(2-aminothiazol-5-yl)(4-methoxyphenyl)methanone | 27053-23-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2-aminothiazol-5-yl)(4-methoxyphenyl)methanone
• 英文别名: (2-Amino-1,3-thiazol-5-yl)-(4-methoxyphenyl)methanone
• CAS: 27053-23-2
• 化学式: C₁₁H₁₀N₂O₂S
• 分子量: 234.279
• InChiKey: DNMCTKABHCXFNA-UHFFFAOYSA-N

物化性质

• 沸点：
  439.4±25.0 °C(Predicted)
• 密度：
  1.327±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  93.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2-aminothiazol-5-yl)(4-methoxyphenyl)methanone 、 1-(1,3-苯并二氧代l-5-基)环丙烷羧酸 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 以33%的产率得到1-(benzo[d][1,3]dioxol-5-yl)-N-(5-(4-methoxybenzoyl)thiazol-2-yl)cyclopropanecarboxamide
  参考文献：
  名称：

  Discovery of novel VX-809 hybrid derivatives as F508del-CFTR correctors by molecular modeling, chemical synthesis and biological assays

  摘要：

  Cystic fibrosis (CF) is the autosomal recessive disorder most recurrent in Caucasian populations. It is caused by different mutations in the cystic fibrosis transmembrane regulator protein (CFTR) gene, with F508del being the most common. During the last years, small-molecule therapy chosen to contrast CF relied on compounds that correct CFTR misfolding and ER retention (correctors such as VX-809), or defective channel gating (potentiators such as VX-770). Combination therapy with the two series of drugs has been applied, leading to the approval of several multi-drugs such as Orkambi. Despite this, this treatment proved to be only partially effective making the search for novel modulators an urgent need to contrast CF. Recently, we reported compound 2a as reference compound of a series of aminoarylthiazole-VX-809 hybrid derivatives exhibiting promising F508del-CFTR corrector ability. Herein, we report exploring the docking mode of the prototype VX-809 and of 2a in order to derive useful guidelines for the rational design of novel optimized analogues. To demonstrate experimentally their effective F508del-CFTR-binding and rescuing potential, the most promising derivatives had been synthesized and evaluated in biological assays including YFP functional assay on F508del-CFTR CFBE41o-cells, trans epithelial electrical resistance (TEER) and surface plasmon resonance (SPR). This multidisciplinary strategy led to the discovery of a second series of hybrids including 7j and 7m endowed with higher potency than the prototype.

  DOI：

  10.1016/j.ejmech.2020.112833
• 作为产物：
  描述：

  alpha-溴-4-甲氧基苯乙酮 在 三乙胺 、 甲胺 作用下， 以 四氢呋喃 为溶剂， 反应 42.0h， 生成 (2-aminothiazol-5-yl)(4-methoxyphenyl)methanone
  参考文献：
  名称：

  Discovery of novel VX-809 hybrid derivatives as F508del-CFTR correctors by molecular modeling, chemical synthesis and biological assays

  摘要：

  Cystic fibrosis (CF) is the autosomal recessive disorder most recurrent in Caucasian populations. It is caused by different mutations in the cystic fibrosis transmembrane regulator protein (CFTR) gene, with F508del being the most common. During the last years, small-molecule therapy chosen to contrast CF relied on compounds that correct CFTR misfolding and ER retention (correctors such as VX-809), or defective channel gating (potentiators such as VX-770). Combination therapy with the two series of drugs has been applied, leading to the approval of several multi-drugs such as Orkambi. Despite this, this treatment proved to be only partially effective making the search for novel modulators an urgent need to contrast CF. Recently, we reported compound 2a as reference compound of a series of aminoarylthiazole-VX-809 hybrid derivatives exhibiting promising F508del-CFTR corrector ability. Herein, we report exploring the docking mode of the prototype VX-809 and of 2a in order to derive useful guidelines for the rational design of novel optimized analogues. To demonstrate experimentally their effective F508del-CFTR-binding and rescuing potential, the most promising derivatives had been synthesized and evaluated in biological assays including YFP functional assay on F508del-CFTR CFBE41o-cells, trans epithelial electrical resistance (TEER) and surface plasmon resonance (SPR). This multidisciplinary strategy led to the discovery of a second series of hybrids including 7j and 7m endowed with higher potency than the prototype.

