1,2-dihydro-4-(N-N-pentylcarbamoyl)-3H-indazol-3-one | 128484-42-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: 1,2-dihydro-4-(N-N-pentylcarbamoyl)-3H-indazol-3-one
• 英文别名: 3-oxo-N-pentyl-1,2-dihydroindazole-4-carboxamide
• CAS: 128484-42-4
• 化学式: C₁₃H₁₇N₃O₂
• 分子量: 247.297
• InChiKey: JIAUOUASSSLCHX-UHFFFAOYSA-N

物化性质

• 熔点：
  167-169 °C
• 沸点：
  404.4±24.0 °C(Predicted)
• 密度：
  1.158±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  70.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,2-dihydro-4-(N-N-pentylcarbamoyl)-3H-indazol-3-one 在 吡啶 、 sodium hydroxide 、 sodium hydride 作用下， 以 甲醇 为溶剂， 反应 2.08h， 生成 1,2-dihydro-2-methyl-4-(N-n-pentylcarbamoyl)-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：

  1-acetyl-3-oxo-N-pentyl-2H-indazole-4-carboxamide 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以77%的产率得到1,2-dihydro-4-(N-N-pentylcarbamoyl)-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

• Heterocyclic agents
  申请人：ICI Pharma

  公开号：US05036083A1

  公开（公告）日：1991-07-30

  The invention concerns a 1,2-dihydro-3H-indazol-3-one derivative of formula I ##STR1## wherein Ra is hydrogen, halogeno, hydroxy, cyano, trifluoromethyl, 1-6C)alkyl or (1-6C)alkoxy; Rb is hydrogen or (1-6C)alkyl; Rc is hydrogen, (1-8C)alkyl or (3-8C)alkenyl; and Y is (1-8C)alkyl, (3-8C)alkenyl or (3-8C)alkynyl, or Y is a group of the formula --A--Q in which A is (1-6C)alkylene or (3-6C)alkenylene, and Q is phenyl, naphthyl, pyridyl, thienyl, isoxazolyl, thiazolyl or thiadiazolyl, which may optionally bear one or two substituents; or a pharmaceutically-acceptable salt thereof; or a (12-4C)alkoxycarbonyl derivative thereof. The invention also concerns processes for the manufacture of an indazol-3-one of the formula I and pharmaceutical compositions containing said indazol-3-one. Also included in the invention is a method of treating various inflammatory or allergic diseases using an indazol-3-one of the formula I and the use of such a compound in the production of a new medicament for such use.

  该发明涉及一种式I的1,2-二氢-3H-吲哚-3-酮衍生物##STR1##其中Ra是氢、卤素、羟基、氰基、三氟甲基、(1-6C)烷基或(1-6C)氧基；Rb是氢或(1-6C)烷基；Rc是氢、(1-8C)烷基或(3-8C)烯基；Y是(1-8C)烷基、(3-8C)烯基或(3-8C)炔基，或Y是式--A--Q的基团，其中A是(1-6C)烷基或(3-6C)烯基，Q是苯基、萘基、吡啶基、噻吩基、异噁唑基、噻唑基或噻二唑基，可能带有一个或两个取代基；或其药用可接受盐；或其(12-4C)烷氧羰基衍生物。该发明还涉及制备式I的吲哚-3-酮的方法和含有所述吲哚-3-酮的制药组合物。该发明还包括使用式I的吲哚-3-酮治疗各种炎症或过敏性疾病的方法，以及利用这种化合物制备新药物用于此类用途。
• 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：——
• US5036083A
  申请人：——

  公开号：US5036083A

  公开（公告）日：1991-07-30
• US5229408A
  申请人：——

  公开号：US5229408A

  公开（公告）日：1993-07-20
• 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.