4-(2-(6-(1H-pyrazol-1-yl)pyridin-3-yl)phenyl)-N-cyclopropylthiazol-2-amine | 1351523-97-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-(2-(6-(1H-pyrazol-1-yl)pyridin-3-yl)phenyl)-N-cyclopropylthiazol-2-amine
• 英文别名: N-cyclopropyl-4-[2-(6-pyrazol-1-ylpyridin-3-yl)phenyl]-1,3-thiazol-2-amine
• CAS: 1351523-97-1
• 化学式: C₂₀H₁₇N₅S
• 分子量: 359.454
• InChiKey: QDTNUZNOPRDHES-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  83.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(2-(6-(1H-pyrazol-1-yl)pyridin-3-yl)phenyl)-N-cyclopropylthiazol-2-amine 、 (2R)-2-(环戊基甲基)-丁二酸 4-叔丁酯 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 乙腈 为溶剂， 以57%的产率得到tert-butyl (R)-4-((4-(2-(6-(1H-pyrazol-1-yl)pyridin-3-yl)phenyl)thiazol-2-yl)(cyclopropyl)amino)-3-(cyclopentylmethyl)-4-oxobutanoate
  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
• 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 13.75h， 生成 4-(2-(6-(1H-pyrazol-1-yl)pyridin-3-yl)phenyl)-N-cyclopropylthiazol-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

文献信息

• [EN] NOVEL COMPOUNDS, PHARMACEUTICAL COMPOSITION AND METHODS FOR USE IN TREATING METABOLIC DISORDERS<br/>[FR] NOUVEAUX COMPOSÉS, LEURS COMPOSITIONS PHARMACEUTIQUES ET MÉTHODES D'UTILISATION DANS LE TRAITEMENT DE TROUBLES MÉTABOLIQUES
  申请人：EUROSCREEN SA

  公开号：WO2011151434A1

  公开（公告）日：2011-12-08

  The present invention is directed to novel compounds of formula (I) and their use in treating metabolic diseases.

  本发明涉及公式（I）的新化合物及其在治疗代谢性疾病中的应用。