N-甲基-纳曲吲哚,C-11 | 111555-57-8

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 中文名称: N-甲基-纳曲吲哚,C-11
• 英文名称: N₁'-methylnaltrindole
• 英文别名: N-Methylnaltrindole；(5R,9R,13S,14S)-17-cyclopropylmethyl-6,7-didehydro-4,5-epoxy-1'-methylindolo[2',3':6,7]morphinan-3,14-diol；(1S,2S,13R,21R)-22-(cyclopropylmethyl)-11-methyl-14-oxa-11,22-diazaheptacyclo[13.9.1.01,13.02,21.04,12.05,10.019,25]pentacosa-4(12),5,7,9,15,17,19(25)-heptaene-2,16-diol
• CAS: 111555-57-8
• 化学式: C₂₇H₂₈N₂O₃
• 分子量: 428.531
• InChiKey: CRTCCMARDBQOKA-NVSKSXHLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  32
• 可旋转键数：
  2
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  57.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-甲基-纳曲吲哚,C-11 、 溴甲苯 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 以72%的产率得到17-(cyclopropylmethyl)-6,7-dehydro-4,5α-epoxy-3-benzyloxy-14-hydroxy-6,7-2',3'-(1'-methyl)-indolomorphinan
  参考文献：
  名称：

  Synthesis of N1′-([11C]methyl)naltrindole ([11C]MeNTI): A radioligand for positron emission tomographic studies of delta opioid receptors

  摘要：

  一种δ类阿片受体拮抗剂--N1′-甲基纳曲吲哚（MeNTI）已被碳-11标记。放射性标记的前体是通过苄基化纳曲吲哚的酚基制备的，收率为 71%。使用[11C]碘甲烷和氢氧化四（正丁基）铵水溶液在二甲基甲酰胺中于 80 °C 下对吲哚氮进行烷基化，然后对苄基保护基团进行氢解（H2，10% Pd-C），得到[11C]MeNTI。放射性合成、高效液相色谱纯化和配制的平均时间（n = 10）为 24 分钟（从爆炸结束算起）。合成结束时获得了放射化学纯度很高的[11C]MeNTI，其平均比活度为 2050 mCi/μmol，放射化学收率（基于[11C]碘甲烷）为 6%。

  DOI：

  10.1002/jlcr.2580360206
• 作为产物：
  描述：

  盐酸纳曲酮 在 palladium on activated charcoal 盐酸 、 氢气 、 溶剂黄146 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、34.48 kPa 条件下， 反应 3.0h， 生成 N-甲基-纳曲吲哚,C-11
  参考文献：
  名称：

  Synthesis of tritiated N1′-alkyl derivatives of the delta opioid receptor ligand naltrindole

  摘要：

  Tritiated N1'-methyI and N1'-ethyl analogues of naltrindole (NTI) have been synthesized for evaluation as radioligands for studies of delta opioid receptors. The two N1'-alkyl-5',7'-dibromoNTI precursors for radiolabeling were prepared by base-promoted alkylation of 2,4-dibromophenylhydrazine with either iodomethane or iodoethane followed by condensation with naltrexone using the Fischer indole synthesis. Catalytic debromotritiation followed by HPLC purification afforded [H-3]MeNTI (17.3 Ci/mmol) and [H-3]EtNTI (22.5 Ci/mmol)with high chemical and radiochemical purities (greater than or equal to 99.8%).

  DOI：

  10.1002/(sici)1099-1344(199702)39:2<115::aid-jlcr947>3.0.co;2-3

文献信息

• An updated synthesis of N ₁ ′‐([ ¹¹ C]methyl)naltrindole for positron emission tomography imaging of the delta opioid receptor
  作者：Tanpreet Kaur、Allen F. Brooks、Brian G. Hockley、Jovany Torres、Bradford D. Henderson、Peter J.H. Scott、Xia Shao

  DOI：10.1002/jlcr.3898

  日期：2021.4

  methoxymethyl acetal (MOM) protecting group which is easily removed with HCl, and employ it in an updated synthesis of [11 C]MeNTI. The new synthesis is fully automated and validated for clinical use. The total synthesis time is 45 min and provides [11 C]MeNTI in good activity yield (49 ± 8 mCi), molar activity (3926 ± 326 Ci/mmol) and radiochemical purity (97 ± 2%).

