去乙酰基消旋卡多曲 | 81110-69-2

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 去乙酰基消旋卡多曲
• 英文名称: benzyl N-<2-(mercaptomethyl)-3-phenylpropanoyl>glycinate
• 英文别名: N-(2-mercaptomethyl-3-phenyl-1-oxopropyl)-glycine benzyl ester；N-[3-Mercapto-2-benzyl-propanoyl]glycine benzyl ester；Benzyl 2-(2-benzyl-3-mercaptopropanamido)acetate；benzyl 2-[(2-benzyl-3-sulfanylpropanoyl)amino]acetate
• CAS: 81110-69-2
• 化学式: C₁₉H₂₁NO₃S
• 分子量: 343.447
• InChiKey: LFABBWTUJCBFQG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  56.4
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• WGK Germany：
  3
• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P305+P351+P338,P330,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  去乙酰基消旋卡多曲 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 氯仿 为溶剂， 反应 8.5h， 生成 N-<2-<<<3-<<(2-amino-3-phenylpropyl)thio>carbonyl>propanoyl>thio>methyl>-3-phenylpropanoyl>glycine benzyl ester
  参考文献：
  名称：

  Mixed-inhibitor-prodrug as a new approach toward systemically active inhibitors of enkephalin-degrading enzymes

  摘要：

  In order to evaluate the possible advantages of potentiating the effects of the endogenous enkephalins, to obtain analgesia without the serious drawbacks of morphine, it was essential to design systemically active compounds which inhibit the two metabolizing enzymes, aminopeptidase N (APN) and neutral endopeptidase 24.11 (NEP). A new concept combining the idea of "prodrug" and "mixed inhibitor" was therefore developed. Given the high efficiency of beta-mercaptoalkylamines as APN inhibitors and of N-(mercaptoacyl) amino acids as NEP inhibitors, compounds associating these molecules through disulfide or thioester bonds, which are known to increase lipophilicity and to favor passage across the blood-brain barrier, have been synthesized. An HPLC study indicated that the disulfide bridge was resistant to serum enzymes but was cleaved by brain membrane homogenates, suggesting that the active inhibitors were released in the central nervous system. The validity of the approach was verified by the efficient antinociceptive responses obtained in the hot plate test in mice after iv administration of disulfide-containing inhibitors (ED50s of from 4 to 26 mg/kg on the jump latency time). The analgesic potencies of the "mixed inhibitor-prodrug" RB 101 [H2NCH(CH2CH2SCH3)CH2SSCH2CH(CH2Ph)CONHCH(CH2Ph)COOCH2Ph] after iv administration were three times greater than those of a similar combined dose of its two constitutive moieties. The separation of the two diastereoisomers constituting RB 101 showed that the analgesia has a stereochemical dependence, the (S,S,S)-isomer being more active than the (S,R,S)-isomer. Furthermore, in the tail flick test in the rat, RB 101 gave 38% analgesia at a dose of 80 mg/kg. Due to its high efficiency and its longer pharmacological effect, RB 101 was selected for a complete study of its analgesic properties.

  DOI：

  10.1021/jm00091a016
• 作为产物：
  描述：

  消旋卡多曲二元酸杂质 在 盐酸 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 氯仿 为溶剂， 反应 2.0h， 生成 去乙酰基消旋卡多曲
  参考文献：
  名称：

  Mixed-inhibitor-prodrug as a new approach toward systemically active inhibitors of enkephalin-degrading enzymes

  摘要：

  In order to evaluate the possible advantages of potentiating the effects of the endogenous enkephalins, to obtain analgesia without the serious drawbacks of morphine, it was essential to design systemically active compounds which inhibit the two metabolizing enzymes, aminopeptidase N (APN) and neutral endopeptidase 24.11 (NEP). A new concept combining the idea of "prodrug" and "mixed inhibitor" was therefore developed. Given the high efficiency of beta-mercaptoalkylamines as APN inhibitors and of N-(mercaptoacyl) amino acids as NEP inhibitors, compounds associating these molecules through disulfide or thioester bonds, which are known to increase lipophilicity and to favor passage across the blood-brain barrier, have been synthesized. An HPLC study indicated that the disulfide bridge was resistant to serum enzymes but was cleaved by brain membrane homogenates, suggesting that the active inhibitors were released in the central nervous system. The validity of the approach was verified by the efficient antinociceptive responses obtained in the hot plate test in mice after iv administration of disulfide-containing inhibitors (ED50s of from 4 to 26 mg/kg on the jump latency time). The analgesic potencies of the "mixed inhibitor-prodrug" RB 101 [H2NCH(CH2CH2SCH3)CH2SSCH2CH(CH2Ph)CONHCH(CH2Ph)COOCH2Ph] after iv administration were three times greater than those of a similar combined dose of its two constitutive moieties. The separation of the two diastereoisomers constituting RB 101 showed that the analgesia has a stereochemical dependence, the (S,S,S)-isomer being more active than the (S,R,S)-isomer. Furthermore, in the tail flick test in the rat, RB 101 gave 38% analgesia at a dose of 80 mg/kg. Due to its high efficiency and its longer pharmacological effect, RB 101 was selected for a complete study of its analgesic properties.

