1-(4-(2,5,8,11,14-pentaoxaheptadec-16-yn-1-yl)benzoyl)azetidin-2-one | 1430096-70-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: 1-(4-(2,5,8,11,14-pentaoxaheptadec-16-yn-1-yl)benzoyl)azetidin-2-one
• CAS: 1430096-70-0
• 化学式: C₂₂H₂₉NO₇
• 分子量: 419.475
• InChiKey: TZPGYXZXRFHFDN-UHFFFAOYSA-N

物化性质

• 沸点：
  535.2±60.0 °C(Predicted)
• 密度：
  1.201±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.28
• 重原子数：
  30.0
• 可旋转键数：
  16.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  83.53
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  1-(4-(2,5,8,11,14-pentaoxaheptadec-16-yn-1-yl)benzoyl)azetidin-2-one 、 在 copper(II) sulfate 、 sodium ascorbate 、 三(3-羟丙基三唑甲基)胺 作用下， 以 叔丁醇 为溶剂， 反应 2.0h， 以100%的产率得到N-((S)-3-((1R,3R,5S)-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl)-1-phenylpropyl)-11-(4-(15-(4-(2-oxoazetidine-1-carbonyl)phenyl)-2,5,8,11,14-pentaoxapentadecyl)-1H-1,2,3-triazol-1-yl)undecanamide
  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：

  丙炔基-四聚乙二醇 在 正丁基锂 、 氯化亚砜 、 乙醇 、 sodium hydride 、 sodium hydroxide 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 11.25h， 生成 1-(4-(2,5,8,11,14-pentaoxaheptadec-16-yn-1-yl)benzoyl)azetidin-2-one
  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

• Chemically Programmed Antibodies As HIV-1 Attachment Inhibitors
  作者：Shinichi Sato、Tsubasa Inokuma、Nobumasa Otsubo、Dennis R. Burton、Carlos F. Barbas

  DOI：10.1021/ml400097z

  日期：2013.5.9

  Herein, we describe the design and application of two small-molecule anti-HIV compounds for the creation of chemically programmed antibodies. N-Acyl-beta-lactam derivatives of two previously described molecules BMS-378806 and BMS-488043 that inhibit the interaction between HIV-1 gp120 and T-cells were synthesized and used to program the binding activity of aldolase antibody 38C2. Discovery of a successful linkage site to BMS-488043 allowed for the synthesis of chemically programmed antibodies with affinity for HIV-1 gp120 and potent HIV-1 neutralization activity. Derivation of a successful conjugation strategy for this family of HIV-1 entry inhibitors enables its application in chemically programmed antibodies and vaccines and may facilitate the development of novel bispecific antibodies and topical microbicides.