4-hydroxy-N-(2-methyl-phenyl)-piperidine

• 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-N-(2-methyl-phenyl)-piperidine
• 英文别名: 1-(o-tolyl)piperidin-4-ol；1-(2-methylphenyl)piperidin-4-ol
• 化学式: C₁₂H₁₇NO
• 分子量: 191.273
• InChiKey: QHPIVNMZWWJPGE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-hydroxy-N-(2-methyl-phenyl)-piperidine 在 吡啶 、 4-二甲氨基吡啶 、 水 、 caesium carbonate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 51.0h， 生成 2-((4S,5S)-4-methyl-1-(4-((1-(o-tolyl)piperidin-4-yl)oxy)phenyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-yl)acetic acid
  参考文献：
  名称：

  Discovery of Potent and Orally Bioavailable Dihydropyrazole GPR40 Agonists

  摘要：

  G protein-coupled receptor 40 (GPR40) has become an attractive target for the treatment of diabetes since it was shown clinically to promote,glucose-stimulated insulin secretion. Herein, we report our efforts to develop highly I selectiveand potent GPR40 agonists with a dual mechanism of action, promoting both ghicose-clependent insulin and incretin secretion. Employing strategies to increase fiolarity and the ratio of sp(3)/sP(2) character of the chemotype, we identified BMS-986118 (compound 4), which showed potent and selective GPR40 agonist activity in vitro. In vivo, compound 4 demonstrated insulinotropic efficacy and GLP-1 secretory effects resulting in improved glucose control in acute animal models.

  DOI：

  10.1021/acs.jmedchem.7b00982
• 作为产物：
  描述：

  4-羟基哌啶 、 2-溴甲苯 在 tris-(dibenzylideneacetone)dipalladium(0) 、 lithium hexamethyldisilazane 、 2-(二环己基膦基)联苯 作用下， 以 四氢呋喃 为溶剂， 反应 22.0h， 以60%的产率得到4-hydroxy-N-(2-methyl-phenyl)-piperidine
  参考文献：
  名称：

  核雄激素受体的小分子拮抗剂治疗去势抵抗性前列腺癌

  摘要：

  在高通量筛选活动确定了硫醚1是核雄激素受体的拮抗剂后，开发了一种用于结构-活性关系（SAR）目的的区域模型，并合成了类似物并在基于细胞的萤光素酶测定法中进行了评估。一种新型的硫醚等排物，环丙烷（1 S，2 R）-27，显示出所需的增强的效能和结构特性（立体比SAR响应，不存在容易氧化的硫原子，低分子量，柔性键数量减少和极性表面积） ，以及药物相似性得分）在C4-2-PSA-rl细胞中的前列腺特异性抗原荧光素酶测定中，有资格作为前列腺癌药物开发的新先导结构。

  DOI：

  10.1021/acsmedchemlett.6b00186

文献信息

• [EN] BENZOXAZEPINES AS INHIBITORS OF MTOR AND METHODS OF THEIR USE AND MANUFACTURE<br/>[FR] BENZOXAZÈPINES COMME INHIBITEURS DE MTOR ET MÉTHODES D'UTILISATION ET DE FABRICATION
  申请人：EXELIXIS INC

  公开号：WO2010138490A1

  公开（公告）日：2010-12-02

  The invention is directed to inhibitors of mTOR and pharmaceutically acceptable salts or solvates thereof, as well as methods of using them. The inhibitors are generally of structural formula wherein the combination of R1 and R2 are as defined herein, and pharmaceutically acceptable salts thereof.

  这项发明涉及 mTOR 的抑制剂及其药用盐或溶剂，以及它们的使用方法。这些抑制剂通常具有结构式，其中 R1 和 R2 的组合如本文所定义，并且其药用盐。
• Small Molecule Antagonists of the Nuclear Androgen Receptor for the Treatment of Castration-Resistant Prostate Cancer
  作者：James K. Johnson、Erin M. Skoda、Jianhua Zhou、Erica Parrinello、Dan Wang、Katherine O’Malley、Benjamin R. Eyer、Mustafa Kazancioglu、Kurtis Eisermann、Paul A. Johnston、Joel B. Nelson、Zhou Wang、Peter Wipf

  DOI：10.1021/acsmedchemlett.6b00186

  日期：2016.8.11

  After a high-throughput screening campaign identified thioether 1 as an antagonist of the nuclear androgen receptor, a zone model was developed for structure–activity relationship (SAR) purposes and analogues were synthesized and evaluated in a cell-based luciferase assay. A novel thioether isostere, cyclopropane (1S,2R)-27, showed the desired increased potency and structural properties (stereospecific