  DOI：

  10.1021/jm00091a016

文献信息

• Trifluoromethyl Thianthrenium Triflate: A Readily Available Trifluoromethylating Reagent with Formal CF₃⁺, CF₃^•, and CF₃^– Reactivity
  作者：Hao Jia、Andreas P. Häring、Florian Berger、Li Zhang、Tobias Ritter

  DOI：10.1021/jacs.1c02606

  日期：2021.5.26

  thianthrenium triflate (TT-CF3+OTf–) as a novel trifluoromethylating reagent, which is conveniently accessible in a single step from thianthrene and triflic anhydride. We demonstrate the use of TT-CF3+OTf– in electrophilic, radical, and nucleophilic trifluoromethylation reactions.

  在这里，我们报告了三氟甲磺酸三氟甲基铊 (TT-CF 3 + OTf – ) 作为一种新型三氟甲基化试剂的合成和应用，该试剂可以方便地从噻蒽和三氟甲磺酸酐一步获得。我们展示了 TT-CF 3 + OTf –在亲电、自由基和亲核三氟甲基化反应中的使用。
• [EN] A TRIFLUOROMETHYL THIANTHRENIUM COMPOUND, PROCESS FOR PREPARING THE SAME AND THE USE THEREOF<br/>[FR] COMPOSÉ DE TRIFLUOROMÉTHYL THIANTHRÉNIUM, SON PROCÉDÉ DE PRÉPARATION ET SON UTILISATION
  申请人：STUDIENGESELLSCHAFT KOHLE MBH

  公开号：WO2022219003A1

  公开（公告）日：2022-10-20

  The present inventions refers a novel trifluoromethyl thianthrenium compound referred to as TT-CF3+X–, a process for preparing the same and the use thereof for trifluoromethylating organic compounds.

  本发明涉及一种新型三氟甲基噻吩铵化合物，称为TT-CF3+X-，制备该化合物的方法以及将其用于有机化合物三氟甲基化的用途。
• US4513009A
  申请人：——

  公开号：US4513009A

  公开（公告）日：1985-04-23
• US5491169A
  申请人：——

  公开号：US5491169A

  公开（公告）日：1996-02-13
• Mixed-inhibitor-prodrug as a new approach toward systemically active inhibitors of enkephalin-degrading enzymes
  作者：Marie Claude Fournie-Zaluski、Pascal Coric、Serge Turcaud、Evelyne Lucas、Florence Noble、Raphael Maldonado、Bernard P. Roques

  DOI：10.1021/jm00091a016

  日期：1992.6

  In order to evaluate the possible advantages of potentiating the effects of the endogenous enkephalins, to obtain analgesia without the serious drawbacks of morphine, it was essential to design systemically active compounds which inhibit the two metabolizing enzymes, aminopeptidase N (APN) and neutral endopeptidase 24.11 (NEP). A new concept combining the idea of "prodrug" and "mixed inhibitor" was therefore developed. Given the high efficiency of beta-mercaptoalkylamines as APN inhibitors and of N-(mercaptoacyl) amino acids as NEP inhibitors, compounds associating these molecules through disulfide or thioester bonds, which are known to increase lipophilicity and to favor passage across the blood-brain barrier, have been synthesized. An HPLC study indicated that the disulfide bridge was resistant to serum enzymes but was cleaved by brain membrane homogenates, suggesting that the active inhibitors were released in the central nervous system. The validity of the approach was verified by the efficient antinociceptive responses obtained in the hot plate test in mice after iv administration of disulfide-containing inhibitors (ED50s of from 4 to 26 mg/kg on the jump latency time). The analgesic potencies of the "mixed inhibitor-prodrug" RB 101 [H2NCH(CH2CH2SCH3)CH2SSCH2CH(CH2Ph)CONHCH(CH2Ph)COOCH2Ph] after iv administration were three times greater than those of a similar combined dose of its two constitutive moieties. The separation of the two diastereoisomers constituting RB 101 showed that the analgesia has a stereochemical dependence, the (S,S,S)-isomer being more active than the (S,R,S)-isomer. Furthermore, in the tail flick test in the rat, RB 101 gave 38% analgesia at a dose of 80 mg/kg. Due to its high efficiency and its longer pharmacological effect, RB 101 was selected for a complete study of its analgesic properties.