4-hydroxy-4-(2-hydroxyphenyl)piperidine | 336882-80-5

• 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: 4-hydroxy-4-(2-hydroxyphenyl)piperidine
• 英文别名: 4-(2-hydroxyphenyl)-4-piperidinol；4-(2-hydroxyphenyl)piperidin-4-ol
• CAS: 336882-80-5
• 化学式: C₁₁H₁₅NO₂
• 分子量: 193.246
• InChiKey: BFGQQXHUIXTRDT-UHFFFAOYSA-N

物化性质

• 沸点：
  347.1±31.0 °C(Predicted)
• 密度：
  1.203±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 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：

  4-hydroxy-4-(2-hydroxyphenyl)piperidine 在 sodium carbonate 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 {2-[1-(3-Dimethylcarbamoyl-3,3-diphenyl-propyl)-4-hydroxy-piperidin-4-yl]-phenoxy}-acetic acid ethyl ester
  参考文献：
  名称：

  New .MU.-Opioid Receptor Agonists with Phenoxyacetic Acid Moiety.

  摘要：

  合成并评估了含有 4-羟基哌啶、哌啶和哌嗪分子的新型μ-阿片受体（MOR）激动剂，以寻找一种外周阿片类镇痛药。在合成的化合物中，[2-[1-[3-（N,N-二甲基氨基甲酰基）-3,3-二苯基丙基]-4-羟基哌啶-4-基]苯氧基]乙酸（8：在离体豚鼠回肠制剂中，具有苯氧乙酸和 4-羟基哌啶分子的 SS620 对 MOR 的激动效力最高，与同类型的 δ- 和 κ- 阿片受体（DOR 和 KOR）相比，它对中国仓鼠卵巢（CHO）-K1 细胞中表达的人类 MOR 也具有选择性。）此外，化合物 8 显示出的 MOR 激动剂活性是洛哌丁胺的 10 倍。此外，化合物 8 在大鼠体内筛选中显示出外周镇痛活性。

  DOI：

  10.1248/cpb.50.292
• 作为产物：
  描述：

  1-benzyl-4-(2-benzyloxy-phenyl)-piperidin-4-ol 在 palladium dihydroxide 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、405.3 kPa 条件下， 反应 6.0h， 以95%的产率得到4-hydroxy-4-(2-hydroxyphenyl)piperidine
  参考文献：
  名称：

  New .MU.-Opioid Receptor Agonists with Phenoxyacetic Acid Moiety.

  摘要：

  合成并评估了含有 4-羟基哌啶、哌啶和哌嗪分子的新型μ-阿片受体（MOR）激动剂，以寻找一种外周阿片类镇痛药。在合成的化合物中，[2-[1-[3-（N,N-二甲基氨基甲酰基）-3,3-二苯基丙基]-4-羟基哌啶-4-基]苯氧基]乙酸（8：在离体豚鼠回肠制剂中，具有苯氧乙酸和 4-羟基哌啶分子的 SS620 对 MOR 的激动效力最高，与同类型的 δ- 和 κ- 阿片受体（DOR 和 KOR）相比，它对中国仓鼠卵巢（CHO）-K1 细胞中表达的人类 MOR 也具有选择性。）此外，化合物 8 显示出的 MOR 激动剂活性是洛哌丁胺的 10 倍。此外，化合物 8 在大鼠体内筛选中显示出外周镇痛活性。

  DOI：

  10.1248/cpb.50.292

文献信息

• [EN] SUBSTITUTED PIPERIDINES THAT INCREASE p53 ACTIVITY AND THE USES THEREOF<br/>[FR] PIPÉRIDINES SUBSTITUÉES QUI ACCROISSENT L'ACTIVITÉ DE P53, ET UTILISATIONS DE CES COMPOSÉS
  申请人：SCHERING CORP

  公开号：WO2011046771A1

  公开（公告）日：2011-04-21

  The present invention provides a compound of Formula (1) as described herein or a pharmaceutically acceptable salt, solvate or ester thereof. The compounds are useful as inhibitors of the HDM2 protein. Also disclosed are pharmaceutical compositions comprising the above compounds and methods of treating cancer using the same.

