4-hydrazinyl-6,7-dimethoxyquinazoline | 91163-69-8

• 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: 4-hydrazinyl-6,7-dimethoxyquinazoline
• 英文别名: 6,7-dimethoxy-4-hydrazino-quinazoline；(6,7-dimethoxy-quinazolin-4-yl)-hydrazine；(6,7-dimethoxyquinazolin-4-yl)hydrazine
• CAS: 91163-69-8
• 化学式: C₁₀H₁₂N₄O₂
• 分子量: 220.231
• InChiKey: VUHSDSWOWMZHQY-UHFFFAOYSA-N

物化性质

• 沸点：
  409.8±55.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  82.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-hydrazinyl-6,7-dimethoxyquinazoline 在 N,N-二异丙基乙胺 、 potassium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 生成 methyl 2-((8,9-dimethoxy-[1,2,4]triazolo[4,3-c]quinazolin-3-yl)thio)acetate
  参考文献：
  名称：

  选择性人 STINGA230 激动剂的结构评估及其在巨噬细胞免疫疗法中的应用

  摘要：

  此前，我们鉴定了一种非核苷酸激动剂 BDW568，它可以选择性激活人类 STING A230等位基因。在这里，我们进一步表征了 BDW568 的机制，并强调了其作为遗传佐剂选择性控制工程化巨噬细胞的激活的潜在用途，这些工程化巨噬细胞组成型表达 STING A230 。我们以 1.95 Å 的分辨率获得了与 BDW-OH（活性代谢物）复合的 STING A230 C 端结构域的晶体结构。结构-活性关系研究表明，BDW568 中的所有三个杂环和 S-乙酸酯侧链对于保留活性至关重要。我们证明，BDW568 可以在用表达 STING A230的慢病毒转导的纯化人原代巨噬细胞中强力激活 I 型干扰素信号传导。相比之下，在缺乏 STING A230等位基因的情况下，BDW568 无法刺激健康供体的人原代外周血单核细胞的先天免疫反应。这种高 STING 变异特异性表明 STING A230激动剂在基于巨噬细胞的治疗方法中具有广阔的应用前景。

  DOI：

  10.1021/acsmedchemlett.4c00048
• 作为产物：
  描述：

  2-氨基-4,5-二甲氧基苯甲酸 在 氯化亚砜 、 一水合肼 作用下， 以 四氢呋喃 为溶剂， 反应 26.0h， 生成 4-hydrazinyl-6,7-dimethoxyquinazoline
  参考文献：
  名称：

  Synthesis and antitumor activity of novel quinazoline derivatives containing thiosemicarbazide moiety

  摘要：

  Series of novel derivatives of quinazoline containing thiosemicarbazide moiety 5 and 9 have been synthesized and tested for their antitumor activities in vitro against a panel of five human cancer cell lines. Bioassay results indicated that most of the prepared compounds exhibited cytotoxicity against various cancer cells. From the structure activity relationships it was found that unsubstituted quinazoline ring and benzene ring or halogen substituted benzene ring in quinazoline derivatives 5 and 9 would be the most favorable for their antitumor activity. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.06.003

文献信息

• Compounds
  申请人：Hummersone Geoffrey Marc

  公开号：US20060199804A1

  公开（公告）日：2006-09-07

  Compounds of formula I: A-B-C  (I) and isomers, salts, solvates, chemically protected forms, and prodrugs thereof wherein: B is selected from the group consisting of: where R N is H or Me; or B is a divalent C 5 heterocyclic residue containing one or two ring heteroatoms; A is: R A3 and R A5 are independently selected from halo, OR O and R AC , where R O is H or Me, and R AC is H or C 1-4 alkyl; X A is selected from N and CR A4 , where R A4 is selected from H, OR O , CH 2 OH, CO 2 H, NHSO 2 Me and NHCOMe; R A2 and R A6 are independently selected from H, halo and OR O ; or R A3 and R A4 together with the carbon atoms to which they are attached, or RA2 and R A3 together with the carbon atoms to which they are attached, may form a C 5-6 heterocylic or heteroaromatic ring, containing at least one nitrogen ring atom; where if X is not N, 1, 2, or 3 of R A2 to R A6 are not H; C is: where X is selected from N and CH, Y is selected from N and CH, and Z is selected from N and CR C6 ; R C3 is selected from H, halo and an optionally substituted N-containing C 5-7 heterocyclic group; R C5 is a group selected from: which group may be selected by one or two C 1-4 alkyl groups or a carboxy group; R C6 is H; or, when X and Y are N, R C5 and R C6 (when Z is CR C6 ) together with the carbon atoms to which they are attached may form a fused C 6 aromatic ring selected from the group consisting of:

