(3R,4R)-4-hydroxymethylpiperidin-3-ol | 1416553-81-5

• 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: (3R,4R)-4-hydroxymethylpiperidin-3-ol
• 英文别名: trans-3-hydroxy-4-piperidinemethanol；(3R,4R)-rel-3-Hydroxy-4-piperidinemethanol；(3R,4R)-4-(hydroxymethyl)piperidin-3-ol
• CAS: 1416553-81-5
• 化学式: C₆H₁₃NO₂
• 分子量: 131.175
• InChiKey: COQKGJIYPZVMSJ-RITPCOANSA-N

物化性质

• 沸点：
  279.0±20.0 °C(Predicted)
• 密度：
  1.111±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  52.5
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3R,4R)-4-hydroxymethylpiperidin-3-ol 、 苯甲醛 在 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 反应 73.0h， 以51%的产率得到(3R,4R)-1-benzyl-4-(hydroxymethyl)piperidin-3-ol
  参考文献：
  名称：

  (+)-金鸡胺酮及其简化衍生物的设计、合成和单胺氧化酶抑制活性

  摘要：

  通过(+)-金鸡胺酮及其对映体的全合成确定了吲哚生物碱(+)-金鸡胺酮的绝对结构。该研究的主要重点是手性顺式-3,4-二取代哌啶的两种对映异构体的对映选择性合成。我们还评估了这些对映体的单胺氧化酶 (MAO) 抑制活性。此外，合成了其结构简化的衍生物，没有任何手性中心。其中两种衍生物显示出比(+)-金鸡胺酮更强的MAO抑制活性。

  DOI：

  10.1021/acsmedchemlett.1c00310
• 作为产物：
  描述：

  (3R,4R)-1-benzyl-4-(hydroxymethyl)piperidin-3-ol 在 palladium on activated carbon 作用下， 以 甲醇 为溶剂， 生成 (3R,4R)-4-hydroxymethylpiperidin-3-ol
  参考文献：
  名称：

  Esters of 3-hydroxy-piperidinemethanol derivatives

  摘要：

  本发明涉及化合物的公式（I），其立体化学异构体，N-氧化物形式或其药学上可接受的酸盐，其中R.sup.1为C.sub.1-6烷氧基，C.sub.2-6烯氧基或C.sub.2-6炔基氧基；R.sup.2为氢或C.sub.1-6烷氧基，或当R.sup.1和R.sup.2结合在一起时，可以形成一个具有以下结构的二价基团，其中在所述的二价基团中，一个或两个氢原子可以被C.sub.1-6烷基取代；R.sup.3为氢或卤素；R.sup.4为氢或C.sub.1-6烷基；L为C.sub.3-6环烷基，C.sub.5-6环戊酮，C.sub.2-6烯基，可选地取代芳基，或L为以下结构的基团-Alk-R.sup.5-，Alk-X--R.sup.6，-Alk-Y--C(.dbd.O)--R.sup.8或-Alk-Y--C(.dbd.O)--NR.sup.10R.sup.11，其中每个Alk为C.sub.1-12烷二基；R.sup.5为氢，氰基，C.sub.1-6烷基磺酰氨基，C.sub.3-6环烷基，C.sub.5-6环戊酮，芳基，二(芳基)甲基或杂环戒系统；R.sup.6为氢，C.sub.1-6烷基，羟基C.sub.1-6烷基，C.sub.3-6环烷基，芳基或杂环戒系统；X为O，S，SO.sub.2或NR.sup.7；其中R.sub.7为氢，C.sub.1-6烷基或芳基；R.sup.8为氢，C.sub.1-6烷基，C.sub.3-6环烷基，芳基，芳基C.sub.1-6烷基，二(芳基)甲基，C.sub.1-6烷氧基或羟基；Y为NR.sup.9或直接键；其中R.sup.9为氢，C.sub.1-6烷基或芳基，R.sup.10和R.sup.11各自独立地为氢，C.sub.1-6烷基，C.sub.3-6环烷基，芳基或芳基C.sub.1-6烷基，或R.sup.10和R.sup.11与携带R.sup.10和R.sup.11的氮原子结合，可以形成一个取代有C.sub.1-6烷基，氨基或单或二(C.sub.1-6烷基)氨基的吡咯烷基或哌啶烷基环，或R.sup.10和R.sup.11与携带R.sup.10和R.sup.11的氮原子结合，可以形成一个取代有C.sub.1-6烷基的哌嗪基或4-吗啉基基团。公开了制备所述产品的方法，包括所述产品的配方以及它们作为药物的用途，特别是用于治疗与胃排空障碍相关的疾病。

