叔-丁基4-[[3-(羟甲基)-1-哌啶基]甲基]哌啶-1-羧酸酯 | 184969-11-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 叔-丁基4-[[3-(羟甲基)-1-哌啶基]甲基]哌啶-1-羧酸酯
• 英文名称: 4-(3-Hydroxymethyl-piperidin-1-ylmethyl)-piperidine-1-carboxylic acid tert-butyl ester
• 英文别名: 1-Boc-4-(3-Hydroxymethylpiperidin-1-ylmethyl)piperidine；tert-butyl 4-[[3-(hydroxymethyl)piperidin-1-yl]methyl]piperidine-1-carboxylate
• CAS: 184969-11-7
• 化学式: C₁₇H₃₂N₂O₃
• 分子量: 312.453
• InChiKey: VCKVNWQIFMJQMX-UHFFFAOYSA-N

物化性质

• 沸点：
  404.9±15.0 °C(Predicted)
• 密度：
  1.061±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  53
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  叔-丁基4-[[3-(羟甲基)-1-哌啶基]甲基]哌啶-1-羧酸酯 在 溶剂黄146 、 三氟乙酸 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 18.0h， 生成 {1-[(1-(2,2-diphenyl-ethyl)-piperidin-4-yl)methyl]-piperidin-3-yl}-methanol
  参考文献：
  名称：

  Identification of SQ609 as a lead compound from a library of dipiperidines

  摘要：

  We recently reported that compounds created around a dipiperidine scaffold demonstrated activity against Mycobacterium tuberculosis (Mtb) (Bogatcheva, E.; Hanrahan, C.; Chen, P.; Gearhart, J.; Sacksteder, K.; Einck, L.; Nacy, C.; Protopopova, M. Bioorg. Med. Chem. Lett. 2010, 20, 201). To optimize the dipiperidine compound series and to select a lead compound to advance into preclinical studies, we evaluated the structure-activity relationship (SAR) of our proprietary libraries. The (piperidin-4-ylmethyl) piperidine scaffold was an essential structural element required for antibacterial activity. Based on SAR, we synthesized a focused library of 313 new dipiperidines to delineate additional structural features responsible for antitubercular activity. Thirty new active compounds with MIC 10-20 mu g/ml on Mtb were identified, but none was better than the original hits of this series, SQ609, SQ614, and SQ615. In Mtb-infected macrophages in vitro, SQ609 and SQ614 inhibited more than 90% of intracellular bacterial growth at 4 mu g/ml; SQ615 was toxic to these cells. In mice infected with Mtb, weight loss was completely prevented by SQ609, but not SQ614, and SQ609 had a prolonged therapeutic effect, extended by 10-15 days, after cessation of therapy. Based on in vitro and in vivo antitubercular activity, SQ609 was identified as the best-in-class dipiperidine compound in the series. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.015
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 草酰氯 、 2,2,2-三氟乙醇 、 3 A molecular sieve 、 sodium cyanoborohydride 、 二甲基亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 叔-丁基4-[[3-(羟甲基)-1-哌啶基]甲基]哌啶-1-羧酸酯
  参考文献：
  名称：

  Synthesis of substituted 4(Z)-(methoxyimino)pentyl-1-piperidines as dual NK1/NK2 inhibitors

  摘要：

  The NK1 and NK2 receptor activity of a series of 5-[(3,5-bis(trifluoromethyl)phenyl)methoxy]-3-(3,4-dichlorophenyl)4(Z)-(methoxyimino)pentyl-1-piperidines was evaluated. Compounds 11d, 11e, 11f, 12a, and 12k were found to be our most potent inhibitors. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00702-2

文献信息

• Synthesis of substituted 4(Z)-(methoxyimino)pentyl-1-piperidines as dual NK1/NK2 inhibitors
  作者：Pauline C Ting、Joe F Lee、John C Anthes、Neng-Yang Shih、John J Piwinski

  DOI：10.1016/s0960-894x(00)00702-2

  日期：2001.2

  The NK1 and NK2 receptor activity of a series of 5-[(3,5-bis(trifluoromethyl)phenyl)methoxy]-3-(3,4-dichlorophenyl)4(Z)-(methoxyimino)pentyl-1-piperidines was evaluated. Compounds 11d, 11e, 11f, 12a, and 12k were found to be our most potent inhibitors. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Identification of SQ609 as a lead compound from a library of dipiperidines
  作者：Elena Bogatcheva、Colleen Hanrahan、Boris Nikonenko、Gladys de los Santos、Venkata Reddy、Ping Chen、Francis Barbosa、Leo Einck、Carol Nacy、Marina Protopopova

  DOI：10.1016/j.bmcl.2011.07.015

  日期：2011.9

  We recently reported that compounds created around a dipiperidine scaffold demonstrated activity against Mycobacterium tuberculosis (Mtb) (Bogatcheva, E.; Hanrahan, C.; Chen, P.; Gearhart, J.; Sacksteder, K.; Einck, L.; Nacy, C.; Protopopova, M. Bioorg. Med. Chem. Lett. 2010, 20, 201). To optimize the dipiperidine compound series and to select a lead compound to advance into preclinical studies, we evaluated the structure-activity relationship (SAR) of our proprietary libraries. The (piperidin-4-ylmethyl) piperidine scaffold was an essential structural element required for antibacterial activity. Based on SAR, we synthesized a focused library of 313 new dipiperidines to delineate additional structural features responsible for antitubercular activity. Thirty new active compounds with MIC 10-20 mu g/ml on Mtb were identified, but none was better than the original hits of this series, SQ609, SQ614, and SQ615. In Mtb-infected macrophages in vitro, SQ609 and SQ614 inhibited more than 90% of intracellular bacterial growth at 4 mu g/ml; SQ615 was toxic to these cells. In mice infected with Mtb, weight loss was completely prevented by SQ609, but not SQ614, and SQ609 had a prolonged therapeutic effect, extended by 10-15 days, after cessation of therapy. Based on in vitro and in vivo antitubercular activity, SQ609 was identified as the best-in-class dipiperidine compound in the series. (C) 2011 Elsevier Ltd. All rights reserved.