2,6,8-trimethylquinazolin-4(3H)-one | 119063-85-3

• 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: 2,6,8-trimethylquinazolin-4(3H)-one
• 英文别名: 2,6,8-trimethyl-3H-quinazolin-4-one；2,6,8-Trimethyl-3H-chinazolin-4-on；3,4-dihydro-2,6,8-trimethylquinazolin-4-one；3,4-Dihydro-2,6,8-trimethylquinazolin-4-one；2,6,8-trimethyl-3H-quinazolin-4-one
• CAS: 119063-85-3
• 化学式: C₁₁H₁₂N₂O
• 分子量: 188.229
• InChiKey: OWDDZTAFUFXSFM-UHFFFAOYSA-N

物化性质

• 熔点：
  266 °C
• 沸点：
  340.1±52.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  41.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2,6,8-trimethylquinazolin-4(3H)-one 在 N-氯代丁二酰亚胺 、 亚硝酸特丁酯 、 potassium tert-butylate 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 10.0h， 生成 8,10-dimethyl-4H,6H-isoxazolo[3',4':3,4]pyrrolo[2,1-b]quinazolin-6-one
  参考文献：
  名称：

  无金属条件下炔丙基取代甲基氮杂芳烃分子内环加成异恶唑稠合三环喹唑啉生物碱衍生物的一锅法合成

  摘要：

  开发了一种方便合成异恶唑稠合三环喹唑啉生物碱的实用方法。该程序通过甲基氮杂芳烃与亚硝酸叔丁酯 (TBN) 的分子内环加成反应，获得多种异恶唑稠合三环喹唑啉生物碱及其衍生物。在此方法中，TBN 充当自由基引发剂和 N-O 的来源。此外，该方案通过在具有广泛底物范围和天然产物功能化的一锅法中顺序硝化和环化形成新的 C-N、C-C 和 C-O 键。

  DOI：

  10.3390/molecules28062787
• 作为产物：
  描述：

  acetic acid-(2-cyano-4,6-dimethyl-anilide) 在 氢氧化钾 作用下， 生成 2,6,8-trimethylquinazolin-4(3H)-one
  参考文献：
  名称：

  Interpretation, Design, and Analysis of Gene Array Expression Experiments

  摘要：

  Experiments using arrays of cDNA targets to compare patterns of gene expression are beginning to play a prominent role in biogerontology, but drawing reliable conclusions from the resulting data sets requires careful application of statistical methods that discriminate chance events from those likely to reflect real differences among the samples under study. This essay discusses flaws in the logic of studies that base their conclusions on ratio calculations alone, reviews the multiple comparison traps inherent in high throughput systems that test a very large number of mRNAs simultaneously, and advocates a two-stage design in which significance testing applied to exploratory data is used to guide a second round of hypothesis-testing experiments conducted in a separate set of experimental samples.

  DOI：

  10.1093/gerona/56.2.b52

文献信息

• Anti-tumor agents
  申请人：Imperial Chemical Industries PLC

  公开号：US04981856A1

  公开（公告）日：1991-01-01

  A quinazoline of the formula: ##STR1## wherein R.sup.1 is alkyl, cycloalkyl, alkenyl, alkynyl, alkoxy, alkylthio, aryl, aryloxy, arylthio, arylalkyl, halogeno, hydroxy or mercapto, or substituted alkyl or alkoxy; wherein R.sup.2 is hydrogen, alkyl, alkenyl or alkynyl, or substituted alkyl or alkanoyl; wherein Ar is phenylene, naphthylene or heterocyclene which is unsubstituted or bears one or more substituents; wherein R.sup.3 is such that R.sup.3 --NH.sub.2 is an amino acid; wherein R.sup.4 is hydrogen or alkyl; wherein R.sup.5 is hydrogen or alkyl; and wherein each of R.sup.6, R.sup.7 and R.sup.8 is hydrogen, hydroxy, alkyl, alkoxy, alkylthio, alkylamino, dialkylamino, phenyl, halogeno, nitro, cyano or amino, or substituted alkyl, alkoxy or alkylthio; provided that at least one of R.sup.4, R.sup.5, R.sup.6, R.sup.7 and R.sup.8 is other than hydrogen; or a pharmaceutically-acceptable salt or ester thereof. The compounds possess anti-tumour activity.

  一种喹唑啉的化学式：##STR1##其中R.sup.1是烷基，环烷基，烯基，炔基，烷氧基，烷硫基，芳基，芳氧基，芳硫基，芳基烷基，卤素，羟基或巯基，或取代烷基或烷氧基;其中R.sup.2是氢，烷基，烯基或炔基，或取代烷基或烷酰基;其中Ar是苯基，萘基或杂环基，未取代或带有一个或多个取代基;其中R.sup.3是R.sup.3--NH.sub.2是氨基酸;其中R.sup.4是氢或烷基;其中R.sup.5是氢或烷基;其中R.sup.6，R.sup.7和R.sup.8中的每一个是氢，羟基，烷基，烷氧基，烷硫基，烷基氨基，二烷基氨基，苯基，卤素，硝基，氰基或氨基，或取代烷基，烷氧基或烷硫基;前提是至少有一个R.sup.4，R.sup.5，R.sup.6，R.sup.7和R.sup.8不是氢;或其药学上可接受的盐或酯。该化合物具有抗肿瘤活性。
• FeCl₃/KI‐Catalyzed Tandem Oxidative Cyclization for Switchable Total Synthesis of Luotonin A, B and Derivatives
  作者：Ying‐Chun Song、Ming‐Xuan Wang、Yun‐Ying Yi、Yu‐Ting Liu、Wen‐Xin Zhang、Zi‐Yue Wang、Yuan‐Yuan Sun、An‐Xin Wu、Yan‐Ping Zhu

