2-chloro-3-(2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}ethyl)-6-methyl-4-[3-(1,3-thiazol-2-yl)-1H-pyrazol-1-yl]pyridine | 491864-74-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-chloro-3-(2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}ethyl)-6-methyl-4-[3-(1,3-thiazol-2-yl)-1H-pyrazol-1-yl]pyridine
• 英文别名: Tert-butyl-[2-[2-chloro-6-methyl-4-[3-(1,3-thiazol-2-yl)pyrazol-1-yl]pyridin-3-yl]ethoxy]-dimethylsilane
• CAS: 491864-74-5
• 化学式: C₂₀H₂₇ClN₄OSSi
• 分子量: 435.065
• InChiKey: ZCTSLXPIQSDBMQ-UHFFFAOYSA-N

物化性质

• 沸点：
  539.9±60.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.92
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  81.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-chloro-3-(2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}ethyl)-6-methyl-4-[3-(1,3-thiazol-2-yl)-1H-pyrazol-1-yl]pyridine 、 2-甲基-4-甲氧基苯胺 在 potassium phosphate 、 tris-(dibenzylideneacetone)dipalladium(0) 、 2-二环己基磷-2'-甲基联苯 作用下， 以 乙二醇二甲醚 为溶剂， 100.0 ℃ 、413.69 kPa 条件下， 反应 0.67h， 生成 3-[2-[tert-butyl(dimethyl)silyl]oxyethyl]-N-(4-methoxy-2-methylphenyl)-6-methyl-4-[3-(1,3-thiazol-2-yl)pyrazol-1-yl]pyridin-2-amine
  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：

  2-{2-chloro-6-methyl-4-[3-(1,3-thiazol-2-yl)-1H-pyrazol-1-yl]-3-pyridinyl}ethanol 、 叔丁基二甲硅基三氟甲磺酸酯 在 2,6-二甲基吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 15.0h， 生成 2-chloro-3-(2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}ethyl)-6-methyl-4-[3-(1,3-thiazol-2-yl)-1H-pyrazol-1-yl]pyridine
  参考文献：
  名称：

  [EN] HETEROARYL- SUBSTITUTED PYRROLO` 2, 3- B! PYRIDINE DERIVATIVES AS CRF RECEPTOR ANTAGONISTS
  [FR] DERIVES PYRROLO[2,3-B]PYRIDINE A SUBSTITUTION HETEROARYLE UTILISES COMME ANTAGONISTES DES RECEPTEURS DU CRF

  摘要：

  本发明提供了化合物的公式（I），包括立体异构体、前药和其药用可接受的盐或溶剂，以及其制备方法，包含它们的药物组合物，以及它们在治疗由促肾上腺皮质激素释放因子（CRF）介导的疾病中的用途。

  公开号：

  WO2004062665A1

文献信息

• [EN] HETEROARYL- SUBSTITUTED PYRROLO` 2, 3- B! PYRIDINE DERIVATIVES AS CRF RECEPTOR ANTAGONISTS<br/>[FR] DERIVES PYRROLO[2,3-B]PYRIDINE A SUBSTITUTION HETEROARYLE UTILISES COMME ANTAGONISTES DES RECEPTEURS DU CRF
  申请人：SB PHARMCO INC

  公开号：WO2004062665A1

  公开（公告）日：2004-07-29

  The present invention provides compounds of formula (I) including stereoisomers, prodrugs and pharmaceutically acceptable salts or solvates thereof, to processes for their preparation, to pharmaceutical compositions containing them and to their use in the treatment of conditions mediated by corticotropin-releasing factor (CRF).

  本发明提供了化合物的公式（I），包括立体异构体、前药和其药用可接受的盐或溶剂，以及其制备方法，包含它们的药物组合物，以及它们在治疗由促肾上腺皮质激素释放因子（CRF）介导的疾病中的用途。
• 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.