  公开号：

  US06096761A1

文献信息

• Condensed derivatives of imidazole useful as pharmaceuticals
  申请人：LABORATOIRE BIODIM

  公开号：EP2913330A1

  公开（公告）日：2015-09-02

  The invention relates to the compounds (I) and their acids and bases salts: wherein: the dotted line indicates a double bond; X is N or C-R1 and Y is N or C-R2, X and Y not being simultaneously N; A is selected from the group consisting of phenyl, naphthyl and (5-11) membered monocyclic or bicyclic unsaturated cycle or heterocycle possibly substituted as defined in the application, and A can also comprise either a further (4-7) membered heterocycle, said heterocycle being a monocycle, fused, saturated or unsaturated, the polycyclic system then comprising up to 14 members and up to 5 heteroatoms selected from N, O and S; B is Hydrogen or a substituent as defined in the application, or B is a (4-10) membered mono or bicyclic saturated or unsaturated heterocycle containing 1-3 heteroatoms selected from N, O and S, and possibly substituted as defined in the application; B not being Hydrogen when X is N and Y is C-R2; R1 is Hydrogen or a substituent as defined in the application; B and R1 cannot be simultaneously Hydrogen; R2 is Hydrogen or Halogen; their preparation, their use in the antibacterial prevention and therapy, alone or in association with antibacterials, antivirulence agents or drugs reinforcing the host innate immunity, and pharmaceutical compositions and associations containing them.

  该发明涉及化合物（I）及其酸盐和碱盐： 其中： 虚线表示双键； X为N或C-R1，Y为N或C-R2，X和Y不同时为N； A选自苯基、萘基和（5-11）成员单环或双环不饱和环或杂环，可能按申请中定义进行取代， A还可以包括另一个（4-7）成员杂环，该杂环为单环、融合、饱和或不饱和，多环系统则包括最多14个成员和最多5个N、O和S中选择的杂原子； B为氢或按申请中定义的取代基，或 B为含有1-3个N、O和S中选择的杂原子的（4-10）成员单环或双环饱和或不饱和杂环，并可能按申请中定义进行取代； 当X为N且Y为C-R2时，B不是氢； R1为氢或按申请中定义的取代基； B和R1不能同时为氢； R2为氢或卤素； 它们的制备，它们在抗菌预防和治疗中的用途，单独或与抗菌药物、抗毒力剂或增强宿主先天免疫力的药物联合使用，以及含有它们的药物组合物和联合物。
• [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。
• Esters of 3-hydroxy-piperidinemethanol derivatives
  申请人：Janssen Pharmaceutica N.V.

