6,8-二甲基喹唑啉-4(3H)-酮 | 79263-04-0

• 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: 6,8-二甲基喹唑啉-4(3H)-酮
• 英文名称: 6,8-dimethylquinazolin-4(3H)-one
• 英文别名: 6,8-dimethyl-3H-quinazolin-4-one；6,8-Dimethyl-3H-chinazolin-4-on；6,8-dimethyl-4(3H)-quinazolinone；6,8-Dimethylquinazolin-4(3H)-one；6,8-dimethyl-3H-quinazolin-4-one
• CAS: 79263-04-0
• 化学式: C₁₀H₁₀N₂O
• 分子量: 174.202
• InChiKey: HZRITHNUYUGNFH-UHFFFAOYSA-N

物化性质

• 熔点：
  244-247 °C(Solv: methanol (67-56-1))
• 沸点：
  335.1±52.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 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：

  6,8-二甲基喹唑啉-4(3H)-酮 在 盐酸 、 氢溴酸 、 sodium methylate 作用下， 生成 3-[3-(3-hydroxy-[2]piperidyl)-2-oxo-propyl]-6,8-dimethyl-3H-quinazolin-4-one
  参考文献：
  名称：

  AN ANTIMALARIAL ALKALOID FROM HYDRANGEA. XV. SYNTHESIS OF 5-, 6-, 7-, AND 8-DERIVATIVES WITH TWO IDENTICAL SUBSTITUENTS

  摘要：

  DOI：

  10.1021/jo01135a015
• 作为产物：
  描述：

  3,5-二甲基-2-氨基苯甲酸 、 甲酰胺 以56%的产率得到
  参考文献：
  名称：

  LEMAHIEU, R. A.;CARSON, M.;NASON, W. C.;PARRISH, D. R.;WELTON, A. F.;BARU+, J. MED. CHEM., 1983, 26, N 3, 420-425

  摘要：

  DOI：

文献信息

• Trans-3-(4-oxo-4H-quinazolin-3-yl)-2-propenoic acid derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US04281127A1

  公开（公告）日：1981-07-28

  Trans-3-(4-oxo-4H-quinazolin-3-yl)-2-propenoic acid derivatives of the formula ##STR1## wherein R.sub.1 is hydrogen, lower alkyl, lower cycloalkyl, lower alkoxy, hydroxy, halo, lower alkykthio, lower alkylsulfinyl, lower alkylsulfonyl, di-(C.sub.1 -C.sub.7)alkyl-N(CH.sub.2).sub.n O-- or 2-hydroxyethoxy; R.sub.2 is hydrogen, lower alkyl or lower alkoxy; R.sub.3 is hydroxy, lower alkoxy, di-(C.sub.1 -C.sub.7)alkyl-N(CH.sub.2).sub.n O-- or di-(C.sub.1 -C.sub.7)alkyl-N(CH.sub.2).sub.n NH--; and n is 2 to 7; provided that at least one of R.sub.1 and R.sub.2 is other than hydrogen, when R.sub.3 is hydroxy, a salt thereof with a pharmaceutically acceptable base, or when R.sub.3 is di-(C.sub.1 -C.sub.7)alkyl-N(CH.sub.2).sub.n O-- or di-(C.sub.1 -C.sub.7)alkyl-N(CH.sub.2).sub.n NH--, a salt thereof with a pharmaceutically acceptable acid, and a process for the preparation thereof, are described. The compounds of formula I are useful as agents in the prevention of allergic reactions.

