1,2-dihydro-2-(5-thiazolylmethyl)-3H-indazol-3-one | 120273-62-3

• 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-2-(5-thiazolylmethyl)-3H-indazol-3-one
• 英文别名: 2-(Thiazol-5-ylmethyl)-1H-indazol-3(2H)-one；2-(1,3-thiazol-5-ylmethyl)-1H-indazol-3-one
• CAS: 120273-62-3
• 化学式: C₁₁H₉N₃OS
• 分子量: 231.278
• InChiKey: KPXSUQVYEHMEMW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  73.5
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2934100090

反应信息

• 作为产物：
  描述：

  2,3-二氢-3-氧代-1H-吲唑-1-羧酸乙酯 在 氢氧化钾 、 三乙胺 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 1.0h， 生成 1,2-dihydro-2-(5-thiazolylmethyl)-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

• METALLOENZYME INHIBITOR COMPOUNDS
  申请人：Viamet Pharmaceuticals, Inc.

  公开号：US20140303157A1

  公开（公告）日：2014-10-09

  The instant invention describes compounds having metalloenzyme modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by such metalloenzymes.

  本发明描述了具有金属酶调节活性的化合物，以及治疗由这些金属酶介导的疾病、疾病或症状的方法。
• 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：——
• US9150527B2
  申请人：——

  公开号：US9150527B2

  公开（公告）日：2015-10-06