(2-([2,4-bis(trifluoromethyl)phenyl]amino)-6-methyl-4-[3-(1,3-thiazol-2-yl)-1H-pyrazol-1-yl]-3-pyridinyl)methanesulfonic sodium salt | 1075253-46-1

• 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: (2-([2,4-bis(trifluoromethyl)phenyl]amino)-6-methyl-4-[3-(1,3-thiazol-2-yl)-1H-pyrazol-1-yl]-3-pyridinyl)methanesulfonic sodium salt
• 英文别名: [2-[2,4-Bis(trifluoromethyl)anilino]-6-methyl-4-[3-(1,3-thiazol-2-yl)pyrazol-1-yl]pyridin-3-yl]methanesulfonic acid
• CAS: 1075253-46-1
• 化学式: C₂₁H₁₅F₆N₅O₃S₂
• 分子量: 563.504
• InChiKey: GPPKSVIUBJGWND-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  37
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  147
• 氢给体数：
  2
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  (2-([2,4-bis(trifluoromethyl)phenyl]amino)-6-methyl-4-[3-(1,3-thiazol-2-yl)-1H-pyrazol-1-yl]-3-pyridinyl)methanesulfonic sodium salt 在 三氯氧磷 作用下， 反应 0.33h， 以49%的产率得到1-[2,4-bis(trifluoromethyl)phenyl]-6-methyl-4-[3-(1,3-thiazol-2-yl)-1H-pyrazol-1-yl]-1,3-dihydroisothiazolo[3,4-b]pyridine
  参考文献：
  名称：

  Dihydropyrrole[2,3-d]pyridine Derivatives as Novel Corticotropin-Releasing Factor-1 Antagonists: Mapping of the Receptor Binding Pocket by in Silico Docking Studies

  摘要：

  In an effort to discover novel CRF-1 receptor antagonists exhibiting improved physicochemical properties, a dihydropirrole[2,3]pyridine scaffold was designed and explored in terms of the SAR of the substitution at the pendent phenyl ring and the nature of the heterocyclic moieties present in the upper region of the molecule. Selective and potent compounds have been discovered endowed with reduced ClogP with respect to compounds known in the literature. Of particular relevance was the finding that the in vitro affinity of the series was maintained by reducing the overall lipophilicity. The results achieved by this exploration enabled the formulation of a novel hypothesis on the nature of the receptor binding pocket of this class of CRF-1 receptor antagonists, making use of in silico docking studies of the putative nonpeptidic antagonist binding site set up in house by homology modeling techniques.

  DOI：

  10.1021/jm800743q
• 作为产物：
  描述：

  N-[2,4-bis(trifluoromethyl)phenyl]-3-(chloromethyl)-6-methyl-4-[3-(1,3-thiazol-2-yl)-1H-pyrazol-1-yl]-2-pyridinamine 在 sodium sulfite 作用下， 以 水 、 乙腈 为溶剂， 反应 0.25h， 以100%的产率得到(2-([2,4-bis(trifluoromethyl)phenyl]amino)-6-methyl-4-[3-(1,3-thiazol-2-yl)-1H-pyrazol-1-yl]-3-pyridinyl)methanesulfonic sodium salt
  参考文献：
  名称：

  Dihydropyrrole[2,3-d]pyridine Derivatives as Novel Corticotropin-Releasing Factor-1 Antagonists: Mapping of the Receptor Binding Pocket by in Silico Docking Studies

  摘要：

  In an effort to discover novel CRF-1 receptor antagonists exhibiting improved physicochemical properties, a dihydropirrole[2,3]pyridine scaffold was designed and explored in terms of the SAR of the substitution at the pendent phenyl ring and the nature of the heterocyclic moieties present in the upper region of the molecule. Selective and potent compounds have been discovered endowed with reduced ClogP with respect to compounds known in the literature. Of particular relevance was the finding that the in vitro affinity of the series was maintained by reducing the overall lipophilicity. The results achieved by this exploration enabled the formulation of a novel hypothesis on the nature of the receptor binding pocket of this class of CRF-1 receptor antagonists, making use of in silico docking studies of the putative nonpeptidic antagonist binding site set up in house by homology modeling techniques.

  DOI：

  10.1021/jm800743q

文献信息

• Dihydropyrrole[2,3-<i>d</i>]pyridine Derivatives as Novel Corticotropin-Releasing Factor-1 Antagonists: Mapping of the Receptor Binding Pocket by in Silico Docking Studies
  作者：Romano Di Fabio、Roberto Arban、Giovanni Bernasconi、Simone Braggio、Frank E. Blaney、Anna M. Capelli、Emiliano Castiglioni、Daniele Donati、Elettra Fazzolari、Emiliangelo Ratti、Aldo Feriani、Stefania Contini、Gabriella Gentile、Damiano Ghirlanda、Fabio M. Sabbatini、Daniele Andreotti、Simone Spada、Carla Marchioro、Angela Worby、Yves St-Denis

  DOI：10.1021/jm800743q

  日期：2008.11.27

  In an effort to discover novel CRF-1 receptor antagonists exhibiting improved physicochemical properties, a dihydropirrole[2,3]pyridine scaffold was designed and explored in terms of the SAR of the substitution at the pendent phenyl ring and the nature of the heterocyclic moieties present in the upper region of the molecule. Selective and potent compounds have been discovered endowed with reduced ClogP with respect to compounds known in the literature. Of particular relevance was the finding that the in vitro affinity of the series was maintained by reducing the overall lipophilicity. The results achieved by this exploration enabled the formulation of a novel hypothesis on the nature of the receptor binding pocket of this class of CRF-1 receptor antagonists, making use of in silico docking studies of the putative nonpeptidic antagonist binding site set up in house by homology modeling techniques.