ethyl 2-((4-fluorophenyl)amino)thiazole-4-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 2-((4-fluorophenyl)amino)thiazole-4-carboxylate
• 英文别名: ethyl 2-p-fluoroanilinothiazole-4-carboxylate；Ethyl 4-((4-fluorophenyl)amino)-3,5-thiazolecarboxylate；ethyl 2-(4-fluoroanilino)-1,3-thiazole-4-carboxylate
• 化学式: C₁₂H₁₁FN₂O₂S
• mdl: MFCD22577411
• 分子量: 266.296
• InChiKey: YKABYQPSVFYYFG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 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：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 2-((4-fluorophenyl)amino)thiazole-4-carboxylate 在 乙醇 、 sodium hydroxide 作用下， 生成 2-[(4-fluorophenyl)amino]-1,3-thiazole-4-carboxylic acid
  参考文献：
  名称：

  4-取代甲氧基苯甲酰基-芳基-噻唑类似物的设计、合成和 SAR 研究作为有效和口服生物可利用的抗癌剂

  摘要：

  为了继续改进之前发表的 4-取代甲氧基苯甲酰基-芳基-噻唑 (SMART) 模板，我们探索了化学多样性的“B”环和“B”到“C”环的连接。此外，为了克服该系列试剂水溶性差的问题，我们引入了极性和可离子化的亲水基团以获得水溶性化合物。例如，基于体内药代动力学 (PK) 研究，设计并合成了一种口服生物可利用的苯基-氨基-噻唑 (PAT) 模板，其中在化合物1 的“A”和“B”环之间插入了一个氨基键. PAT 模板通过抑制微管蛋白聚合保持了对癌细胞系的纳摩尔 (nM) 范围效力，并且在体外不易受到 P-糖蛋白介导的多药耐药性的影响，与 SMART 模板相比，溶解度和生物利用度显着提高 ( 45a – c (PAT)与1（智能））。

  DOI：

  10.1021/jm2003427
• 作为产物：
  描述：

  丙酮酸乙酯 在 溴 、 sodium carbonate 作用下， 以 neat (no solvent) 为溶剂， 生成 ethyl 2-((4-fluorophenyl)amino)thiazole-4-carboxylate
  参考文献：
  名称：

  无溶剂合成bacillamide类似物作为新型细胞毒性和抗炎药

  摘要：

  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

  DOI：

  10.1016/j.ejmech.2016.07.033

文献信息

• Thiazole derivatives, their preparation and their use in the treatment
  申请人：Sankyo Company Limited

  公开号：US04933355A1

  公开（公告）日：1990-06-12

  Compounds of formula (I): ##STR1## in which: R.sup.1 and R.sup.2 are independently hydrogen, alkyl, aliphatic hydrocarbon groups having one or two carbon-carbon double or treble bonds, cycloalkyl, aryl, substituted aryl, aralkyl, substituted aralkyl, alkanoyl, alkenyol, cycloalkylcarbonyol, arylcarbonyl, substituted arylcarbonyl, arylalkanoyl, substituted arylalkanoyl, arylalkenoyl, substituted arylalkenoyl, alkoxycarbonyl, aryloxycarbonyl, substituted aryloxycarbonyl, aralkyloxycarbonyl, substituted aralkyloxycarbonyl, optionally substituted carbamoyl or thiocarbamoyol, alkylsulfonyl, haloalkylsulfonyl, arylsulfonyl, substituted arylsulfonyl, alkylthio, arylthio and substituted arylthio, or R.sup.1 and R.sup.2, together with the nitrogen atom to which they are attached, form a nitrogen-containing heterocyclic group; one of R.sup.a and R.sup.b is hydrogen, alkyl or halogen, and the other of R.sup.a and R.sup.b is a group of formula (II): ##STR2## R.sup.4 is hydrogen, carboxy, protected carboxy or optionally substituted carbamoyl; R.sup.5 is hydrogen, or carboxyalkyl or protected carboxyalkyl in which the alkyl part is C.sub.1 -C.sub.6 ; n=0, 1 or 2; X is oxygen or sulfur; are useful in the treatment of the complications attendant upon diabetes and may be prepared by condensation of a thiazolidine or rhodanine compound with a compound corresponding to the remainder of the molecule of the compound of formula (I).

