2-((4-氯苯基)氨基)噻唑-4-羧酸乙酯 | 165682-93-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 2-((4-氯苯基)氨基)噻唑-4-羧酸乙酯
• 英文名称: ethyl 2-((4-chlorophenyl)amino)thiazole-4-carboxylate
• 英文别名: Ethyl 2-(4-chlorophenylamino)-4-thiazolecarboxylate；ethyl 2-(4-chloroanilino)-1,3-thiazole-4-carboxylate
• CAS: 165682-93-9
• 化学式: C₁₂H₁₁ClN₂O₂S
• mdl: MFCD08166530
• 分子量: 282.751
• InChiKey: ULUBAPWNHROTEU-UHFFFAOYSA-N

物化性质

• 沸点：
  408.1±51.0 °C(Predicted)
• 密度：
  1.382±0.06 g/cm3(Predicted)
• 溶解度：
  DMSO:20.0(最大浓度 mg/mL);70.7(最大浓度 mM)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.166
• 拓扑面积：
  79.5
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 海关编码：
  2934100090
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302
• 储存条件：
  -20℃

制备方法与用途

靶点

OCT3；OCT4

用途

O4I2是一种有效的Oct3/4诱导剂，有助于iPSC的产生。

活性研究

O4I2能够激活HEK293和胚胎NCCIT细胞中的Oct3/4表达，并促进Oct-缺失的HeLa细胞和终末分化的人成纤维细胞的多能性转变。此外，它还能诱导其他与多能性相关的基因，如Lin28和Nanog。

反应信息

• 作为反应物：
  描述：

  2-((4-氯苯基)氨基)噻唑-4-羧酸乙酯 在 盐酸 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 74.0h， 生成 2-((4-chlorophenyl)amino)-N-(3-(dimethylamino)-propyl)thiazole-4-carboxamide
  参考文献：
  名称：

  Ethyl 2-((4-Chlorophenyl)amino)thiazole-4-carboxylate and Derivatives Are Potent Inducers of Oct3/4

  摘要：

  The octamer-binding transcription factor 4 (Oct3/4) is a master gene in the transcriptional regulatory network of pluripotent cells. Repression of Oct3/4 in embryonic stem cells (ESCs) is associated with cell differentiation and loss of pluripotency, whereas forced overexpression in cooperation with other transcriptional factors, such as Nanog, Sox2, and Lin28, can reprogram somatic cells back into pluripotent cells, termed induced pluripotent stem cells (iPSCs). However, random integration and potential tumorigenic transformation caused by viral transduction limit the clinical application of iPSCs. By performing a cell-based high throughput screening (HTS) campaign, we identified several potential small molecules as inducers of Oct3/4 expression. Here we report a lead structure ethyl 2-((4-chlorophenyl)amino)- thiazole-4-carboxylate, termed O4I2, showing high activity in enforcing Oct3/4 expression. On the basis of chemical expansion, we further identified derivatives having increased activities toward Oct3/4 induction. Thus, O4I2 and its derivatives should provide a new class of small molecules suitable for iPSC generation.

  DOI：

  10.1021/acs.jmedchem.5b00226
• 作为产物：
  描述：

  N-ethoxycarbonyl-N'-4-chlorophenylthiourea 在 乙胺 作用下， 以 乙醇 、 水 为溶剂， 反应 12.0h， 生成 2-((4-氯苯基)氨基)噻唑-4-羧酸乙酯
  参考文献：
  名称：

  在甲型流感病毒核蛋白三聚化过程中破坏保守的盐桥。

  摘要：

  流感感染中的抗病毒药物耐药性已成为对公共卫生的主要威胁。为了开发广谱的流感抑制剂来解决耐药性问题，我们之前确定了高度保守的核蛋白三聚体E339 ... R416盐桥为靶标，化合物1为通过EC50破坏盐桥的抑制剂甲型流感病毒= 2.7μM（A / WSN / 1933）。我们通过基于结构的方法进一步修饰了该化合物，并进行了抗病毒活性筛选，以鉴定化合物29和30的EC50值分别为110和120 nM，并且没有可测量的宿主细胞毒性。与临床使用的神经氨酸酶抑制剂相比，这两种化合物对耐药性A型流感病毒株和B型流感病毒显示出更好的活性，

  DOI：

  10.1021/acs.jmedchem.9b01244

文献信息

• Solvent-free synthesis of bacillamide analogues as novel cytotoxic and anti-inflammatory agents
  作者：Sunil Kumar、Ranjana Aggarwal、Virender Kumar、Rachna Sadana、Bhumi Patel、Pawan Kaushik、Dhirender Kaushik

