neolymphostin A

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: neolymphostin A
• 英文别名: neolymphostin；N-[11-amino-6-(3-methoxyprop-2-enoyl)-2,7-diazatricyclo[6.3.1.04,12]dodeca-1(12),2,4,6,8,10-hexaen-9-yl]-2-methylpropanamide
• 化学式: C₁₈H₁₈N₄O₃
• 分子量: 338.366
• InChiKey: OKZVXALNOKYCRL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.82
• 重原子数：
  25.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  106.67
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  neolymphostin A 在 copper(ll) sulfate pentahydrate 、 碳酸氢钠 、 sodium ascorbate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.17h， 生成 N-(8-amino-4-(3-(2-(4-(14-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-3-oxo-6,9,12-trioxa-2-azatetradecyl)-1H-1,2,3-triazol-1-yl)ethoxy)-3-methoxypropanoyl)pyrrolo[4,3,2-de]quinolin-6-yl)isobutyramide
  参考文献：
  名称：

  Novel PIKK inhibitor antibody-drug conjugates: Synthesis and anti-tumor activity

  摘要：

  Novel neolymphostin-based antibody-drug conjugate (ADC) precursors were synthesized either through amide couplings between both cleavable and non-cleavable linkers and neolymphostin derivatives, or through Cu(I)-catalyzed acetylene-azide click cycloadditon between non-cleavable linkers and neolymphostin acetal derivatives. These precursors were site-specifically conjugated to cysteine mutant trastuzumab-A114C to provide neolymphostin-based ADCs. Preliminary in vitro data indicated that the corresponding ADCs were active against HER2-expressing tumor cell lines, thus providing a proof-of-concept for using neolymphostin as ADC-based anticancer agents.

  DOI：

  10.1016/j.bmcl.2019.01.009

文献信息

• PYRROLO[4,3,2-DE]QUINOLIN-8-AMINE COMPOUNDS AND METHODS OF THEIR PREPARATION AND USE
  申请人：Wyeth LLC

  公开号：EP2340251A1

  公开（公告）日：2011-07-06
• JP2012500206A
  申请人：——

  公开号：JP2012500206A

  公开（公告）日：2012-01-05
• US8486961B2
  申请人：——

  公开号：US8486961B2

  公开（公告）日：2013-07-16
• [EN] PYRROLO[4,3,2-DE]QUINOLIN-8-AMINE COMPOUNDS AND METHODS OF THEIR PREPARATION AND USE<br/>[FR] COMPOSÉS PYRROLO[4,3,2-DE]QUINOLÉIN-8-AMINES ET LEURS PROCÉDÉS DE PRÉPARATION ET D'UTILISATION
  申请人：WYETH CORP

  公开号：WO2010019659A1

  公开（公告）日：2010-02-18

  The present invention relates to compounds of formula (I) methods of their use, processes for their preparation and isolated actinomycetes strains capable of preparing pyrrolo[4,3,2-de]quinolin-8-amine compounds.
• Novel PIKK inhibitor antibody-drug conjugates: Synthesis and anti-tumor activity
  作者：Dahui Zhou、Jeffrey Casavant、Edmund I. Graziani、Haiyin He、Jeffrey Janso、Frank Loganzo、Sylvia Musto、Nathan Tumey、Christopher J. O'Donnell、Russell Dushin

  DOI：10.1016/j.bmcl.2019.01.009

  日期：2019.4

  Novel neolymphostin-based antibody-drug conjugate (ADC) precursors were synthesized either through amide couplings between both cleavable and non-cleavable linkers and neolymphostin derivatives, or through Cu(I)-catalyzed acetylene-azide click cycloadditon between non-cleavable linkers and neolymphostin acetal derivatives. These precursors were site-specifically conjugated to cysteine mutant trastuzumab-A114C to provide neolymphostin-based ADCs. Preliminary in vitro data indicated that the corresponding ADCs were active against HER2-expressing tumor cell lines, thus providing a proof-of-concept for using neolymphostin as ADC-based anticancer agents.