(S)-N-(4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)-3-cyano-7-(2,3-dihydroxypropoxy)quinolin-6-yl)-2-(1,2-dithiolan-4-yl)acetamide

• 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: (S)-N-(4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)-3-cyano-7-(2,3-dihydroxypropoxy)quinolin-6-yl)-2-(1,2-dithiolan-4-yl)acetamide
• 英文别名: US10246444, Example 92；N-[4-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]-3-cyano-7-[(2S)-2,3-dihydroxypropoxy]quinolin-6-yl]-2-(dithiolan-4-yl)acetamide
• 化学式: C₃₁H₂₈ClFN₄O₅S₂
• 分子量: 655.171
• InChiKey: UVWRRZRGHPHHLL-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  44
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  187
• 氢给体数：
  4
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  2-氯-4-硝基苯酚 在 盐酸 、 N¹-((ethylimino)methylene)-N³,N³-dimethylpropane-1,3-diamine hydrochloride 、 potassium carbonate 、 氯化铵 、 caesium carbonate 、 potassium hydroxide 、 锌 作用下， 以 N-甲基吡咯烷酮 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 异丙醇 、 丙酮 为溶剂， 反应 110.67h， 生成 (S)-N-(4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)-3-cyano-7-(2,3-dihydroxypropoxy)quinolin-6-yl)-2-(1,2-dithiolan-4-yl)acetamide
  参考文献：
  名称：

  1,2-DITHIOLANE AND DITHIOL COMPOUNDS USEFUL IN TREATING MUTANT EGFR-MEDIATED DISEASES AND CONDITIONS

  摘要：

  该发明的组合物包括1,2-二硫杂环烷、二硫醇和相关化合物，可用作治疗剂，用于治疗和预防与EGFR活性异常相关的疾病和病况。

  公开号：

  US20180208584A1

文献信息

• 1,2-dithiolane and dithiol compounds useful in treating mutant EGFR-mediated diseases and conditions
  申请人：Sabila Biosciences LLC

  公开号：US10246444B2

  公开（公告）日：2019-04-02

  Compositions of the invention comprise 1,2-dithiolane, dithiol and related compounds useful as therapeutic agents for the treatment and prevention of diseases and conditions associated with aberrant EGFR activity.

  本发明的组合物包括 1,2-二硫环戊烷、二硫醇及相关化合物，可作为治疗剂用于治疗和预防与表皮生长因子受体活性异常相关的疾病和病症。
• Potent dual EGFR/Her4 tyrosine kinase inhibitors containing novel (1,2-dithiolan-4-yl)acetamides
  作者：Tarek S. Mansour、Ranga R. Pallepati、Vishnu Basetti

  DOI：10.1016/j.bmcl.2020.127288

  日期：2020.8

  Modifications at C-6 and C-7 positions of 3-cyanoquinolines 6 and 7 led to potent inhibitors of the ErbB family of kinases particularly against EGFR(WT) and Her4 enzymes in the radioisotope filter binding assay. The lead (4, SAB402) displayed potent dual biochemical activities with EGFR(WT)/Her4 IC50, ratio of 80 due to its potent inhibition of Her4 activity (IC50, 0.03 nM), however, the selectivity towards activating mutations (EGFR(L858R), EGFR(ex19del)) was decreased. Inhibitor 4 also exhibited excellent growth inhibition in seven different cancer types and reduced cell viability in female NMRI nude mice in the intraperitoneally implanted hollow fibers which have been loaded with MOLT-4 (leukemia) and NCI-H460 (NSCLC) cells in a statistically significant manner.
• 1,2-DITHIOLANE AND DITHIOL COMPOUNDS USEFUL IN TREATING MUTANT EGFR-MEDIATED DISEASES AND CONDITIONS
  申请人：Sabila Biosciences LLC

  公开号：US20180208584A1

  公开（公告）日：2018-07-26

  Compositions of the invention comprise 1,2-dithiolane, dithiol and related compounds useful as therapeutic agents for the treatment and prevention of diseases and conditions associated with aberrant EGFR activity.

  该发明的组合物包括1,2-二硫杂环烷、二硫醇和相关化合物，可用作治疗剂，用于治疗和预防与EGFR活性异常相关的疾病和病况。