6-硝基-4-氨基喹唑啉 | 49675-68-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 6-硝基-4-氨基喹唑啉
• 英文名称: 6-nitroquinazoline-4-(3H)-imine
• 英文别名: 6-nitroquinazolin-4-(3H)-imine；6-Nitroquinazolin-4-amine
• CAS: 49675-68-5
• 化学式: C₈H₆N₄O₂
• 分子量: 190.161
• InChiKey: ZFFCTRQTOAVIJS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  97.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-硝基-4-氨基喹唑啉 在 palladium on activated charcoal 、 Raney 30 氢气 、 溶剂黄146 、 三氟乙酸 作用下， 以 乙二醇甲醚 为溶剂， 反应 2.0h， 生成 2-desamino-5,8-dideazaisoaminopterin
  参考文献：
  名称：

  Studies on the antitumor effects of analogues of 5,8-dideazaisofolic acid and 5,8-dideazaisoaminopterin

  摘要：

  Six new analogues of 5,8-dideazaisofolic acid and 5,8-dideazaisoaminopterin were synthesized in an effort to obtain enhanced antitumor activity. The modifications included the replacement of the 2-amino group by hydrogen or methyl as well as the inclusion of a methyl substituent at position 9. Based upon activity against L1210 leukemia cells in culture, three of the new analogues together with one compound described previously were evaluated for cytotoxicity in vitro using three human tumor cell lines (Cole 320 DM, Hep G2 and HL-60). The most effective compound was 2-desamino-N-9-methyl-5,8-dideazaisoaminopterin (2c) with the HL-60 cells being the most sensitive to its cytotoxic effects. These analogues were evaluated in vitro as inhibitors of dihydrofolate reductase (DHFR) and thymidylate synthase (TS) from human as well as bacterial (Lactobacillus casei) sources. All four of the 4-amino analogues were most effective toward L. casei DHFR compared with human DHFR, with 2-desamino-2-methyl-5,8-dideazaisoaminopterin (2d) and its 9-methyl derivative (2e) having 818- and 430-fold greater selectivity (L. caseilhuman). Most of the compounds studied were found to be only modest inhibitors of human TS (I-50 values = 1.5 to 20 mu M) and were therefore at least 40-fold less inhibitory than 10-propargyl-5,8-dideazafolic acid. Nevertheless, reversal of cytotoxicity studies with thymidine, hypoxanthine and folinic acid using the HL-60 cell line suggested that TS is the primary target for these analogues.

  DOI：

  10.1016/0006-2952(95)00203-c
• 作为产物：
  描述：

  4-氯-6-硝基喹唑啉 在 甲醇 、 氨 、 铜 作用下， 生成 6-硝基-4-氨基喹唑啉
  参考文献：
  名称：

  Tsuda et al., Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1943, vol. 63, p. 445,447

  摘要：

  DOI：

文献信息

• Microwave-assisted thermal decomposition of formamide: a tool for coupling a pyrimidine ring with an aromatic partner
  作者：Yvonnick Loidreau、Thierry Besson

  DOI：10.1016/j.tet.2011.05.010

  日期：2011.7

  reaction mixture via microwave-assisted thermal decomposition of formamide may represent a significant improvement over existing methods for coupling a pyrimidine ring with an aromatic partner. This work aims at alerting readers on the probability to observe interesting phenomena and reactions when this very powerful heating mode is associated with thermally unstable reagents.

  通过微波辅助的甲酰胺的热分解在反应混合物中快速有效地生成CO和NH 3可能代表对现有的将嘧啶环与芳族伴侣偶合的方法的重大改进。这项工作的目的是在这种非常强大的加热模式与热不稳定的试剂相关联时，提醒读者注意观察有趣现象和反应的可能性。
• Lactam inhibitors of factor Xa and method
  申请人：——

  公开号：US20020025957A1

  公开（公告）日：2002-02-28

  Lactam inhibitors are provided which have the structure 1 including pharmaceutically acceptable salts thereof and all stereoisomers thereof, and prodrug esters thereof, wherein n is 1 to 5; and and R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 10a , 10 11 and R 12 are as defined herein. These compounds are inhibitors of Factor Xa and thus are useful as anticoagulants. A method for treating cardiovascular diseases associated with thromboses is also provided.

