4-[(5S)-5-[1,1-dimethyl-2-oxo-2-(1,3,4-thiadiazol-2-ylamino)ethyl]-5H-[1]benzopyrano[2,3-b]pyridin-2-yl]benzoic acid | 1008115-02-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 4-[(5S)-5-[1,1-dimethyl-2-oxo-2-(1,3,4-thiadiazol-2-ylamino)ethyl]-5H-[1]benzopyrano[2,3-b]pyridin-2-yl]benzoic acid
• 英文别名: 4-[(5S)-5-[2-methyl-1-oxo-1-(1,3,4-thiadiazol-2-ylamino)propan-2-yl]-5H-chromeno[2,3-b]pyridin-2-yl]benzoic acid
• CAS: 1008115-02-3
• 化学式: C₂₅H₂₀N₄O₄S
• 分子量: 472.524
• InChiKey: WTOAAUGTOXEPOY-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  143
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-[(5S)-5-[1,1-dimethyl-2-oxo-2-(1,3,4-thiadiazol-2-ylamino)ethyl]-5H-[1]benzopyrano[2,3-b]pyridin-2-yl]benzoic acid 在 氯化铵 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 乙腈 为溶剂， 反应 12.0h， 以35%的产率得到(5S)-2-[4-(aminocarbonyl)phenyl]-α,α-dimethyl-N-(1,3,4-thiadiazol-2-yl)-5H-[1]benzopyrano[2,3-b]pyridin-5-acetamide
  参考文献：
  名称：

  Azaxanthene Based Selective Glucocorticoid Receptor Modulators: Design, Synthesis, and Pharmacological Evaluation of (S)-4-(5-(1-((1,3,4-Thiadiazol-2-yl)amino)-2-methyl-1-oxopropan-2-yl)-5H-chromeno[2,3-b]pyridin-2-yl)-2-fluoro-N,N-dimethylbenzamide (BMS-776532) and Its Methylene Homologue (BMS-791826)

  摘要：

  Structurally novel 5H-chromeno[2,3-b]pyridine (azaxanthene) selective glucocorticoid receptor (GR) modulators have been identified. A screening paradigm utilizing cellular assays of GR-mediated transrepression of proinflammatory transcription factors and transactivation of GR-dependent genes combined with three physiologically relevant assays of cytokine induction in human whole blood has allowed for the identification of high affinity, selective GR ligands that display a broad range of pharmacological profiles. Agonist efficacy in reporter assays can be tuned by halogenation of a pendent phenyl ring and correlates well with efficacy for cytokine inhibition in human whole blood. A hypothetical binding mode is proposed, invoking an expanded ligand binding pocket resembling that of arylpyrazole-bound GR structures. Two compounds of dose structural similarity (35 and 37; BMS-776532 and BMS-791826, respectively) have been found to maintain distinct and consistent levels of partial agonist efficacy across several assays, displaying anti-inflammatory activity comparable to that of prednisolone 2 in suppressing cytokine production in whole blood and in rodent models of acute and chronic inflammation.

  DOI：

  10.1021/jm200879j