  在高通量筛选活动确定了硫醚1是核雄激素受体的拮抗剂后，开发了一种用于结构-活性关系（SAR）目的的区域模型，并合成了类似物并在基于细胞的萤光素酶测定法中进行了评估。一种新型的硫醚等排物，环丙烷（1 S，2 R）-27，显示出所需的增强的效能和结构特性（立体比SAR响应，不存在容易氧化的硫原子，低分子量，柔性键数量减少和极性表面积） ，以及药物相似性得分）在C4-2-PSA-rl细胞中的前列腺特异性抗原荧光素酶测定中，有资格作为前列腺癌药物开发的新先导结构。
• Improved Functional Group Compatibility in the Palladium-Catalyzed Synthesis of Aryl Amines
  作者：Michele C. Harris、Xiaohua Huang、Stephen L. Buchwald

  DOI：10.1021/ol0262688

  日期：2002.8.1

  use of Pd2dba3 with bulky, electron-rich ligands 1 or 2 and LiN(TMS)2 as the base for the coupling of amines with aryl halides containing hydroxyl, amide, or enolizable keto groups is described. This protocol expands the utility of palladium-catalyzed C-N bond formation by allowing for the use of aryl halides containing these functional groups, obviating the need for protecting group manipulations

  [反应：见正文]描述了将Pd2dba3与庞大的富电子配体1或2和LiN（TMS）2用作胺与含有羟基，酰胺或可烯丙基酮基的芳基卤化物偶合的基础。通过允许使用含有这些官能团的芳基卤化物，该方案扩展了钯催化的CN键形成的应用，从而避免了对保护基团的操作。
• AZOLECARBOXAMIDE DERIVATIVE
  申请人：Sugasawa Keizo

  公开号：US20090286766A1

  公开（公告）日：2009-11-19

  Provided is an agent for treating or preventing urinary frequency, urinary urgency and urinary, incontinence which are associated with overactive bladder, a lower urinary tract disease such as interstitial cystitis and chronic prostatitis accompanied by lower urinary tract pain, and various diseases accompanied by pain. A novel azolecarboxamide derivative in which an azole ring such as thioazole or oxazole is bonded to a benzene ring, pyridine ring or pyrimidine ring through carboxamide was confirmed to have a potent trkA receptor-inhibitory activity and found to be an agent for treating or preventing lower urinary tract disease and various diseases accompanied by pain, which is excellent in efficacy and safety, and thus the present invention was accomplished.

  提供了一种用于治疗或预防与过度活跃膀胱、下泌尿道疾病（如间质性膀胱炎和慢性前列腺炎伴随下泌尿道疼痛）以及伴随疼痛的各种疾病相关的尿频、尿急和尿失禁的药剂。一种新型的唑烷羧酰胺衍生物，其中唑环（如硫唑环或噁唑环）通过羧酰胺键连接到苯环、吡啶环或嘧啶环上，被证实具有强效的trkA受体抑制活性，并被发现是一种用于治疗或预防下泌尿道疾病和伴随疼痛的各种疾病的药剂，其疗效和安全性优异，因此本发明得以完成。
• SMALL MOLECULE INHIBITORS OF THE NUCLEAR TRANSLOCATION OF ANDROGEN RECEPTOR FOR THE TREATMENT OF CASTRATION-RESISTANT PROSTATE CANCER
  申请人：University of Pittsburgh - Of the Commonwealth System of Higher Education

  公开号：US20160257657A1

  公开（公告）日：2016-09-08

  A compound, or a pharmaceutically acceptable salt or ester thereof, according to formula I: R 20 —(Z) b —(Y) c —(R 21 ) a —(X) d —R 22 —R 23 wherein R 20 is aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl, substituted heterocycloalkyl, alkoxy, aryloxy, a thio-containing group, or a seleno-containing group; Z is alkanediyl, substituted alkanediyl, cycloalkanediyl, or substituted cycloalkanediyl; Y is S, O, S(═O), —S(═O)(═O)—, or NR 10 , wherein R 10 is H or alkyl; R 21 is alkanediyl, substituted alkanediyl, cycloalkanediyl, substituted cycloalkanediyl alkadienyl, substituted alkadienyl, alkatrienyl, substituted alkatrienyl; X is —C(═O)—, —S(═O)(═O)—, or —N(H)C(═O)—; R 22 includes at least one divalent amino radical; R 23 is aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl, substituted heterocycloalkyl, alkoxy, aryloxy, a thio-containing group, or a seleno-containing group; a, b, c, and d independently are 0 or 1.

  根据公式I，化合物或其药学上可接受的盐或酯，其中R20为芳基，取代芳基，杂环芳基，取代杂环芳基，杂环烷基，取代杂环烷基，烷氧基，芳基氧基，含硫基或含硒基；Z为烷二基，取代烷二基，环烷二基或取代环烷二基；Y为S，O，S(═O)，—S(═O)(═O)—或NR10，其中R10为H或烷基；R21为烷二基，取代烷二基，环烷二基，取代环烷二基，烯丙基，取代烯丙基，烯三基或取代烯三基；X为—C(═O)—，—S(═O)(═O)—或—N(H)C(═O)—；R22至少包括一个二价氨基基团；R23为芳基，取代芳基，杂环芳基，取代杂环芳基，杂环烷基，取代杂环烷基，烷氧基，芳基氧基，含硫基或含硒基；a、b、c和d独立地为0或1。