3-amino-6,7-dimethoxy-2-methylquinazolin-4(3H)-one | 66299-68-1

• 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: 3-amino-6,7-dimethoxy-2-methylquinazolin-4(3H)-one
• 英文别名: 6,7-dimethoxy-2-methylquinazolin-4(3H)-one；3-amino-6,7-dimethoxy-2-methyl-3H-quinazolin-4-one；3-amino-6,7-dimethoxy-2-methyl-3,4-dihydroquinazolin-4-one；3-amino-6,7-dimethoxy-2-methylquinazolin-4-one
• CAS: 66299-68-1
• 化学式: C₁₁H₁₃N₃O₃
• mdl: MFCD06019314
• 分子量: 235.243
• InChiKey: ZRWQQVCMYRGUPA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.272
• 拓扑面积：
  77.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-amino-6,7-dimethoxy-2-methylquinazolin-4(3H)-one 在 potassium carbonate 、 potassium iodide 作用下， 以 甲苯 、 乙腈 为溶剂， 反应 10.0h， 生成 N-(6,7-dimethoxy-2-methyl-4-oxoquinazolin-3(4H)-yl)-2-[4-(furan-2-carbonyl)piperazin-1-yl]acetamide
  参考文献：
  名称：

  Molecular modeling study and synthesis of quinazolinone-arylpiperazine derivatives as α1-adrenoreceptor antagonists

  摘要：

  Three series of new 2-[(4-substituted piperazin-1-yl) methyliquinazolin-4(3H)-ones 4a-c, Ethyl 6,7-dimethoxy-4-oxo-3-[2-(4-substituted piperazin-1-yl)acetamido/propanamido]-3,4-dihydroquinazoline-2-carboxylates 9a-f and their 2-methyl analogues 13a-I were designed and synthesized as promising alpha(1)-adrenoceptor antagonists. The final compounds were evaluated for their in vivo hypotensive activity in normotensive cats. The most potent hypotensive quinazolinone derivatives 4b, 9e, 13i, 13j were further tested on isolated thoracic aortic rings of male Wister rats. All the tested compounds displayed alpha(1)-blocking activity with IC50 ranging from 0.2 to 0.4 mM less than prazosin. Furthermore, in the present work, molecular modeling study using Accelrys Discovery Studio 2.1 software was performed by mapping the synthesized compounds to the alpha(1)-adrenoceptor antagonist hypothesis in order to predict their mechanism of action. Compound 13j which has the best-fitting score displayed the highest in vivo and in vitro activity among the tested compounds. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.11.045
• 作为产物：
  描述：

  2-(乙酰基氨基)-4,5-二甲氧基苯甲酸 在 hydrazine hydrate 作用下， 生成 3-amino-6,7-dimethoxy-2-methylquinazolin-4(3H)-one
  参考文献：
  名称：

  Molecular modeling study and synthesis of quinazolinone-arylpiperazine derivatives as α1-adrenoreceptor antagonists

  摘要：

  Three series of new 2-[(4-substituted piperazin-1-yl) methyliquinazolin-4(3H)-ones 4a-c, Ethyl 6,7-dimethoxy-4-oxo-3-[2-(4-substituted piperazin-1-yl)acetamido/propanamido]-3,4-dihydroquinazoline-2-carboxylates 9a-f and their 2-methyl analogues 13a-I were designed and synthesized as promising alpha(1)-adrenoceptor antagonists. The final compounds were evaluated for their in vivo hypotensive activity in normotensive cats. The most potent hypotensive quinazolinone derivatives 4b, 9e, 13i, 13j were further tested on isolated thoracic aortic rings of male Wister rats. All the tested compounds displayed alpha(1)-blocking activity with IC50 ranging from 0.2 to 0.4 mM less than prazosin. Furthermore, in the present work, molecular modeling study using Accelrys Discovery Studio 2.1 software was performed by mapping the synthesized compounds to the alpha(1)-adrenoceptor antagonist hypothesis in order to predict their mechanism of action. Compound 13j which has the best-fitting score displayed the highest in vivo and in vitro activity among the tested compounds. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.11.045

文献信息

• Quinazolin-4-one derivatives
  申请人：Itai Akiko

  公开号：US20060229324A1

  公开（公告）日：2006-10-12

  A medicament having an inhibitory activity against hematopoietic prostaglandin D2 synthase, which comprises as an active ingredient a compound represented by the following general formula (I) or a salt thereof: wherein X represents a group represented by the formula —N═C(R 5 )— or the formula —NH—CH(R 5 )—, R 1 , R 2 , R 3 , and R 4 represent a hydrogen atom, a halogen atom, a C 1 to C 6 alkyl group, or a hydroxy group, R 5 represents a C 1 to C 6 alkyl group or a C 6 to C 10 aryl group, and R represents an amino group.

