2-(4-phenylbutyl)-1,2-dihydro-3H-indazol-3-one | 120273-79-2

• 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-(4-phenylbutyl)-1,2-dihydro-3H-indazol-3-one
• 英文别名: 2-(4-Phenyl-butyl)-1,2-dihydro-indazol-3-one；2-(4-phenylbutyl)-1H-indazol-3-one
• CAS: 120273-79-2
• 化学式: C₁₇H₁₈N₂O
• 分子量: 266.343
• InChiKey: VMGHZFARQGLROM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 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：

  2-nitro-N-(4-phenylbutyl)benzamide 在 sodium hydroxide 、 锌 作用下， 以 乙醇 为溶剂， 反应 20.0h， 以43%的产率得到2-(4-phenylbutyl)-1,2-dihydro-3H-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

• Photocatalyst‐free Synthesis of Indazolones under CO ₂ Atmosphere
  作者：Tianbao Yang、Huiai Lu、Renhua Qiu、Ling Hong、Shuang‐Feng Yin、Nobuaki Kambe

  DOI：10.1002/asia.201900306

  日期：2019.5.2

  A convenient photocatalyst‐free method for the synthesis of redox‐active 1,2‐dihydro‐3H‐indazol‐3‐one derivatives from (2‐nitroaryl)methanol and amines was developed. The reaction proceeded efficiently at room temperature by irradiation of UV light under CO2 atmosphere (1.0 atm, flow) without any photocatalysts or additives. This mild, operationally simple method shows wide functional tolerance. The

  开发了一种简便的无光催化剂方法，可从（2-硝基芳基）甲醇和胺类合成氧化还原活性的1,2-二氢-3 H-吲唑-3-酮衍生物。在室温下，通过在无任何光催化剂或添加剂的情况下，通过在CO 2气氛（1.0 atm，流量）下照射紫外线，使反应有效地进行。这种温和，操作简单的方法显示出广泛的功能公差。由CO 2和胺原位形成的氨基甲酸酯被认为是该反应的关键。已发现通过本方法合成的某些化合物具有较高的抗癌活性，可降低癌细胞系HeLa，MCF-7和U87的活力。
• BRUNEAU, P.;DELVARE, C.;EDWARDS, M. P.;MCMILLAN, R. M., J. MED. CHEM. , 34,(1991) N, C. 1028-1036
  作者：BRUNEAU, P.、DELVARE, C.、EDWARDS, M. P.、MCMILLAN, R. M.

  DOI：——

  日期：——
• 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.