  本发明提供了如下所述的化合物的化学式（1）或其药学上可接受的盐、溶剂合物或酯。这些化合物可用作HDM2蛋白的抑制剂。还公开了包含上述化合物的药物组合物以及使用它们治疗癌症的方法。
• [EN] (4-PHENYL-PIPERIDIN-1-YL)-[5-1H-PYRAZOL-4YL)-THIOPHEN-3-YL]-METHANONE COMPOUNDS AND THEIR USE<br/>[FR] COMPOSÉS DE (4-PHÉNYL-PIPÉRIDIN-1-YL)-[5-1H-PYRAZOL-4-YL)-THIOPHÉN-3-YL]-MÉTHANONE ET LEUR UTILISATION
  申请人：UNIV EDINBURGH

  公开号：WO2011033255A1

  公开（公告）日：2011-03-24

  The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain (4-phenyl-piperidin-1-yl)- [5-(1 H-pyrazol-4-yl)-thiophen-3-yl]-methanone compounds that, inter alia, inhibit 11 β-hydroxysteroid dehydrogenase type 1 (11 β-HSD1 ). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit 1 1 β-hydroxysteroid dehydrogenase type 1; to treat disorders that are ameliorated by the inhibition of 11 β-hydroxysteroid dehydrogenase type 1; to treat the metabolic syndrome, which includes disorders such as type 2 diabetes and obesity, and associated disorders including insulin resistance, hypertension, lipid disorders and cardiovascular disorders such as ischaemic (coronary) heart disease; to treat CNS disorders such as mild cognitive impairment and early dementia, including Alzheimer's disease; etc.

  本发明一般涉及治疗化合物领域。更具体地说，本发明涉及某些（4-苯基-哌啶-1-基）-[5-(1 H-吡唑-4-基)-噻吩-3-基]-甲酮化合物，其中包括抑制11β-羟基甾酮脱氢酶1（11β-HSD1）的作用。本发明还涉及包含这些化合物的药物组合物，以及利用这些化合物和组合物在体外和体内抑制11β-羟基甾酮脱氢酶1的用途；治疗通过抑制11β-羟基甾酮脱氢酶1而得到改善的疾病；治疗代谢综合征，其中包括2型糖尿病和肥胖等疾病，以及相关疾病，包括胰岛素抵抗、高血压、脂质紊乱和缺血性（冠状动脉）心脏病等心血管疾病；治疗轻度认知障碍和早期痴呆等中枢神经系统疾病，包括阿尔茨海默病等。
• 4-hydroxy-4-phenylpiperidine derivatives and pharmaceuticals containing the same
  申请人：SSP Co., LTD

  公开号：US06362203B1

  公开（公告）日：2002-03-26

  Described is a 4-hydroxy-4-phenylpiperidine derivative represented by the following formula (1): [wherein, R1 and R2 are the same or different and each independently represents a hydrogen atom, a lower alkyl, or the like, R3 represents a hydrogen atom or a group —(CR4R5)n—Y (in which, R4 and R5 each represents a hydrogen atom or a lower alkyl group, Y represents a group —COOR6, —CONR7R8, —OR9 or —OCOR10 (in which R6, R9 and R10 each independently represents a hydrogen atom, a lower alkyl group, or the like, R7 and R8 are the same or different and each independently represents a hydrogen atom, a lower alkyl group, or the like), and n stands for 1 to 6)], or salt thereof. The compound exhibits excellent peripheral analgesic action.

