NIH 10772 | 160625-35-4

• 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: NIH 10772
• 英文别名: (1S,9S,13S)-1,13-dimethyl-10-[(4-nitrophenyl)methyl]-10-azatricyclo[7.3.1.02,7]trideca-2(7),3,5-trien-4-ol
• CAS: 160625-35-4
• 化学式: C₂₁H₂₄N₂O₃
• 分子量: 352.433
• InChiKey: PHISTALAMDWUTJ-OREJSRFESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  26
• 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：
  69.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  NIH 10772 在 tin(ll) chloride 作用下， 以 乙醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 2.0h， 生成 (+)-(2S,6S,11S)-3-(4-isothiocyanatobenzyl)-6,11-dimethyl-1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocin-8-ol
  参考文献：
  名称：

  Synthesis of (+)-cis-N-(4-Isothiocyanatobenzyl)-N-normetazocine, an Isothiocyanate Derivative of N-Benzylnormetazocine as Acylant Agent for the σ₁ Receptor

  摘要：

  (+)-顺式-N-(4-异硫氰酸苯甲基)-N-去甲吗啡酮（BNIT）（(+)-(4）被设计并合成，作为强效且选择性的α受体配体(+)-顺式-N-苄基-N-去甲吗啡酮的衍生物，用于不可逆地阻断α受体结合位点。使用不同浓度（0.1、1 和 5 μM）的BNIT预处理大鼠脑膜，导致了选择性α受体配体[H-3]-(+)-戊唑嗪结合能力的浓度依赖性降低。使用[H-3]-1,3-双(2-甲苯基)-胍（[H-3]-DTG，一种σ₁和σ₂受体的配体）进行的结合实验表明，BNIT仅阻断了[H-3]-DTG结合中的σ₁受体部分。

  DOI：

  10.1021/jm010501a
• 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 4.0h， 生成 NIH 10772
  参考文献：
  名称：

  (+)-cis-N-(para-, meta-, and ortho-substituted benzyl)-N-normetazocines: Synthesis and binding affinity at the [3H]-(+)-pentazocine-labeled (.sigma.1) site and quantitative structure-affinity relationship studies

  摘要：

  sigma l receptor ligands have potential pharmacological significance as antipsychotic drugs, as tools in the study of drug-induced motor function disorders, and as radiopharmaceutical imaging agents for the noninvasive imaging of malignant tumors in human subjects. A series of substituted N-benzyl-N-normetazocines were synthesized and their binding affinity at the sigma l receptor evaluated in order to examine the details of the structure-affinity relationships (SAR) of a previously determined high-affinity lead compound, (+)-cis-N-benzyl-N-normetazocine (K-i = 0.67 nM). Variation in the benzyl substituents of these compounds produced a 1590-fold range in affinity at the sigma l receptor from the unsubstituted benzyl analog to the lowest affinity p-tert-butylbenzyl analog (K-i - 1066 nM). The nanomolar binding affinity for the sigma l receptor of (+)-cis-N-(4-fluorobenzyl)-N-normetzocine suggests that this analog may be a useful PET imaging agent.

  DOI：

  10.1021/jm00003a019

文献信息

• (+)-cis-N-(para-, meta-, and ortho-substituted benzyl)-N-normetazocines: Synthesis and binding affinity at the [3H]-(+)-pentazocine-labeled (.sigma.1) site and quantitative structure-affinity relationship studies
  作者：S. Wayne Mascarella、Xu Bai、Wanda Williams、Bethel Sine、Wayne D. Bowen、F. Ivy Carroll

  DOI：10.1021/jm00003a019

  日期：1995.2

  sigma l receptor ligands have potential pharmacological significance as antipsychotic drugs, as tools in the study of drug-induced motor function disorders, and as radiopharmaceutical imaging agents for the noninvasive imaging of malignant tumors in human subjects. A series of substituted N-benzyl-N-normetazocines were synthesized and their binding affinity at the sigma l receptor evaluated in order to examine the details of the structure-affinity relationships (SAR) of a previously determined high-affinity lead compound, (+)-cis-N-benzyl-N-normetazocine (K-i = 0.67 nM). Variation in the benzyl substituents of these compounds produced a 1590-fold range in affinity at the sigma l receptor from the unsubstituted benzyl analog to the lowest affinity p-tert-butylbenzyl analog (K-i - 1066 nM). The nanomolar binding affinity for the sigma l receptor of (+)-cis-N-(4-fluorobenzyl)-N-normetzocine suggests that this analog may be a useful PET imaging agent.
• Synthesis of (+)-<i>cis</i>-<i>N</i>-(4-Isothiocyanatobenzyl)-<i>N</i>-normetazocine, an Isothiocyanate Derivative of <i>N</i>-Benzylnormetazocine as Acylant Agent for the σ₁ Receptor
  作者：Giuseppe Ronsisvalle、Orazio Prezzavento、Agostino Marrazzo、Franco Vittorio、Michele Massimino、Giovanna Murari、Santi Spampinato

  DOI：10.1021/jm010501a

  日期：2002.6.1

  (+)-cis-N-(4-Isothiocyanatobenzyl)-N-normetazocine (BNIT) (+)-(4) was designed and synthesized as a derivative of the potent and selective a, receptor ligand (+)-cis-N-benzyl-N-normetazocine for irreversibly blocking a, binding sites. Pretreatment of guinea pig brain membranes with BNIT (0.1, 1, and 5 muM) caused a concentration-dependent loss of binding of the selective a, ligand [H-3]-(+)-pentazocine. Binding experiments with [H-3]-1,3-di(2-tolyl)-guanidine ([H-3]-DTG), a ligand of sigma(1) and sigma(2) receptors, showed that pretreatment with BNIT blocked only the sigma(1) component of [H-3]-DTG binding.

  (+)-顺式-N-(4-异硫氰酸苯甲基)-N-去甲吗啡酮（BNIT）（(+)-(4）被设计并合成，作为强效且选择性的α受体配体(+)-顺式-N-苄基-N-去甲吗啡酮的衍生物，用于不可逆地阻断α受体结合位点。使用不同浓度（0.1、1 和 5 μM）的BNIT预处理大鼠脑膜，导致了选择性α受体配体[H-3]-(+)-戊唑嗪结合能力的浓度依赖性降低。使用[H-3]-1,3-双(2-甲苯基)-胍（[H-3]-DTG，一种σ₁和σ₂受体的配体）进行的结合实验表明，BNIT仅阻断了[H-3]-DTG结合中的σ₁受体部分。