5-carbonitrile-4-chloro-6-(2,3-dimethoxyphenyl)-2-(methylthio)pyrimidine | 898254-57-4

• 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: 5-carbonitrile-4-chloro-6-(2,3-dimethoxyphenyl)-2-(methylthio)pyrimidine
• 英文别名: 4-Chloro-6-(2,3-dimethoxyphenyl)-2-methylsulfanylpyrimidine-5-carbonitrile
• CAS: 898254-57-4
• 化学式: C₁₄H₁₂ClN₃O₂S
• 分子量: 321.787
• InChiKey: HGCIFHVDTZNQLP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  93.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-carbonitrile-4-chloro-6-(2,3-dimethoxyphenyl)-2-(methylthio)pyrimidine 在 lithium hydroxide 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 sodium ethanolate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 N-tert-butyl-5-amino-4-(2,3-dimethoxyphenyl)-2-(methylthio)thieno[2,3-d]pyrimidine-6-carboxamide
  参考文献：
  名称：

  Evaluation of Small-Molecule Modulators of the Luteinizing Hormone/Choriogonadotropin and Thyroid Stimulating Hormone Receptors:  Structure−Activity Relationships and Selective Binding Patterns

  摘要：

  The substituted thieno[ 2,3-d] pyrimidine 3 ( Org 41841), a partial agonist for the luteinizing hormone/choriogonadotropin receptor ( LHCGR) and the closely related thyroid-stimulating hormone receptor ( TSHR), was fundamentally altered, and the resulting analogues were analyzed for their potencies, efficacies, and specificities at LHCGR and TSHR. Chemical modification of the parent compound combined with prior mutagenesis of TSHR provided compelling experimental evidence in support of computational models of 3 binding to TSHR and LHCGR within their transmembrane cores. Biochemical analysis of a specific modification to the chemical structure of 3 provides additional evidence of a H-bond between the ligand and a glutamate residue in transmembrane helix 3, which is conserved in both receptors. Several key interactions were surveyed to determine their respective biochemical roles in terms of both van der Waals dimensions and hydrogen bond capacity and the respective relationship to biological activity.

  DOI：

  10.1021/jm060247s
• 作为产物：
  描述：

  5-carbonitrile-1,6-dihydro-4-(2,3-dimethoxyphenyl)-2-(methylthio)-6-oxopyrimidine 在 三氯氧磷 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.0h， 生成 5-carbonitrile-4-chloro-6-(2,3-dimethoxyphenyl)-2-(methylthio)pyrimidine
  参考文献：
  名称：

  Evaluation of Small-Molecule Modulators of the Luteinizing Hormone/Choriogonadotropin and Thyroid Stimulating Hormone Receptors:  Structure−Activity Relationships and Selective Binding Patterns

  摘要：

  The substituted thieno[ 2,3-d] pyrimidine 3 ( Org 41841), a partial agonist for the luteinizing hormone/choriogonadotropin receptor ( LHCGR) and the closely related thyroid-stimulating hormone receptor ( TSHR), was fundamentally altered, and the resulting analogues were analyzed for their potencies, efficacies, and specificities at LHCGR and TSHR. Chemical modification of the parent compound combined with prior mutagenesis of TSHR provided compelling experimental evidence in support of computational models of 3 binding to TSHR and LHCGR within their transmembrane cores. Biochemical analysis of a specific modification to the chemical structure of 3 provides additional evidence of a H-bond between the ligand and a glutamate residue in transmembrane helix 3, which is conserved in both receptors. Several key interactions were surveyed to determine their respective biochemical roles in terms of both van der Waals dimensions and hydrogen bond capacity and the respective relationship to biological activity.

  DOI：

  10.1021/jm060247s

文献信息

• Evaluation of Small-Molecule Modulators of the Luteinizing Hormone/Choriogonadotropin and Thyroid Stimulating Hormone Receptors:  Structure−Activity Relationships and Selective Binding Patterns
  作者：Susanna Moore、Holger Jaeschke、Gunnar Kleinau、Susanne Neumann、Stefano Costanzi、Jian-kang Jiang、John Childress、Bruce M. Raaka、Anny Colson、Ralf Paschke、Gerd Krause、Craig J. Thomas、Marvin C. Gershengorn

  DOI：10.1021/jm060247s

  日期：2006.6.1

  The substituted thieno[ 2,3-d] pyrimidine 3 ( Org 41841), a partial agonist for the luteinizing hormone/choriogonadotropin receptor ( LHCGR) and the closely related thyroid-stimulating hormone receptor ( TSHR), was fundamentally altered, and the resulting analogues were analyzed for their potencies, efficacies, and specificities at LHCGR and TSHR. Chemical modification of the parent compound combined with prior mutagenesis of TSHR provided compelling experimental evidence in support of computational models of 3 binding to TSHR and LHCGR within their transmembrane cores. Biochemical analysis of a specific modification to the chemical structure of 3 provides additional evidence of a H-bond between the ligand and a glutamate residue in transmembrane helix 3, which is conserved in both receptors. Several key interactions were surveyed to determine their respective biochemical roles in terms of both van der Waals dimensions and hydrogen bond capacity and the respective relationship to biological activity.