3,11-dihydroxy-14-(5-hydroxy-4-methoxy-2-methylphenyl)-2,12-dimethoxy-6H-[1]benzopyrano[4',3':4,5]pyrrolo[2,1-a]isoquinolin-6-one | 1456517-60-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 3,11-dihydroxy-14-(5-hydroxy-4-methoxy-2-methylphenyl)-2,12-dimethoxy-6H-[1]benzopyrano[4',3':4,5]pyrrolo[2,1-a]isoquinolin-6-one
• 英文别名: 7,17-Dihydroxy-12-(5-hydroxy-4-methoxy-2-methylphenyl)-8,16-dimethoxy-4-oxa-1-azapentacyclo[11.8.0.02,11.05,10.014,19]henicosa-2(11),5,7,9,12,14,16,18,20-nonaen-3-one；7,17-dihydroxy-12-(5-hydroxy-4-methoxy-2-methylphenyl)-8,16-dimethoxy-4-oxa-1-azapentacyclo[11.8.0.02,11.05,10.014,19]henicosa-2(11),5,7,9,12,14,16,18,20-nonaen-3-one
• CAS: 1456517-60-4
• 化学式: C₂₉H₂₃NO₈
• 分子量: 513.504
• InChiKey: LRJIEZPKWFBSEJ-UHFFFAOYSA-N

物化性质

• 密度：
  1.46±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  38
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  119
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-甲氧基-4-甲基苯酚 在 N-溴代丁二酰亚胺(NBS) 、 四(三苯基膦)钯 、 叔丁基锂 、 三氯化硼 、 N,N-二异丙基乙胺 、 cesium fluoride 、 2,3-二氯-5,6-二氰基-1,4-苯醌 、 silver(l) oxide 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 乙醇 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 62.0h， 生成 3,11-dihydroxy-14-(5-hydroxy-4-methoxy-2-methylphenyl)-2,12-dimethoxy-6H-[1]benzopyrano[4',3':4,5]pyrrolo[2,1-a]isoquinolin-6-one
  参考文献：
  名称：

  Synthesis, Resolution, and Biological Evaluation of Atropisomeric (aR)- and (aS)-16-Methyllamellarins N: Unique Effects of the Axial Chirality on the Selectivity of Protein Kinases Inhibition

  摘要：

  The total synthesis of the optically active (aR)- and (aS)-16-methyllamellarins N (3a and 3b) was achieved via resolution on HPLC chiral stationary phase. The kinase inhibitory activities of both enantiomers were evaluated on eight protein Icinases relevant to cancer and neurodegenerative diseases (CDKI/cyclin B, CDK2/cyclin A, CDK5/p25, GSK-3 alpha/beta, PIM1, DYRK1A, CLIO, and CK1). Isomer (aR)-3b exhibited potent but nonselective inhibition on all protein kinases except CK1, while (aS)-3a selectively inhibited only GSK-3 alpha/beta, PIM1, and DYRKIA. The different inhibition profiles of (aS)-3a and (aR)-3b were elucidated by docking simulation studies. Although parental lamellarin N (2) inhibited the action of topoisomerase I, both (aS)-3a and (aR)-3b showed no inhibition of this enzyme. The phenotypic scytotoxic activities of 2, (aS)-3a, and (aR)-3b on three cancer cell lines (HeLa, SH-SYSY, and IMR32) changed according to their topoisomerase I and protein kinase inhibitory activities.

  DOI：

  10.1021/jm400719y

文献信息

• FOURTH-GENERATION EGFR TYROSINE KINASE INHIBITOR
  申请人：NAGASAKI UNIVERSITY

  公开号：US20210122759A1

  公开（公告）日：2021-04-29

  Provided is a compound having a tyrosine kinase inhibitory activity specific to C797S resistant mutant EGFR (particularly C797S tertiary-resistant mutant EGFR) and is useful as a C797S resistant mutant EGFR (particularly C797S mutant tertiary-resistant EGFR) specific tyrosine kinase inhibitor, an agent for preventing and/or treating non-small cell lung cancer with resistance mutant EGFR and the like, and the like. A compound represented by the formula (I): wherein X is O or NH, R 1 and R 2 are each independently a hydrogen atom or an optionally substituted hydrocarbon group; R 3 and R 4 are each independently a hydrogen atom, a halogen atom or an optionally substituted hydrocarbon group, and R 5 and R 6 are each independently an optionally substituted hydrocarbon group, excluding the following compounds: or a salt thereof.

  提供一种具有特异性抑制C797S耐药突变EGFR的酪氨酸激酶抑制活性的化合物（特别是C797S三级耐药突变EGFR），并且可用作C797S耐药突变EGFR（特别是C797S突变三级耐药EGFR）特异性酪氨酸激酶抑制剂，用于预防和/或治疗具有耐药突变EGFR的非小细胞肺癌等药剂等。一种由以下式（I）表示的化合物：其中X为O或NH，R1和R2分别为氢原子或可选择取代的碳氢基团；R3和R4分别为氢原子、卤素原子或可选择取代的碳氢基团，而R5和R6分别为可选择取代的碳氢基团，但不包括以下化合物：或其盐。
• Synthesis, Resolution, and Biological Evaluation of Atropisomeric (a<i>R</i>)- and (a<i>S</i>)-16-Methyllamellarins N: Unique Effects of the Axial Chirality on the Selectivity of Protein Kinases Inhibition
  作者：Kenyu Yoshida、Ryosuke Itoyama、Masashi Yamahira、Junji Tanaka、Nadège Loaëc、Olivier Lozach、Emilie Durieu、Tsutomu Fukuda、Fumito Ishibashi、Laurent Meijer、Masatomo Iwao

  DOI：10.1021/jm400719y

  日期：2013.9.26

  The total synthesis of the optically active (aR)- and (aS)-16-methyllamellarins N (3a and 3b) was achieved via resolution on HPLC chiral stationary phase. The kinase inhibitory activities of both enantiomers were evaluated on eight protein Icinases relevant to cancer and neurodegenerative diseases (CDKI/cyclin B, CDK2/cyclin A, CDK5/p25, GSK-3 alpha/beta, PIM1, DYRK1A, CLIO, and CK1). Isomer (aR)-3b exhibited potent but nonselective inhibition on all protein kinases except CK1, while (aS)-3a selectively inhibited only GSK-3 alpha/beta, PIM1, and DYRKIA. The different inhibition profiles of (aS)-3a and (aR)-3b were elucidated by docking simulation studies. Although parental lamellarin N (2) inhibited the action of topoisomerase I, both (aS)-3a and (aR)-3b showed no inhibition of this enzyme. The phenotypic scytotoxic activities of 2, (aS)-3a, and (aR)-3b on three cancer cell lines (HeLa, SH-SYSY, and IMR32) changed according to their topoisomerase I and protein kinase inhibitory activities.