6-(3-Hydroxybenzyl)-4-methyl-2-(methylthio)-4H-thieno[2',3':4,5]pyrrolo[2,3-d]pyridazin-5(6H)-one | 1222851-21-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并吡咯类
• 英文名称: 6-(3-Hydroxybenzyl)-4-methyl-2-(methylthio)-4H-thieno[2',3':4,5]pyrrolo[2,3-d]pyridazin-5(6H)-one
• 英文别名: 10-[(3-hydroxyphenyl)methyl]-7-methyl-4-methylsulfanyl-3-thia-7,10,11-triazatricyclo[6.4.0.02,6]dodeca-1(8),2(6),4,11-tetraen-9-one
• CAS: 1222851-21-9
• 化学式: C₁₇H₁₅N₃O₂S₂
• 分子量: 357.457
• InChiKey: OTXBRGQBUGOLIY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-(3-Hydroxybenzyl)-4-methyl-2-(methylthio)-4H-thieno[2',3':4,5]pyrrolo[2,3-d]pyridazin-5(6H)-one 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 生成 2-methylsulfinyl-4-methyl-6-[(3-hydroxyphenyl)methyl]-4H-thieno[3,2-b]pyrrole[3,2-d] pyridazinone
  参考文献：
  名称：

  Evaluation of thieno[3,2-b]pyrrole[3,2-d]pyridazinones as activators of the tumor cell specific M2 isoform of pyruvate kinase

  摘要：

  Cancer cells have distinct metabolic needs that are different from normal cells and can be exploited for development of anti-cancer therapeutics. Activation of the tumor specific M2 form of pyruvate kinase (PKM2) is a potential strategy for returning cancer cells to a metabolic state characteristic of normal cells. Here, we describe activators of PKM2 based upon a substituted thieno[3,2-b]pyrrole[3,2-d]pyridazinone scaffold. The synthesis of these agents, structure-activity relationships, analysis of activity at related targets (PKM1, PKR and PKL) and examination of aqueous solubility are investigated. These agents represent the second reported chemotype for activation of PKM2. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2010.04.015
• 作为产物：
  描述：

  10-[(3-Methoxyphenyl)methyl]-7-methyl-4-methylsulfanyl-3-thia-7,10,11-triazatricyclo[6.4.0.02,6]dodeca-1(8),2(6),4,11-tetraen-9-one 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 6-(3-Hydroxybenzyl)-4-methyl-2-(methylthio)-4H-thieno[2',3':4,5]pyrrolo[2,3-d]pyridazin-5(6H)-one
  参考文献：
  名称：

  Evaluation of thieno[3,2-b]pyrrole[3,2-d]pyridazinones as activators of the tumor cell specific M2 isoform of pyruvate kinase

  摘要：

  Cancer cells have distinct metabolic needs that are different from normal cells and can be exploited for development of anti-cancer therapeutics. Activation of the tumor specific M2 form of pyruvate kinase (PKM2) is a potential strategy for returning cancer cells to a metabolic state characteristic of normal cells. Here, we describe activators of PKM2 based upon a substituted thieno[3,2-b]pyrrole[3,2-d]pyridazinone scaffold. The synthesis of these agents, structure-activity relationships, analysis of activity at related targets (PKM1, PKR and PKL) and examination of aqueous solubility are investigated. These agents represent the second reported chemotype for activation of PKM2. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2010.04.015

文献信息

• PYRUVATE KINASE ACTIVATORS FOR USE FOR INCREASING LIFETIME OF THE RED BLOOD CELLS AND TREATING ANEMIA
  申请人：Agios Pharmaceuticals, Inc.

  公开号：EP2704719B1

  公开（公告）日：2018-02-21
• METHODS OF USING PYRUVATE KINASE ACTIVATORS
  申请人：Su Shin-San M.

  公开号：US20140148444A1

  公开（公告）日：2014-05-29

  Described herein are compounds that activate pyruvate kinase, for use in a method for increasing lifetime of the red blood cells, for regulating 2,3-diphosphoglycerate levels in blood and for treating sickle cell anemia.
• US9403792B2
  申请人：——

  公开号：US9403792B2

  公开（公告）日：2016-08-02
• [EN] PYRUVATE KINASE ACTIVATORS FOR USE FOR INCREASING LIFETIME OF THE RED BLOOD CELLS AND TREATING ANEMIA<br/>[FR] ACTIVATEURS DE PYRUVATE KINASE DESTINÉS À ÊTRE UTILISÉS POUR ALLONGER LA DURÉE DE VIE DES ÉRYTHROCYTES ET TRAITER L'ANÉMIE
  申请人：AGIOS PHARMACEUTICALS INC

  公开号：WO2012151450A1

  公开（公告）日：2012-11-08

  Described herein are compounds that activate pyruvate kinase, for use in a method for increasing lifetime of the red blood cells, for regulating 2, 3 - diphosphoglycerate levels in blood and for treating sickle cell anemia.