  化合物的化学式I： A-B-C  (I) 及其异构体、盐、溶剂合物、化学保护形式和前药，其中： B选自以下组合： 其中R N 为H或Me； 或B是含有一个或两个环异原子的二价C 5 杂环残基； A为： R A3 和R A5 独立选择自卤、OR O 和R AC ，其中R O 为H或Me，R AC 为H或C 1-4 烷基； X A 选自N和CR A4 ，其中R A4 选自H、OR O 、CH 2 OH、CO 2 H、NHSO 2 Me和NHCOMe； R A2 和R A6 独立选择自H、卤素和OR O ； 或R A3 和R A4 与它们连接的碳原子一起，或RA2和R A3 与它们连接的碳原子一起，可形成含有至少一个氮环原子的C 5-6 杂环或杂芳环； 如果X不是N，则R A2 至R A6 中的1、2或3个不是H； C为： 其中X选自N和CH，Y选自N和CH，Z选自N和CR C6 ； R C3 选自H、卤素和可选择性取代的含氮C 5-7 杂环基； R C5 为以下组合之一： 该组合可由一个或两个C 1-4 烷基或一个羧基选择； R C6 为H； 或者，当X和Y为N时，R C5 和R C6 （当Z为CR C6 时）与它们连接的碳原子可形成所选自的融合C 6 芳香环之一：
• Isatin-benzoazine molecular hybrids as potential antiproliferative agents: synthesis and in vitro pharmacological profiling
  作者：Hatem Abdel-Aziz、Wagdy Eldehna、Adam Keeton、Gary Piazza、Adnan Kadi、Mohamed Attwa、Ali Abdelhameed、Mohamed Attia

  DOI：10.2147/dddt.s140164

  日期：——

  of isatin-quinazoline (6a-f and 7a-e)/phthalazine (8a-f)/quinoxaline (9a-f) hybrids. The antiproliferative activity of the target hybrids was assessed towards HT-29 (colon), ZR-75 (breast) and A-549 (lung) human cancer cell lines. Hybrids 8b-d emerged as the most active antiproliferative congener in this study. Compound 8c induced apoptosis via increasing caspase 3/7 activity by about 5-fold in the

  在继续致力于开发有效的基于Isatin的抗癌剂方面，我们采用了分子杂交方法来设计和合成四套不同的Isatin-喹唑啉（6a-f和7a-e）/酞嗪（8a） -f）/喹喔啉（9a-f）杂种。评估了目标杂种对HT-29（结肠），ZR-75（乳腺癌）和A-549（肺）人癌细胞系的抗增殖活性。杂种8b-d成为本研究中最活跃的抗增殖同源物。化合物8c通过在A-549人癌细胞系中使胱天蛋白酶3/7活性增加约5倍来诱导凋亡。另外，在细胞周期效应测定中，它表现出G1期增加而S和G2 / M期减少。此外，其抑制浓度的50％值为9。对多重耐药的NCI-H69AR肺癌细胞株为5 µM。杂合体8c还通过与大鼠肝微粒体一起孵育进行了体外代谢研究，并借助液相色谱-质谱法分析了所得代谢产物。
• 1-(6,7-Dimethoxyquinazol-4-yl)semicarbazides
  申请人：Boehringer Ingelheim KG

  公开号：US04546102A1

  公开（公告）日：1985-10-08

  Compounds of the formula ##STR1## wherein R.sub.1 is hydrogen, alkyl of 1 to 4 carbon atoms or trifluoromethyl; R.sub.2, R.sub.3 and R.sub.4 are each independently hydrogen, methyl or ethyl; R.sub.5 is hydrogen, alkyl of 1 to 8 carbon atoms, phenyl-(alkyl of 1 to 8 carbon atoms), cycloalkyl of 3 to 7 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonyl-methyl, phenyl, substituted phenyl, naphthyl or substituted naphthyl; or R.sub.4 and R.sub.5, together with each other, are alkylene of 4 to 5 carbon atoms, optionally interrupted by --O-- or --NR.sub.6 --, where R.sub.6 is alkyl of 1 to 4 carbon atoms; and non-toxic, pharmacologically acceptable acid addition salts thereof. The compounds as well as their salts are useful as cardiotonics.

