4-[[4-(phenylmethyl)-1-piperidinyl]methyl]-piperidine | 276873-03-1

• 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: 4-[[4-(phenylmethyl)-1-piperidinyl]methyl]-piperidine
• 英文别名: 4-Benzyl-1-(piperidin-4-ylmethyl)piperidine
• CAS: 276873-03-1
• 化学式: C₁₈H₂₈N₂
• 分子量: 272.434
• InChiKey: PXXKNMJIANICFH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (E)-3,7-二甲基-2,6-辛二烯醛 、 4-[[4-(phenylmethyl)-1-piperidinyl]methyl]-piperidine 在 溶剂黄146 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 18.0h， 以0.01 g的产率得到4-benzyl-1-((1-((2E)-3,7-dimethylocta-2,6-dien-1-yl)piperidine-4-yl)methyl)piperidine
  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：

  4-哌啶甲醇 在 盐酸 、 N-甲基吲哚酮 、 四丙基高钌酸铵 、 3 A molecular sieve 、 三乙酰氧基硼氢化钠 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 2.0h， 生成 4-[[4-(phenylmethyl)-1-piperidinyl]methyl]-piperidine
  参考文献：
  名称：

  CCR3 antagonists: a potential new therapy for the treatment of asthma. Discovery and structure–activity relationships

  摘要：

  CCR3 antagonist leads with IC50 values in the muM range were converted into low nM binding compounds that displayed in vitro inhibition of human eosinophil chemotaxis induced by human eotaxin. In particular, 4-benzylpiperidin-1-yl-n-propylureas and erythro-3-(4-benzyl-2-(alpha-hydroxyalkyl)piperidin-1-yl)-n-propylureas (obtained via Beak reaction of N-BOC-4-benzylpiperidine) exhibited single digit nanomolar IC50 values for CCR3. (C) 2002 Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(02)00206-8

文献信息

• Heterocycyclic piperidines as modulators of chemokine receptor activity
  申请人：——

  公开号：US06331545B1

  公开（公告）日：2001-12-18

  The present application describes modulators of CCR3 of formula (I): or pharmaceutically acceptable salt forms thereof, useful for the prevention of asthma and other allergic diseases.

  本申请描述了公式 (I) 的CCR3调节剂或其药用盐形式，可用于预防哮喘和其他过敏疾病。
• Heterocyclic piperidines as modulators of chemokine receptor activity
  申请人：——

  公开号：US20020119980A1

  公开（公告）日：2002-08-29

  The present application describes modulators of CCR3 of formula (I): 1 or pharmaceutically acceptable salt forms thereof, useful for the prevention of asthma and other allergic diseases.

  本申请描述了CCR3的调节剂的公式(I):1或其药学上可接受的盐形式，用于预防哮喘和其他过敏性疾病。
• HETEROCYCLIC PIPERIDINES AS MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY
  申请人：Ko S. Soo

  公开号：US20070299057A9

  公开（公告）日：2007-12-27

  The present application describes modulators of CCR3 of formula (I): or pharmaceutically acceptable salt forms thereof, useful for the prevention of asthma and other allergic diseases.

  本申请描述了CCR3调节剂的化学式(I)或其药学上可接受的盐形式，可用于预防哮喘和其他过敏性疾病。
• US6331545B1
  申请人：——

  公开号：US6331545B1

  公开（公告）日：2001-12-18
• US6759411B2
  申请人：——

  公开号：US6759411B2

  公开（公告）日：2004-07-06