ethyl 2-amino-4-cyclopropylthiazole-5-carboxylate | 1205561-31-4

• 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-amino-4-cyclopropylthiazole-5-carboxylate
• 英文别名: Ethyl 2-amino-4-cyclopropyl-1,3-thiazole-5-carboxylate
• CAS: 1205561-31-4
• 化学式: C₉H₁₂N₂O₂S
• 分子量: 212.272
• InChiKey: WWOBXWRMODSKOF-UHFFFAOYSA-N

物化性质

• 沸点：
  363.9±30.0 °C(Predicted)
• 密度：
  1.353±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  2.0
• 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：

  ethyl 2-amino-4-cyclopropylthiazole-5-carboxylate 在 盐酸 、 potassium trimethylsilonate 、 sodium hydride 、 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 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 mineral oil 为溶剂， 反应 55.0h， 生成 4-cyclopropyl-N-(trans-5-hydroxy-2-adamantyl)-2-(2-hydroxyethoxy)thiazole-5-carboxamide
  参考文献：
  名称：

  Optimization of Brain Penetrant 11β-Hydroxysteroid Dehydrogenase Type I Inhibitors and in Vivo Testing in Diet-Induced Obese Mice

  摘要：

  11 beta-Hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) has been widely considered by the pharmaceutical industry as a target to treat metabolic syndrome in type II diabetics. We hypothesized that central nervous system (CNS) penetration might be required to see efficacy. Starting from a previously reported pyrimidine compound, we removed hydrogen-bond donors to yield 3, which had modest CNS penetration. More significant progress was achieved by changing the core to give 40, which combines good potency and CNS penetration. Compound 40 was dosed to diet-induced obese (DIO) mice and gave excellent target engagement in the liver and high free exposures of drug, both peripherally and in the CNS. However, no body weight reduction or effects on glucose or insulin were observed in this model. Similar data were obtained with a structurally diverse thiazole compound 51. This work casts doubt on the hypothesis that localized tissue modulation of 11 beta-HSD1 activity alleviates metabolic syndrome.

  DOI：

  10.1021/jm4016729
• 作为产物：
  描述：

  3-环丙基-3-羰基-丙酸乙酯 在 氯化亚砜 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 ethyl 2-amino-4-cyclopropylthiazole-5-carboxylate
  参考文献：
  名称：

  Optimization of Brain Penetrant 11β-Hydroxysteroid Dehydrogenase Type I Inhibitors and in Vivo Testing in Diet-Induced Obese Mice

  摘要：

  11 beta-Hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) has been widely considered by the pharmaceutical industry as a target to treat metabolic syndrome in type II diabetics. We hypothesized that central nervous system (CNS) penetration might be required to see efficacy. Starting from a previously reported pyrimidine compound, we removed hydrogen-bond donors to yield 3, which had modest CNS penetration. More significant progress was achieved by changing the core to give 40, which combines good potency and CNS penetration. Compound 40 was dosed to diet-induced obese (DIO) mice and gave excellent target engagement in the liver and high free exposures of drug, both peripherally and in the CNS. However, no body weight reduction or effects on glucose or insulin were observed in this model. Similar data were obtained with a structurally diverse thiazole compound 51. This work casts doubt on the hypothesis that localized tissue modulation of 11 beta-HSD1 activity alleviates metabolic syndrome.

  DOI：

  10.1021/jm4016729

文献信息

• [EN] FLUORALKENYL COMPOUNDS, PROCESS FOR PREPARATION AND USE THEREOF<br/>[FR] COMPOSÉS FLUOROALCÉNYLES, PROCÉDÉ POUR LEUR PRÉPARATION ET LEUR UTILISATION
  申请人：PI INDUSTRIES LTD

  公开号：WO2019123196A1

  公开（公告）日：2019-06-27

  The present invention disclosed fluoralkenyl compounds of general formula (I), wherein; R, R1, R2, R3, A and integers n, m and k are as defined in description. The present invention further discloses use of the compounds of general formula (I) to protect crops by controlling or preventing against undesired phytopathogenic microorganisms such as nematodes and phytopathogenic fungi.

  本发明揭示了一般式（I）的氟烯基化合物，其中；R、R1、R2、R3、A和整数n、m和k的定义如描述所示。本发明进一步揭示了利用一般式（I）的化合物来通过控制或预防线虫和植物病原真菌等不受欢迎的植物病原微生物来保护作物。
• [EN] THIAZOLE DERIVATIVES AS STEAROYL COA DESATURASE INHIBITORS<br/>[FR] DÉRIVÉS DE THIAZOLE EN TANT QU'INHIBITEURS DE STÉAROYL-COA DÉSATURASE
  申请人：GLENMARK PHARMACEUTICALS SA

  公开号：WO2010007482A3

  公开（公告）日：2010-12-02
• FLUORALKENYL COMPOUNDS, PROCESS FOR PREPARATION AND USE THEREOF
  申请人：PI Industries Ltd.

  公开号：EP3728204A1

  公开（公告）日：2020-10-28