2-methylsulfinyl-4-methyl-6-[(3-methoxyphenyl)methyl]-4H-thieno[3,2-b]pyrrole[3,2-d]pyridazinone | 1221186-52-2

• 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: 2-methylsulfinyl-4-methyl-6-[(3-methoxyphenyl)methyl]-4H-thieno[3,2-b]pyrrole[3,2-d]pyridazinone
• 英文别名: 6-[(3-Methoxyphenyl)methyl]-4-methyl-2-methylsulfinyl-5-thieno[3,4]pyrrolo[1,3-d]pyridazinone；10-[(3-methoxyphenyl)methyl]-7-methyl-4-methylsulfinyl-3-thia-7,10,11-triazatricyclo[6.4.0.02,6]dodeca-1(8),2(6),4,11-tetraen-9-one
• CAS: 1221186-52-2
• 化学式: C₁₈H₁₇N₃O₃S₂
• 分子量: 387.483
• InChiKey: MORBXZMIXGYQDB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  111
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 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 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-methoxyphenyl)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

文献信息

• [EN] ACTIVATORS OF HUMAN PYRUVATE KINASE<br/>[FR] ACTIVATEURS DE LA PYRUVATE KINASE HUMAINE
  申请人：US HEALTH

  公开号：WO2011137089A1

  公开（公告）日：2011-11-03

  Disclosed are pyruvate kinase M2 activators which are compounds of Formula (I), including those of Formula (II), wherein A1, A2, L, R, R1 to R3, X1 to X3, k, n, and m are as defined herein, that are useful in treating a number of diseases that are treatable by the activation of PKM2, for example, cancer. A1 -NR-L-A2 (I)

  公开了一些丙酮酸激酶M2激活剂，这些激活剂是化合物式(I)的化合物，包括化合物式(II)，其中A1、A2、L、R、R1至R3、X1至X3、k、n和m的定义如下，在治疗通过激活PKM2可治疗的多种疾病中有用，例如癌症。 A1 -NR-L-A2 (I)
• ACTIVATORS OF HUMAN PYRUVATE KINASE
  申请人：Boxer Matthew B.

  公开号：US20130109672A1

  公开（公告）日：2013-05-02

  Disclosed are pyruvate kinase M2 activators which are compounds of Formula (I), including those of Formula (II), wherein A 1 , A 2 , L, R, R 1 to R 3 , X 1 to X 3 , k, n, and m are as defined herein, that are useful in treating a number of diseases that are treatable by the activation of PKM2, for example, cancer. A 1 -NR-L-A 2 (I).

  本发明涉及一种丙酮酸激酶M2活化剂，包括式(I)中的化合物，其中包括式(II)中的化合物，其中A1、A2、L、R、R1到R3、X1到X3、k、n和m的定义如本文所述，这些化合物可用于治疗许多可通过激活PKM2来治疗的疾病，例如癌症。其中，A1-NR-L-A2(I)。
• 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.
• PKM2 ACTIVATORS IN COMBINATION WITH REACTIVE OXYGEN SPECIES FOR TREATMENT OF CANCER
  申请人：TOLERO PHARMACEUTICALS, INC.

  公开号：US20200237766A1

  公开（公告）日：2020-07-30

  Combination therapies for treatment of cancer are provided. The disclosed methods comprise administration of a PKM2 activator and an anti-cancer drug having a mechanism of action that increases production of reactive oxygen species in cancer cells to a patient in need thereof.
• US9403792B2
  申请人：——

  公开号：US9403792B2

  公开（公告）日：2016-08-02