2-(pyrrolidin-1-yl)methyl-3-hydroxy piperidine | 125104-40-7

• 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: 2-(pyrrolidin-1-yl)methyl-3-hydroxy piperidine
• 英文别名: 2-(1-pyrrolidinylmethyl)-3-piperidinol；2-(Pyrrolidinylmethyl)-3-piperidinol；2-(pyrrolidin-1-ylmethyl)piperidin-3-ol
• CAS: 125104-40-7
• 化学式: C₁₀H₂₀N₂O
• 分子量: 184.282
• InChiKey: BDGJVEBHIAMPHL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  35.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  potassium carbonate 、 2-(pyrrolidin-1-yl)methyl-3-hydroxy piperidine 、 2',3',4'-三氯苯乙酮 以 甲醇 、 乙酸乙酯 为溶剂， 生成 1-(3,4-dichlorophenyl)acetyl-2-(pyrrolidin-1-yl)methyl-3-hydroxy piperidine hydrochloride
  参考文献：
  名称：

  N-Acylated azacyclic compounds, processes for their preparations and their use as medications

  摘要：

  化合物，或其配合物或盐，其化学式为（I）：其中：RCO是一种酰基，其中基团R包含一个取代或未取代的碳环芳香族或杂环芳香族环；R₁和R₂分别是氢、C₁₋₆烷基、C₂₋₆烯基、C₃₋₆环烷基或C₄₋₁₂环烷基烷基，或者一起形成一个C₂₋₈支链或线性聚亚甲基或C₂₋₆烯基烷基，可选地取代有一个杂原子；R₃是氢、C₁₋₆烷基或苯基，或R₃与R₁一起形成一个-(CH₂)₃-或-(CH₂)₄-基团；R₄和R₅分别是氢、羟基、卤素、C₁₋₆烷基或芳基，前提是R₄和R₅不能同时为氢；p是从1到4的整数，对于治疗疼痛或低钠血症状是有用的。

  公开号：

  EP0447704A1
• 作为产物：
  描述：

  2-(吡咯烷-1-甲基)吡啶-3-醇 在 氧化铂 水 、 二氯甲烷 、 sodium hydroxide 、 crude product 作用下， 以 溶剂黄146 为溶剂， 25.0~140.0 ℃ 、14.22 kPa 条件下， 反应 44.0h， 以to give the title compound as a waxy solid, (6.17 g) m.p. 45°-50°的产率得到2-(pyrrolidin-1-yl)methyl-3-hydroxy piperidine
  参考文献：
  名称：

  Spiropiperidine derivatives

  摘要：

  公开了式(I)的化合物：##STR1## 其中R.sub.1代表羟基、C.sub.1-6烷基、C.sub.1-6羟基烷基、C.sub.1-6羧基烷基、苯基、氧代、氨基、羧基、酰胺基、--NR.sub.4 COR.sub.5（其中R.sub.4和R.sub.5均表示C.sub.1-6烷基）、可选地取代的甲基亚甲基或与其连接的碳原子共同形成一个含有一个或多个杂原子的5或6元环；R.sub.2和R.sub.3相同或不同，分别为C.sub.1-6烷基或C.sub.3-6烯基；或--NR.sub.2 R.sub.3形成一个5元环（可选地包含一个邻氧原子）或6元环，该环可选地含有一个不饱和单元，并且未经取代或经过羟基、氧代、可选地取代的甲基亚甲基、--COR.sub.6（其中R.sub.6表示C.sub.1-6烷基、OR或--NHR，R表示氢、C.sub.1-6烷基、芳基、ar（C.sub.1-6）烷基）或.dbd.NOR.sub.8（其中R.sub.8表示C.sub.1-6烷基）取代；X表示直接键、--CH.sub.2 --或--CH.sub.2 0--；Ar表示取代的苯基基团；以及其生理上可接受的盐。这些化合物被指出用于疼痛和脑缺血的治疗。还公开了它们的制备过程和中间体以及含有它们的制药组合物。

