ethyl 4-(2-amino-1,3-thiazol-4-yl)butanoate | 154404-96-3

• 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 4-(2-amino-1,3-thiazol-4-yl)butanoate
• 英文别名: Ethyl 2-amino-4-thiazolebutanoate
• CAS: 154404-96-3
• 化学式: C₉H₁₄N₂O₂S
• 分子量: 214.288
• InChiKey: KQSHBCRHDPATSR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  14
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 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：

  4-(((2-(trifluoromethyl)phenyl)amino)methyl)benzoic acid 、 ethyl 4-(2-amino-1,3-thiazol-4-yl)butanoate 在 吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 生成
  参考文献：
  名称：

  Discovery of potent liver-selective stearoyl-CoA desaturase-1 (SCD1) inhibitors, thiazole-4-acetic acid derivatives, for the treatment of diabetes, hepatic steatosis, and obesity

  摘要：

  SCD1 is a rate-limiting enzyme in the conversion of saturated fatty acids to monounsaturated fatty acids. SCD1 inhibitors have potential effects on obesity, diabetes, acne, and cancer, but the adverse effects associated with SCD1 inhibition in the skin and eyelids are impediments to clinical development. To avoid mechanism-based adverse effects, we explored the compounds that selectively inhibit SCD1 in the liver in an ex vivo assay. Starting from a systemically active lead compound, we focused on the physicochemical properties tPSA and cLogP to minimize exposure in the off-target tissues. This effort led to the discovery of thiazole-4-acetic acid analog 48 as a potent and liver-selective SCD1 inhibitor. Compound 48 exhibited significant effects in rodent models of diabetes, hepatic steatosis, and obesity, with sufficient safety margins in a rat toxicology study with repeated dosing. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.09.003
• 作为产物：
  描述：

  硫脲 、 dimethyl (1,2-epoxy-3-oxo-cyclohex-1-yl)phosphonate 以 乙醇 为溶剂， 反应 168.0h， 以6%的产率得到ethyl 4-(2-amino-1,3-thiazol-4-yl)butanoate
  参考文献：
  名称：

  A new heteroannulation method to 2-cyclohexenone, mediated by phosphonate auxiliaries. Synthesis of 4,5,6,7-tetrahydrobenzothiazole derivatives

  摘要：

  Dimethyl (1,2-epoxy-3-oxocyclohex-1-yl)phosphonate 7, easily available from 2-cyclohexen-1-one, affords the new (tetrahydrobenzothiazolyl)phosphonates 10 upon reaction with thiocarboxamides 8. This cyclocondensation proceeds with regioselective conjunction of the bis-nucleophile 8 to carbonyl group and adjacent oxirane carbon of the epoxide precursor. On treatment with alkali the 5,6-dihydro-7(4H)benzothiazolones 12 are obtained from compounds 10, or from the intermediately formed bicyclic dihydroxy derivatives 9. Reaction of the corresponding cyclopentylphosphonate 14 with thiobenzamide (8b) yields the cyclopentathiazole derivative 15 as a single isomer, the dihydro-thiazole moiety being now annulated regio- and cis-stereoselectively to both oxirane carbons of the epoxyphosphonate.

  DOI：

  10.1007/bf00817312

文献信息

• Discovery of potent liver-selective stearoyl-CoA desaturase-1 (SCD1) inhibitors, thiazole-4-acetic acid derivatives, for the treatment of diabetes, hepatic steatosis, and obesity
  作者：Tetsuya Iida、Minoru Ubukata、Ikuo Mitani、Yuichi Nakagawa、Katsuya Maeda、Hiroto Imai、Yosuke Ogoshi、Takahiro Hotta、Shohei Sakata、Ryuhei Sano、Hisayo Morinaga、Tamotsu Negoro、Shinichi Oshida、Masahiro Tanaka、Takashi Inaba

  DOI：10.1016/j.ejmech.2018.09.003

  日期：2018.10

  SCD1 is a rate-limiting enzyme in the conversion of saturated fatty acids to monounsaturated fatty acids. SCD1 inhibitors have potential effects on obesity, diabetes, acne, and cancer, but the adverse effects associated with SCD1 inhibition in the skin and eyelids are impediments to clinical development. To avoid mechanism-based adverse effects, we explored the compounds that selectively inhibit SCD1 in the liver in an ex vivo assay. Starting from a systemically active lead compound, we focused on the physicochemical properties tPSA and cLogP to minimize exposure in the off-target tissues. This effort led to the discovery of thiazole-4-acetic acid analog 48 as a potent and liver-selective SCD1 inhibitor. Compound 48 exhibited significant effects in rodent models of diabetes, hepatic steatosis, and obesity, with sufficient safety margins in a rat toxicology study with repeated dosing. (C) 2018 Elsevier Masson SAS. All rights reserved.
• A new heteroannulation method to 2-cyclohexenone, mediated by phosphonate auxiliaries. Synthesis of 4,5,6,7-tetrahydrobenzothiazole derivatives
  作者：E. �hler

  DOI：10.1007/bf00817312

  日期：——

  Dimethyl (1,2-epoxy-3-oxocyclohex-1-yl)phosphonate 7, easily available from 2-cyclohexen-1-one, affords the new (tetrahydrobenzothiazolyl)phosphonates 10 upon reaction with thiocarboxamides 8. This cyclocondensation proceeds with regioselective conjunction of the bis-nucleophile 8 to carbonyl group and adjacent oxirane carbon of the epoxide precursor. On treatment with alkali the 5,6-dihydro-7(4H)benzothiazolones 12 are obtained from compounds 10, or from the intermediately formed bicyclic dihydroxy derivatives 9. Reaction of the corresponding cyclopentylphosphonate 14 with thiobenzamide (8b) yields the cyclopentathiazole derivative 15 as a single isomer, the dihydro-thiazole moiety being now annulated regio- and cis-stereoselectively to both oxirane carbons of the epoxyphosphonate.