2-methyl-4H-thieno[3,2-b]pyrrole-5-carbohydrazide

• 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-methyl-4H-thieno[3,2-b]pyrrole-5-carbohydrazide
• 化学式: C₈H₉N₃OS
• mdl: MFCD14796107
• 分子量: 195.245
• InChiKey: YZAOXWFLTXXOSP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  99.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-methyl-4H-thieno[3,2-b]pyrrole-5-carbohydrazide 在 劳森试剂 作用下， 以 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 24.0h， 生成 2-methyl-5-methylthieno[2',3':4,5]pyrrolo[1,2-d][1,2,4]triazine-8(7H)-thione
  参考文献：
  名称：

  Discovery of thienopyrrolotriazine derivatives to protect mitochondrial function against Aβ-induced neurotoxicity

  摘要：

  Recovery of mitochondrial dysfunction has gained increasing attention as an alternative therapeutic strategy for Alzheimer's disease (AD). Recent studies suggested that the 18 kDa mitochondrial translocator protein (TSPO) has the potential to serve as a drug target for the treatment of AD. In this study, we generated a structure-based pharmacophore model and virtually screened a commercial library, identifying SVH07 as a virtual hit, which contained a tricyclic core structure, thieno[2',3':4,5]pyrrolo[1,2-d] [1,2,4]triazine group. A series of SVH07 analogues were synthesized and their effects on the mitochondrial membrane potential and ATP production were determined by using neuronal cells under A beta-induced toxicity. Among these analogues, compound 26 significantly recovered mitochondrial membrane depolarization and ATP production. In vitro binding assays indicated that SVH07 and 26 showed high affinities to TSPO with the IC50 values in a nanomolar range. We believe that compound 26 is a promising lead compound for the development of TSPO-targeted mitochondrial functional modulators with therapeutic potential in AD. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.09.033
• 作为产物：
  描述：

  5-甲基-2-噻吩甲醛 在 sodium methylate 、 一水合肼 作用下， 以 甲醇 、 乙醇 、 甲苯 为溶剂， 反应 34.5h， 生成 2-methyl-4H-thieno[3,2-b]pyrrole-5-carbohydrazide
  参考文献：
  名称：

  Discovery of thienopyrrolotriazine derivatives to protect mitochondrial function against Aβ-induced neurotoxicity

  摘要：

  Recovery of mitochondrial dysfunction has gained increasing attention as an alternative therapeutic strategy for Alzheimer's disease (AD). Recent studies suggested that the 18 kDa mitochondrial translocator protein (TSPO) has the potential to serve as a drug target for the treatment of AD. In this study, we generated a structure-based pharmacophore model and virtually screened a commercial library, identifying SVH07 as a virtual hit, which contained a tricyclic core structure, thieno[2',3':4,5]pyrrolo[1,2-d] [1,2,4]triazine group. A series of SVH07 analogues were synthesized and their effects on the mitochondrial membrane potential and ATP production were determined by using neuronal cells under A beta-induced toxicity. Among these analogues, compound 26 significantly recovered mitochondrial membrane depolarization and ATP production. In vitro binding assays indicated that SVH07 and 26 showed high affinities to TSPO with the IC50 values in a nanomolar range. We believe that compound 26 is a promising lead compound for the development of TSPO-targeted mitochondrial functional modulators with therapeutic potential in AD. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.09.033

文献信息

• [EN] NLRP3 INFLAMMASOME INHIBITORS<br/>[FR] INHIBITEURS D'INFLAMMASOME NLRP3
  申请人：NOVARTIS AG

  公开号：WO2020021447A1

  公开（公告）日：2020-01-30

  The present invention relates to novel thienopyrrolotriazinacetamide compounds of Formula (I): wherein R1, R2 and R3 are defined herein, which inhibit NOD-like receptor protein 3 (NLRP3) inflammasome activity. The invention further relates to the processes for their preparation, pharmaceutical compositions and medicaments containing them, and their use in the treatment of diseases and disorders mediated by NLRP3.

  本发明涉及一种新型噻吡咯三唑酰胺化合物的化学式（I）：其中R1、R2和R3如本文所定义，该化合物抑制NOD样受体蛋白3（NLRP3）炎症小体活性。该发明还涉及它们的制备过程、含有它们的药物组合物和药物，以及它们在治疗由NLRP3介导的疾病和紊乱中的用途。
• NLRP3 INFLAMMASOME INHIBITORS
  申请人：Novartis AG

  公开号：EP3827008A1

  公开（公告）日：2021-06-02
• Discovery of thienopyrrolotriazine derivatives to protect mitochondrial function against Aβ-induced neurotoxicity
  作者：TaeHun Kim、Woo Seung Son、Mohammad Neaz Morshed、Ashwini M. Londhe、Seo Yun Jung、Jong-Hyun Park、Woo-Kyu Park、Sang Min Lim、Ki Duk Park、Sung Jin Cho、Kyu-Sung Jeong、Jiyoun Lee、Ae Nim Pae

  DOI：10.1016/j.ejmech.2017.09.033

  日期：2017.12

  Recovery of mitochondrial dysfunction has gained increasing attention as an alternative therapeutic strategy for Alzheimer's disease (AD). Recent studies suggested that the 18 kDa mitochondrial translocator protein (TSPO) has the potential to serve as a drug target for the treatment of AD. In this study, we generated a structure-based pharmacophore model and virtually screened a commercial library, identifying SVH07 as a virtual hit, which contained a tricyclic core structure, thieno[2',3':4,5]pyrrolo[1,2-d] [1,2,4]triazine group. A series of SVH07 analogues were synthesized and their effects on the mitochondrial membrane potential and ATP production were determined by using neuronal cells under A beta-induced toxicity. Among these analogues, compound 26 significantly recovered mitochondrial membrane depolarization and ATP production. In vitro binding assays indicated that SVH07 and 26 showed high affinities to TSPO with the IC50 values in a nanomolar range. We believe that compound 26 is a promising lead compound for the development of TSPO-targeted mitochondrial functional modulators with therapeutic potential in AD. (C) 2017 Elsevier Masson SAS. All rights reserved.