Di Paolo、P Wallace、J. M. Walker、W. D. Bowen

  DOI：10.1021/jm00093a014

  日期：1992.7

  their sigma-1 ([3H]-(+)-3-PPP or [3H]-(+)-pentazocine), PCP ([3H]TCP), and mu opioid ([3H]DAMGO) receptor binding affinities. (+)-N-Benzyl-N-normetazocine [(+)-10)] possessed subnanomolar affinities for the sigma site, Ki = 0.67. The analog (+)-10 showed greater than 14,000- and 2400-fold selectivity, respectively, for the sigma receptor relative to the PCP and mu opioid receptors. The N-substituted

  N-烯丙基-N-去甲甲氮嗪的光学对映体（2; SKF 10047，NANM）是用于σ受体分类的原始化合物，与其他受体（例如PCP（NMDA），阿片类和多巴胺受体）不同。后来的研究表明（+）-N-（二甲基烯丙基）-N-去甲偶氮辛[（+）-4，（+）-戊三嗪]对sigma受体更有效且更具选择性。为了获得更多的结构-活性关系信息，制备了几种N-取代的N-正甲氮嗪类似物，并对其σ-1（[3H]-（+）-3-PPP或[3H]-（+）-戊唑嗪进行了评估），PCP（[3H] TCP）和mu阿片类药物（[3H] DAMGO）受体结合亲和力。（+）-N-苄基-N-去甲偶氮辛[（+）-10）对sigma位点具有亚纳摩尔亲和力，Ki = 0.67。类似物（+）-10的选择性分别超过14,000和2400倍，相对于PCP和mu阿片类药物受体来说是σ受体。N-取代的N-去甲氮嗪对sigma位点是对映选择性的。（+）