6-ethoxycarbonyl-7-hydroxy-5-(4-methoxyphenyl)-7-(3,4-methylenedioxyphenyl)-7H-cyclopenta[c]pyridine | 482641-85-0

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 6-ethoxycarbonyl-7-hydroxy-5-(4-methoxyphenyl)-7-(3,4-methylenedioxyphenyl)-7H-cyclopenta[c]pyridine
• CAS: 482641-85-0
• 化学式: C₂₅H₂₁NO₆
• 分子量: 431.445
• InChiKey: XGTLWZVSOUOGFD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.43
• 重原子数：
  32.0
• 可旋转键数：
  5.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  87.11
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  6-ethoxycarbonyl-7-hydroxy-5-(4-methoxyphenyl)-7-(3,4-methylenedioxyphenyl)-7H-cyclopenta[c]pyridine 在 palladium on activated charcoal 硫酸 、 氢气 作用下， 以 乙醇 为溶剂， 生成 (5RS,6RS,7SR)-6-ethoxycarbonyl-5-(4-methoxyphenyl)-6,7-dihydro-7-(3,4-methylenedioxyphenyl)-5H-cyclopenta[c]pyridine
  参考文献：
  名称：

  6-Carboxy-5,7-diarylcyclopenteno[1,2-b]pyridine derivatives

  摘要：

  Compounds (2-5) with a 6-carboxy-5,7-diarylcyclopentenopyridine skeleton were designed, synthesized, and identified as a new class of potent non-peptide endothelin receptor antagonists. The regio-isomer 2 was found to show potent inhibitory activity with an IC50 value of 2.4 nM against I-125-labeled ET-1 binding to human ETA receptors and a 170-fold selectivity for ETA over ETB receptors. Furthermore, 2 displayed more potent in vivo activity than did the indan-type compound I in a mouse ET-1 induced lethality model, suggesting the potential of 2 as a new lead structure. Derivatization Oil Substituted phenyl groups at the 5- and 7-positions of 2 revealed that a 3,4-methylenedioxyphenyl group at the 5-position and a 4-methoxyphenyl group at the 7-position were optimal for binding affinity. Further derivatization of 2 by incorporating a substituent into the 2-position of the 4-methoxyphenyl group led to the identification of a more potent ETA selective antagonist 2p with an IC50 Value of 0.87 nM for ETA receptors and a 470-fold selectivity. In addition, 2p showed highly potent in vivo efficacy (AD(50): 0.04 mg/kg) in the lethality model. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00122-0
• 作为产物：
  描述：

  4-(4-Methoxy-benzoyl)-nicotinoyl chloride 在 magnesium 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 生成 6-ethoxycarbonyl-7-hydroxy-5-(4-methoxyphenyl)-7-(3,4-methylenedioxyphenyl)-7H-cyclopenta[c]pyridine
  参考文献：
  名称：

  6-Carboxy-5,7-diarylcyclopenteno[1,2-b]pyridine derivatives

  摘要：

  Compounds (2-5) with a 6-carboxy-5,7-diarylcyclopentenopyridine skeleton were designed, synthesized, and identified as a new class of potent non-peptide endothelin receptor antagonists. The regio-isomer 2 was found to show potent inhibitory activity with an IC50 value of 2.4 nM against I-125-labeled ET-1 binding to human ETA receptors and a 170-fold selectivity for ETA over ETB receptors. Furthermore, 2 displayed more potent in vivo activity than did the indan-type compound I in a mouse ET-1 induced lethality model, suggesting the potential of 2 as a new lead structure. Derivatization Oil Substituted phenyl groups at the 5- and 7-positions of 2 revealed that a 3,4-methylenedioxyphenyl group at the 5-position and a 4-methoxyphenyl group at the 7-position were optimal for binding affinity. Further derivatization of 2 by incorporating a substituent into the 2-position of the 4-methoxyphenyl group led to the identification of a more potent ETA selective antagonist 2p with an IC50 Value of 0.87 nM for ETA receptors and a 470-fold selectivity. In addition, 2p showed highly potent in vivo efficacy (AD(50): 0.04 mg/kg) in the lethality model. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00122-0