1-[(1-decahydronaphthalen-2-ylpiperidin-4-yl)methyl]piperidin-4-ol | 1208260-56-3

• 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: 1-[(1-decahydronaphthalen-2-ylpiperidin-4-yl)methyl]piperidin-4-ol
• 英文别名: SQ613；1-[(1-Decalin-2-yl-4-piperidyl)methyl]piperidin-4-ol；1-[[1-(1,2,3,4,4a,5,6,7,8,8a-decahydronaphthalen-2-yl)piperidin-4-yl]methyl]piperidin-4-ol
• CAS: 1208260-56-3
• 化学式: C₂₁H₃₈N₂O
• 分子量: 334.546
• InChiKey: MQKKNLRQVDNVEW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  26.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-[(1-decahydronaphthalen-2-ylpiperidin-4-yl)methyl]piperidin-4-ol 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.25h， 以0.057 g的产率得到1-({1-[3-(4-hydroxyphenyl)-1-methylpropyl]piperidin-4-yl}methyl)piperidin-4-ol
  参考文献：
  名称：

  Discovery of dipiperidines as new antitubercular agents

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2009.10.135
• 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-decahydronaphthalen-2-ylpiperidin-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

• METHODS OF USE AND COMPOSITIONS FOR THE DIAGNOSIS AND TREATMENT OF INFECTIOUS DISEASES
  申请人：PROTOPOPOVA MARINA NIKOLAEVNA

  公开号：US20100273826A1

  公开（公告）日：2010-10-28

  Methods and compositions for treating disease caused by infectious agents, particularly tuberculosis. In particular, methods and compositions comprising substituted diamines for the treatment of infectious diseases are provided. In one embodiment, these methods and compositions are used for the treatment of mycobacterial infections, including, but not limited to, tuberculosis.
• US7652039B2
  申请人：——

  公开号：US7652039B2

  公开（公告）日：2010-01-26
• US8198303B2
  申请人：——

  公开号：US8198303B2

  公开（公告）日：2012-06-12