6-hydroxy-9,10-dimethoxy-6,6a-dihydroisoindolo[2,1-a]quinazoline-5,11-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 6-hydroxy-9,10-dimethoxy-6,6a-dihydroisoindolo[2,1-a]quinazoline-5,11-dione
• 英文别名: 6-hydroxy-9,10-dimethoxy-6,6a-dihydroisoindolo-[2,1-a]quinazolin-5,11-dione；6-hydroxy-9,10-dimethoxy-6aH-isoindolo[2,3-a]quinazoline-5,11-dione
• 化学式: C₁₇H₁₄N₂O₅
• 分子量: 326.309
• InChiKey: IAFZYFFFFKCLNS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  79.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-溴己酸乙酯 、 6-hydroxy-9,10-dimethoxy-6,6a-dihydroisoindolo[2,1-a]quinazoline-5,11-dione 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 以74%的产率得到ethyl 6-(9,10-dimethoxy-5,11-dioxoisoindolo[2,1-a]quinazolin-6(5H,6aH,11H)-yloxy)-hexanoate
  参考文献：
  名称：

  合成新型含喹唑啉的异羟肟酸作为潜在的HDAC / VEGFR抑制剂。具有吡咯烷酮开环的异常重排和含有四环的3-N-羟基喹唑啉片段的脱水

  摘要：

  开发了合成途径并获得了新的异羟肟酸作为HDAC / VEGFR2的潜在抑制剂，包括以喹唑啉酮片段为“帽”的四环。对获得的化合物进行进一步的生物学测试将为评估所选研究方向的实际前景提供机会。

  DOI：

  10.1016/j.tetlet.2019.151315
• 作为产物：
  描述：

  2-甲酰基-3,4-二甲氧基-苯甲酸 、 2-氨基苯甲酰胺 在 对甲苯磺酸 作用下， 以 氯苯 为溶剂， 反应 7.0h， 以92%的产率得到6-hydroxy-9,10-dimethoxy-6,6a-dihydroisoindolo[2,1-a]quinazoline-5,11-dione
  参考文献：
  名称：

  异羟肟酸衍生物对血管生成模拟的影响

  摘要：

  摘要 — 血管生成拟态，即由高度恶性表型的肿瘤细胞形成的血管通道，目前被认为是肿瘤的额外血液供应系统。体内实验研究反复证明，在血管密度低的肿瘤区域形成血管通道。据推测，这些通道在肿瘤内形成的网络可以维持体内平衡并防止其内的早期坏死。在这项工作中，研究了基于一个分子中喹唑啉和异羟肟酸组合的双功能化合物抑制肿瘤细胞迁移和血管生成拟态的能力。

  DOI：

  10.1134/s106816202002017x

文献信息

• ISOINDOLO[2, 1-A]QUINAZOLINE DERIVATIVES FOR STABILIZATION OF ORGANIC MATERIALS
  申请人：BASF SE

  公开号：US20150087755A1

  公开（公告）日：2015-03-26

  The present invention relates to a composition, which comprises a) an organic material susceptible to oxidative, thermal or light-induced degradation, which is a polymer, an oligohydroxy compound, a wax, a fat or a mineral oil, with the proviso that the polymer is not a polypeptide, agar-agar or a component of agar-agar and the oligohydroxy compound is not glucose or a component of agar-agar; and b) a compound of formula (I) n is 1, 2, 3 or 4; when n is 1, R 5 is H, C 1 -C 30 -alkyl, C 3 -C 10 -cycloalkyl, C 6 -C 10 -aryl, which is unsubstituted or substituted by C 1 -C 8 -alkyl, C 1 -C 8 -alkoxy, halogen or one phenyl, C 7 -C 13 -aralkyl, C 2 -C 22 -alkenyl, C 3 -C 12 -alkinyl, OH, C 1 -C 30 -alkyloxy, C 3 -C 10 -cycloalkyloxy, C 6 -C 12 -aryloxy, C 7 -C 13 -aralkyloxy, hydroxy-C 1 -C 8 -alkyl, carboxy-C 1 -C 12 -alkyl, C 1 -C 12 -alkoxycarbonyl-C 1 -C 12 -alkyl, C 2 -C 30 -alkyl, which is interrupted by one or more oxygen atoms, C 2 -C 16 -alkyl, which is interrupted by one sulfur atom, or NR′ 1 R′ 2 ; when n is 2, R 5 is C 1 -C 12 -alkane-diyl, C 6 -C 14 -arylene, C 4 -C 8 -cycloalkane-bis-(C 1 -C 4 -alkylene), C 6 -C 14 -arene-bis-(C 1 -C 4 -alkylene), C 4 -C 24 -alkane-diyl, which is interrupted by one or more oxygen atoms, C 4 -C 20 -alkane-diyl, which is interrupted by one or more —NH—, —N(C 1 -C 8 -alkyl)- or —N(hydroxy-C 1 -C 8 -alkyl)-, piperazine-N,N′-bis-(C 1 -C 4 -alkylene) or C 2 -C 10 -alkane-diyl, which is interrupted by one sulfur atom; R 1 to R 4 and R 6 to R 9 are each independently from each other H, C 1 -C 12 -alkyl, C 3 -C 10 -cycloalkyl, C 3 -C 22 -alkenyl, C 1 -C 12 -alkoxy, C 1 -C 12 -alkylsulfanyl, hydroxy-C 1 -C 8 -alkyl, halogen, NR″ 1 R″ 2 , NO 2 , CN, phenyl, phenyloxy or R 1 and R 2 or R 2 and R 3 or R 3 and R 4 or R 6 and R 7 or R 7 and R 8 or R 8 and R 9 are linked together to form a five- or 6-membered alicylic, aromatic or heterocyclic ring together with their 2 corresponding carbons atoms, to which they are attached.
• US9321902B2
  申请人：——