  DOI：10.1002/adsc.202301322

  日期：2024.3.19

  A total synthesis strategy was developed for the synthesis of luotonin A, B and their analogues using synergistic FeCl3/KI-catalyzed oxidative cyclization. This protocol utilizes cheap and widely available N-propargyl 2-methyl-quinazolinones and arylamines under mild conditions, and it has a wide substrate scope and high atom economy. Different natural products (luotonin A, B and derivatives) can be

  开发了利用协同 FeCl3/KI 催化氧化环化合成洛豆素 A、B 及其类似物的全合成策略。该方案在温和条件下利用廉价且广泛使用的N-炔丙基2-甲基喹唑啉酮和芳胺，具有较宽的底物范围和较高的原子经济性。不同的天然产物（洛豆素 A、B 和衍生物）可以通过独特的可切换方法合成。从洛调色素B到洛调色素E的进一步转化以及天然产物的结构修饰证明了该方法的潜在应用。此外，还可以用所报道的方案修改喜树碱以提供羟基取代的产物。
• Anti-tumour agents
  申请人：IMPERIAL CHEMICAL INDUSTRIES PLC

  公开号：EP0284338A2

  公开（公告）日：1988-09-28

  A quinazoline of the formula:- wherein R1 is alkyl, cycloalkyl, alkenyl, alkynyl, alkoxy, alkylthio, aryl, aryloxy, arylthio, arylalkyl, halogeno, hydroxy or mercapto, or substituted alkyl or alkoxy; wherein R2 is hydrogen, alkyl, alkenyl or alkynyl, or substituted alkyl or alkanoyl; wherein Ar is phenylene, naphthylene or heterocyclene which is unsubstituted or bears one or more substituents; wherein R3 is such that R3-NH2 is an amino acid; wherein R4 is hydrogen or alkyl; wherein R5 is hydrogen or alkyl; and wherein each of R6, R7 and R8 is hydrogen, hydroxy, alkyl, alkoxy, alkylthio, alkylamino, dialkylamino, phenyl, halogeno, nitro, cyano or amino, or substituted alkyl, alkoxy or alkylthio; provided that at least one of R4, R5, R6, R7 and R8 is other than hydrogen; or a pharmaceutically-acceptable salt or ester thereof. The compounds possess anti-tumour activity.

  式中的一种喹唑啉：- 其中 R1 是烷基、环烷基、烯基、炔基、烷氧基、烷硫基、芳基、芳氧基、芳硫基、芳烷基、卤素、羟基或巯基，或取代的烷基或烷氧基； 其中 R2 是氢、烷基、烯基或炔基，或取代的烷基或烷酰基； 其中 Ar 是未被取代或带有一个或多个取代基的亚苯基、萘基或杂环； 其中 R3 是 R3-NH2 是氨基酸； 其中 R4 是氢或烷基 其中 R5 是氢或烷基；以及 其中 R6、R7 和 R8 各为氢、羟基、烷基、烷氧基、烷硫基、烷基氨基、二烷基氨基、苯基、卤素、硝基、氰基或氨基，或取代的烷基、烷氧基或烷硫基； 条件是 R4、R5、R6、R7 和 R8 中至少有一个不是氢； 或其药学上可接受的盐或酯。这些化合物具有抗肿瘤活性。
• Synthesis and SAR optimization of quinazolin-4(3H)-ones as poly(ADP-ribose)polymerase-1 inhibitors
  作者：Shridhar S. Kulkarni、Satyakam Singh、Janki R. Shah、Woon-Kai Low、Tanaji T. Talele

  DOI：10.1016/j.ejmech.2012.02.001

  日期：2012.4

  We have demonstrated that quinazolin-4(3H)-one, a nicotinamide (NI) mimic with PARP-1 inhibitory activity in the high micromolar range (IC50 = 5.75 mu M) could be transformed into highly active derivatives with only marginal increase in molecular weight. Convenient one to two synthetic steps allowed us to explore extensive SAR at the 2-, and 5- through 8-positions of the quinazolin-4(3H)-one scaffold. Substitutions at the 2- and 8-positions were found to be most favorable for improved PARP-1 inhibition. The amino group at 8-position resulted in compound 22 with an IC50 value of 0.76 mu M. Combination of the 8-amino substituent with an additional methyl substituent at the 2-position provided the most potent compound 31 [8-amino-2-methylquinazolin-4(3H)-one, IC50 = 0.4 mu M] in the present study. Compound 31 inhibited the proliferation of Brca1-deficient cells with an IC50 value of 49.0 mu M and displayed >10-fold selectivity over wild type counterparts. Binding models of these derivatives within the active site of PARP-1 have further supported the SAR data and will be useful for future lead optimization efforts. (C) 2012 Elsevier Masson SAS. All rights reserved.
• Bhattacharyya; Bose; Ray, Journal of the Indian Chemical Society, 1929, vol. 6, p. 282
  作者：Bhattacharyya、Bose、Ray

  DOI：——

  日期：——