3-氨基-2-噻吩甲酰肼 | 137844-98-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 中文名称: 3-氨基-2-噻吩甲酰肼
• 英文名称: 3-aminothiophene-2-carbohydrazide
• CAS: 137844-98-5
• 化学式: C₅H₇N₃OS
• mdl: MFCD00277433
• 分子量: 157.196
• InChiKey: GKLNRCFUWGEIHR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  109
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-氨基-2-噻吩甲酰肼 在 Ni-Raney 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以20%的产率得到3-氨基噻吩-2-甲酰胺
  参考文献：
  名称：

  Synthesis and characterization of 1,2,4-triazolo[1,5-a]pyrimidine-2-carboxamide-based compounds targeting the PA-PB1 interface of influenza A virus polymerase

  摘要：

  Influenza viruses (Flu) are responsible for seasonal epidemics causing high rates of morbidity, which can dramatically increase during severe pandemic outbreaks. Antiviral drugs are an indispensable weapon to treat infected people and reduce the impact on human health, nevertheless anti-Flu armamentarium still remains inadequate. In search for new anti-Flu drugs, our group has focused on viral RNA-dependent RNA polymerase (RdRP) developing disruptors of PA-PB1 subunits interface with the best compounds characterized by cycloheptathiophene-3-carboxamide and 1,2,4-triazolo[1,5-a]pyrimidine-2-carboxamide scaffolds. By merging these moieties, two very interesting hybrid compounds were recently identified, starting from which, in this paper, a series of analogues were designed and synthesized. In particular, a thorough exploration of the cycloheptathiophene-3-carboxamide moiety led to acquire important SAR insight and identify new active compounds showing both the ability to inhibit PA-PB1 interaction and viral replication in the micromolar range and at non-toxic concentrations. For few compounds, the ability to efficiently inhibit PA-PB1 subunits interaction did not translate into anti-Flu activity. Chemical/physical properties were investigated for a couple of compounds suggesting that the low solubility of compound 14, due to a strong crystal lattice, may have impaired its antiviral activity. Finally, computational studies performed on compound 23, in which the phenyl ring suitably replaced the cycloheptathiophene, suggested that, in addition to hydrophobic interactions, H-bonds enhanced its binding within the PAC cavity.

  DOI：

  10.1016/j.ejmech.2020.112944
• 作为产物：
  描述：

  3-氨其噻吩-2-甲酸乙酯 在 一水合肼 作用下， 以 乙醇 为溶剂， 以89%的产率得到3-氨基-2-噻吩甲酰肼
  参考文献：
  名称：

  2-（1,3,4-恶二唑-2（3H）-硫酮）-3-氨基-5-芳基噻吩并[2,3-b]吡啶作为DRAK2抑制剂的合成及其构效关系研究

  摘要：

  近年来，DAPK相关的凋亡诱导蛋白激酶2（DRAK2）已成为治疗各种自身免疫性疾病和预防器官移植后移植排斥的有希望的靶标。但是，尚未发现用于发现DRAK2新型小分子抑制剂的药物化学优化方案。导致了苯并噻吩类似物的发现专有化合物文库的筛选，其中显示的亲和常数（ķ d 0.25μ）值中号。芯支架的变化时，可以得到一系列5- arylthieno [2,3-的取代模式的b ]与强的结合亲和力的吡啶（ķ d = 0.008μ中号代表最有力的代表）。这些化合物还显示出在功能生化DRAK2酶测定有前途的活性，与IC 50值的0.029μ中号为最有效的同类。最有效的化合物的选择性分析表明，它们在DAPK激酶家族中缺乏选择性。但是，效力较低的类似物之一是DRAK2的选择性配体，可以用作合成选择性有效的DRAK2抑制剂的起点。

  DOI：

  10.1002/cmdc.201402234

文献信息

• 3-Aminothiophene-2-Acylhydrazones: Non-Toxic, Analgesic and Anti-Inflammatory Lead-Candidates
  作者：Yolanda Silva、Christian Reyes、Gildardo Rivera、Marina Alves、Eliezer Barreiro、Magna Moreira、Lídia Lima

  DOI：10.3390/molecules19068456

  日期：——

  Different chemotypes are described as anti-inflammatory. Among them the N-acylhydrazones (NAH) are highlighted by their privileged structure nature, being present in several anti-inflammatory drug-candidates. In this paper a series of functionalized 3-aminothiophene-2-acylhydrazone derivatives 5a–i were designed, synthesized and bioassayed. These new derivatives showed great anti-inflammatory and analgesic potency and efficacy. Compounds 5a and 5d stand out in this respect, and were also active in CFA-induced arthritis in rats. After daily treatment for seven days with 5a and 5d (50 µmol/Kg), by oral administration, these compounds were not renal or hepatotoxic nor immunosuppressive. Compounds 5a and 5d also displayed good drug-scores and low risk toxicity calculated in silico using the program OSIRIS Property Explorer.

