1-[(1-(2-phenoxy-ethyl)-piperidin-4-yl)methyl]-piperidin-4-ol | 1334173-99-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-[(1-(2-phenoxy-ethyl)-piperidin-4-yl)methyl]-piperidin-4-ol
• 英文别名: 1-[[1-(2-Phenoxyethyl)-4-piperidyl]methyl]piperidin-4-ol；1-[[1-(2-phenoxyethyl)piperidin-4-yl]methyl]piperidin-4-ol
• CAS: 1334173-99-7
• 化学式: C₁₉H₃₀N₂O₂
• 分子量: 318.459
• InChiKey: VCWRPWIDUAUXNI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  35.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-叔丁氧羰基哌啶-4-甲醛 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 66.0h， 生成 1-[(1-(2-phenoxy-ethyl)-piperidin-4-yl)methyl]-piperidin-4-ol
  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