1-({1-[3-(4-hydroxyphenyl)-1-methylpropyl]piperidin-4-yl}methyl)piperidin-4-ol | 627052-30-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 1-({1-[3-(4-hydroxyphenyl)-1-methylpropyl]piperidin-4-yl}methyl)piperidin-4-ol
• 英文别名: SQ614；1-[[1-[3-(4-Hydroxyphenyl)-1-methyl-propyl]-4-piperidyl]methyl]piperidin-4-ol；1-[[1-[4-(4-hydroxyphenyl)butan-2-yl]piperidin-4-yl]methyl]piperidin-4-ol
• CAS: 627052-30-6
• 化学式: C₂₁H₃₄N₂O₂
• 分子量: 346.513
• InChiKey: NTUBXCRSSNLKDY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  46.9
• 氢给体数：
  2
• 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-[3-(4-hydroxyphenyl)-1-methylpropyl]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

文献信息

• Discovery of dipiperidines as new antitubercular agents
  作者：Elena Bogatcheva、Colleen Hanrahan、Ping Chen、Jacqueline Gearhart、Katherine Sacksteder、Leo Einck、Carol Nacy、Marina Protopopova

  DOI：10.1016/j.bmcl.2009.10.135

  日期：2010.1

  As part of our ongoing research effort to develop new therapeutics for treatment of tuberculosis (TB), we synthesized a combinatorial library of 10,358 compounds on solid support using a pool-and-split technique and tested the resulting compounds for activity against Mycobacterium tuberculosis. Structure activity relationship (SAR) evaluation identified new compounds with antitubercular activity, including a novel hit series that is structurally unrelated to any existing antitubercular drugs, dipiperidines. Dipiperidine representatives exhibited MIC values as low as 7.8 mu M, the ability to induce promoter Rv0341 activated in response to cell wall biosynthesis inhibition, relatively low nonspecific cellular toxicity in the range of 30-162 mu M, and log P values less than 4. (C) 2009 Elsevier Ltd. All rights reserved.
• US7652039B2
  申请人：——

  公开号：US7652039B2

  公开（公告）日：2010-01-26