  式(I)的化合物：##STR1##其中：R.sup.1和R.sup.2分别是氢、烷基、具有一个或两个碳-碳双键或三键的脂肪烃基、环烷基、芳基、取代的芳基、芳基烷基、取代的芳基烷基、烷酰基、烯酰基、环烷基羰基、芳基羰基、取代的芳基羰基、芳基烷酰基、取代的芳基烷酰基、芳基烯酰基、取代的芳基烯酰基、烷氧羰基、芳氧羰基、取代的芳氧羰基、芳基烷氧羰基、取代的芳基烷氧羰基、可选地取代的氨基甲酰基或硫代氨基甲酰基、烷磺酰基、卤代烷基磺酰基、芳基磺酰基、取代的芳基磺酰基、烷硫基、芳硫基和取代的芳硫基，或R.sup.1和R.sup.2与它们连接的氮原子一起形成含氮杂环基团；R.sup.a和R.sup.b中的一个是氢、烷基或卤素，另一个是具有式(II)的基团：##STR2##R.sup.4是氢、羧基、保护羧基或可选地取代的氨基甲酰基；R.sup.5是氢，或者是碳链部分为C.sub.1-C.sub.6的羧基烷基或保护羧基烷基；n=0, 1或2；X是氧或硫；这些化合物在治疗糖尿病并发症方面是有用的，可以通过将噻唑烷或罗丹宁化合物与符合式(I)的化合物的分子余下部分对应的化合物缩合来制备。
• Thiazole derivatives, their preparation and their use in the treatment of diabetes complications
  申请人：Sankyo Company Limited

  公开号：EP0337819A1

  公开（公告）日：1989-10-18

  Compounds of formula (I): in which: R1 and R2 are independently hydrogen, alkyl, aliphatic hydrocarbon groups having one or two carbon-carbon double or treble bonds, cycloalkyl, aryl, substituted aryl, aralkyl, substituted aralkyl, alkanoyl, alkenoyl, cycloalkylcarbonyl, arylcarbonyl, substituted arylcaronyl, arylalkanoyl, substituted arylalkanoyl, arylalkenoyl, substituted arylalkenoyl, alkoxycarbonyl, aryloxycarbonyl, substituted aryloxycarbonyl, aralkyloxycarbonyl, substituted aralkyloxycarbonyl, optionally substituted carbamoyl or thiocarbamoyl, alkylsulphonyl, haloalkylsulphonyl, arylsulphonyl, substituted arylsulphonyl, alkylthio, arylthio and substituted arylthio, or R1 and R2, together with the nitrogen atom to which they are attached, form a nitrogen-containing heterocyclic group; one of Ra and Rb is hydrogen, alkyl or halogen, and the other of Ra and Rb is a group of formula (II): R4 is hydrogen, carboxy, protected carboxy or optionally substituted carbamoyl; R5 is hydrogen, or carboxyalkyl or protected carboxyalkyl in which the alkyl part is C1 -Cs; n = 0, 1 or 2; X is oxygen or sulphur; are useful in the treatment of the complications attendant upon diabetes and may be prepared by condensation of a thiazolidine or rhodanine compound with a compound corresponding to the remainder of the molecule of the compound of formula (I).

  式(I)化合物： 其中 R1 和 R2 独立地为氢、烷基、具有一个或两个碳碳双键或三键的脂族烃基、环烷基、芳基、取代芳基、烷酰基、烯酰基、环烷基羰基、芳基羰基、取代芳基羰基、芳基烷酰基、取代芳基烷酰基、芳基烯酰基、取代芳基烯酰基、烷氧基羰基、芳氧基羰基、芳氧基羰基、芳烷氧基羰基、取代芳氧基羰基、芳烷氧基羰基、芳烷氧基羰基、取代芳烷氧基羰基、选择性取代氨基甲酰基或硫代氨基甲酰基、烷氧基羰基、芳氧基羰基、取代的芳氧基羰基、烷氧基羰基、取代的芳氧基羰基、任选取代的氨基甲酰基或硫代氨基甲酰基、烷基磺酰基、卤代烷基磺酰基、芳基磺酰基、取代的芳基磺酰基、烷硫基、芳硫基和取代的芳硫基，或 R1 和 R2 与它们所连接的氮原子一起形成含氮杂环基团；Ra 和 Rb 中的一个是氢、烷基或卤素，Ra 和 Rb 中的另一个是式 (II) 基团： R4 是氢、羧基、受保护的羧基或任选取代的氨基甲酰基；R5 是氢、羧基烷基或受保护的羧基烷基，其中烷基部分是 C1-Cs；n = 0、1 或 2；X 是氧或硫； 可通过噻唑烷或罗丹宁化合物与对应于式（I）化合物分子剩余部分的化合物缩合制备。
• WO2006/58905
  申请人：——

  公开号：——

  公开（公告）日：——
• Ethyl 2-((4-Chlorophenyl)amino)thiazole-4-carboxylate and Derivatives Are Potent Inducers of Oct3/4
  作者：Xinlai Cheng、Hiroki Yoshida、Dena Raoofi、Sawsan Saleh、Hamed Alborzinia、Frank Wenke、Axel Göhring、Stefanie Reuter、Nancy Mah、Heiko Fuchs、Miguel A. Andrade-Navarro、James Adjaye、Sheraz Gul、Jochen Utikal、Ralf Mrowka、Stefan Wölfl

  DOI：10.1021/acs.jmedchem.5b00226

  日期：2015.8.13

  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.
• US4933355A
  申请人：——

  公开号：US4933355A

  公开（公告）日：1990-06-12