  描述了一种由以下式子（1）表示的4-羟基-4-苯基哌啶衍生物：[其中，R1和R2相同或不同，每个独立地表示氢原子、低碳基或类似物，R3表示氢原子或基团—(CR4R5)n—Y（其中，R4和R5各自表示氢原子或低碳基，Y表示基团—COOR6、—CONR7R8、—OR9或—OCOR10（其中，R6、R9和R10各自独立地表示氢原子、低碳基或类似物，R7和R8相同或不同，每个独立地表示氢原子、低碳基或类似物），n表示1到6）]，或其盐。该化合物表现出优异的周围镇痛作用。
• 2,2-Diphenylbutanamide derivatives and medicines containing the same
  申请人：——

  公开号：US20040034104A1

  公开（公告）日：2004-02-19

  2,2-Diphenylbutanamide derivatives represented by the following formula (1): 1 [wherein A represents —(CH 2 ) n — (n is 1 or 2) or a methine (CH) group; when A is —CH 2 —, B represents a methine group or a nitrogen atom, with A and B forming a single bond; when A is —(CH 2 ) 2 —, B represents a nitrogen atom, with A and B forming a single bond; when A is a methine group, B represents a quaternary carbon atom, with A and B forming a double bond; each of R 1 and R 2 , which are identical to or different from each other, represents a hydrogen atom, a lower alkyl group, or a cycloalkyl group, or R 1 and R 2 may form a heterocyclic ring together with the adjacent nitrogen atom; and Ar represents an optionally substituted phenyl group, bicyclic aromatic ring, monocyclic heterocyclic ring, bicyclic heterocyclic ring, or fluorene group]; or salts of the derivatives. The derivatives or salts thereof exhibit excellent &mgr;-opioid agonist activity and analgesic activity against neuropathic pain, and are useful as medicines such as peripheral analgesic drugs and neuropathic pain relieving drugs.

  以下式子（1）所表示的2,2-二苯基丁酰胺衍生物： 1[其中，A代表—（CH2）n—（n为1或2）或甲基（CH）基团；当A为— —时，B代表甲基基团或氮原子，A和B形成单键；当A为—（ ）2—时，B代表氮原子，A和B形成单键；当A为甲基基团时，B代表四价碳原子，A和B形成双键；R1和R2各自表示氢原子、低碳基或环烷基，或者R1和R2与相邻氮原子一起形成杂环；Ar表示可选取代的苯基、双环芳香环、单环杂环环、双环杂环环或芴基；以及其衍生物的盐。] 这些衍生物或其盐表现出优异的μ-阿片受体激动剂活性和对神经病理性疼痛的镇痛活性，可用作外周镇痛药和神经病理性疼痛缓解药等药物。
• (4-Phenyl-piperidin-1-yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanone Compounds and Their Use
  申请人：Webster Scott Peter

  公开号：US20120172393A1

  公开（公告）日：2012-07-05

  The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain (4-phenyl-piperidin-1-yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanone compounds that, inter alia, inhibit 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit 11β-hydroxysteroid dehydrogenase type 1; to treat disorders that are ameliorated by the inhibition of 11β-hydroxysteroid dehydrogenase type 1; to treat the metabolic syndrome, which includes disorders such as type 2 diabetes and obesity, and associated disorders including insulin resistance, hypertension, lipid disorders and cardiovascular disorders such as ischaemic (coronary) heart disease; to treat CNS disorders such as mild cognitive impairment and early dementia, including Alzheimer's disease; etc.

  本发明涉及治疗化合物领域。更具体地说，本发明涉及某些(4-苯基哌啶-1-基)-[5-(1H-吡唑-4-基)-噻吩-3-基]-甲酮化合物，其中包括抑制11β-羟化类固醇脱氢酶1型(11β-HSD1)的化合物。本发明还涉及包含此类化合物的制药组合物的使用，以及在体外和体内使用此类化合物和组合物以抑制11β-羟化类固醇脱氢酶1型；治疗由抑制11β-羟化类固醇脱氢酶1型改善的疾病；治疗代谢综合征，包括2型糖尿病和肥胖症等疾病，以及相关疾病，包括胰岛素抵抗、高血压、脂质代谢异常和心血管疾病，如缺血性(冠状)心脏病；治疗轻度认知障碍和早期痴呆等中枢神经系统疾病，包括阿尔茨海默病等。