2-肼基-5,6-二甲基-1,3-苯并噻唑 | 53065-22-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 中文名称: 2-肼基-5,6-二甲基-1,3-苯并噻唑
• 中文别名: 2-肼基-5,6-二甲基苯并[D]噻唑
• 英文名称: 2-hydrazinyl-5,6-dimethylbenzo[d]thiazole
• 英文别名: 5,6-Dimethyl-2-hydrazinobenzothiazol；(5,6-dimethyl-1,3-benzothiazol-2-yl)hydrazine
• CAS: 53065-22-8
• 化学式: C₉H₁₁N₃S
• mdl: MFCD17178523
• 分子量: 193.272
• InChiKey: QNPPOSLNDDRPTR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.222
• 拓扑面积：
  79.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6,7-二氢-5H-喹啉-8-酮 、 2-肼基-5,6-二甲基-1,3-苯并噻唑 在 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 5.0h， 以79%的产率得到(E)-2-(2-(6,7-dihydroquinolin-8(5H)-ylidene)hydrazinyl)-5,6-dimethylbenzo[d]thiazole
  参考文献：
  名称：

  Novel Triapine Derivative Induces Copper-Dependent Cell Death in Hematopoietic Cancers

  摘要：

  Triapine, an iron chelator that inhibits ribonucleotide reductase, has been evaluated in clinical trials for cancer treatment. Triapine in combination with other chemotherapeutic agents shows promising efficacy in certain hematologic malignancies; however, it is less effective against many advanced solid tumors, probably due to the unsatisfactory potency and pharmacokinetic properties. In this report, we developed a triapine derivative IC2S (10) with potent antitumor activity. 10 Preferentially inhibited the proliferation of hematopoietic cancers by inducing mitochondria reactive oxygen species production and mitochondrial dysfunction. Unlike triapine, 10 executed cytotoxic action in a copper-dependent manner. 10 Induced up-expression of thioredoxin-interacting protein resulted in decreased thioredoxin activity to permit c-Jun N-terminal kinase and p38 activation and ultimately led to the execution of the cell death program. Remarkedly, 10 showed good bioavailability and inhibited tumor growth in mouse xenograft models. Taken together, our study identifies compound 10 as a copper-dependent antitumor agent, which may be applied to the treatment of hematopoietic cancers.

  DOI：

  10.1021/acs.jmedchem.8b01996
• 作为产物：
  描述：

  2-氨基-5,6-二甲基苯并噻唑 在 盐酸 、 一水合肼 、 sodium nitrite 作用下， 以 乙醇 、 水 为溶剂， 反应 27.0h， 生成 2-肼基-5,6-二甲基-1,3-苯并噻唑
  参考文献：
  名称：

  一系列新型的2-（1,2-二氢-3-氧代-3H-吡唑-2-基）苯并噻唑的合成与抗菌评价。

  摘要：

  选择2-（1,2-二氢-3-氧代-3H-吡唑-2-基）苯并噻唑支架作为发现新型抗菌化合物的中心核心结构。氧代-吡唑部分以及苯并部分上的取代基的系统变化导致产生了一个小而集中的苯并噻唑文库，该库进行了抗菌筛选。在第一轮筛选中，确定了化合物对六种代表性微生物的活性。对于最有效的同类物，确定了针对金黄色葡萄球菌和铜绿假单胞菌的MIC值。结构-活性关系研究清楚地表明，细微的结构变化在很大程度上影响抗菌活性。最有效的同类物显示的MIC值为3.30μM。

  DOI：

  10.1002/cbdv.201000241

文献信息

• Synthesis and Antibacterial Evaluation of a Novel Series of 2-(1,2-Dihydro-3-oxo-3H-pyrazol-2-yl)benzothiazoles
  作者：Alessandro Stella、Kenneth Segers、Steven De Jonghe、Bart Vanderhoydonck、Jef Rozenski、Jozef Anné、Piet Herdewijn

  DOI：10.1002/cbdv.201000241

  日期：2011.2

  The 2-(1,2-dihydro-3-oxo-3H-pyrazol-2-yl)benzothiazole scaffold was selected as a central core structure for the discovery of novel antibacterial compounds. A systematic variation of the substituents on the oxo-pyrazole moiety, as well as on the benzo moiety, led to the creation of a small and focused library of benzothiazoles that was subjected to antibacterial screening. In a first round of screening

  选择2-（1,2-二氢-3-氧代-3H-吡唑-2-基）苯并噻唑支架作为发现新型抗菌化合物的中心核心结构。氧代-吡唑部分以及苯并部分上的取代基的系统变化导致产生了一个小而集中的苯并噻唑文库，该库进行了抗菌筛选。在第一轮筛选中，确定了化合物对六种代表性微生物的活性。对于最有效的同类物，确定了针对金黄色葡萄球菌和铜绿假单胞菌的MIC值。结构-活性关系研究清楚地表明，细微的结构变化在很大程度上影响抗菌活性。最有效的同类物显示的MIC值为3.30μM。
• Exchange amination process for preparing 2-hydrazinobenzothiazoles
  申请人：Eli Lilly and Company

  公开号：US03937714A1

  公开（公告）日：1976-02-10

  Improved process for the preparation of 2-hydrazinobenzothiazoles, comprising the reaction of corresponding 2-aminobenzothiazoles with hydrazine in the presence of acid, preferably in a selected solvent.

  改进的2-肼基苯并噻唑制备工艺，包括在酸性条件下，将相应的2-氨基苯并噻唑与肼反应，最好在选定的溶剂中进行。
• US3937714A
  申请人：——

  公开号：US3937714A

  公开（公告）日：1976-02-10
• Novel Triapine Derivative Induces Copper-Dependent Cell Death in Hematopoietic Cancers
  作者：Ge Chen、Chunyi Niu、Jianhua Yi、Lin Sun、Hengyi Cao、Yanjia Fang、Taijie Jin、Ying Li、Chunli Lou、Jingwu Kang、Wanguo Wei、Jidong Zhu

  DOI：10.1021/acs.jmedchem.8b01996

  日期：2019.3.28

  Triapine, an iron chelator that inhibits ribonucleotide reductase, has been evaluated in clinical trials for cancer treatment. Triapine in combination with other chemotherapeutic agents shows promising efficacy in certain hematologic malignancies; however, it is less effective against many advanced solid tumors, probably due to the unsatisfactory potency and pharmacokinetic properties. In this report, we developed a triapine derivative IC2S (10) with potent antitumor activity. 10 Preferentially inhibited the proliferation of hematopoietic cancers by inducing mitochondria reactive oxygen species production and mitochondrial dysfunction. Unlike triapine, 10 executed cytotoxic action in a copper-dependent manner. 10 Induced up-expression of thioredoxin-interacting protein resulted in decreased thioredoxin activity to permit c-Jun N-terminal kinase and p38 activation and ultimately led to the execution of the cell death program. Remarkedly, 10 showed good bioavailability and inhibited tumor growth in mouse xenograft models. Taken together, our study identifies compound 10 as a copper-dependent antitumor agent, which may be applied to the treatment of hematopoietic cancers.