N-cyclopropyl-4-phenylthiazol-2-amine | 866769-75-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-cyclopropyl-4-phenylthiazol-2-amine
• 英文别名: N-cyclopropyl-4-phenyl-1,3-thiazol-2-amine
• CAS: 866769-75-7
• 化学式: C₁₂H₁₂N₂S
• mdl: MFCD06196650
• 分子量: 216.307
• InChiKey: URFHHXBOXFVOCY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  53.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2'-溴苯乙酮 在 aluminum (III) chloride 、 正丁基锂 、 溴 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 为溶剂， 反应 7.75h， 生成 (2-(2-(cyclopropylamino)thiazol-4-yl)phenyl)boronic acid 、 N-cyclopropyl-4-phenylthiazol-2-amine
  参考文献：
  名称：

  N-Thiazolylamide-based free fatty-acid 2 receptor agonists: Discovery, lead optimization and demonstration of off-target effect in a diabetes model

  摘要：

  Free fatty acid-2 (FFA2) receptor is a G-protein coupled receptor of interest in the development of therapeutics in metabolic and inflammatory disease areas. The discovery and optimization of an N-thiazolylamide carboxylic acid FFA2 agonist scaffold is described. Dual key objectives were to i) evaluate the potential of this scaffold for lead optimization in particular with respect to safety de-risking physicochemical properties, i.e. lipophilicity and aromatic content, and ii) to demonstrate the utility of selected lead analogues from this scaffold in a pertinent in vivo model such as oral glucose tolerance test (OGTT). As such, a concomitant improvement in bioactivity together with lipophilic ligand efficiency (LLE) and fraction sp3 content (Fsp(3)) parameters guided these efforts. Compound 10 was advanced into studies in mice on the basis of its optimized profile vs initial lead 1 (Delta LLE = 0.3, Delta Fsp(3) = 0.24). Although active in OGTT, 10 also displayed similar activity in the FFA2-knockout mice. Given this off-target OGTT effect, we discontinued development of this FFA2 agonist scaffold.

  DOI：

  10.1016/j.bmc.2018.09.015