(-)-(3S,4S)-3-hydroxy-1-(phenylmethyl)piperidine-4-methanol | 39478-61-0

• 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: (-)-(3S,4S)-3-hydroxy-1-(phenylmethyl)piperidine-4-methanol
• 英文别名: (3S,4S)-1-benzyl-4-(hydroxymethyl)piperidin-3-ol；trans-N-Benzyl-4-hydroxymethyl-3-hydroxypiperidin；(+)-trans-1-(Phenylmethyl)-3-hydroxy-4-piperidinemethanol
• CAS: 39478-61-0；41632-37-5；41632-38-6；58322-72-8
• 化学式: C₁₃H₁₉NO₂
• 分子量: 221.299
• InChiKey: PAZOUOCFOKZLSA-QWHCGFSZSA-N

物化性质

• 沸点：
  361.5±32.0 °C(Predicted)
• 密度：
  1.156±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  43.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (-)-(3S,4S)-3-hydroxy-1-(phenylmethyl)piperidine-4-methanol 在 钯 氢气 作用下， 以 甲醇 为溶剂， 以yielding 12 g of (±)-trans-3-hydroxy-4-piperidinemethanol (interm. 1-a) (used in next reaction step without further purification)的产率得到(+/-)-trans-4-(Hydroxymethyl)piperidin-3-ol
  参考文献：
  名称：

  4-(aminomethyl)-piperidine benzamides for treating gastrointestinal disorders

  摘要：

  本发明涉及一种化合物，其化学式为（I）1a立体化学异构体形式，其N-氧化物形式或药学上可接受的酸盐形式，其中-R1-R2-是一个化学式的二价基团，在所述的二价基团中，一个或两个氢原子可以被C1-6烷基或羟基取代；R3是氢或卤素；R4是氢或C1-6烷基；R5是氢或C1-6烷基；L是C3-6环烷基，氧代C5-6环烷基，C2-6烯基，或L是化学式-Alk-R6-，Alk-X-R7，-Alk-Y-C(═O)-R9，或-Alk-Y-C(═O)-NR11R12的基团，其中每个Alk是C1-12烷基二亚基；R6是氢，氨基，氰基，C1-6烷基磺酰氨基，C3-6环烷基，氧代C5-6环烷基，芳基或杂环环系统；R7是氢，C1-6烷基，羟基C1-6烷基，C3-6环烷基，芳基或杂环环系统；X是O，S，SO2或NR8；其中R8是氢或C1-6烷基；R9是氢，C1-6烷基，C3-6环烷基，C1-6烷氧基，羟基或芳基；Y是直接键或NR10；其中R10是氢或C1-6烷基；R11和R12各自独立地是氢，C1-6烷基，C3-6环烷基，或R11和R12与氮原子结合可以形成一个可选取代的吡咯烷基，哌啶基，哌嗪基或4-吗啉基环。本发明还公开了制备所述产品的方法，包含所述产品的制剂以及其作为药物的用途，特别是用于治疗或预防胃肠道疾病。

  公开号：

  US20030181456A1
• 作为产物：
  描述：

  1-苄基-3-氧杂-4-哌啶甲酸乙酯 在 lithium aluminium tetrahydride 、 [(R)-RuCl(p-cymene)BINAP]Cl 、 氢气 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 150.0 ℃ 、10.0 MPa 条件下， 反应 2.5h， 生成 (-)-(3S,4S)-3-hydroxy-1-(phenylmethyl)piperidine-4-methanol
  参考文献：
  名称：