  描述了不同化学类型的抗炎药物，其中N-酰基脲（NAH）因其特权结构的性质而受到关注，存在于多个抗炎候选药物中。本文设计、合成了系列功能化的3-氨基噻吩-2-酰基脲衍生物5a-i，并进行了生物活性测试。这些新衍生物显示出极佳的抗炎和镇痛活性及疗效。化合物5a和5d在这方面尤为突出，对大鼠弗氏完全佐剂诱导的关节炎也有效。连续七天每日口服给予5a和5d（50 μmol/Kg），这些化合物未见肾毒性、肝毒性或免疫抑制作用。借助OSIRIS Property Explorer程序，化合物5a和5d还显示了良好的药物评分和低风险毒性。
• Syntheses, crystal structures, thermal stabilities, CT-DNA, and BSA binding characteristics of a new acylhydrazone and its Co(II), Cu(II), and Zn(II) complexes
  作者：Jing-Jing Liu、Xiang-Rong Liu、Shun-Sheng Zhao、Zai-Wen Yang、Zheng Yang

  DOI：10.1080/00958972.2020.1758316

  日期：2020.4.2

  Abstract A new acylhydrazone (C12H12N4OS, HL) and its three transition metal complexes [M(HL)2](NO3)2 (M = Co, I; Cu, II; Zn, III) have been synthesized. The structures of above four compounds were determined by single-crystal X-ray diffraction analyses. HL belonged to orthorhombic system and Pbca space group. I and II belonged to triclinic system and P-1 space group, whereas III belonged to monoclinic

  摘要 合成了一种新的酰腙（C12H12N4OS，HL）及其三种过渡金属配合物[M(HL)2](NO3)2（M = Co，I；Cu，II；Zn，III）。以上四种化合物的结构均通过单晶X射线衍射分析确定。HL属于正交系和Pbca空间群。I和II属于三斜晶系和P-1空间群，而III属于单斜晶系和P21/C空间群。通过热重分析研究了四种化合物的热稳定性，它们的最大热分解峰温度均超过 240 °C，显示出较高的热稳定性。四种化合物与 CT-DNA 的结合行为由紫外可见吸收光谱、粘度和微量热实验确定，所有这些都呈现嵌入模式。通过荧光光谱和微量热实验测定了四种化合物与BSA的相互作用，显示出静态猝灭效应，结合常数KA为（8.32±0.36）×103M-1，（1.44±0.40）×105M-1，（ HL、I、II 和 III 分别为 7.59 ± 0.09) × 104 M−1 和 (4.68 ± 0.45)
• Pyrazolo[3,4-c]pyridazines from hydrazine and aminothiophenecarboxylates
  作者：Manfred G. Reinecke、Thomas A. Woodrow、E. Sherwood Brown

  DOI：10.1021/jo00029a046

  日期：1992.1
• Huddleston, Patrick R.; Barker, John M.; Adamczewska, Yolante Z., Journal of Chemical Research, Miniprint, 1993, # 2, p. 548 - 575
  作者：Huddleston, Patrick R.、Barker, John M.、Adamczewska, Yolante Z.、Wood, Michael L.、Holmes, David

  DOI：——

  日期：——
• Synthesis and Structure-Activity Relationship Studies of 2-(1,3,4-Oxadiazole-2(3<i>H</i>)-thione)-3-amino-5-arylthieno[2,3-<i>b</i>]pyridines as Inhibitors of DRAK2
  作者：Piotr Leonczak、Ling-Jie Gao、Anna Teresa Ramadori、Eveline Lescrinier、Jef Rozenski、Steven De Jonghe、Piet Herdewijn

  DOI：10.1002/cmdc.201402234

  日期：2014.11

  recent years, DAPK‐related apoptosis‐inducing protein kinase 2 (DRAK2) has emerged as a promising target for the treatment of a variety of autoimmune diseases and for the prevention of graft rejection after organ transplantation. However, medicinal chemistry optimization campaigns for the discovery of novel small‐molecule inhibitors of DRAK2 have not yet been published. Screening of a proprietary compound

  近年来，DAPK相关的凋亡诱导蛋白激酶2（DRAK2）已成为治疗各种自身免疫性疾病和预防器官移植后移植排斥的有希望的靶标。但是，尚未发现用于发现DRAK2新型小分子抑制剂的药物化学优化方案。导致了苯并噻吩类似物的发现专有化合物文库的筛选，其中显示的亲和常数（ķ d 0.25μ）值中号。芯支架的变化时，可以得到一系列5- arylthieno [2,3-的取代模式的b ]与强的结合亲和力的吡啶（ķ d = 0.008μ中号代表最有力的代表）。这些化合物还显示出在功能生化DRAK2酶测定有前途的活性，与IC 50值的0.029μ中号为最有效的同类。最有效的化合物的选择性分析表明，它们在DAPK激酶家族中缺乏选择性。但是，效力较低的类似物之一是DRAK2的选择性配体，可以用作合成选择性有效的DRAK2抑制剂的起点。