  DOI：

  10.1016/j.ejmech.2020.112833

文献信息

• 2-氨基-5-酰基噻唑衍生物及其合成方法
  申请人：湖南中医药大学

  公开号：CN110117263B

  公开（公告）日：2020-12-25

  本发明涉及有机化合物合成技术，公开了一种2‑氨基‑5‑酰基噻唑衍生物及其合成方法。所述2‑氨基‑5‑酰基噻唑衍生物的结构如式(Ⅰ)所示，在式(Ⅰ)中R选自C1‑C12的直链、支链、环状烷基或烯基，取代或未取代的C6‑C12芳基，或者取代或未取代的含有氮原子、氧原子和硫原子中的至少一种的杂环基团；该类化合物的合成方法是在惰性气体氛围中，在反应溶剂和催化剂存在下，β‑酰氧基烯胺类化合物与硫、氰胺进行反应。本发明方法的产率较高，反应体系简单，反应条件温和，用料来源广泛，成本低廉且环境友好。
• Electrochemical enaminone C–H thiolation/C–N amination cascade for thiazole synthesis and its diastereoselective dearomatization
  作者：Haijin Guo、Yunyun Liu、Chengping Wen、Jie-Ping Wan

  DOI：10.1039/d2gc01644c

  日期：——

  An electrochemical method for the synthesis of 2-aminothiazoles via aryl ring construction using enaminones and thioureas is reported. The cascade enamine C–H thiolation and C–N amination constitutes a major transformation for the thiazole ring formation. Moreover, a simple modification of electrochemical conditions enables the tunable dearomatization of the thiazole ring via vicinal dialkoxylation

  报道了一种使用烯胺酮和硫脲通过芳环结构合成 2-氨基噻唑的电化学方法。级联烯胺 C-H 硫醇化和 C-N 胺化构成噻唑环形成的主要转变。此外，对电化学条件的简单修改能够通过连位二烷氧基化对噻唑环进行可调节的脱芳构化，从而合成具有优异非对映选择性的具有季碳中心的 4,5-二烷氧基噻唑啉。
• Cyan dye-releasing compounds for use in the production of diffusion transfer colour images
  申请人：AGFA-GEVAERT naamloze vennootschap

  公开号：EP0216957A1

  公开（公告）日：1987-04-08

  In a dye diffusion transfer process the use of a photosentive element incorporating in operative association with at least one alkali-permeable silver halide hydrophilic colloid emulsion layer at least one redox-controlled dye-releasing compound in ballasted non-diffusing state that can split off selectively image-wise a diffusible cyan azo-thiazole dye in function of development of said silver halide emulsion layer.

  在一种染料扩散转移工艺中，使用一种光敏元件，该元件与至少一个碱渗透性卤化银亲水胶体乳液层有效结合，其中至少有一个氧化还原控制的染料释放化合物处于压载非扩散状态，可根据所述卤化银乳液层的发展情况，选择性地从图像上分离出可扩散的偶氮噻唑青色染料。
• Synthesis of 2-Amino-5-acylthiazoles by a Tertiary Amine-Promoted One-Pot Three-Component Cascade Cyclization Using Elemental Sulfur as a Sulfur Source
  作者：Rong-Geng Fu、Yong Wang、Fei Xia、Hao-Lin Zhang、Yuan Sun、Duo-Wen Yang、Ye-Wei Wang、Peng Yin

  DOI：10.1021/acs.joc.9b02032

  日期：2019.9.20

  A novel one-pot three-component cascade cyclization strategy for the synthesis of 2-amino-5-acylthiazoles using enaminones, cyanamide, and elemental sulfur has been developed. The reported methods have demonstrated good tolerance of various functional groups. Up to 28 2-amino-5-acylthiazole compounds bearing diverse structural differences were successfully synthesized from easily obtained starting materials with moderate to excellent yields. Our method provides an effective way for the access of valuable and potentially bioactive 2-amino-5-acylthiazole derivatives.
• Patel,H. et al., Indian Journal of Chemistry, 1970, vol. 8, p. 376 - 377
  作者：Patel,H. et al.

  DOI：——

  日期：——