  一种具有对造血前列腺素D2合成酶抑制活性的药物，其包括以下一般式（I）所代表的化合物或其盐作为活性成分： 其中X代表由式—N═C(R5)—或式—NH—CH(R5)—所代表的基团，R1、R2、R3和R4代表氢原子、卤原子、C1到C6烷基或羟基，R5代表C1到C6烷基或C6到C10芳基，R代表氨基。
• Synthesis and Characterization of Some New Quinoxalin-2(1H)one and 2-Methyl-3H-quinazolin-4-one Derivatives Targeting the Onset and Progression of CRC with SAR, Molecular Docking, and ADMET Analyses
  作者：Nahed El-Sayed、Taghreed Al-Otaibi、Mona Alonazi、Vijay Masand、Assem Barakat、Zainab Almarhoon、Abir Ben Bacha

  DOI：10.3390/molecules26113121

  日期：——

  The pathogenesis of colorectal cancer is a multifactorial process. Dysbiosis and the overexpression of COX-2 and LDHA are important effectors in the initiation and development of the disease through chromosomal instability, PGE2 biosynthesis, and induction of the Warburg effect, respectively. Herein, we report the in vitro testing of some new quinoxalinone and quinazolinone Schiff’s bases as: antibacterial, COX-2 and LDHA inhibitors, and anticolorectal agents on HCT-116 and LoVo cells. Moreover, molecular docking and SAR analyses were performed to identify the structural features contributing to the biological activities. Among the synthesized molecules, the most active cytotoxic agent, (6d) was also a COX-2 inhibitor. In silico ADMET studies predicted that (6d) would have high Caco-2 permeability, and %HIA (99.58%), with low BBB permeability, zero hepatotoxicity, and zero risk of sudden cardiac arrest, or mutagenicity. Further, (6d) is not a potential P-gp substrate, instead, it is a possible P-gpI and II inhibitor, therefore, it can prevent or reverse the multidrug resistance of the anticancer drugs. Collectively, (6d) can be considered as a promising lead suitable for further optimization to develop anti-CRC agents or glycoproteins inhibitors.

  结直肠癌的发病机制是一个多因素的过程。肠道菌群失调以及COX-2和LDHA的过度表达是通过染色体不稳定性、PGE2合成和Warburg效应的诱导在疾病的发生和发展中起重要作用的效应因子。在这里，我们报道了一些新的喹喔啉酮和喹唑啉酮席夫碱在HCT-116和LoVo细胞上的体外测试，作为抗菌剂、COX-2和LDHA抑制剂以及抗结直肠癌药物。此外，进行了分子对接和SAR分析，以确定对生物活性有贡献的结构特征。在合成的分子中，最活性的细胞毒剂(6d)也是COX-2抑制剂。体外ADMET研究预测(6d)将具有高的Caco-2渗透性，以及%HIA（99.58%），低BBB渗透性，零肝毒性，零突发性心脏骤停风险或致突变性。此外，(6d)不是潜在的P-gp底物，相反，它是可能的P-gpI和II抑制剂，因此，它可以预防或逆转抗癌药物的多药耐药性。总的来说，(6d)可以被认为是一个有前途的引物，适合进一步优化以开发抗CRC药物或糖蛋白抑制剂。
• Lempert-Sreter, Magda; Lempert, Karoly; Moeller, Joergen, Journal of the Chemical Society. Perkin transactions I, 1984, # 6, p. 1143 - 1152
  作者：Lempert-Sreter, Magda、Lempert, Karoly、Moeller, Joergen

  DOI：——

  日期：——
• LEMPERT-SRETER M.; LEMPERT K.; BRUCK P.; TOTH G., ACTA CHIM. ACAD. SCI. HUNG. <ACAS-A2>, 1977, 94, NO 4, 391-401
  作者：LEMPERT-SRETER M.、 LEMPERT K.、 BRUCK P.、 TOTH G.

  DOI：——

  日期：——
• Molecular modeling study and synthesis of quinazolinone-arylpiperazine derivatives as α1-adrenoreceptor antagonists
  作者：Sahar Mahmoud Abou-Seri、Khaled Abouzid、Dalal A. Abou El Ella

  DOI：10.1016/j.ejmech.2010.11.045

  日期：2011.2

  Three series of new 2-[(4-substituted piperazin-1-yl) methyliquinazolin-4(3H)-ones 4a-c, Ethyl 6,7-dimethoxy-4-oxo-3-[2-(4-substituted piperazin-1-yl)acetamido/propanamido]-3,4-dihydroquinazoline-2-carboxylates 9a-f and their 2-methyl analogues 13a-I were designed and synthesized as promising alpha(1)-adrenoceptor antagonists. The final compounds were evaluated for their in vivo hypotensive activity in normotensive cats. The most potent hypotensive quinazolinone derivatives 4b, 9e, 13i, 13j were further tested on isolated thoracic aortic rings of male Wister rats. All the tested compounds displayed alpha(1)-blocking activity with IC50 ranging from 0.2 to 0.4 mM less than prazosin. Furthermore, in the present work, molecular modeling study using Accelrys Discovery Studio 2.1 software was performed by mapping the synthesized compounds to the alpha(1)-adrenoceptor antagonist hypothesis in order to predict their mechanism of action. Compound 13j which has the best-fitting score displayed the highest in vivo and in vitro activity among the tested compounds. (C) 2010 Elsevier Masson SAS. All rights reserved.