3-异硫氰酸基苯胺 | 75190-55-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-异硫氰酸基苯胺
• 英文名称: Benzenamine, 3-isothiocyanato-
• 英文别名: 3-isothiocyanatoaniline
• CAS: 75190-55-5
• 化学式: C₇H₆N₂S
• 分子量: 150.204
• InChiKey: WVVXNESNQXEEQV-UHFFFAOYSA-N

物化性质

• 熔点：
  49-51 °C
• 沸点：
  324.3±25.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 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：
  70.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-异硫氰酸基苯胺 、 3,5-二甲基吡唑-1-硝酸咪 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-((3-aminophenyl)carbamothioyl)-3,5-dimethyl-1H-pyrazole-1-carboximidamide
  参考文献：
  名称：

  Structure–activity relationship study of 2,4-diaminothiazoles as Cdk5/p25 kinase inhibitors

  摘要：

  Cdk5/p25 has emerged as a principle therapeutic target for numerous acute and chronic neurodegenerative diseases, including Alzheimer's disease. A structure-activity relationship study of 2,4-diaminothiazole inhibitors revealed that increased Cdk5/p25 inhibitory activity could be accomplished by incorporating pyridines on the 2-amino group and addition of substituents to the 2- or 3-position of the phenyl ketone moiety. Interpretation of the SAR results for many of the analogs was aided through in silico docking with Cdk5/p25 and calculating protein hydrations sites using WaterMap. Finally, improved in vitro mouse microsomal stability was also achieved. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.140

文献信息

• Synthesis and Biological Evaluation of <i>N</i>-Aryl-5-aryloxazol-2-amine Derivatives as 5-Lipoxygenase Inhibitors
  作者：Jee Hee Suh、Eul Kgun Yum、Young Sik Cho

  DOI：10.1248/cpb.c15-00033

  日期：——

  We describe the synthesis and biological evaluation of N-aryl-5-aryloxazol-2-amine derivatives that are able to inhibit 5-lipoxygenase (5-LOX), a key enzyme of leukotriene synthesis, for the treatment of inflammation-related diseases including asthma and rheumatoid arthritis. A novel structural moiety containing oxazole was initially identified from a chemical library using an in vitro enzymatic and cell-based assay, and its synthesized oxazole derivatives were further examined to develop a structure–activity relationship (SAR). SAR analysis demonstrated that a hydroxyl or amino group at the p-position on N-phenyl was essential for the 5-LOX-inhibitory activities of the derivatives, and that other halogen and methyl group-substituted derivatives affected the potency, positively or negatively. As a result, derivatives selected through first-round screening were further optimized using a cell-based assay and an in vivo assay to develop a potent, selective 5-LOX inhibitor. A final hit exhibited an improved efficacy in arachidonic acid-induced ear edema when applied topically but not orally. Moreover, it showed the additional advantage of sustainable antiinflammatory activity over a reference compound, zileuton. Taken together, chemical entities bearing an oxazole scaffold could be promising as therapeutic drugs for the treatment of chronic inflammatory skin disorders.

  我们描述了能够抑制白三烯合成关键酶 5-脂氧合酶（5-LOX）的 N-芳基-5-芳基恶唑-2-胺衍生物的合成和生物学评价，这些衍生物可用于治疗包括哮喘和类风湿性关节炎在内的炎症相关疾病。利用体外酶促和细胞检测法从化学库中初步鉴定出了一种含有噁唑的新型结构分子，并进一步研究了其合成的噁唑衍生物，以建立结构-活性关系（SAR）。SAR 分析表明，N-苯基 p 位上的羟基或氨基对衍生物的 5-LOX 抑制活性至关重要，而其他卤素和甲基取代的衍生物会对药效产生或正或负的影响。因此，通过第一轮筛选选出的衍生物利用细胞检测和体内检测进行了进一步优化，以开发出一种强效、选择性的 5-LOX 抑制剂。最终发现的一种衍生物在花生四烯酸诱发的耳部水肿方面具有更好的疗效。此外，与参考化合物齐鲁通（zileuton）相比，它还具有持续抗炎活性的额外优势。综上所述，含有噁唑支架的化学实体有望成为治疗慢性皮肤炎症的药物。
• Structure–activity relationship study of 2,4-diaminothiazoles as Cdk5/p25 kinase inhibitors
  作者：Joydev K. Laha、Xuemei Zhang、Lixin Qiao、Min Liu、Snigdha Chatterjee、Shaughnessy Robinson、Kenneth S. Kosik、Gregory D. Cuny

  DOI：10.1016/j.bmcl.2011.01.140

  日期：2011.4

  Cdk5/p25 has emerged as a principle therapeutic target for numerous acute and chronic neurodegenerative diseases, including Alzheimer's disease. A structure-activity relationship study of 2,4-diaminothiazole inhibitors revealed that increased Cdk5/p25 inhibitory activity could be accomplished by incorporating pyridines on the 2-amino group and addition of substituents to the 2- or 3-position of the phenyl ketone moiety. Interpretation of the SAR results for many of the analogs was aided through in silico docking with Cdk5/p25 and calculating protein hydrations sites using WaterMap. Finally, improved in vitro mouse microsomal stability was also achieved. (C) 2011 Elsevier Ltd. All rights reserved.