2-((S)-1-Naphthalen-1-yl-ethyl)-1,2-dihydro-indazol-3-one | 120274-33-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-((S)-1-Naphthalen-1-yl-ethyl)-1,2-dihydro-indazol-3-one
• 英文别名: 2-[(1S)-1-naphthalen-1-ylethyl]-1H-indazol-3-one
• CAS: 120274-33-1
• 化学式: C₁₉H₁₆N₂O
• 分子量: 288.349
• InChiKey: AOOSKFQNKDXJCS-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  N-((S)-1-Naphthalen-1-yl-ethyl)-2-nitro-benzamide 在 sodium hydroxide 、 锌 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以30%的产率得到2-((S)-1-Naphthalen-1-yl-ethyl)-1,2-dihydro-indazol-3-one
  参考文献：
  名称：

  Indazolinones, a new series of redox-active 5-lipoxygenase inhibitors with built-in selectivity and oral activity

  摘要：

  Since the hypothetical mechanisms of hydroperoxydation of arachidonic acid by, respectively, 5-lipoxygenase (5-LPO) and cyclooxygenase (CO) involve a redox cycle, a compound which reduces 5-LPO and CO to their inactive state would give a nonselective inhibitor of both enzymes. Structural modifications of such a compound could be expected to give improved potency and selectivity for 5-LPO and oral activity. Such an approach has led to the discovery of 1,2-dihydroindazol-3-ones which are potent 5-LPO inhibitors with various degrees of selectivity. Structure-activity relationship studies indicated that while N-1,N-2-unsubstituted and N-1-substituted derivatives are orally inactive, N-2-alkyl derivatives are orally active and inhibit both 5-LPO and CO. In contrast, N-2-benzyl derivatives are selective for 5-LPO but possess only weak oral activity. Further structural modifications have identified ICI 207968 [1,2-dihydro-2-(3-pyridylmethyl)-3H-indazol-3-one, 21a] which combines potent oral activity and high selectivity. Methemoglobin (MHb) induction by 21a in dog blood precluded its development for clinical use. Attempts at dissociating 5-LPO inhibitory properties and MHb formation showed that MHb formation in vitro seemed to be related to the redox potential of the compounds whereas 5-LPO inhibition was not. This study led to a series of 4-(N-n-pentylcarbamoyl)indazolinones which maintained in vitro 5-LPO potency but did not induce MHb.

  DOI：

  10.1021/jm00107a023

文献信息

• Indazolinones, a new series of redox-active 5-lipoxygenase inhibitors with built-in selectivity and oral activity
  作者：P. Bruneau、C. Delvare、M. P. Edwards、R. M. McMillan

  DOI：10.1021/jm00107a023

  日期：1991.3

  Since the hypothetical mechanisms of hydroperoxydation of arachidonic acid by, respectively, 5-lipoxygenase (5-LPO) and cyclooxygenase (CO) involve a redox cycle, a compound which reduces 5-LPO and CO to their inactive state would give a nonselective inhibitor of both enzymes. Structural modifications of such a compound could be expected to give improved potency and selectivity for 5-LPO and oral activity. Such an approach has led to the discovery of 1,2-dihydroindazol-3-ones which are potent 5-LPO inhibitors with various degrees of selectivity. Structure-activity relationship studies indicated that while N-1,N-2-unsubstituted and N-1-substituted derivatives are orally inactive, N-2-alkyl derivatives are orally active and inhibit both 5-LPO and CO. In contrast, N-2-benzyl derivatives are selective for 5-LPO but possess only weak oral activity. Further structural modifications have identified ICI 207968 [1,2-dihydro-2-(3-pyridylmethyl)-3H-indazol-3-one, 21a] which combines potent oral activity and high selectivity. Methemoglobin (MHb) induction by 21a in dog blood precluded its development for clinical use. Attempts at dissociating 5-LPO inhibitory properties and MHb formation showed that MHb formation in vitro seemed to be related to the redox potential of the compounds whereas 5-LPO inhibition was not. This study led to a series of 4-(N-n-pentylcarbamoyl)indazolinones which maintained in vitro 5-LPO potency but did not induce MHb.