  式为##STR1##的化合物，其中R.sub.1是氢、1至4个碳原子的烷基或三氟甲基；R.sub.2、R.sub.3和R.sub.4各自独立地是氢、甲基或乙基；R.sub.5是氢、1至8个碳原子的烷基、苯基-(1至8个碳原子的烷基)、3至7个碳原子的环烷基、(1至4个碳原子的烷氧基)甲酰基甲基、苯基、取代苯基、萘基或取代萘基；或者R.sub.4和R.sub.5互相结合，是4至5个碳原子的亚烷基，可选地被--O--或--NR.sub.6 --中断，其中R.sub.6是1至4个碳原子的烷基；以及其非毒性、药理学上可接受的酸盐。这些化合物及其盐可用作心力衰竭药。
• mTOR inhibitor compounds
  申请人：Kudos Pharmaceuticals Ltd.

  公开号：US07504397B2

  公开（公告）日：2009-03-17

  Compounds of formula I: A-B-C  (I) and isomers, salts, solvates, chemically protected forms, and prodrugs thereof are provided, wherein variables A, B and C are defined herein and wherein such compounds act as mTor inhibitors.

  本文提供了公式I：A-B-C及其异构体、盐、溶剂合物、化学保护形式和前药，其中变量A、B和C在此定义，这些化合物作为mTor抑制剂。
• COMPOUNDS
  申请人：Hummersone Marc Geoffrey

  公开号：US20100130473A1

  公开（公告）日：2010-05-27

  Compounds of formula (I): A-B—C and isomers, salts, solvates, chemically protected forms, and prodrugs thereof wherein: B is selected from the group consisting of formula (i) where R N is H or Me; or B is a divalent C 5 heterocyclic residue containing one or two ring heteroatoms; A is formula (ii) R A3 and R A5 are independently selected from halo, OR O and R AC , where R O is H or Me, and R AC is H or C 1-4 alkyl; X A is selected from N and CR A4 , where R A4 is selected from H, OR O , CH 2 OH, CO 2 H, NHSO 2 Me and NHCOMe; R A2 and R A6 are independently selected from H, halo and OR O ; or R A3 and R A4 together with the carbon atoms to which they are attached, or RA2 and R A3 together with the carbon atoms to which they are attached, may form a C 5-6 heterocylic or heteroaromatic ring, containing at least one nitrogen ring atom; where if X is not N, 1, 2, or 3 of R A2 to R A6 are not H; C is formula (iii) where X is selected from N and CH, Y is selected from N and CH, and Z is selected from N and CR C6 ; R C3 is selected from H, halo and an optionally substituted N-containing C 5-7 heterocyclic group; R C5 is a group selected from formula (iv) which group may be selected by one or two C 1-4 alkyl groups or a carboxy group; R C6 is H; or, when X and Y are N, R C5 and R C6 (when Z is CR C6 ) together with the carbon atoms to which they are attached may form a fused C 6 aromatic ring selected from the group consisting of formula (v).

  化合物的化学式（I）：A-B-C及其异构体，盐，溶剂合物，化学保护形式和前药，其中：B选自式（i）的群，其中RN为H或Me；或B是含有一个或两个环杂原子的二价C5杂环残基；A为式（ii）RA3和RA5分别独立选择自卤，ORO和RAC，其中RO为H或Me，而RAC为H或C1-4烷基；XA选自N和CRA4，其中RA4选自H，ORO，CH2OH，CO2H，NHSO2Me和NHCOMe；RA2和RA6分别独立选择自H，卤和ORO；或RA3和RA4与它们附着的碳原子一起，或RA2和RA3与它们附着的碳原子一起，可以形成一个含有至少一个氮环原子的C5-6杂环或杂芳烃环；如果XA不是N，则RA2至RA6中的1、2或3个不是H；C为式（iii）其中X选自N和CH，Y选自N和CH，Z选自N和CRC6；RC3选自H，卤和一个可选取代的含N的C5-7杂环基团；RC5是从式（iv）中选择的一个或两个C1-4烷基或羧基；RC6为H；或当X和Y为N时，RC5和RC6（当Z为CRC6时）与它们附着的碳原子一起可以形成所选自式（v）的群中的融合C6芳香环。