5-azidomethylthiophene-2-carboxylic acid methyl ester | 503470-01-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 5-azidomethylthiophene-2-carboxylic acid methyl ester
• 英文别名: methyl 5-(azidomethyl)thiophene-2-carboxylate
• CAS: 503470-01-7
• 化学式: C₇H₇N₃O₂S
• 分子量: 197.217
• InChiKey: KTPQLXUJTOZWEY-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：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  68.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-azidomethylthiophene-2-carboxylic acid methyl ester 在 N-甲基吗啉 、 溶剂黄146 、 锌 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 2-Hydroxy-5-[(5-methoxycarbonylthiophen-2-yl)methylsulfamoyl]benzoic acid
  参考文献：
  名称：

  Identification of Potent and Selective Small-Molecule Inhibitors of Caspase-3 through the Use of Extended Tethering and Structure-Based Drug Design

  摘要：

  The design, synthesis, and in vitro activities of a series of potent and selective small-molecule inhibitors of caspase-3 are described. From extended tethering, a salicylic acid fragment was identified as having binding affinity for the S-4 pocket of caspase-3. X-ray crystallography and molecular modeling of the initial tethering hit resulted in the synthesis of 4, which reversibly inhibited caspase-3 with a K-i = 40 nM. Further optimization led to the identification of a series of potent and selective inhibitors with K-i values in the 20-50 nM range. One of the most potent compounds in this series, 66b, inhibited caspase-3 with a K-i = 20 nM and selectivity of 8-500-fold for caspase-3 vs a panel of seven caspases (1, 2, and 4-8). A high-resolution X-ray cocrystal structure of 4 and 66b supports the predicted binding modes of our compounds with caspase-3.

  DOI：

  10.1021/jm020230j
• 作为产物：
  描述：

  5-甲基噻吩-2-羧酸甲酯 在 N-溴代丁二酰亚胺(NBS) 、 sodium azide 、 过氧化苯甲酰 作用下， 以 四氯化碳 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.0h， 生成 5-azidomethylthiophene-2-carboxylic acid methyl ester
  参考文献：
  名称：

  Design, Synthesis, and Biological Activity of Novel, Potent, and Selective (Benzoylaminomethyl)thiophene Sulfonamide Inhibitors of c-Jun-N-Terminal Kinase

  摘要：

  Several lines of evidence support the hypothesis that c-Jun N-terminal kinases (JNKs) play a critical role in a wide range of disease states including cell death (apoptosis)-related and inflammatory disorders (epilepsy, brain, heart and renal ischemia, neurodegenerative diseases, multiple sclerosis, rheumatoid arthritis, and inflammatory bowel syndrome). The screening of a compound collection led to the identification of a 2-(benzoylaminomethyl)thiophene sulfonamide (AS004509, compound I) as a potent and selective JNK inhibitor. Chemistry and structure-activity relationship (SAR) studies performed around this novel kinase-inhibiting motif indicated that the left and central parts of the molecule were instrumental to maintaining potency at the enzyme. Accordingly, we investigated the JNK-inhibiting properties of a number of variants of the right-hand moiety of the molecule, which led to the identification of 2-(benzoylaminomethyl)thiophene sulfonamide benzotriazole (AS600292, compound 50a), the first potent and selective JNK inhibitor of this class which demonstrates a protective action against neuronal cell death induced by growth factor and serum deprivation.

  DOI：

  10.1021/jm031112e

文献信息

• Anti-metastatic Inhibitors of Lysyl Oxidase (LOX): Design and Structure–Activity Relationships
  作者：Leo Leung、Dan Niculescu-Duvaz、Deborah Smithen、Filipa Lopes、Cedric Callens、Robert McLeary、Grazia Saturno、Lawrence Davies、Mohammed Aljarah、Michael Brown、Louise Johnson、Alfonso Zambon、Tim Chambers、Delphine Ménard、Natasha Bayliss、Ruth Knight、Laura Fish、Rae Lawrence、Mairi Challinor、HaoRan Tang、Richard Marais、Caroline Springer

  DOI：10.1021/acs.jmedchem.9b00335

  日期：2019.6.27

  Lysyl oxidase (LOX) is a secreted copper-dependent amine oxidase that cross-links collagens and elastin in the extracellular matrix and is a critical mediator of tumor growth and metastatic spread. LOX is a target for cancer therapy, and thus the search for therapeutic agents against LOX has been widely sought. We report herein the medicinal chemistry discovery of a series of LOX inhibitors bearing

  赖氨酰氧化酶（LOX）是一种分泌型铜依赖性胺氧化酶，可在细胞外基质中交联胶原蛋白和弹性蛋白，并且是肿瘤生长和转移性扩散的关键介质。LOX是癌症治疗的靶标，因此已经广泛寻求抗LOX的治疗剂。我们在这里报告了一系列带有氨基亚甲基噻吩（AMT）支架的LOX抑制剂的药物化学发现。高通量筛选提供了最初的结果。结构活性关系（SAR）研究导致在LOX酶活性测定中发现亚微摩尔半数最大抑制浓度（IC50）的AMT抑制剂。进一步的SAR优化产生了口服生物可用的LOX抑制剂CCT365623，具有良好的抗LOX效能，选择性，药代动力学特性，
• WO2006/65703
  申请人：——

  公开号：——

  公开（公告）日：——
• Synthesis and antiplasmodial activity of new heteroaryl derivatives of 7-chloro-4-aminoquinoline
  作者：Manolo Casagrande、Anna Barteselli、Nicoletta Basilico、Silvia Parapini、Donatella Taramelli、Anna Sparatore

  DOI：10.1016/j.bmc.2012.07.040

  日期：2012.10

  With the aim to investigate the effect of different heterocyclic rings linked to the 4-aminoquinoline nucleus on the antimalarial activity, a set of 7-chloro-N-(heteroaryl)-methyl-4-aminoquinoline and 7-chloro-N-(heteroaryl)-4-aminoquinoline was synthesized and tested in vitro against D-10 (CQ-S) and W-2 (CQ-R) strains of Plasmodium falciparum. All compounds exhibited from moderate to high antiplasmodial activities. The activity was strongly influenced both by the presence of a methylenic group, as a spacer between the 4-aminoquinoline and the heterocyclic ring, and by the presence of a basic head. The most potent molecules inhibited the growth of both CQ-S and CQ-R strains of P. falciparum with IC50 < 30 nM and were not toxic against human endothelial cells. These results confirm that the presence of an heteroaryl moiety in the side chain of 7-chloro-4-aminoquinoline is useful for the design and development of new powerful antimalarial agents. (C) 2012 Elsevier Ltd. All rights reserved.
• PYRIDO PYRIMIDINONES, DIHYDRO PYRIMIDO PYRIMIDINONES AND PTERIDINONES USEFUL AS RAF KINASE INHIBITORS
  申请人：Oslob Johan D.

  公开号：US20110059976A1

  公开（公告）日：2011-03-10

  The present invention provides compounds having the formula: wherein A-B together represent one of the following structures: and n, R 1 , R 2 , R 3 , R 4 , L 1 , L 2 , Y and Z are as defined in classes and subclasses herein, and pharmaceutical compositions thereof, as described generally and in subclasses herein, which compounds are useful as inhibitors of protein kinase (e.g., RAF), and thus are useful, for example, for the treatment of RAF mediated diseases.
• US7767687B2
  申请人：——

  公开号：US7767687B2

  公开（公告）日：2010-08-03