  公开号：

  US05114945A1

文献信息

• Piperidine derivatives
  申请人：GLAXO GROUP LIMITED

  公开号：EP0330461A3

  公开（公告）日：1990-10-17

  Compounds are disclosed of formula (I) wherein R₁ represents hydroxy, C₁₋₆ alkyl, C₁₋₆ hydroxyalkyl, C₁₋₆ carboxyalkyl, phenyl, oxo, amino, carboxy, amido, -NR₄COR₅ (where R₄ and R₅ both represent C₁₋₆ alkyl), optionally substituted methylidene or, together with the carbon atom to which it is attached, R₁ forms a 5 or 6-membered ring containing one or more heteroatoms; R₂ and R₃ are the same or different and are C₁₋₆ alkyl or C₃₋₆ alkenyl; or -NR₂R₃ forms a 5-membered (optionally containing an oxygen atom adjacent to the nitrogen) or a 6-membered ring, which ring optionally contains one unit of unsaturation and which is unsubstituted or substituted by hydroxy, oxo, optionally substituted methylidene, -COR₆ (where R₆ represents C₁₋₆ alkyl, OR₇ or -NHR₇, and R₇ represents hydrogen, C₁₋₆ alkyl, aryl, ar(C₁₋₆)alkyl) or =NOR₈ (where R₈ represents C₁₋₆ alkyl); X represents a direct bond, -CH₂- or -CH₂O-; Ar represents a substituted phenyl moiety; and physiologically acceptable salts thereof.The compounds are indicated as useful for the treatment of pain and cerebral ischaemia.Processes and intermediates for their preparation and pharmaceutical compositions containing them are also disclosed.

  披露了公式(I)的化合物，其中 R₁代表羟基，C₁₋₆烷基，C₁₋₆羟烷基，C₁₋₆羧烷基，苯基，氧代，氨基，羧基，酰胺，-NR₄COR₅（其中R₄和R₅都代表C₁₋₆烷基），可选地取代的亚甲基，或者与它连接的碳原子一起，R₁形成一个含有一个或多个杂原子的5或6元环； R₂和R₃相同或不同，是C₁₋₆烷基或C₃₋₆烯丙基；或者-NR₂R₃形成一个5元环（可选地含有与氮原子相邻的氧原子）或6元环，该环可选地含有一个不饱和单元，并且该环未取代或被羟基，氧代，可选地取代的亚甲基，-COR₆（其中R₆代表C₁₋₆烷基，OR₇或-NHR₇，R₇代表氢，C₁₋₆烷基，芳基，芳(C₁₋₆)烷基）或=NOR₈（其中R₈代表C₁₋₆烷基）取代； X代表直接键，-CH₂-或-CH₂O-； Ar代表取代的苯基部分； 以及它们的生理可接受盐。 这些化合物被指出用于治疗疼痛和脑缺血。还披露了它们的制备过程和中间体以及含有它们的药物组合物。
• Heterocyclic piperidinyl compounds having analgesic effect
  申请人：Dr. L. Zambeletti SpA

  公开号：US05089507A1

  公开（公告）日：1992-02-18

  A compound, or a solvate or salt thereof, of formula (I): ##STR1## in which: RCO is an acyl group in which the group R contains a substituted or unsubstituted carbocyclic aromatic or heterocyclic aromatic ring; R.sub.1 and R.sub.2 are independently hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.3-6 cycloalkyl or C.sub.4-12 cycloalkylalkyl groups, or together form a C.sub.2-8 branched or linear polymethylene or C.sub.2-6 alkenylene group, optionally substituted with a hetero-atom, R.sub.3 is hydrogen, C.sub.1-6 alkyl or phenyl, or R.sub.3 together with R.sub.1 form a --(CH.sub.2).sub.3 -- or --(CH.sub.2).sub.4 -- group; R.sub.4 and R.sub.5 are independently hydrogen, hydroxyl, halogen, C.sub.1-6 alkyl or aryl, provided both R.sub.4 and R.sub.5 are not simultaneously hydrogen; and p is an integer from 1 to 4, is useful for the treatment of pain or hyponatraemic disease states.

  化合物，或其配合物或盐，化学式（I）如下：##STR1## 其中：RCO是一种酰基，其中基团R包含一个取代或未取代的碳环芳香族或杂环芳香族环；R.sub.1和R.sub.2分别是氢、C.sub.1-6烷基、C.sub.2-6烯基、C.sub.3-6环烷基或C.sub.4-12环烷基烷基基团，或者一起形成一个C.sub.2-8支链或线性聚亚甲基或C.sub.2-6烯基基团，可选择地取代一个杂原子，R.sub.3是氢、C.sub.1-6烷基或苯基，或R.sub.3与R.sub.1一起形成一个--(CH.sub.2).sub.3--或--(CH.sub.2).sub.4--基团；R.sub.4和R.sub.5分别是氢、羟基、卤素、C.sub.1-6烷基或芳基，只要R.sub.4和R.sub.5不同时是氢；p是1到4之间的整数，用于治疗疼痛或低钠血症疾病状态。
• Azacyclic derivatives useful as medicaments
  申请人：Smithkline Beecham Farmaceutici S.p.A.

