N-((1R,3s,5S)-8-Benzyl-8-azabicyclo[3.2.1]octan-3-yl)isobutyramide | 376348-67-3

• 物质功能分类: 有机原料 - 氨基化合物 - 酰胺类化合物
• 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: N-((1R,3s,5S)-8-Benzyl-8-azabicyclo[3.2.1]octan-3-yl)isobutyramide
• 英文别名: exo-N-(8-benzyl-8-azabicyclo[3.2.1]oct-3-yl)-2-methylpropanamide；N-(8-benzyl-8-azabicyclo[3.2.1]octan-3-yl)isobutyramide；N-(8-benzyl-8-azabicyclo[3.2.1]oct-3-yl-exo)-2-methylpropionamide；N-(8-benzyl-8-aza-bicyclo[3.2.1]oct-3-yl)-isobutyramide
• CAS: 376348-67-3
• 化学式: C₁₈H₂₆N₂O
• 分子量: 286.417
• InChiKey: ABOGULQHPLDMLL-OSYLJGHBSA-N

物化性质

• 熔点：
  138-140 °C
• 沸点：
  449.1±34.0 °C(Predicted)
• 密度：
  1.09±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿、二氯甲烷

计算性质

• 辛醇/水分配系数(LogP)：
  2.95
• 重原子数：
  21.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  32.34
• 氢给体数：
  1.0
• 氢受体数：
  2.0

安全信息

• 危险性防范说明：
  P264,P280,P302+P352,P337+P313,P305+P351+P338,P362+P364,P332+P313
• 危险性描述：
  H315,H319

反应信息

• 作为反应物：
  描述：

  N-((1R,3s,5S)-8-Benzyl-8-azabicyclo[3.2.1]octan-3-yl)isobutyramide 在 五氯化磷 作用下， 以 2-甲基-2-丁醇 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 N'-(1-(((1R,3s,5S)-8-benzyl-8-azabicyclo[3.2.1]octan-3-yl)imino)-2-methylpropyl)acetohydrazide
  参考文献：
  名称：

  Preparation and Activities of Macromolecule Conjugates of the CCR5 Antagonist Maraviroc

  摘要：

  CCR5 antagonists are among the most advanced approaches in HIV therapy and may also be relevant to treatment of graft-versus-host disease and Staphylococcus aureus infection. To expand the potential of the only approved CCR5 antagonist, Maraviroc, we studied derivatives that would enable functional linkage of Maraviroc to long-lived carriers. Through targeted synthesis, we discovered an effective linkage site on Maraviroc and demonstrate the potential of these derivatives to prepare potent chemically programmed antibodies and PEGylated derivatives. The resulting compounds effectively neutralized a variety of HIV-1 isolates. Both chemically programmed antibody and PEGylation approaches extend the neutralization activity of serum circulating Maraviroc. Derivation of a successful conjugation strategy for Maraviroc should further enable its use in chemically programmed vaccines, novel bispecific antibodies, and topical microbicides.

  DOI：

  10.1021/ml400370w
• 作为产物：
  描述：

  tert-butyl (3-exo-8-benzyl-8-azabicyclo[3.2.1]oct-3-yl)carbamate 在 盐酸 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 2.0h， 生成 N-((1R,3s,5S)-8-Benzyl-8-azabicyclo[3.2.1]octan-3-yl)isobutyramide
  参考文献：
  名称：

  Preparation and Activities of Macromolecule Conjugates of the CCR5 Antagonist Maraviroc

  摘要：

  CCR5 antagonists are among the most advanced approaches in HIV therapy and may also be relevant to treatment of graft-versus-host disease and Staphylococcus aureus infection. To expand the potential of the only approved CCR5 antagonist, Maraviroc, we studied derivatives that would enable functional linkage of Maraviroc to long-lived carriers. Through targeted synthesis, we discovered an effective linkage site on Maraviroc and demonstrate the potential of these derivatives to prepare potent chemically programmed antibodies and PEGylated derivatives. The resulting compounds effectively neutralized a variety of HIV-1 isolates. Both chemically programmed antibody and PEGylation approaches extend the neutralization activity of serum circulating Maraviroc. Derivation of a successful conjugation strategy for Maraviroc should further enable its use in chemically programmed vaccines, novel bispecific antibodies, and topical microbicides.

  DOI：

  10.1021/ml400370w

文献信息

• Asymmetric Synthesis of Maraviroc (UK-427,857)
  作者：Gui-Ling Zhao、Shuangzheng Lin、Aleš Korotvička、Luca Deiana、Martin Kullberg、Armando Córdova

  DOI：10.1002/adsc.201000287

  日期：2010.9.10

  The asymmetric synthesis of Maraviroc (UK‐427,857), a chemochine receptor 5 (CCR‐5) receptor antagonist, based on an expeditious organocatalytic enantioselective assembly of the chiral β‐amino aldehyde key fragment is presented. The reactions were performed on a gram‐scale and allow for the rapid construction of new Maraviroc analogues.