  公开号：US06096761A1

  公开（公告）日：2000-08-01

  The present invention of compounds of formula (I), ##STR1## a stereochemically isomeric form thereof, an N-oxide form thereof or a pharmaceutically acceptable acid addition salt thereof, R.sup.1 is C.sub.1-6 alkyloxy, C.sub.2-6 alkenyloxy or C.sub.2-6 alkynyloxy; R.sup.2 is hydrogen or C.sub.1-6 alkyloxy, or when taken together R.sup.1 and R.sup.2 may form a bivalent radical of formula wherein in said bivalent radicals one or two hydrogen atoms may be substituted with C.sub.1-6 alkyl; R.sup.3 is hydrogen or halo; R.sup.4 is hydrogen or C.sub.1-6 alkyl; L is C.sub.3-6 cycloalkyl, C.sub.5-6 cycloalkanone, C.sub.2-6 alkenyl optionally substituted with aryl, or L is a radical of formula -Alk-R.sup.5 -, Alk-X--R.sup.6, -Alk-Y--C(.dbd.O)--R.sup.8, or -Alk-Y--C(.dbd.O)--NR.sup.10 R.sup.11 wherein each Alk is C.sub.1-12 alkanediyl; and R.sup.5 is hydrogen, cyano, C.sub.1-6 alkylsulfonylamino, C.sub.3-6 cycloalkyl, C.sub.5-6 cycloalkanone, aryl, di(aryl)methyl or a heterocyclic ringsystem; R.sup.6 is hydrogen, C.sub.1-6 alkyl, hydroxyC.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, aryl or heterocyclic ringsystem; X is O, S, SO.sub.2 or NR.sup.7 ; said R.sub.7 being hydrogen, C.sub.1-6 alkyl or aryl; R.sup.8 is hydrogen, C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, aryl, arylC.sub.1-6 alkyl, di(aryl)methyl, C.sub.1-6 alkyloxy or hydroxy; Y is NR.sup.9 or a direct bond; said R.sup.9 being hydrogen, C.sub.1-6 alkyl or aryl R.sup.10 and R.sup.11 each independently are hydrogen, C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, aryl or arylC.sub.1-6 alkyl, or R.sup.10 and R.sup.11 combined with the nitrogen atom bearing R.sup.10 and R.sup.11 may form a pyrrolidinyl or piperidinyl ring both being optionally substituted with C.sub.1-6 alkyl, amino or mono or di(C.sub.1-6 alkyl)amino, or said R.sup.10 and R.sup.11 combined with the nitrogen bearing R.sup.10 and R.sup.11 may form a piperazinyl or 4-morpholinyl radical both being optionally substituted with C.sub.1-6 alkyl. 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公式（I），其立体化学异构体，N-氧化物形式或其药学上可接受的酸盐，其中R.sup.1为C.sub.1-6烷氧基，C.sub.2-6烯氧基或C.sub.2-6炔基氧基；R.sup.2为氢或C.sub.1-6烷氧基，或当R.sup.1和R.sup.2结合在一起时，可以形成一个具有以下结构的二价基团，其中在所述的二价基团中，一个或两个氢原子可以被C.sub.1-6烷基取代；R.sup.3为氢或卤素；R.sup.4为氢或C.sub.1-6烷基；L为C.sub.3-6环烷基，C.sub.5-6环戊酮，C.sub.2-6烯基，可选地取代芳基，或L为以下结构的基团-Alk-R.sup.5-，Alk-X--R.sup.6，-Alk-Y--C(.dbd.O)--R.sup.8或-Alk-Y--C(.dbd.O)--NR.sup.10R.sup.11，其中每个Alk为C.sub.1-12烷二基；R.sup.5为氢，氰基，C.sub.1-6烷基磺酰氨基，C.sub.3-6环烷基，C.sub.5-6环戊酮，芳基，二(芳基)甲基或杂环戒系统；R.sup.6为氢，C.sub.1-6烷基，羟基C.sub.1-6烷基，C.sub.3-6环烷基，芳基或杂环戒系统；X为O，S，SO.sub.2或NR.sup.7；其中R.sub.7为氢，C.sub.1-6烷基或芳基；R.sup.8为氢，C.sub.1-6烷基，C.sub.3-6环烷基，芳基，芳基C.sub.1-6烷基，二(芳基)甲基，C.sub.1-6烷氧基或羟基；Y为NR.sup.9或直接键；其中R.sup.9为氢，C.sub.1-6烷基或芳基，R.sup.10和R.sup.11各自独立地为氢，C.sub.1-6烷基，C.sub.3-6环烷基，芳基或芳基C.sub.1-6烷基，或R.sup.10和R.sup.11与携带R.sup.10和R.sup.11的氮原子结合，可以形成一个取代有C.sub.1-6烷基，氨基或单或二(C.sub.1-6烷基)氨基的吡咯烷基或哌啶烷基环，或R.sup.10和R.sup.11与携带R.sup.10和R.sup.11的氮原子结合，可以形成一个取代有C.sub.1-6烷基的哌嗪基或4-吗啉基基团。公开了制备所述产品的方法，包括所述产品的配方以及它们作为药物的用途，特别是用于治疗与胃排空障碍相关的疾病。
• 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。