  描述了一种合成高选择性δ阿片受体（DOR）拮抗剂放射性示踪剂N1'-（[11 C]甲基）纳曲吲哚（[11 C]MeNTI）的新方法。最初的合成需要在 11 C 标记后氢化苄基保护基团，这在现代放射化学实验室中具有挑战性，这些实验室往往高度自动化并根据当前的良好生产规范进行操作。为了应对这一挑战，我们描述了一种新型 MeNTI 前体的开发，该前体带有一个可以用 HCl 轻松去除的甲氧基甲基缩醛 (MOM) 保护基团，并将其用于 [11 C]MeNTI 的更新合成中。新的合成是完全自动化的，并且经过验证可用于临床。总合成时间为 45 分钟，并以良好的活性产率 (49 ± 8 mCi) 提供 [11 C]MeNTI，
• Therapeutic Agent for Constipation
  申请人：Suzuki Tsutomu

  公开号：US20090069363A1

  公开（公告）日：2009-03-12

  A therapeutic and/or prophylactic agent for constipation induced by a compound having an opioid μ receptor agonist activity, which agent comprises as an effective ingredient a compound having an opioid δ receptor antagonist activity, e.g., a compound of Formula (I): (wherein R 1 represents hydrogen, lower alkyl, cycloalkyl lower alkyl or the like; R 2 and R 3 independently represent hydrogen, hydroxy or the like; R 4 is hydrogen, hydroxy or the like; R 5 is hydrogen; R 4 and R 5 may optionally form —O— or the like; R 6 represents hydrogen, lower alkyl or the like (wherein X represents —O— or —N(R 10 )— or the like; R 7 , R 8 , R 9a and R 9b independently represent hydrogen, lower alkyl, lower alkoxycarbonyl or the like; r represents an integer of 0 to 5; Y represents —CH— or the like; Z represents a crosslinkage composed of 2 to 5 atoms) or a pharmaceutically acceptable salt thereof or a solvate of either.

  一种治疗和/或预防由具有μ受体激动剂活性的化合物引起的便秘的药物，该药物包括作为有效成分的具有δ受体拮抗剂活性的化合物，例如，式（I）的化合物：（其中R1代表氢，低碳基，环烷基低碳基或类似物；R2和R3独立地代表氢，羟基或类似物；R4代表氢，羟基或类似物；R5代表氢；R4和R5可以选择形成-O-或类似物；R6代表氢，低碳基或类似物（其中X代表-O-或-N（R10）-或类似物；R7、R8、R9a和R9b独立地代表氢，低碳基，低碳酰氧基或类似物；r表示0到5的整数；Y代表-CH-或类似物；Z代表由2到5个原子组成的交联）或其药学上可接受的盐或其溶剂化物。
• Application of the message-address concept in the design of highly potent and selective non-peptide .delta. opioid receptor antagonists
  作者：P. S. Portoghese、M. Sultana、H. Nagase、A. E. Takemori

  DOI：10.1021/jm00397a001

  日期：1988.2
• Therapeutic Agent for Nausea and/or Vomiting
  申请人：Suzuki Tsutomu

  公开号：US20090292124A1

  公开（公告）日：2009-11-26

  A therapeutic and/or prophylactic agent for nausea and/or vomiting is provided. A therapeutic and/or prophylactic agent for nausea and/or vomiting, comprising a compound of the Formula (I) or a pharmaceutically acceptable salt or solvate thereof: R 1 and R 2 are each independently hydrogen or lower alkyl; R 3 is hydrogen or lower alkoxycarbonyl; and R 4 is hydrogen or lower alkyl; with the proviso that all of R 1 to R 3 are not simultaneously hydrogen; and R 1 and R 4 are not simultaneously hydrogen).
• Synthesis of N1′-([11C]methyl)naltrindole ([11C]MeNTI): A radioligand for positron emission tomographic studies of delta opioid receptors
  作者：John R. Lever、Chris M. Kinter、Hayden T. Ravert、John L. Musachio、William B. Mathews、Robert F. Dannals

  DOI：10.1002/jlcr.2580360206

  日期：1995.2

  A delta opioid receptor antagonist, N1′-methylnaltrindole (MeNTI), has been labeled with carbon-11. The precursor for radiolabeling was prepared in 71% yield by benzylation of the phenolic moiety of naltrindole. Alkylation of the indole nitrogen using [11C]iodomethane and aqueous tetra(n-butyl)ammonium hydroxide at 80 °C in dimethylformamide followed by hydrogenolysis (H2, 10% Pd-C) of the benzyl protecting group gave [11C]MeNTI. The average (n = 10) time for radiosynthesis, HPLC purification and formulation was 24 min from end-of-bombardment. [11C]MeNTI of high radiochemical purity was obtained at end-of-synthesis with an average specific activity of 2050 mCi/μmol and radiochemical yield, based on [11C]iodomethane, of 6%.

  一种δ类阿片受体拮抗剂--N1′-甲基纳曲吲哚（MeNTI）已被碳-11标记。放射性标记的前体是通过苄基化纳曲吲哚的酚基制备的，收率为 71%。使用[11C]碘甲烷和氢氧化四（正丁基）铵水溶液在二甲基甲酰胺中于 80 °C 下对吲哚氮进行烷基化，然后对苄基保护基团进行氢解（H2，10% Pd-C），得到[11C]MeNTI。放射性合成、高效液相色谱纯化和配制的平均时间（n = 10）为 24 分钟（从爆炸结束算起）。合成结束时获得了放射化学纯度很高的[11C]MeNTI，其平均比活度为 2050 mCi/μmol，放射化学收率（基于[11C]碘甲烷）为 6%。