  DOI：10.1016/j.ejmech.2016.07.033

  日期：2016.11

  aryl/heteroaryl/amino/aminoarylthiazole-4-carboxamides as bacillamide analogues having structural variation at position-2 of thiazole ring. Bacillamide and its analogues were evaluated for their cytotoxic activity against three cancer cell lines (HCT-116, MDA-MD-231 and JURKAT cell lines) using colorimetric cell proliferation assay. Compounds 17a and 17b exhibited potent anti-cell proliferation activity

  bacillamide（一种海洋来源的生物活性类胰蛋白酶生物碱）的十四种类似物的合成已通过高效的收敛途径完成。本无溶剂方案涉及在初始步骤中形成噻唑环，然后在2-羟基-4,6存在下，取代的2-烷基/芳基/杂芳基/氨基/氨基芳基噻唑-4-羧酸乙酯与色胺之间进行酰胺偶联。 -二甲基嘧啶，一种固相催化剂，可产生N- [2-（1 H-吲哚-3-基）乙基] -2-烷基/芳基/杂芳基/氨基/氨基芳基噻唑-4-羧酰胺作为bacillamide类似物，在噻唑环的2位具有结构变化。使用比色细胞增殖测定法评估了巴西酰胺及其类似物对三种癌细胞系（HCT-116，MDA-MD-231和JURKAT细胞系）的细胞毒活性。化合物17a和17b对这些细胞系表现出有效的抗细胞增殖活性，IC 50值分别在〜3.0μM和〜0.1-0.6μM范围内。初步的作用机制研究表明，这些化合物可启动caspase依赖性细胞凋亡。另外，化合物16d，16f，17a和17d
• [EN] CYANOTRIAZOLE COMPOUNDS<br/>[FR] COMPOSÉS CYANOTRIAZOLE
  申请人：OTSUKA PHARMA CO LTD

  公开号：WO2015008872A1

  公开（公告）日：2015-01-22

  This invention relates to a cyanotriazole compound represented by the formula (1):, wherein each symbols are defined in the specification, or a salt thereof. The compound or a salt thereof stimulates the citric acid cycle activity and/or improves hyperglycemia with less side effects, and excellent safety, and therefore, it is useful for treating and/or preventing diseases or disorders on which citric acid cycle activation and/or improvement of hyperglycemia has a prophylactic and/or therapeutic effect, for example, diabetes, impaired glucose tolerance, insulin resistance, diabetic complications, obesity, dyslipidemia, hepatic steatosis, atherosclerosis and/or cardiovascular disease, as well as diseases or disorders that would benefit from stimulating energy expenditure.

  本发明涉及一种由式（1）表示的氰基三唑化合物，其中每个符号在规范中定义，或其盐。该化合物或其盐刺激柠檬酸循环活性和/或改善高血糖，副作用较少，安全性优异，因此，它对于治疗和/或预防柠檬酸循环激活和/或改善高血糖具有预防和/或治疗作用的疾病或疾病具有用处，例如糖尿病，糖耐量受损，胰岛素抵抗，糖尿病并发症，肥胖，血脂异常，肝脂肪变性，动脉粥样硬化和/或心血管疾病，以及那些受益于刺激能量消耗的疾病或疾病。
• [EN] NOVEL THIAZOLE DERIVATES<br/>[FR] NOUVEAUX DERIVES DE THIAZOLE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2005058887A1

  公开（公告）日：2005-06-30

  The present invention relates to compounds of formula (I)wherein R1, R2, R3 and R4 are as defined in the description and claims, and pharmaceutically acceptable salts thereof, for use as therapeutically active substances. The compounds are useful for the treatment and/or prophylaxis of diseases which are associated with the modulation of CB 1 receptors.

  本发明涉及式（I）的化合物，其中R1、R2、R3和R4如描述和索赔中所定义，并其药用盐，用作治疗活性物质。这些化合物可用于与CB 1受体调节相关的疾病的治疗和/或预防。
• Thiazole derivatives
  申请人：Nettekoven Heinrich Matthias

  公开号：US20050153962A1

  公开（公告）日：2005-07-14

  The present invention relates to compounds of formula (I) wherein R 1 , R 2 , R 3 and R 4 are as defined in the description and claims, and pharmaceutically acceptable salts thereof, for use as therapeutically active substances. The compounds are useful for the treatment and/or prophylaxis of diseases which are associated with the modulation of CB1 receptors, including obesity.

  本发明涉及式(I)的化合物，其中R1，R2，R3和R4如描述和要求中所定义，并且其药学上可接受的盐，用作治疗活性物质。这些化合物对于治疗和/或预防与CB1受体调节相关的疾病，包括肥胖症，是有用的。
• CYANOTRIAZOLE COMPOUNDS
  申请人：OTSUKA PHARMACEUTICAL CO., LTD.

  公开号：US20160229816A1

  公开（公告）日：2016-08-11

  This invention relates to a cyanotriazole compound represented by the formula (1): wherein each symbols are defined in the specification, or a salt thereof. The compound or a salt thereof stimulates the citric acid cycle activity and/or improves hyperglycemia with less side effects, and excellent safety, and therefore, it is useful for treating and/or preventing diseases or disorders on which citric acid cycle activation and/or improvement of hyperglycemia has a prophylactic and/or therapeutic effect, for example, diabetes, impaired glucose tolerance, insulin resistance, diabetic complications, obesity, dyslipidemia, hepatic steatosis, atherosclerosis and/or cardiovascular disease, as well as diseases or disorders that would benefit from stimulating energy expenditure.

  本发明涉及一种由式（1）表示的氰基三唑化合物，其中每个符号在规范中有定义，或其盐。该化合物或其盐刺激柠檬酸循环活性和/或改善高血糖症的副作用较小，安全性优异，因此，它对于治疗和/或预防柠檬酸循环激活和/或改善高血糖症具有预防和/或治疗作用的疾病或疾病具有用处，例如糖尿病、糖耐量受损、胰岛素抵抗、糖尿病并发症、肥胖症、血脂异常、脂肪肝、动脉粥样硬化和/或心血管疾病，以及那些从刺激能量消耗中受益的疾病或疾病。