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

• [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。
• 4-(aminomethyl)-piperidine benzamides for treating gastrointestinal disorders
  申请人：Janssen Pharmaceutica, N.V.

  公开号：US06544997B1

  公开（公告）日：2003-04-08

  The present invention of compounds of formula (I) a stereochemically isomeric form thereof, an N-oxide form thereof or a pharmaceutically acceptable acid addition salt thereof, —R1—R2— is a bivalent radical of formula wherein in said bivalent radicals one or two hydrogen atoms may be substituted with C1-6alkyl or hydroxy; R3 is hydrogen or halo; R4 is hydrogen or C1-6alkyl; R5 is hydrogen or C1-6alkyl; L is C3-6cycloalkyl, oxoC5-6cycloalkyl, C2-6alkenyl, or L is a radical of formula —Alk—R6—, Alk—X—R7, —Alk—Y—C(═O)—R9, or —Alk—Y—C(═O)—NR11R12 wherein each Alk is C1-12alkanediyl; and R6 is hydrogen, amino, cyano, C1-6alkylsulfonylamino, C3-6cycloalkyl, oxoC5-6cycloalkyl, aryl or a heterocyclic ringsystem; R7 is hydrogen, C1-6alkyl, hydroxyC1-6alkyl, C3-6cycloalkyl, aryl or a heterocyclic ringsystem; X is O, S, SO2 or NR8; said R8 being hydrogen or C1-6alkyl; R9 is hydrogen, C1-6alkyl, C3-6cycloalkyl, C1-6alkyloxy, hydroxy or aryl; Y is a direct bond or NR10; said R10 being hydrogen, or C1-6alkyl; R11 and R12 each independently are hydrogen, C1-6alkyl, C3-6cycloalkyl, or R11 and R12 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 or preventing gastrointestinal disorders.

  本发明涉及化合物的公式(I)，其立体化学异构体形式，N-氧化物形式或药用可接受的酸加成盐形式，其中—R1—R2—是一个公式的双价基团，在所述双价基团中，一个或两个氢原子可以被C1-6烷基或羟基取代；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，氧代C5-6环烷基，C2-6烯基，或L为公式—Alk—R6—、Alk—X—R7、—Alk—Y—C(═O)—R9或—Alk—Y—C(═O)—NR11R12的基团，其中每个Alk为C1-12烷二基；R6为氢、氨基、氰基、C1-6烷基磺酰氨基、C3-6环烷基、氧代C5-6环烷基、芳基或杂环体；R7为氢、C1-6烷基、羟基C1-6烷基、C3-6环烷基、芳基或杂环体；X为O、S、SO2或NR8；其中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、羟基或芳基；Y为直接键或NR10；其中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选择性取代的吡咯烷基、哌啶基、哌嗪基或4-吗啉基环。公开了制备所述产品的方法、包含所述产品的配方以及它们作为药物的用途，特别用于治疗或预防胃肠道疾病。