Methyl 7-methoxy-3-(4-methoxyphenyl)-4-oxoquinazoline-5-carboxylate | 887468-79-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Methyl 7-methoxy-3-(4-methoxyphenyl)-4-oxoquinazoline-5-carboxylate
• CAS: 887468-79-3
• 化学式: C₁₈H₁₆N₂O₅
• 分子量: 340.335
• InChiKey: MILFHMVUSVMKLH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  77.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Methyl 7-methoxy-3-(4-methoxyphenyl)-4-oxoquinazoline-5-carboxylate 在 lithium aluminium tetrahydride 、 18-冠醚-6 、 potassium acetate 、 三溴化硼 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 43.0h， 生成 7-Hydroxy-5-(hydroxymethyl)-3-(4-hydroxyphenyl)-3,4-dihydroquinazolin-4-one
  参考文献：
  名称：

  Synthesis and Characterization of 3-Arylquinazolinone and 3-Arylquinazolinethione Derivatives as Selective Estrogen Receptor Beta Modulators

  摘要：

  On the basis of the stucture of genistein, a new series of 3-arylquinazolines was prepared and tested for their estrogen receptor (ER) alpha and beta affinities. 5,7-Dihydroxy-3 -(4-hydroxyphenyl)-4(3H)-quinazolinone (1aa) acts as an agonist on both ER subtypes. It has 62-fold higher binding affinity [IC50(ER beta) = 179 nM] and 38-fold higher functional potency in a transcription assay [EC50(ER beta) = 76 nM] with ER beta than with ER alpha, thus improving upon the selectivity of genistein. All of the analogues showed preferential binding affinity for ER. Many are also more potent in activating transcription by ER beta than by ER alpha. Transformation of the C=O functionality at position 4 into a C=S group provided 5,7-dihydroxy-3-(4-hydroxyphenyl)4(3H)-quinazolinethione (1ba), which acts as an agonist on both ER subtypes but has 56-fold higher binding affinity for ER beta over ER alpha [IC50(ER beta) = 47 nM] and 215-fold higher potency in the transcription assay [EC50(ER beta) = 13 nM]. These ER beta-selective compounds may represent valuable tools in understanding the differences in structure and biological function of ER beta and ER alpha.

  DOI：

  10.1021/jm0509389
• 作为产物：
  描述：

  4,6-二甲氧基-2,3-二氧代吲哚啉 在 palladium diacetate 、 sodium hydroxide 、 双氧水 、 sodium hydride 、 三乙胺 、 二苯基丙基膦 、 lithium chloride 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 、 xylene 为溶剂， 反应 29.67h， 生成 Methyl 7-methoxy-3-(4-methoxyphenyl)-4-oxoquinazoline-5-carboxylate
  参考文献：
  名称：

  Synthesis and Characterization of 3-Arylquinazolinone and 3-Arylquinazolinethione Derivatives as Selective Estrogen Receptor Beta Modulators

  摘要：

  On the basis of the stucture of genistein, a new series of 3-arylquinazolines was prepared and tested for their estrogen receptor (ER) alpha and beta affinities. 5,7-Dihydroxy-3 -(4-hydroxyphenyl)-4(3H)-quinazolinone (1aa) acts as an agonist on both ER subtypes. It has 62-fold higher binding affinity [IC50(ER beta) = 179 nM] and 38-fold higher functional potency in a transcription assay [EC50(ER beta) = 76 nM] with ER beta than with ER alpha, thus improving upon the selectivity of genistein. All of the analogues showed preferential binding affinity for ER. Many are also more potent in activating transcription by ER beta than by ER alpha. Transformation of the C=O functionality at position 4 into a C=S group provided 5,7-dihydroxy-3-(4-hydroxyphenyl)4(3H)-quinazolinethione (1ba), which acts as an agonist on both ER subtypes but has 56-fold higher binding affinity for ER beta over ER alpha [IC50(ER beta) = 47 nM] and 215-fold higher potency in the transcription assay [EC50(ER beta) = 13 nM]. These ER beta-selective compounds may represent valuable tools in understanding the differences in structure and biological function of ER beta and ER alpha.

  DOI：

  10.1021/jm0509389

文献信息

• WO2006/116401
  申请人：——

  公开号：——

  公开（公告）日：——
• US7456188B1
  申请人：——

  公开号：US7456188B1

  公开（公告）日：2008-11-25
• Synthesis and Characterization of 3-Arylquinazolinone and 3-Arylquinazolinethione Derivatives as Selective Estrogen Receptor Beta Modulators
  作者：Timur Güngör、Ying Chen、Rajasree Golla、Zhengping Ma、James R. Corte、John P. Northrop、Bin、John K. Dickson、Terry Stouch、Rong Zhou、Susan E. Johnson、Ramakrishna Seethala、Jean H. M. Feyen

  DOI：10.1021/jm0509389

  日期：2006.4.1

  On the basis of the stucture of genistein, a new series of 3-arylquinazolines was prepared and tested for their estrogen receptor (ER) alpha and beta affinities. 5,7-Dihydroxy-3 -(4-hydroxyphenyl)-4(3H)-quinazolinone (1aa) acts as an agonist on both ER subtypes. It has 62-fold higher binding affinity [IC50(ER beta) = 179 nM] and 38-fold higher functional potency in a transcription assay [EC50(ER beta) = 76 nM] with ER beta than with ER alpha, thus improving upon the selectivity of genistein. All of the analogues showed preferential binding affinity for ER. Many are also more potent in activating transcription by ER beta than by ER alpha. Transformation of the C=O functionality at position 4 into a C=S group provided 5,7-dihydroxy-3-(4-hydroxyphenyl)4(3H)-quinazolinethione (1ba), which acts as an agonist on both ER subtypes but has 56-fold higher binding affinity for ER beta over ER alpha [IC50(ER beta) = 47 nM] and 215-fold higher potency in the transcription assay [EC50(ER beta) = 13 nM]. These ER beta-selective compounds may represent valuable tools in understanding the differences in structure and biological function of ER beta and ER alpha.