SQ-609 | 627052-25-9

• 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: SQ-609
• 英文别名: 1-{[1-(1-adamantylmethyl)piperidin-4-yl]methyl}piperidin-4-ol；1-[[1-(1-adamantylmethyl)piperidin-4-yl]methyl]piperidin-4-ol
• CAS: 627052-25-9
• 化学式: C₂₂H₃₈N₂O
• 分子量: 346.557
• InChiKey: YUBKDPOCUHUSLW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  6.0
• 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

• 作为产物：
  描述：

  1-金刚烷甲醇 在 溶剂黄146 、 二甲基亚砜 、 三氟乙酸酐 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 18.66h， 生成 SQ-609
  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

• COMBINATION THERAPY TO TREAT MYCOBACTERIUM DISEASES
  申请人：Locher Christopher Phillip

  公开号：US20140045791A1

  公开（公告）日：2014-02-13

  The present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof wherein X and R are as defined herein. The compounds of formula (I) are useful as gyrase and/or topoisomerase IV inhibitors for treating bacterial infections. The compounds of formula (I) either possess a broad range of anti-bacterial activity and advantageous toxicological properties or are prodrugs of compounds having said activity.

  本发明涉及式(I)化合物或其药学上可接受的盐，其中X和R的定义如本文所述。式(I)化合物可用作抑制DNA旋转酶和/或拓扑异构酶IV的抑制剂，用于治疗细菌感染。式(I)化合物具有广泛的抗菌活性和优越的毒理学特性，或者是具有该活性的前药。
• ANTI-TUBERCULAR DRUGS: COMPOSITIONS AND METHODS
  申请人：PROTOPOPOVA Marina Nikolaevna

  公开号：US20090192173A1

  公开（公告）日：2009-07-30

  Methods and compositions for treating disease caused by infectious agents, particularly tuberculosis. In particular, methods and compositions comprising substituted ethylene 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. In certain embodiments, the present invention comprises compositions comprising novel substituted ethylene diamine compounds further comprising antitubercular agents such as rifampicin, isoniazid, pyrazinamide and ethambutol.

  本发明提供了用于治疗由传染性病原体引起的疾病，特别是结核病的方法和组合物。具体而言，提供了用于治疗传染病的取代乙二胺的方法和组合物。在一个实施例中，这些方法和组合物用于治疗分枝杆菌感染，包括但不限于结核病。在某些实施例中，本发明包括包含新型取代乙二胺化合物的组合物，进一步包括抗结核药物如利福平、异烟肼、吡嗪酰胺和乙胺丁醇。
• 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.
• 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