tert-butyl (3R,4R)-4-(aminomethyl)-3-hydroxypiperidine-1-carboxylate

• 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: tert-butyl (3R,4R)-4-(aminomethyl)-3-hydroxypiperidine-1-carboxylate
• 英文别名: (3R,4R)-tert-butyl 4-(aminomethyl)-3-hydroxypiperidine-1-carboxylate
• 化学式: C₁₁H₂₂N₂O₃
• 分子量: 230.307
• InChiKey: GAGALXYDHSHHCD-BDAKNGLRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  75.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (3R,4R)-4-(aminomethyl)-3-hydroxypiperidine-1-carboxylate 在 盐酸 、 N,N-二异丙基乙胺 作用下， 以 2-甲基-2-丁醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 49.25h， 生成 (±)-trans-4-methylbenzyl 1-[4-(pyrimidin-2-ylamino)methylpiperidin-3-ol-1-yl] carboxylate
  参考文献：
  名称：

  Radiolabelling of 1,4-disubstituted 3-[18F]fluoropiperidines and its application to new radiotracers for NR2B NMDA receptor visualization

  摘要：

  为了开发一种新颖且有用的正电子发射断层扫描(PET)示踪剂构建模块，我们研究了1,4-二取代的3-[18F]氟哌啶的放射性标记。事实上，3-氟哌啶已成为药物化学中含哌啶化合物的药物调控的有用构建模块。我们研究了具有供电子和吸电子N-取代基的取代哌啶的放射性氟化。在具有苯甲基或丁基等供电子N-取代基的情况下，观察到了构型保留和令人满意的氟-18掺入产率高达80%。在导致形成氨基甲酸酯或酰胺功能的吸电子N-取代基的情况下，掺入产率取决于4-取代基(2至63%)。该构建模块的放射性标记被应用于NR2B NMDA受体拮抗剂的自动化放射合成，并通过市售的放射化学模块实现。对三种放射性示踪剂的体内评估显示出最低的脑摄取，与活体脑内NR2B NMDA受体的成像不兼容。然而，观察到了适度的放射性代谢，特别是没有观察到放射性氟化物的脱氟作用，这表明氟-18原子的3-位置的稳定性。总之，即使NR2B NMDA受体拮抗剂的评估未能显示出满意的PET成像性质，1,4-二取代的3-[18F]氟哌啶部分仍可能对开发其他PET示踪剂具有价值。

  DOI：

  10.1039/c2ob26378e
• 作为产物：
  描述：

  1,1-dimethylethyl (trans)-3-hydroxy-4-[[(phenylmethyl)amino]methyl]-1-piperidinecarboxylate 在 palladium 10% on activated carbon 氢气 作用下， 生成 tert-butyl (3R,4R)-4-(aminomethyl)-3-hydroxypiperidine-1-carboxylate
  参考文献：
  名称：

  [EN] HYDROXYCARBONYLPHENYL SUBSTITUTED 4-(AMINOMETHYL)-PIPERIDINE BENZAMIDES AS 5HT4-ANTAGONISTS
  [FR] 4-(AMINOMETHYL)-PIPERIDINE BENZAMIDES SUBSTITUES PAR HYDROXYCARBONYLPHENYLE, UTILISES COMME ANTAGONISTES DES RECEPTEURS 5HT4

  摘要：

  本发明涉及具有5HT4拮抗性质的式(I)的新化合物。该发明还涉及制备这种新化合物的方法，包括该新化合物的药物组合物以及该化合物的药用。

  公开号：

  WO2005003121A1
• 作为试剂：
  描述：

  1,1-dimethylethyl (trans)-3-hydroxy-4-[[(phenylmethyl)amino]methyl]-1-piperidinecarboxylate 、 氢气 在 钯 tert-butyl (3R,4R)-4-(aminomethyl)-3-hydroxypiperidine-1-carboxylate 作用下， 以 甲醇 为溶剂， 以yielding 1,1-dimethylethyl(3R-trans)-4-(aminomethyl)-3-hydroxy-1-piperidinecarboxylate (intermediate 61)的产率得到tert-butyl (3R,4R)-4-(aminomethyl)-3-hydroxypiperidine-1-carboxylate
  参考文献：
  名称：

  4-(Aminomethyl)-piperidine benzamides as 5ht4 - antagonists

  摘要：

  本发明涉及具有5HT4拮抗性质的式（I）新化合物。本发明还涉及制备这种新化合物的方法，包含这种新化合物的药物组合物以及这些化合物作为药物的用途。

  公开号：

  US20060281753A1

文献信息

• Radiolabelling of 1,4-disubstituted 3-[18F]fluoropiperidines and its application to new radiotracers for NR2B NMDA receptor visualization
  作者：Radouane Koudih、Gwénaëlle Gilbert、Martine Dhilly、Ahmed Abbas、Louisa Barré、Danièle Debruyne、Franck Sobrio