  公开号：EP0361791A2

  公开（公告）日：1990-04-04

  A compound, or a solvate or salt thereof, of formula (I): in which: RCO is an acyl group in which the group R contains a substituted or unsubstituted carbocyclic aromatic or heterocyclic aromatic ring; R₁ and R₂ are independently hydrogen, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₃₋₆ cycloalkyl or C₄₋₁₂ cycloalkylalkyl groups, or together form a C₂₋₈ branched or linear polymethylene or C₂₋₆ alkenylene group, optionally substituted with a hetero-atom, R₃ is hydrogen, C₁₋₆ alkyl or phenyl, or R₃ together with R₁ form a -(CH₂)₃- or -(CH₂)₄- group; R₄ and R₅ are independently hydrogen, hydroxyl, halogen, C₁₋₆ alkyl or aryl, provided both R₄ and R₅ are not simultaneously hydrogen; and p is an integer from 1 to 4, is useful for the treatment of pain or hyponatraemic disease states.

  一种式(I)化合物或其溶液或盐： 其中 RCO 是酰基，其中基团 R 含有取代或未取代的碳环芳香环或杂环芳香环； R₁ 和 R₂ 独立地为氢、C₁₋₆ 烷基、C₂₋₆ 烯基、C₃₋₆ 环烷基或 C₄₋₁₂ 环烷基烷基、或共同形成 C₂₋₈支链或线性聚亚甲基或 C₂₋₆烯基，可选被杂原子取代、 R₃ 是氢、C₁₋₆ 烷基或苯基，或 R₃ 与 R₁ 共同形成 -(CH₂)₃- 或 -(CH₂)₄- 基团； R₄ 和 R₅ 独立地为氢、羟基、卤素、C₁₋₆ 烷基或芳基，但 R₄ 和 R₅ 不能同时为氢；且 p 为 1 至 4 的整数、 可用于治疗疼痛或低钠血症状态。
• New .kappa.-receptor agonists based upon a 2-[(alkylamino)methyl]piperidine nucleus
  作者：David I. C. Scopes、Norman F. Hayes、David E. Bays、David Belton、John Brain、Dearg S. Brown、Duncan B. Judd、Andrew B. McElroy、Clive A. Meerholz

  DOI：10.1021/jm00081a009

  日期：1992.2

  The syntheses of some 1-[(3,4-dichlorophenyl)acetyl]2-[(alkylamino)methyl]peperidines and their activities as kappa-opioid receptor agonists are described. Selected structural modifications are made to the basic moiety and at the 2-, 3-, 4-, 5-, and 6-positions on the piperidine nucleus to enable structure-activity relationships to be delineated. As a result, some highly potent and selective kappa-receptor agonists have been identified. In particular, this has been achieved by introduction of oxygen-containing functionality into the 4-position of the piperidine nucleus or the 3-position of the pyrrolidinylmethyl side chain. Thus, 1-[(3,4-dichlorophenyl)acetyl]2-[[1-(3-oxopyrrolidinyl)methyl]?? piperidine (10) possesses high activity in the rabbit vas deferens (LCD, kappa-specific tissue) (IC50 = 0.20 nM) and is a potent antiociceptive agent, as determined by the mouse acetylcholine-induced abdominal constriction test (MAC) (ED50 = 0.06 mg/kg sc). The spirocyclic analogue 8-[3,4-dichlorophenyl)acetyl]7-(1-pyrrolidinylmethyl)-1,4-dioxa-8-azaspiro[4.5]decane (39) showed exceptionally potent activity: LVD, IC50 = 0.10 nM; MAC, ED50 = 0.001 mg/kg, sc. Both 10 and 39 displayed high selectivity for kappa-opioid receptors over both mu- and delta-opioid receptor subtypes.
• US5114945A
  申请人：——

  公开号：US5114945A

  公开（公告）日：1992-05-19