endo-1-(8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole | 478696-46-7

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 英文名称: endo-1-(8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole
• 英文别名: 1-(8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole
• CAS: 478696-46-7
• 化学式: C₁₅H₁₉N₃
• 分子量: 241.336
• InChiKey: BJGOIXDGNKKASK-ITGUQSILSA-N

物化性质

• 沸点：
  434.7±38.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18.0
• 可旋转键数：
  1.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  29.85
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  endo-1-(8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole 、 1-[4-(2-Bromoacetyl)-4-phenylpiperidin-1-yl]-2,2-dimethylpropan-1-one 在 三乙胺 作用下， 以 乙醚 、 苯 为溶剂， 反应 12.0h， 生成
  参考文献：
  名称：

  Novel 4,4-Disubstituted Piperidine-Based C–C Chemokine Receptor-5 Inhibitors with High Potency against Human Immunodeficiency Virus-1 and an Improved human Ether-a-go-go Related Gene (hERG) Profile

  摘要：

  We recently described (J. Med. Chem. 2008, 51, 6538-6546) a novel class of CCR5 antagonists with strong anti-HIV potency. Herein, we detail SAR converting leads 1 and 2 to druglike molecules. The pivotal structural motif enabling this transition was the secondary sulfonamide substituent. Further fine-tuning of the substituent pattern in the sulfonamide paved the way to enhancing potency and bioavailability and minimizing hERG inhibition, resulting in discovery of clinical compound 122 (GSK163929).

  DOI：

  10.1021/jm200279v
• 作为产物：
  描述：

  1-(8-benzyl-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole 在 palladium(II) hydroxide/carbon 甲酸铵 作用下， 以 乙醇 为溶剂， 反应 2.5h， 生成 endo-1-(8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole
  参考文献：
  名称：

  [EN] PIPERIDINE DERIVATIVES AS CCR5 ANTAGONISTS
  [FR] ANTAGONISTES DE CCR5 UTILES COMME AGENTS THERAPEUTIQUES

  摘要：

  公开号：

  WO2004054974A3

文献信息

• [EN] THERAPEUTIC COMPOUNDS<br/>[FR] COMPOSÉS THÉRAPEUTIQUES
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2011011652A1

  公开（公告）日：2011-01-27

  The present invention relates to compounds of Formula (I) and (Ia) useful in the treatment of CCR5-related diseases and disorders, for example, the prevention or treatment of an HIV infection, and in the treatment of the resulting acquired immune deficiency syndrome (AIDS).

  本发明涉及一种在治疗与CCR5相关的疾病和疾病中有用的化合物，例如，预防或治疗HIV感染，以及治疗由此导致的获得性免疫缺陷综合症（AIDS）。
• Pyrrolidine modulators of CCR5 chemokine receptor activity
  申请人：——

  公开号：US20020198178A1

  公开（公告）日：2002-12-26

  Pyrrolidine compounds of Formula I: 1 (wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8a , R 8b , j, k, l, m, and n are defined herein) are described. The compounds are modulators of CCR5 chemokine receptor activity. The compounds are useful, for example, in the prevention or treatment of infection by HIV and the treatment of AIDS, as compounds or pharmaceutically acceptable salts, or as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.

  本文描述了式I:1中的吡咯烷化合物（其中R1、R2、R3、R4、R5、R6、R7、R8a、R8b、j、k、l、m和n在此处定义）。这些化合物是CCR5趋化因子受体活性的调节剂。这些化合物可用于预防或治疗HIV感染和治疗艾滋病，作为化合物或药物可接受的盐或作为药物组成部分，可选地与其他抗病毒药物、免疫调节剂、抗生素或疫苗组合使用。本文还描述了治疗艾滋病的方法以及预防或治疗HIV感染的方法。
• Cyclopropyl compounds as ccr5 antagonists
  申请人：Peckham Poole Jennifer

  公开号：US20060052408A1

  公开（公告）日：2006-03-09

  The present invention relates to compounds of formula (I), or pharmaceutically acceptable derivatives thereof, useful in the treatment of CCR5-related diseases and disorders, for example, useful in the inhibition of HIV replication, the prevention or treatment of an HIV infection, and in the treatment of the resulting acquired immune deficiency syndrome (AIDS).

  本发明涉及式（I）的化合物或其药学上可接受的衍生物，用于治疗与CCR5相关的疾病和障碍，例如，用于抑制HIV复制，预防或治疗HIV感染，并用于治疗由此导致的获得性免疫缺陷综合症（AIDS）。
• HETEROCYCLIC COMPOUNDS AS CCR5 ANTAGONISTS
  申请人：AQUINO Christopher Joseph

  公开号：US20090053172A1

  公开（公告）日：2009-02-26

  The present invention relates to compounds of formula (I), or pharmaceutically acceptable derivatives thereof, useful in the treatment of CCR5-related diseases and disorders, for example, useful in the inhibition of HIV replication, the prevention or treatment of an HIV infection, and in the treatment of the resulting acquired immune deficiency syndrome (AIDS).

  本发明涉及式(I)化合物或其药学上可接受的衍生物，用于治疗CCR5相关的疾病和障碍，例如，用于抑制HIV复制，预防或治疗HIV感染，并用于治疗由此导致的获得性免疫缺陷综合症（AIDS）。
• [2-(4-Phenyl-4-piperidinyl)ethyl]amine based CCR5 antagonists: derivatizations at the N-terminal of the piperidine ring
  作者：Maosheng Duan、Christopher Aquino、Robert Ferris、Wieslaw M. Kazmierski、Terry Kenakin、Cecilia Koble、Pat Wheelan、Chris Watson、Michael Youngman

  DOI：10.1016/j.bmcl.2009.02.014

  日期：2009.3

  Several series of CCR5 antagonists have been discovered by derivatization at the N-terminal of the piperidine ring of the core template 2. Some derivatives exhibited potent inhibition against HIV-1 infection. The pharmacokinetic properties of the lead compounds 11a, 14a, 15b, and 16b have been evaluated in vivo. (C) 2009 Elsevier Ltd. All rights reserved.