  DOI：10.1039/c2ob26378e

  日期：——

  In order to develop a novel and useful building block for the development of radiotracers for positron emission tomography (PET), we studied the radiolabelling of 1,4-disubstituted 3-[18F]fluoropiperidines. Indeed, 3-fluoropiperidine became a useful building block in medicinal chemistry for the pharmacomodulation of piperidine-containing compounds. The radiofluorination was studied on substituted piperidines with electron-donating and electron-withdrawing N-substituents. In the instance of electron-donating N-substituents such as benzyl or butyl, configuration retention and satisfactory fluoride-18 incorporation yields up to 80% were observed. In the case of electron-withdrawing N-substituents leading to carbamate or amide functions, the incorporation yields depend on the 4-susbtitutent (2 to 63%). The radiolabelling of this building block was applied to the automated radiosynthesis of NR2B NMDA receptor antagonists and effected by a commercially available radiochemistry module. The in vivo evaluation of three radiotracers demonstrated minimal brain uptakes incompatible with the imaging of NR2B NMDA receptors in the living brain. Nevertheless, moderate radiometabolism was observed and, in particular, no radiodefluorination was observed which demonstrates the stability of the 3-position of the fluorine-18 atom. In conclusion, the 1,4-disubstituted 3-[18F]fluoropiperidine moiety could be of value in the development of other radiotracers for PET even if the evaluation of the NR2B NMDA receptor antagonists failed to demonstrate satisfactory properties for PET imaging of this receptor.

  为了开发用于正电子发射断层扫描（PET）示踪剂的新颖且有用的构建模块，我们研究了1,4-二取代的3-[18F]氟哌啶的放射性标记。实际上，3-氟哌啶已成为药物化学中含哌啶化合物的药效调控的有用构建模块。我们在具有供电子和吸电子N-取代基的取代哌啶上研究了放射性氟化。对于具有供电子N-取代基（如苄基或丁基）的情况，观察到了构型保持和令人满意的氟-18掺入产率，高达80％。在导致形成氨基甲酸酯或酰胺功能的吸电子N-取代基的情况下，掺入产率取决于4-取代基（2至63％）。该构建模块的放射性标记被应用于NR2B NMDA受体拮抗剂的自动放射合成，并通过商用的放射化学模块实现。对三种放射性示踪剂的体内评估显示，其脑摄取量极低，与在活脑中成像NR2B NMDA受体不兼容。然而，观察到了中等程度的放射性代谢，特别是未观察到放射性去氟化，这表明氟-18原子的3位点的稳定性。总之，1,4-二取代的3-[18F]氟哌啶部分可能对开发其他PET示踪剂有价值，即使NR2B NMDA受体拮抗剂的评估未能显示出适用于该受体PET成像的令人满意的特性。
• [EN] COMPOUNDS ACTIVE TOWARDS NUCLEAR RECEPTORS<br/>[FR] COMPOSÉS ACTIFS VIS-À-VIS DES RÉCEPTEURS NUCLÉAIRES
  申请人：NUEVOLUTION AS

  公开号：WO2021124279A1

  公开（公告）日：2021-06-24

  Disclosed are compounds active towards nuclear receptors, pharmaceutical compositions containing the compounds and use of the compounds in therapy.

  揭示了对核受体活性的化合物，包含这些化合物的药物组合物以及这些化合物在治疗中的用途。
• [EN] PIPERIDINE-CONTAINING COMPOUNDS AND USE THEREOF<br/>[FR] COMPOSÉS CONTENANT DE LA PIPÉRIDINE ET LEURS UTILISATIONS
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2010080864A1

  公开（公告）日：2010-07-15

  A method for preventing and/or treating a metabolic disease, cerebrovascular disease, etc. which comprises administering to a mammal an effective amount of the compound of the formula (I) wherein all symbols have the same meanings as defined in the specification; a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof. And a novel compound of the formula (I-1): wherein all symbols have the same meanings as defined in the specification; a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof has an anti-diabetic effect and a neuroprotective effect. Accordingly, the compound of the formula (I) and the compound of the formula (I-1) are useful in a method for preventing and/or treating for a metabolic disease such as diabetes, cerebrovascular disease such as stroke, etc.

