2-(吡啶-3-基甲基)-1H-吲唑-3-酮 | 120273-58-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 中文名称: 2-(吡啶-3-基甲基)-1H-吲唑-3-酮
• 英文名称: 1,2-dihydro-2-(3-pyridyl)methyl-3H-indazol-3-one
• 英文别名: 2-(3-Pyridylmethyl)indazolinone；2-(pyridin-3-ylmethyl)-1H-indazol-3-one
• CAS: 120273-58-7
• 化学式: C₁₃H₁₁N₃O
• 分子量: 225.25
• InChiKey: SKZAIZCDZYPCRF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  45.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-<methyl>pyridine 在 sodium hydroxide 、 锌 作用下， 以 乙醇 为溶剂， 反应 9.0h， 以54%的产率得到2-(吡啶-3-基甲基)-1H-吲唑-3-酮
  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

• 1,2-dihydro-3H-indazole-3-one derivatives
  申请人：IMPERIAL CHEMICAL INDUSTRIES PLC

  公开号：EP0355970A1

  公开（公告）日：1990-02-28

  The invention concerns a 1,2-dihydro-3H-indazol-3-one derivative of formula I 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 (1-4C)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.

  本发明涉及式 I 的 1,2-二氢-3H-吲唑-3-酮衍生物 其中Ra是氢、卤素、羟基、氰基、三氟甲基、(1-6C)烷基或(1-6C)烷氧基； Rb 是氢或 (1-6C) 烷基 Rc 是氢、(1-8C)烷基或(3-8C)烯基；以及 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）亚烷基或（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，可任选带有一个或两个取代基； 或其药学上可接受的盐； 或其(1-4C)烷氧基羰基衍生物。 本发明还涉及式 I 的吲唑-3-酮的制造工艺和含有所述吲唑-3-酮的药物组合物。本发明还包括一种使用式 I 的吲唑-3-酮治疗各种炎症或过敏性疾病的方法，以及使用这种化合物生产用于这种用途的新药物。
• 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：——
• Use of Ltb4 Inhibitors for the Treatment of B-Cell Leukemias and Lymphomas
  申请人：Claesson Hans-Erik

  公开号：US20080081835A1

  公开（公告）日：2008-04-03

  The invention relates to the use of an inhibitor of the biosynthesis and/or function of LTB 4 for the manufacture of a medicament for the treatment of B-cell chronic lymphocytic leukemia (B-CLL), B-prolymphocytic leukemia (B-PLL) or B-cell lymphoma. Preferably, the inhibitor of the biosynthesis and/or function of LTB 4 is the inhibitor of 5-LO BWA4C or the inhibitor of FLAP MK-886.
• Method and composition for treating inflammatory disorders
  申请人：Pereswetoff-Morath Lena

  公开号：US20090220583A1

  公开（公告）日：2009-09-03

  There is provided homogeneous pharmaceutical compositions for the treatment of inflammatory disorders comprising an antiinflammatory and/or antihistaminic active ingredient, a polar lipid liposome and a pharmaceutically-acceptable aqueous carrier.
• Method and Composition for Treating Inflammatory Disorders
  申请人：Meda AB

  公开号：US20160166508A1

  公开（公告）日：2016-06-16

  There is provided homogeneous pharmaceutical compositions for the treatment of inflammatory disorders comprising an antiinflammatory and/or antihistaminic active ingredient, a polar lipid liposome and a pharmaceutically-acceptable aqueous carrier.