  对映体纯的顺式和反式-3-氟-2,4-二恶英-9-氮杂-3-磷酸环钙蛋白3-氧化物作为乙酰胆碱模拟物和乙酰胆碱酯酶抑制剂的合成和表征

  摘要：

  标题化合物为P（3）轴向和P（3）赤道取代的顺式和反式构型9-苄基-3-氟-2,4-二氧杂-9-氮杂-3-磷酸钙素3-氧化物（ = 9-苄基-3-氟-2,4-二氧杂-9-氮杂-3-磷酸双环[4.4.0]癸烷3-氧化物= 7-苄基-2-氟六氢-4 H -1,3,2-二氧杂磷基制备[4,5 - c ]吡啶2-氧化物）（ee> 99％）并充分表征（方案2和4）。绝对构型由其前体，对映体纯的1-苄基3-羟基哌啶4-羧酸乙酯和1-苄基3-羟基哌啶-4-甲醇分配而得。作为乙酰胆碱的结构固定和构象受限的磷类似物，标题化合物代表乙酰胆碱模拟物，是研究与乙酰胆碱酯酶的分子相互作用的合适探针。通过动力学方法确定，所有化合物都是该酶的中度不可逆抑制剂。

  DOI：

  10.1002/hlca.201000457
• 作为试剂：
  描述：

  (1-苄基-1,2,3,6-四氢吡啶-4-基)甲醇 、 硼烷 、 sodium hydroxide 、 双氧水 、 (-)-(3S,4S)-3-hydroxy-1-(phenylmethyl)piperidine-4-methanol 在 钯 氮 、 水 、 potassium carbonate 、 二氯甲烷 、 magnesium sulfate 、 乙腈 、 (-)-(3S,4S)-3-hydroxy-1-(phenylmethyl)piperidine-4-methanol 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 26.0h， 以was obtained (Yield: 50.1%) b)的产率得到(+/-)-trans-4-(Hydroxymethyl)piperidin-3-ol
  参考文献：
  名称：

  Bicyclic benzamides of 3- or 4-substituted 4-(aminomethyl)-piperidine derivatives

  摘要：

  本发明涉及式（I）化合物，其立体化学异构体形式，N-氧化物形式或其药学上可接受的酸加合盐形式，其中R1和R2结合形成式的双价基团，在所述双价基团中，一个或两个氢原子可以被C1-6烷基取代；R3是氢或卤素；R4是氢或C1-6烷基；R5是氢或C1-6烷基；L是C3-6环烷基，C5-6环戊酮，C2-6烯基，或L是公式-Alk-R6-，Alk-X-R7，-Alk-Y-C(═O)-R9或-Alk-Y-C(═O)-NR11R12的基团，其中每个Alk是C1-12烷二基；R6是氢，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是氢，C1-6烷基，羟基C1-6烷基，C3-6环烷基或杂环环系；X是O、S、SO2或NR8；所述R8是氢或C1-6烷基；R9是氢，C1-6烷基，C3-6环烷基，C1-6烷氧基或羟基；Y是NR10或直接键；所述R10是氢或C1-6烷基；R11和R12各自独立地是氢，C1-6烷基，C3-6环烷基，或R11和R12与氮原子结合形成可选择取代的吡咯烷基，哌啶基，哌嗪基或4-吗啉基环。揭示了制备上述产品的方法，包含上述产品的配方和其作为药物的用途，特别是用于治疗与胃排空障碍有关的疾病。

  公开号：

  US20040058958A1

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。
• Design, Synthesis, and Monoamine Oxidase Inhibitory Activity of (+)-Cinchonaminone and Its Simplified Derivatives
  作者：Yuta Sato、Naoko Oyobe、Takao Ogawa、Sayo Suzuki、Hiroshi Aoyama、Tomonori Nakamura、Hiromichi Fujioka、Satoshi Shuto、Mitsuhiro Arisawa

  DOI：10.1021/acsmedchemlett.1c00310

  日期：2021.9.9

  The absolute structure of an indole alkaloid (+)-cinchonaminone by total synthesis of both (+)-cinchonaminone and its enantiomer was determined. The main focus of the study was the enantioselective synthesis of both enantiomers of a chiral cis-3,4-disubstituted piperidine. We also evaluated monoamine oxidase (MAO) inhibitory activities of these enantiomers. Furthermore, its structurally simplified

  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。
• Monocyclic benzamides of 3- or 4-substituted 4-(aminomethyl)-piperidine derivatives
  申请人：——

  公开号：US20030078427A1

  公开（公告）日：2003-04-24

  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 is C 1-6 alkyloxy, C 2-6 alkenyloxy or C 2-6 alkynyl-oxy; R 2 is hydrogen, C 1-6 alkyl C 1-6 alkyloxy; 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 cyclo-alkanone, 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, S, 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.

