(R)-3-benzyl-4-(cyclopropyl(4-(2,5-dichlorophenyl)thiazol-2-yl)amino)-4-oxobutanoic acid | 1229363-11-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-3-benzyl-4-(cyclopropyl(4-(2,5-dichlorophenyl)thiazol-2-yl)amino)-4-oxobutanoic acid
• 英文别名: (3R)-3-benzyl-4-[cyclopropyl-[4-(2,5-dichlorophenyl)-1,3-thiazol-2-yl]amino]-4-oxobutanoic acid
• CAS: 1229363-11-4
• 化学式: C₂₃H₂₀Cl₂N₂O₃S
• 分子量: 475.395
• InChiKey: LCRQPJWEPVZEBE-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  98.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-溴-1-(2,5-二氯苯基)乙酮 在 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 1.0h， 生成 (R)-3-benzyl-4-(cyclopropyl(4-(2,5-dichlorophenyl)thiazol-2-yl)amino)-4-oxobutanoic acid
  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

• COMPOUNDS, PHARMACEUTICAL COMPOSITION AND METHODS FOR USE IN TREATING METABOLIC DISORDERS
  申请人：Hoveyda Hamid

  公开号：US20110230477A1

  公开（公告）日：2011-09-22

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

  本发明涉及式（I）的新化合物及其在治疗代谢性疾病方面的应用。
• Compounds, pharmaceutical composition and methods for use in treating metabolic disorders
  申请人：Euroscreen S.A.

  公开号：EP2364297A1

  公开（公告）日：2011-09-14
• [EN] COMPOUNDS, PHARMACEUTICAL COMPOSITION AND METHODS FOR USE IN TREATING METABOLIC DISORDERS<br/>[FR] COMPOSÉS, COMPOSITION PHARMACEUTIQUE ET MÉTHODES POUR APPLICATION AU TRAITEMENT DE TROUBLES MÉTABOLIQUES
  申请人：EUROSCREEN SA

  公开号：WO2010066682A1

  公开（公告）日：2010-06-17

  The present invention is directed to novel compounds of formula (I) and their use in treating metabolic diseases.
• [EN] COMPOUNDS, PHARMACEUTICAL COMPOSITION AND METHODS FOR USE IN TREATING GASTROINTESTINAL DISORDERS<br/>[FR] COMPOSÉS, COMPOSITION PHARMACEUTIQUE ET PROCÉDÉS POUR UTILISATION DANS LE TRAITEMENT DE TROUBLES GASTRO-INTESTINAUX
  申请人：EUROSCREEN SA

  公开号：WO2011076732A1

  公开（公告）日：2011-06-30

  The present invention relates to compounds of formula (I) useful in treating and/or preventing gastrointestinal disorders.
• [EN] COMPOUNDS, PHARMACEUTICAL COMPOSITION AND METHODS FOR USE IN TREATING INFLAMMATORY DISEASES<br/>[FR] COMPOSÉS, COMPOSITION PHARMACEUTIQUE ET PROCÉDÉS POUR UTILISATION DANS LE TRAITEMENT DE MALADIES INFLAMMATOIRES
  申请人：EUROSCREEN SA

  公开号：WO2011076734A1

  公开（公告）日：2011-06-30

  The present invention relates to compounds of formula (I) (I) useful in treating and/or preventing inflammatory diseases.