exo-1-(8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole | 280762-26-7

• 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: exo-1-(8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole
• 英文别名: 1-[(3-endo)-8-azabicyclo[3.2.1]oct-3-yl]-2-methyl-1H-benzimidazole
• CAS: 280762-26-7
• 化学式: C₁₅H₁₉N₃
• 分子量: 241.336
• InChiKey: BJGOIXDGNKKASK-CLLJXQQHSA-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：

  exo-1-(8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole 、 1,1-dimethylethyl(4-oxo-2-phenylbutyl)(phenylsulfonyl)carbamate 在 三乙酰氧基硼氢化钠 作用下， 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Synthesis and evaluation of 2-phenyl-1,4-butanediamine-based CCR5 antagonists for the treatment of HIV-1

  摘要：

  We describe the synthesis and potency of a novel series of N-substituted 2-phenyl- and 2-methyl-2-phenyl-1,4-diaminobutane- based CCR5 antagonists. Compounds 7a and 12f were found to be potent in anti-HIV assays and bioavailable in the low-dose rat PK model. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.030
• 作为产物：
  描述：

  exo-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， 以1.06 g的产率得到exo-1-(8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole
  参考文献：
  名称：

  Discovery of Bioavailable 4,4-Disubstituted Piperidines as Potent Ligands of the Chemokine Receptor 5 and Inhibitors of the Human Immunodeficiency Virus-1

  摘要：

  We describe robust chemical approaches toward putative CCR5 scaffolds designed in our laboratories. Evaluation of analogues in the (125)I-[MIP-1 beta] binding and Ba-L-HOS antiviral assays resulted in the discovery of 64 and 68 in the 4,4-disubstitited piperidine class H, both potent CCR5 ligands (pIC(50) = 8.30 and 9.00, respectively) and HIV-1 inhibitors (pIC(50) = 7.80 and 7.84, respectively, in Ba-L-HOS assay). In addition, 64 and 68 were bioavailable in rodents, establishing them as lead molecules for further optimization toward CCR5 clinical candidates.

  DOI：

  10.1021/jm800598a

文献信息

• 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）。
• 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
  作者：Wieslaw M. Kazmierski、Don L. Anderson、Christopher Aquino、Brian A. Chauder、Maosheng Duan、Robert Ferris、Terrence Kenakin、Cecilia S. Koble、Dan G. Lang、Maggie S Mcintyre、Jennifer Peckham、Christian Watson、Pat Wheelan、Andrew Spaltenstein、Mary B. Wire、Angilique Svolto、Michael Youngman

  DOI：10.1021/jm200279v

  日期：2011.6.9

  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).
• [EN] CYCLOPROPYL COMPOUNDS AS CCR5 ANTAGONISTS<br/>[FR] COMPOSES DE CYCLOPROPYLE SERVANT D'ANTAGONISTES DE CCR5
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2004055010A3

  公开（公告）日：2004-12-23
• EP1569931B1
  申请人：——

  公开号：EP1569931B1

  公开（公告）日：2008-10-08