  本发明涉及式（I）化合物，其立体化学异构体形式，其N-氧化物形式或其药学上可接受的酸加成盐，其中R1为C1-6烷氧基，C2-6烯氧基或C2-6炔氧基；R2为氢，C1-6烷基或C1-6烷氧基；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，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，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烷氧基或羟基；Y为NR10或直接键；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与氮原子结合可以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，包含所述产品的配方以及其作为药物的用途，特别是用于治疗与胃排空障碍有关的疾病。
• Gastrokinetic monocyclic benzamides of 3- or 4-substituted 4-(aminomethyl)-piperidine derivatives
  申请人：Janssen Pharmaceutica N.V.

  公开号：US06452013B1

  公开（公告）日：2002-09-17

  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 is C1-6alkyloxy, C2-6alkenyloxy or C2-6alkynyl-oxy; R2 is hydrogen, C1-6alkyl C1-6alkyloxy; R3 is hydrogen or halo; R4 is hydrogen or C1-6alkyl; R5 is hydrogen or C1-6alkyl; L is C3-6cycloalkyl, C5-6cycloalkanone, 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, cyano, C1-6alkylsulfonylamino, C3-6cycloalkyl, C5-6cycloalkanone, or a heterocyclic ringsystem; R7 is hydrogen, C1-6alkyl, hydroxyC1-6alkyl, C3-6cycloalkyl, 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 or hydroxy; Y is NR10 or a direct bond; 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 conditions which are related to impairment of gastric emptying.

  本发明涉及式（I）化合物，其立体化学异构体形式，其N-氧化物形式或其药学上可接受的酸加成盐，其中R1是C1-6烷氧基，C2-6烯氧基或C2-6炔基氧基；R2是氢，C1-6烷基或C1-6烷氧基；R3是氢或卤素；R4是氢或C1-6烷基；R5是氢或C1-6烷基；L是C3-6环烷基，C5-6环烷酮，C2-6烯基，或L是式—Alk—R6—，Alk—X—R7，-Alk-Y—C（═O）—R9或-Alk-Y—C（═O）—NR11R12的基团，其中每个Alk是C1-12烷二基；R6是氢，氰基，C1-6烷基磺酰胺基，C3-6环烷基，C5-6环烷酮或杂环环系；R7是氢，C1-6烷基，羟基C1-6烷基，C3-6环烷基或杂环环系；X是O，S，SO2或NR8；其中R8是氢或C1-6烷基；R9是氢，C1-6烷基，C3-6环烷基，C1-6烷氧基或羟基；Y是NR10或直接键；其中R10是氢或C1-6烷基；R11和R12各自独立地是氢，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方法，包含所述产品的制剂以及它们作为药物的用途，特别是用于治疗与胃排空障碍有关的疾病。
• 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.

  本发明涉及公式(I)的化合物，其立体化学异构体形式，其N-氧化物形式或其药学上可接受的酸加合物盐，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炔氧基；R.sup.2为氢或C.sub.1-6烷氧基，或当R.sup.1和R.sup.2一起取时，它们可以形成式的双价基团，其中在所述双价基团中，一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环己酮，C.sub.2-6烯基（可选地取代芳基），或L为式的基团，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环己酮，芳基，二（芳基）甲基或杂环环系；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，芳基或杂环环系；X为O，S，SO.sub.2或NR.sup.7；所述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；所述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与带有R.sup.10和R.sup.11的氮原子结合，可以形成带有C.sub.1-6烷基，氨基或单或二（C.sub.1-6烷基）氨基取代的吡咯烷基或哌嗪基环，或者所述R.sup.10和R.sup.11与带有R.sup.10和R.sup.11的氮原子结合，可以形成带有C.sub.1-6烷基取代的哌嗪基或4-吗啉基基团。本发明还公开了制备这些产品的方法、包含这些产品的配方以及它们作为医药的用途，特别是用于治疗与胃排空障碍有关的疾病。