  一种预防和/或治疗代谢性疾病、脑血管疾病等的方法，包括向哺乳动物施用化合物的有效量，其化学式为(I)，其中所有符号的含义与规范中定义的相同；其盐、N-氧化物、溶剂合物或前药。以及化学式(I-1)的新化合物：其中所有符号的含义与规范中定义的相同；其盐、N-氧化物、溶剂合物或前药具有抗糖尿病作用和神经保护作用。因此，化合物(I)和化合物(I-1)在预防和/或治疗代谢性疾病如糖尿病、脑血管疾病如中风等方面是有用的。
• [EN] 4-(AMINOMETHYL)-PIPERIDINE BENZAMIDES AS 5HT4-ANTAGONISTS<br/>[FR] 4-(AMINOMETHYL)-PIPERIDINE BENZAMIDES SERVANT D'ANTAGONISTES DE 5HT4
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2005000838A1

  公开（公告）日：2005-01-06

  The present invention is concerned with novel compounds of formula (I) having 5HT4-antagonistic properties. The invention further relates to methods for preparing such novel compounds, pharmaceutical compositions comprising said novel compounds as well as the use as a medicine of said compounds.

  本发明涉及具有5HT4拮抗性质的式(I)的新化合物。该发明还涉及制备这种新化合物的方法，包括将该新化合物作为药物的药物组合物以及该化合物的药用用途。
• Bicyclic benzamides of 3- or 4-substituted 4-(aminomethyl)-piperidine derivatives
  申请人：——

  公开号：US20020086879A1

  公开（公告）日：2002-07-04

  The present invention of compounds of formula (I) 1 a stereochemically isomeric form thereof, an N-oxide form thereof or a pharmaceutically acceptable acid addition salt thereof, R 1 and R 2 taken together form a bivalent radical of formula wherein in said bivalent radicals one or two hydrogen atoms may be substituted with C 1-6 alkyl; R 3 is hydrogen or halo; R 4 is hydrogen or C 1-6 alkyl; R 5 is hydrogen or C 1-6 alkyl; L is C 3-6 cycloalkyl, C 5-6 cycloalkanone, C 2-6 alkenyl, or L is a radical of formula —Alk—R 6 —, Alk—X—R 7 , —Alk—Y—C(═O)—R 9 , or —Alk—Y—C(═O)— NR 11 R 12 wherein each Alk is C 1-12 alkanediyl; and R 6 is hydrogen, cyano, C 1-6 alkylsulfonylamino, C 3-6 cycloalkyl, C 5-6 cycloalkanone, or a heterocyclic ringsystem; R 7 is hydrogen, C 1-6 alkyl, hydroxyC 1-6 alkyl, C 3-6 cycloalkyl, or a heterocyclic ringsystem; X is O, SO 2 or NR 8 ; said R 8 being hydrogen or C 1-6 alkyl; R 9 is hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 alkyloxy or hydroxy; Y is NR 10 or a direct bond; said R 10 being hydrogen, or C 1-6 alkyl; R 11 and R 12 each independently are hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, or R 11 and R 12 combined with the nitrogen atom may form an optionally substituted pyrrolidinyl, piperidinyl, piperazinyl or 4-morpholinyl ring. Processes for preparing said products, formulations comprising said products and their use as a medicine are disclosed, in particular for treating conditions which are related to impairment of gastric emptying.

  本发明涉及化合物的一种以及其立体化学异构体形式，N-氧化物形式或药学上可接受的酸加合物盐，其中R1和R2结合在一起形成以下式的二价基团，其中在所述二价基团中一个或两个氢原子可被C1-6烷基取代；R3为氢或卤素；R4为氢或C1-6烷基；R5为氢或C1-6烷基；L为C3-6环烷基，C5-6环戊酮，C2-6烯基，或L为以下式的基团—Alk—R6—，Alk—X—R7，—Alk—Y—C(═O)—R9或—Alk—Y—C(═O)—NR11R12，其中每个Alk为C1-12烷二基；R6为氢，氰基，C1-6烷基磺酰氨基，C3-6环烷基，C5-6环戊酮或杂环环系；R7为氢，C1-6烷基，羟基C1-6烷基，C3-6环烷基或杂环环系；X为O，SO2或NR8；R8为氢或C1-6烷基；R9为氢，C1-6烷基，C3-6环烷基，C1-6烷氧基或羟基；Y为NR10或直接键；R10为氢或C1-6烷基；R11和R12各自独立地为氢，C1-6烷基，C3-6环烷基，或R11和R12与氮原子结合可形成可选择取代的吡咯烷基，哌啶基，哌嗪基或4-吗啉基环。公开了制备所述产品的过程，包括所述产品的制剂以及它们作为药物的用途，特别用于治疗与胃排空障碍有关的病症。