N-((R)-1-Naphthalen-1-yl-ethyl)-2-nitro-benzamide | 120275-76-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-((R)-1-Naphthalen-1-yl-ethyl)-2-nitro-benzamide
• 英文别名: N-[(1R)-1-naphthalen-1-ylethyl]-2-nitrobenzamide
• CAS: 120275-76-5
• 化学式: C₁₉H₁₆N₂O₃
• 分子量: 320.348
• InChiKey: OFGFAYMHELQQCF-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  74.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-((R)-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25%的产率得到1,2-dihydro-2-[1(R)-(1-naphthyl)ethyl]-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
• 作为产物：
  描述：

  邻硝基苯甲酸 在 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 N-((R)-1-Naphthalen-1-yl-ethyl)-2-nitro-benzamide
  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

• Therapeutic preparations
  申请人：IMPERIAL CHEMICAL INDUSTRIES PLC

  公开号：EP0284174A1

  公开（公告）日：1988-09-28

  The invention concerns pharmaceutical compositions containing a 1,2-dihydro-3H-indazol-3-one derivative of the formula I wherein Ra is hydrogen, halogeno, nitro, hydroxy, (2-6C)alkanoyloxy, (1-6C)alkyl, (1-6C)alkoxy, fluoro-(1-4C)alkyl, (2-6C)alkanoyl, amino, (1-6C)alkylamino, di-[(1-4C)alkyl]amino, (2-6C)alkanoylamino or hydroxy-­(1-6C)alkyl; Rb is hydrogen, halogeno, (1-6C)alkyl or (1-6C)alkoxy; and Y is a group of the formula -A¹-X-A²-Q in which A¹ is (1-6C)alkylene, (3-6C)alkenylene, (3-6C)alkynylene or cyclo(3-6C)alkylene, or A¹ is phenylene; X is oxy, thio, sulphinyl, sulphonyl, imino, (1-­6C)alkylimino, (1-6C)alkanoylimino, iminocarbonyl or phenylene, or X is a direct link to A²; A² is (1-6C)alkylene, (3-6C)alkenylene or (3-­6C)alkynylene or A² is cyclo(3-6C)alkylene or is a direct link to Q, or the group A¹-X-A² is a direct link to Q; or Y is (2-10)alkyl, (3-­10C)alkenyl or (3-6C)alkynyl; and Q is aryl or heteroaryl. The invention also provides novel 1,2-dihydro-3H-indazol-3-­ones, processes for their production and the use of 1,2-dihydro-3H-­indazol-3-one for the manufacture of medicaments for the treatment of various allergic and inflammatory diseases.

  本发明涉及含有式 I 的 1,2-二氢-3H-吲唑-3-酮衍生物的药物组合物 其中Ra是氢、卤素、硝基、羟基、(2-6C)烷酰氧基、(1-6C)烷基、(1-6C)烷氧基、氟-(1-4C)烷基、(2-6C)烷酰基、氨基、(1-6C)烷基氨基、二[(1-4C)烷基]氨基、(2-6C)烷酰氨基或羟基-(1-6C)烷基；Rb 是氢、卤素、(1-6C)烷基或 (1-6C)烷氧基；以及 Y 是式 -A¹-X-A²-Q 的基团，其中 A¹ 是 (1-6C)亚烷基、(3-6C)烯基、(3-6C)炔基或环(3-6C)亚烷基，或 A¹ 是亚苯基；X 是氧基、硫代、亚砜基、磺酰基、亚氨基、(1-6C)烷基亚氨基、(1-6C)烷酰亚氨基、亚氨基羰基或亚苯基，或 X 是与 A² 的直接连接；A²是(1-6C)亚烷基、(3-6C)亚烯基或(3-6C)亚炔基，或A²是环(3-6C)亚烷基，或与Q直接相连，或基团A¹-X-A²与Q直接相连；或Y是(2-10)烷基、(3-10C)亚烯基或(3-6C)亚炔基；且Q是芳基或杂芳基。 本发明还提供了新型 1,2-二氢-3H-吲唑-3-酮、其生产工艺以及 1,2-二氢-3H-吲唑-3-酮用于制造治疗各种过敏性和炎症性疾病的药物。
• US5173496A
  申请人：——

  公开号：US5173496A

  公开（公告）日：1992-12-22
• 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.