2-(4-Methoxy-2-methyl-phenylamino)-1H-thieno[3,2-d]pyrimidin-4-one | 134372-85-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: 2-(4-Methoxy-2-methyl-phenylamino)-1H-thieno[3,2-d]pyrimidin-4-one
• 英文别名: 2-(4-methoxy-2-methylanilino)-3H-thieno[3,2-d]pyrimidin-4-one
• CAS: 134372-85-3
• 化学式: C₁₄H₁₃N₃O₂S
• 分子量: 287.342
• InChiKey: SJNKSOUAEPHZDY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  91
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(4-Methoxy-2-methyl-phenylamino)-1H-thieno[3,2-d]pyrimidin-4-one 在 三氯氧磷 作用下， 反应 3.0h， 生成 N²-(4-Methoxy-2-methyl-phenyl)-N⁴-methyl-N⁴-phenyl-thieno[3,2-d]pyrimidine-2,4-diamine; hydrochloride
  参考文献：
  名称：

  Reversible Inhibitors of the Gastric (H+/K+)-ATPase. 5. Substituted 2,4-Diaminoquinazolines and Thienopyrimidines

  摘要：

  Quinazolines bearing a secondary 4-(arylamino) substituent demonstrate an SAR for inhibition of the gastric (H+/K+)-ATPase different from the previously described 3-acylquinolines, suggesting that, although these compounds are also K+-competitive, they probably bind to the enzyme in a different orientation. Compounds bearing a tertiary 4-(arylamino) substituent, however, in particular 4-(N-methylarylamino), appear to possess an SAR quite similar to the 3-acylquinolines. We show that this arises from the effect of the N-methylation, which is to orientate the 4-(arylamino) substituent syn to C-5, analogous to the 3-acylquinolines. Compounds possessing both a 4-(N-methylarylamino) substituent and a 2-(arylamino) substituent proved to be very potent, K+-competitive inhibitors of K+-stimulated ATPase activity with K-i values down to 12 nM. Some compounds also proved to be effective inhibitors of stimulated acid secretion in both the rat and dog when dosed intravenously. However, although a number of these demonstrated activity after oral administration in the dog, the level and variability precluded further evaluation.

  DOI：

  10.1021/jm00014a027
• 作为产物：
  描述：

  2-甲基-4-甲氧基苯胺 、 2-ethylsulfanyl-3H-thieno[3,2-d]pyrimidin-4-one 反应 20.0h， 生成 2-(4-Methoxy-2-methyl-phenylamino)-1H-thieno[3,2-d]pyrimidin-4-one
  参考文献：
  名称：

  Reversible Inhibitors of the Gastric (H+/K+)-ATPase. 5. Substituted 2,4-Diaminoquinazolines and Thienopyrimidines

  摘要：

  Quinazolines bearing a secondary 4-(arylamino) substituent demonstrate an SAR for inhibition of the gastric (H+/K+)-ATPase different from the previously described 3-acylquinolines, suggesting that, although these compounds are also K+-competitive, they probably bind to the enzyme in a different orientation. Compounds bearing a tertiary 4-(arylamino) substituent, however, in particular 4-(N-methylarylamino), appear to possess an SAR quite similar to the 3-acylquinolines. We show that this arises from the effect of the N-methylation, which is to orientate the 4-(arylamino) substituent syn to C-5, analogous to the 3-acylquinolines. Compounds possessing both a 4-(N-methylarylamino) substituent and a 2-(arylamino) substituent proved to be very potent, K+-competitive inhibitors of K+-stimulated ATPase activity with K-i values down to 12 nM. Some compounds also proved to be effective inhibitors of stimulated acid secretion in both the rat and dog when dosed intravenously. However, although a number of these demonstrated activity after oral administration in the dog, the level and variability precluded further evaluation.

  DOI：

  10.1021/jm00014a027

文献信息

• Substituted thienopyrimidine derivatives, their preparation, pharmaceutical compositions and medical use
  申请人：SMITHKLINE BEECHAM INTERCREDIT B.V.

  公开号：EP0404356B1

  公开（公告）日：1993-09-22
• US5280026A
  申请人：——

  公开号：US5280026A

  公开（公告）日：1994-01-18
• Reversible Inhibitors of the Gastric (H+/K+)-ATPase. 5. Substituted 2,4-Diaminoquinazolines and Thienopyrimidines
  作者：Robert J. Ife、Thomas H. Brown、Peter Blurton、David J. Keeling、Colin A. Leach、Malcolm L. Meeson、Michael E. Parsons、Colin J. Theobald

  DOI：10.1021/jm00014a027

  日期：1995.7

  Quinazolines bearing a secondary 4-(arylamino) substituent demonstrate an SAR for inhibition of the gastric (H+/K+)-ATPase different from the previously described 3-acylquinolines, suggesting that, although these compounds are also K+-competitive, they probably bind to the enzyme in a different orientation. Compounds bearing a tertiary 4-(arylamino) substituent, however, in particular 4-(N-methylarylamino), appear to possess an SAR quite similar to the 3-acylquinolines. We show that this arises from the effect of the N-methylation, which is to orientate the 4-(arylamino) substituent syn to C-5, analogous to the 3-acylquinolines. Compounds possessing both a 4-(N-methylarylamino) substituent and a 2-(arylamino) substituent proved to be very potent, K+-competitive inhibitors of K+-stimulated ATPase activity with K-i values down to 12 nM. Some compounds also proved to be effective inhibitors of stimulated acid secretion in both the rat and dog when dosed intravenously. However, although a number of these demonstrated activity after oral administration in the dog, the level and variability precluded further evaluation.