5,7-dimethoxy-3-(4-methoxyphenyl)-4(3H)-quinazolinethione | 628687-02-5

• 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: 5,7-dimethoxy-3-(4-methoxyphenyl)-4(3H)-quinazolinethione
• 英文别名: BMS-408407；5,7-dimethoxy-3-(4-methoxyphenyl)quinazoline-4-thione
• CAS: 628687-02-5
• 化学式: C₁₇H₁₆N₂O₃S
• 分子量: 328.392
• InChiKey: OXCTVMRNAQSAIV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  75.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5,7-dimethoxy-3-(4-methoxyphenyl)-4(3H)-quinazolinethione 在 吡啶盐酸盐 、 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 以60%的产率得到5,7-dihydroxy-3-(4-hydroxyphenyl)-4(3H)-quinazolinethione
  参考文献：
  名称：

  3-Arylquinazoline derivatives as selective estrogen receptor beta modulators

  摘要：

  提供具有雌激素受体β（ERβ）调节活性的新型喹唑啉衍生物，其具有一般式I1，其中X为O或S；A和B分别为CR′″或N；R、R′和R″分别为氢、烷基、苄基、对甲氧基苄基、烯丙基或Si（R4）3，其中至少有一个为氢；R′″为氢、卤素、CF3、OR5、S（O）nR6、NR7R8、环烷基或烷基；R1、R2和R3分别为氢、卤素、CF3、OR5、S（O）nR6、NR7R8、环烷基或烷基；R4为烷基；R5、R6、R7和R8在每个官能团中分别为氢、环烷基或烷基；n为0至2的整数。此外，提供一种用于预防、抑制或治疗与雌激素受体相关的病理状况进展或发作的方法，以及含有这类化合物的药物组合物。

  公开号：

  US20030220227A1
• 作为产物：
  描述：

  1,2-dihydro-5,7-dimethoxy-3,1-benzoxazine-2,4-dione 在 劳森试剂 、 4-二甲氨基吡啶 作用下， 以 N,N-二甲基乙酰胺 、 甲苯 为溶剂， 反应 28.0h， 生成 5,7-dimethoxy-3-(4-methoxyphenyl)-4(3H)-quinazolinethione
  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

• 3-Arylquinazoline derivatives as selective estrogen receptor beta modulators
  申请人：——

  公开号：US20030220227A1

  公开（公告）日：2003-11-27

  Novel quinazoline derivatives possessing activity as estrogen receptor beta (ER&bgr;) modulators are provided which have the general formula I 1 wherein X is O or S; A and B are each independently CR′″ or N; R, R′ and R″ are each independently hydrogen, alkyl, benzyl, p-methoxybenzyl, allyl, or Si(R 4 ) 3 , wherein at least one of R, R′ and R″ is hydrogen; R′″ is hydrogen, halogen, CF 3 , OR 5 , S(O) n R 6 , NR 7 R 8 , cycloalkyl or alkyl; R 1 , R 2 and R 3 are each independently hydrogen, halogen, CF 3 , OR 5 , S(O) n R 6 , NR 7 R 8 , cycloalkyl or alkyl; R 4 is a alkyl; R 5 , R 6 , R 7 and R 8 in each functional group are each independently hydrogen, cycloalkyl or alkyl; and n is an integer from 0 to 2. In addition, a method is provided for preventing, inhibiting or treating the progression or onset of pathological conditions associated with the estrogen receptor and to pharmaceutical compositions containing such compounds.

  提供具有雌激素受体β（ERβ）调节活性的新型喹唑啉衍生物，其具有一般式I1，其中X为O或S；A和B分别为CR′″或N；R、R′和R″分别为氢、烷基、苄基、对甲氧基苄基、烯丙基或Si（R4）3，其中至少有一个为氢；R′″为氢、卤素、CF3、OR5、S（O）nR6、NR7R8、环烷基或烷基；R1、R2和R3分别为氢、卤素、CF3、OR5、S（O）nR6、NR7R8、环烷基或烷基；R4为烷基；R5、R6、R7和R8在每个官能团中分别为氢、环烷基或烷基；n为0至2的整数。此外，提供一种用于预防、抑制或治疗与雌激素受体相关的病理状况进展或发作的方法，以及含有这类化合物的药物组合物。
• 3-arylquinazoline derivatives as selective estrogen receptor beta modulators
  申请人：Bristol-Myers Squibb Company

  公开号：US07381730B2

  公开（公告）日：2008-06-03

  Novel quinazoline derivatives possessing activity as estrogen receptor beta (ERβ) modulators are provided which have the general formula I wherein X is O or S; A and B are each independently CR′″ or N; R, R′ and R″ are each independently hydrogen, alkyl, benzyl, p-methoxybenzyl, allyl, or Si(R4)3, wherein at least one of R, R′ and R″ is hydrogen; R′″ is hydrogen, halogen, CF3, OR5, S(O)nR6, NR7R8, cycloalkyl or alkyl; R1, R2 and R3 are each independently hydrogen, halogen, CF3, OR5, S(O)nR6, NR7R8, cycloalkyl or alkyl; R4 is a alkyl; R5, R6, R7 and R8 in each functional group are each independently hydrogen, cycloalkyl or alkyl; and n is an integer from 0 to 2. In addition, a method is provided for preventing, inhibiting or treating the progression or onset of pathological conditions associated with the estrogen receptor and to pharmaceutical compositions containing such compounds.

  提供了具有雌激素受体β（ERβ）调节剂活性的新型喹唑啉衍生物，其具有通式I，其中X为O或S；A和B分别独立地为CR′″或N；R、R′和R″分别独立地为氢、烷基、苯甲基、对甲氧基苯甲基、烯丙基或Si（R4）3，其中至少一个为氢；R′″为氢、卤素、CF3、OR5、S（O）nR6、NR7R8、环烷基或烷基；R1、R2和R3分别独立地为氢、卤素、CF3、OR5、S（O）nR6、NR7R8、环烷基或烷基；R4为烷基；每个功能组中的R5、R6、R7和R8分别独立地为氢、环烷基或烷基；n为0到2的整数。此外，还提供了一种用于预防、抑制或治疗与雌激素受体相关的病理状况的方法，并提供了含有这些化合物的药物组合物。
• US7381730B2
  申请人：——

  公开号：US7381730B2

  公开（公告）日：2008-06-03
• 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.