  基于手性β-氨基醛键片段的快速有机催化对映选择性组装，提出了趋化因子受体5（CCR-5）受体Maraviroc（UK-427,857）的不对称合成。反应以克为单位进行，可以快速构建新的Maraviroc类似物。
• Development of a Bulk Enabling Route to Maraviroc (UK-427,857), a CCR-5 Receptor Antagonist
  作者：Sarah J. Haycock-Lewandowski、Alexander Wilder、Jens Åhman

  DOI：10.1021/op8000614

  日期：2008.11.21

  A bulk enabling synthesis of the CCR-5 receptor antagonist, Maraviroc (UK-427,857) (1), is presented. Synthesis of the three key fragments, β-amino ester 3, 4,4-difluorohexanecarboxylic acid (2), and 1,3,4-triazole-substituted tropane fragment 4 are described. Coupling strategies for these fragments are discussed and described, including synthetic challenges, protection strategies, impurity generation

  提出了能够合成CCR-5受体拮抗剂Maraviroc（UK-427,857）（1）的物质。三个关键片段的合成，β氨基酯3，4,4- difluorohexanecarboxylic酸（2），和1,3,4-三唑基取代的莨菪烷片段4中描述。对这些片段的偶联策略进行了讨论和描述，包括合成挑战，保护策略，杂质生成以及最终发展成1的路线的最终放大。
• Asymmetric Mannich Reaction and Construction of Axially Chiral Sulfone-Containing Styrenes in One Pot from α-Amido Sulfones Based on the Waste–Reuse Strategy
  作者：Dongmei Li、Yu Tan、Lei Peng、Shan Li、Nan Zhang、Yidong Liu、Hailong Yan

  DOI：10.1021/acs.orglett.8b02087

  日期：2018.8.17

  simultaneous asymmetric Mannich reaction and the construction of axially chiral sulfone-containing styrenes in one pot from α-amido sulfones based on the waste–reuse strategy was demonstrated. A series of chiral β-amino diesters and axially chiral sulfone-containing styrenes with various functional groups were synthesized in good to excellent yields and enantioselectivities under mild conditions. In

  证明了同时不对称曼尼希反应和基于废物-再利用策略的一锅中由α-酰胺基砜构建的轴向手性含砜基苯乙烯的结构。在温和条件下，以良好至极佳的收率和对映选择性，合成了一系列具有各种官能团的手性β-氨基二酯和轴向手性含砜基的苯乙烯。此外，该方案已成功应用于合成抗HIV药物Maraviroc和手性三氯衍生物。
• AMIDE COMPOUNDS, THEIR PHARMACEUTICAL COMPOSITIONS, THEIR PREPARATION METHOD AND THEIR USES
  申请人：Long Yaqiu

  公开号：US20110251192A1

  公开（公告）日：2011-10-13

  The present invention pertains to the field of pharmaceutical chemistry and discloses 8-(3-aminopropyl)-3-exo-8-azabicyclo[3.2.1]octane-3-amino amide compounds represented by formula I, the pharmaceutical compositions, the preparation method and the use thereof. Such compounds or pharmaceutically acceptable salts thereof can be used as an antagonist of CCR5 in preparing medicaments for treating diseases mediated by CCR5, particularly HIV infection, asthma, rheumatoid arthritis, autoimmune diseases and chronic obstructive pulmonary diseases (COPD).

  本发明涉及制药化学领域，揭示了由式I代表的8-(3-氨丙基)-3-外消旋-8-氮杂双环[3.2.1]辛烷-3-氨基酰胺化合物，以及药物组合物、制备方法和使用方法。这些化合物或其药用可接受盐可用作CCR5的拮抗剂，用于制备治疗由CCR5介导的疾病的药物，特别是HIV感染、哮喘、类风湿性关节炎、自身免疫疾病和慢性阻塞性肺病（COPD）的药物。
• PREPARATION AND UTILITY OF CCR5 INHIBITORS
  申请人：Gant Thomas G.

  公开号：US20080146605A1

  公开（公告）日：2008-06-19

  Disclosed herein are substituted 8-azabicyclo[3.2.1]octane-based anti-infective agents of Formula I, processes of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.

  本文披露了基于取代的8-氮杂双环[3.2.1]辛烷的抗感染剂的化学式I，其制备方法，药物组合物以及使用方法。