N-(5-acetyl-4-methylthiazol-2-yl)-2,2-diphenylacetamide

• 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: N-(5-acetyl-4-methylthiazol-2-yl)-2,2-diphenylacetamide
• 英文别名: IGS-2.68；N-(5-acetyl-4-methyl-1,3-thiazol-2-yl)-2,2-diphenylacetamide
• 化学式: C₂₀H₁₈N₂O₂S
• 分子量: 350.441
• InChiKey: DRLPCECXQVGBMI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  87.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  二苯基乙酰氯 、 5-乙酰基-2-氨基-4-甲基噻唑 以 四氢呋喃 为溶剂， 反应 0.17h， 以37%的产率得到N-(5-acetyl-4-methylthiazol-2-yl)-2,2-diphenylacetamide
  参考文献：
  名称：

  Deciphering the Inhibition of the Neuronal Calcium Sensor 1 and the Guanine Exchange Factor Ric8a with a Small Phenothiazine Molecule for the Rational Generation of Therapeutic Synapse Function Regulators

  摘要：

  Protein-protein interactions (PPIs) are known to play an essential role between the neuronal calcium sensor 1 (NCS-l) and the guanine exchange factor Ric8a to regulate synapse function, emerging as a draggable interface for synaptopathies such as the fragile X syndrome (FXS). Recently, the phenothiazine FD44 has been identified as an inhibitor of this PPI, decreasing the abnormally high synapse number and enhancing associative learning in a FXS animal model.Here, we have integrated advanced experimental and computational studies to obtain important structural insights into Drosophila NCS-1/FD44 recognition to understand the basis of its affinity and specificity and generate improved PPI regulators. This has allowed the identification of a new small drug-liKe molecule, IGS-1.76, which efficiently inhibits the human NCS-l/Ric8a complex with improved binding potency. The crystal structure of the Drosophila NCS-l/IGS-1.76 complex demonstrates that the new inhibitor, although chemically different from FD44, shares the same mechanism of action and constitutes a new hit candidate for FXS.

  DOI：

  10.1021/acs.jmedchem.8b00088

文献信息

• FLAVOR COMPOSITIONS AND PET FOOD PRODUCTS CONTAINING THE SAME
  申请人：Mars, Incorporated

  公开号：EP3229610B1

  公开（公告）日：2021-06-09