  公式为##STR1##的Trans-3-(4-oxo-4H-quinazolin-3-yl)-2-propenoic acid衍生物，其中R.sub.1为氢、较低烷基、较低环烷基、较低烷氧基、羟基、卤素、较低烷硫基、较低烷基磺基、较低烷基砜基、二-(C.sub.1 -C.sub.7)烷基-N(CH.sub.2).sub.n O--或2-羟基乙氧基；R.sub.2为氢、较低烷基或较低烷氧基；R.sub.3为羟基、较低烷氧基、二-(C.sub.1 -C.sub.7)烷基-N(CH.sub.2).sub.n O--或二-(C.sub.1 -C.sub.7)烷基-N(CH.sub.2).sub.n NH--；n为2至7；要求至少R.sub.1和R.sub.2中的一个不是氢，当R.sub.3为羟基时，其与药用可接受的碱的盐，或当R.sub.3为二-(C.sub.1 -C.sub.7)烷基-N(CH.sub.2).sub.n O--或二-(C.sub.1 -C.sub.7)烷基-N(CH.sub.2).sub.n NH--时，其与药用可接受的酸的盐，以及其制备方法。公式I的化合物可用作预防过敏反应的药物。
• Photoinduced, Silver(I)-Mediated Synthesis of Ester-Substituted Fused Quinazolinones via Cascade Alkoxycarbonylation/Cyclization of Heterocycles Bearing Unactivated Alkenes
  作者：Hui-Xin Xiao、Pan-Pan Li、Bin Pan、Wu Liang、Fei Du、Yu Yu

  DOI：10.1021/acs.joc.3c00280

  日期：2023.5.5

  A new cascade alkoxycarbonylation/cyclization reaction of heterocycle-bearing unactivated alkenes is disclosed. The transformation is mediated by silver carbonate under photoirradiation. This method provides efficient access to pharmaceutically valuable molecules and natural product analogues containing quinazolinone-fused esters. Furthermore, this protocol is compatible with a variety of quinazolinone-bearing

  公开了一种新的带有杂环的未活化烯烃的级联烷氧基羰基化/环化反应。这种转化是由碳酸银在光照射下介导的。该方法提供了对含有喹唑啉酮稠合酯的具有药学价值的分子和天然产物类似物的有效途径。此外，该协议与各种含喹唑啉酮的未活化烯烃和烷基草酰氯兼容，这些烯烃和烷基草酰氯很容易从丰富的醇和草酰氯中制备出来。
• Visible-light-promoted photoredox-catalyzed N-aminoalkylation of quinazolinones with simple alkylamide
  作者：Yi-Jie Gu、Wenwen Cui、De-Lu Jiang、Hua Yuan、Xiao-Wei Liang、Shou-Guo Wang

  DOI：10.1016/j.tetlet.2023.154801

  日期：2023.11

  A metal free visible-light promoted direct coupling of simple alkylamides and quinazolinones via CH bond oxidative cross-coupling to access highly functionalized N-aminoalkyl quinazolinones was reported. This protocol serves as a straightforward strategy for N-aminoalkylation transformation of quinazolinones employing tert-butyl peroxybenzoate as oxidant under visible-light irradiation condition. This

  据报道，无金属可见光促进简单烷基酰胺和喹唑啉酮通过C H 键氧化交叉偶联直接偶联，以获得高度官能化的N -氨基烷基喹唑啉酮。该方案是在可见光照射条件下使用过苯甲酸叔丁酯作为氧化剂对喹唑啉酮进行N -氨基烷基化转化的简单策略。该工艺具有无金属、反应条件温和以及对多种官能团的耐受性的特点。合成上重要且高度官能化的N-氨基烷基喹唑啉酮具有中等至良好的产率和高化学选择性。
• (E)-3-(4-oxo-4H-quinazolin-3-yl)-2-propenoic acids, a new series of antiallergy agents
  作者：Ronald A. LeMahieu、Mathew Carson、William C. Nason、David R. Parrish、Ann F. Welton、Herman W. Baruth、Bohdan Yaremko

  DOI：10.1021/jm00357a018

  日期：1983.3

  A series of substituted (E)-3-(4-oxo-4H-quinazolin-3-yl)-2-propenoic acids was prepared and evaluated in the rat passive cutaneous anaphylaxis (PCA) test for antiallergic activity. Alkoxy, alkylthio, and isopropyl substituents at the 6- or 8-positions provided highly potent compounds. Conversion to the Z isomer, reduction of the side chain double bond, or reduction of the quinazoline ring resulted in substantial loss of activity. Among the analogues that exhibited oral activity in the PCA test, (E)-3-[6-(methylthio)-4-oxo-4H-quinazolin-3-yl]-2-propenoic acid (5i) was the most potent.
• 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.