  公开号：US9321902B2

  公开（公告）日：2016-04-26
• [EN] ISOINDOLO[2,1-A]QUINAZOLINE DERIVATIVES FOR STABILIZATION OF ORGANIC MATERIALS<br/>[FR] DÉRIVÉS D'ISOINDOLO[2,1-A]QUINAZOLINE POUR STABILISATION DE MATIÈRES ORGANIQUES
  申请人：BASF SE

  公开号：WO2013139799A1

  公开（公告）日：2013-09-26

  The present invention relates to a composition, which comprises a) an organic material susceptible to oxidative, thermal or light-induced degradation, which is a polymer, an oligohydroxy compound, a wax, a fat or a mineral oil, with the proviso that the polymer is not a polypeptide, agar-agar or a component of agar-agar and the oligohydroxy compound is not glucose or a component of agar-agar; and b) a compound of formula (I) n is 1, 2, 3 or 4; when n is 1, R5 is H, C1-C30-alkyl, C3-C10-cycloalkyl, C6-C10-aryl, which is unsubstituted or substituted by C1-C8-alkyl, C1-C8-alkoxy, halogen or one phenyl, C7-C13-aralkyl, C2-C22-alkenyl, C3-C12-alkinyl, OH, C1-C30-alkyloxy, C3-C10-cycloalkyloxy, C6-C12-aryloxy, C7-C13-aralkyloxy, hydroxy-C1-C8-alkyl, carboxy-C1-C12-alkyl, C1-C12-alkoxycarbonyl-C1-C12-alkyl, C2-C30-alkyl, which is interrupted by one or more oxygen atoms, C2-C16-alkyl, which is interrupted by one sulfur atom, or NR'1R'2; when n is 2, R5 is C1-C12-alkane-diyl, C6-C14-arylene, C4-C8-cycloalkane-bis-(C1-C4-alkylene), C6-C14-arene-bis-(C1-C4-alkylene), C4-C24-alkane-diyl, which is interrupted by one or more oxygen atoms, C4-C20-alkane-diyl, which is interrupted by one or more -NH-, -N(C1-C8-alkyl)- or -N(hydroxy-C1-C8-alkyl)-, piperazine-N,N'-bis-(C1-C4-alkylene) or C2-C10-alkane-diyl, which is interrupted by one sulfur atom; R1 to R4 and R6 to R9 are each independently from each other H, C1-C12-alkyl, C3-C10-cycloalkyl, C3-C22-alkenyl, C1-C12-alkoxy, C1-C12-alkylsulfanyl, hydroxy-C1-C8-alkyl, halogen, NR"1R"2, NO2, CN, phenyl, phenyloxy or R1 and R2 or R2 and R3 or R3 and R4 or R6 and R7 or R7 and R8 or R8 and R9 are linked together to form a five- or 6-membered alicylic, aromatic or heterocyclic ring together with their 2 corresponding carbons atoms, to which they are attached.
• Synthesis of new quinazoline-containing hydroxamic acids as potential HDAC/VEGFR inhibitors. Unusual rearrangements with pyrrolidone ring opening and dehydration of 3-N-hydroxyquinazoline fragment containing tetracycles
  作者：Anton V. Kolotaev、Karine R. Matevosyan、Vasiliy N. Osipov、Derenik S. Khachatryan

  DOI：10.1016/j.tetlet.2019.151315

  日期：2019.12

  Synthesis pathways were developed and new hydroxamic acids were obtained as potential inhibitors of HDAC/VEGFR2, including tetracycles containing quinazolinone fragment as a “cap”. Further biological testing of the obtained compounds will give an opportunity to estimate the real prospects of the chosen research direction.

  开发了合成途径并获得了新的异羟肟酸作为HDAC / VEGFR2的潜在抑制剂，包括以喹唑啉酮片段为“帽”的四环。对获得的化合物进行进一步的生物学测试将为评估所选研究方向的实际前景提供机会。
• Effect of Derivatives of Hydroxamic Acids on Vasculogenic Mimicry
  作者：A. A. Vartanian、D. A. Khochenkov、Yu. A. Khochenkova、Yu. S. Machkova、D. S. Khachatryan、A. V. Kolotaev、A. N. Balaev、K. A. Ohmanovich、V. N. Osipov

  DOI：10.1134/s106816202002017x

  日期：2020.3

  formation of a network of these channels inside the tumor maintains homeostasis and prevents early necrosis within it. In this work, bifunctional compounds based on a combination of quinazoline and hydroxamic acid in one molecule were examined for the ability to inhibit the migration of tumor cells and vasculogenic mimicry.

  摘要 — 血管生成拟态，即由高度恶性表型的肿瘤细胞形成的血管通道，目前被认为是肿瘤的额外血液供应系统。体内实验研究反复证明，在血管密度低的肿瘤区域形成血管通道。据推测，这些通道在肿瘤内形成的网络可以维持体内平衡并防止其内的早期坏死。在这项工作中，研究了基于一个分子中喹唑啉和异羟肟酸组合的双功能化合物抑制肿瘤细胞迁移和血管生成拟态的能力。