  提供了具有以下结构的内酰胺抑制剂 1 ，包括其药用可接受的盐及其所有立体异构体，以及其前药酯，其中n为1至5；和 和R 1 ，R 2 ，R 3 ，R 4 ，R 5 ，R 6 ，R 7 ，R 8 ，R 9 ，R 10 ，R 10a ，10 11 和R 12 如本文所定义。这些化合物是因子Xa的抑制剂，因此可用作抗凝剂。还提供了一种用于治疗与血栓相关的心血管疾病的方法。
• Design and Synthesis of Novel Quinazoline Derivatives and Their Evaluation as PI3Ks Inhibitors
  作者：Omar Maged El-Said、Mostafa Mohamed Hamed、Stefan Laufer、Ashraf Hassan Abadi

  DOI：10.1248/cpb.c14-00560

  日期：——

  The aim of this work was to synthesize 4-acetamido-, 4-amino- and 4-oxo-6-substituted aminoquinazolines and to evaluate them as phosphoinositide 3-kinases (PI3Ks) inhibitors. The respective chemotype was designed based on combining the structural features of two previously reported scaffolds acting as potent PI3Kγ inhibitors, which are quinazoline derivatives and amino-heterocyclic derivatives. In vitro enzymatic assay at 10 µM against all the eight human PI3K isoforms showed that an unsubstituted benzamide group at position 6 and an acetyl group at N4 gave the best inhibitory activity on PI3Kγ. Interestingly, compounds 5a and 5e showed a significant, inhibitory effect on Class II PI3K-C2γ. This is of high value since there are very few inhibitors for this isoform reported in the literature.

  本研究的目的是合成4-乙酰氨基、4-氨基和4-氧代-6-取代氨基喹唑啉，并评估它们作为磷脂酰肌醇3-激酶（PI3Ks）抑制剂的潜力。相应的化学类型是基于结合两种先前报道的作为强效PI3Kγ抑制剂的结构特征设计的，这两种结构分别是喹唑啉衍生物和氨基杂环衍生物。在10 µM浓度下进行的体外酶活性测定表明，在6位位置上未取代的苯酰胺基团和N4位置上的乙酰基组合在PI3Kγ上表现出最佳的抑制活性。有趣的是，化合物5a和5e对II类PI3K-C2γ表现出显著的抑制作用。这一点非常重要，因为文献中报道的针对该同种型的抑制剂极少。
• Polycyclic N-heterocyclic compounds, part 67: Reaction of 6,7-substituted N-(quinazolin-4-yl)amidine derivatives with hydroxylamine hydrochloride: Formation of in vitro inhibitors of pentosidine
  作者：Kensuke Okuda、Hideki Muroyama、Takashi Hirota

  DOI：10.1002/jhet.695

  日期：2011.11

  Reactions of N‐(quinazolin‐4‐yl)amidines and their amide oximes with hydroxylamine hydrochloride gave cyclization products that were formed by an initial ring cleavage of the pyrimidine component followed by a ring closure formation of 1,2,4‐oxadiazole to give N‐[2‐([1,2,4]oxadiazol‐5‐yl)phenyl]formamide oximes. All isolated products were evaluated for in vitro inhibitory activity on the formation

  的反应ñ - （喹唑啉-4-基）脒和与盐酸羟胺它们的酰胺肟，得到由嘧啶成分的初始环切割被形成的环化产物，随后的-1,2,4-恶二唑，得到环闭合形成N- [2-（[[1,2,4]恶二唑-5-基）苯基]甲酰胺肟。评价所有分离的产物对戊糖苷形成的体外抑制活性，戊糖苷是代表性的高级糖基化终产物之一。一些产品显示出对戊糖苷形成的显着抑制活性。J.杂环化​​学。（2011）。
• Sodium salt of
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US04429126A1

  公开（公告）日：1984-01-31

  Quinazoline derivatives of the formulae: ##STR1## wherein A.sup.1 is ##STR2## A.sup.2 is ##STR3## R.sup.1 is hydrogen, carboxy or esterified carboxy, R.sub.a.sup.1 and R.sub.b.sup.1 are esterified carboxy, R.sup.2 and R.sup.3 are hydrogen, alkyl, halogen, nitro, amino, alkoxy, aryloxy, alkylthio, alkylpiperazinyl, acylamino or dialkylamino which may be substituted with hydroxy, R.sup.4 is hydrogen, alkyl, hydroxy, alkoxy, alkenyloxy, dialkylamino or 2,2-dialkoxycarbonylvinylamino R.sub.a.sup.4 is hydrogen, alkyl, hydroxy, alkoxy, alkenyloxy or dialkylamino, R.sup.5 is alkyl or alkenyl, and R.sup.6 is carboxy or esterified carboxy.

  Quinazoline衍生物的化学式如下：##STR1## 其中A.sup.1是##STR2## A.sup.2是##STR3## R.sup.1是氢、羧基或酯化羧基，R.sub.a.sup.1和R.sub.b.sup.1是酯化羧基，R.sup.2和R.sup.3是氢、烷基、卤素、硝基、氨基、烷氧基、芳氧基、烷硫基、烷基哌嗪基、酰胺基或二烷基胺基，可能被羟基取代，R.sup.4是氢、烷基、羟基、烷氧基、烯烯氧基、二烷基胺基或2,2-二烷氧羰基乙烯氨基，R.sub.a.sup.4是氢、烷基、羟基、烷氧基、烯烯氧基或二烷基胺基，R.sup.5是烷基或烯烃基，R.sup.6是羧基或酯化羧基。