2,5-dimethyl-4-(N-propyl-N-cyclopropylmethyl-amino)-pyrimidine-6-carboxylic acid, ethyl ester | 744253-41-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2,5-dimethyl-4-(N-propyl-N-cyclopropylmethyl-amino)-pyrimidine-6-carboxylic acid, ethyl ester
• 英文别名: 2,5-dimethyl-4-(N-propyl-N-cyclopropylmethyl-amino)-pyrimidine-6-carboxylic acid,ethyl ester
• CAS: 744253-41-6
• 化学式: C₁₆H₂₅N₃O₂
• 分子量: 291.393
• InChiKey: IBZPKLQYAUWDFO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  55.32
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  2,5-dimethyl-4-(N-propyl-N-cyclopropylmethyl-amino)-pyrimidine-6-carboxylic acid, ethyl ester 在 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成
  参考文献：
  名称：

  Synthesis of benzoylpyrimidines as antagonists of the corticotropin-releasing factor-1 receptor

  摘要：

  A series of benzoylpyrimidines derived from the anilinepyrimidine CRF1 antagonists were synthesized. Several synthetic routes were developed to explore the SAR of this series of compounds. Compounds such as 8d (K-i = 15 nM) exhibited high binding affinities at the human CRF1 receptor. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.05.072
• 作为产物：
  描述：

  草酰丙酸二乙酯 在 sodium ethanolate 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 生成 2,5-dimethyl-4-(N-propyl-N-cyclopropylmethyl-amino)-pyrimidine-6-carboxylic acid, ethyl ester
  参考文献：
  名称：

  Synthesis of benzoylpyrimidines as antagonists of the corticotropin-releasing factor-1 receptor

  摘要：

  A series of benzoylpyrimidines derived from the anilinepyrimidine CRF1 antagonists were synthesized. Several synthetic routes were developed to explore the SAR of this series of compounds. Compounds such as 8d (K-i = 15 nM) exhibited high binding affinities at the human CRF1 receptor. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.05.072

文献信息

• Amino substituted pyrimidines and triazines
  申请人：Neurocrine Biosciences, Inc.

  公开号：US06288060B1

  公开（公告）日：2001-09-11

  Pyrimidines and triazines of formula (I) wherein R is C1-6alkyl, amino, mono- or diC1-6alkylamino; R1 is hydrogen, C1-6alkyl, C3-6alkenyl, hydroxyC1-6alkyl or C1-6alkyloxy-C1-6alkyl; R2 is C1-6alkyl, mono- or diC3-6cycloalkylmethyl, phenylmethyl, substituted phenylmethyl, C1-6alkyloxy-C1-6alkyl, hydroxyC1-6alkyl, C1-6alkyloxycarbonylC1-6alkyl, C3-6alkenyl; or R1 and R2 taken together with the nitrogen to which they are attached may form a pyrrolidinyl, morpholinyl or piperidinyl group; X is N or CR3; R3 is hydrogen or C1-6alkyl; R4 is phenyl or substituted phenyl; A is  or —CR7R8— wherein R5 and R6 each independently are hydrogen or C1-4alkyl; R7 is hydrogen or OH, R8 is hydrogen or C1-6alkyl; having CRF receptor antagonistic properties; pharmaceutical compositions containing these compounds as active ingredients; methods of treating disorders related to hypersecretion of CRF such as depression, anxiety, substance abuse, by administering an effective amount of a compound of formula (I).

  式(I)中的嘧啶和三嗪，其中R是C1-6烷基，氨基，单或双C1-6烷基氨基；R1是氢，C1-6烷基，C3-6烯基，羟基C1-6烷基或C1-6烷氧基-C1-6烷基；R2是C1-6烷基，单或双C3-6环烷基甲基，苯基甲基，取代苯基甲基，C1-6烷氧基-C1-6烷基，羟基C1-6烷基，C1-6烷氧羰基C1-6烷基，C3-6烯基；或R1和R2连同它们所附着的氮原子可能形成吡咯烷基，吗啉基或哌啶基；X是N或CR3；R3是氢或C1-6烷基；R4是苯基或取代苯基；A是或- CR7R8-，其中R5和R6各自独立地是氢或C1-4烷基；R7是氢或OH，R8是氢或C1-6烷基；具有CRF受体拮抗作用；含有这些化合物作为活性成分的制药组合物；通过给予式(I)化合物的有效量来治疗与CRF过度分泌相关的疾病，例如抑郁症，焦虑症，物质滥用的方法。