2-[4-(1-Aminoethyl)phenyl]-1lambda6,2-thiazolidine-1,1-dione | 1016744-86-7

• 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: 2-[4-(1-Aminoethyl)phenyl]-1lambda6,2-thiazolidine-1,1-dione
• 英文别名: 1-[4-(1,1-dioxo-1,2-thiazolidin-2-yl)phenyl]ethanamine
• CAS: 1016744-86-7
• 化学式: C₁₁H₁₆N₂O₂S
• mdl: MFCD09813596
• 分子量: 240.326
• InChiKey: ZYDYTIIIADYIDK-UHFFFAOYSA-N

物化性质

• 沸点：
  407.2±47.0 °C(Predicted)
• 密度：
  1.279±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.454
• 拓扑面积：
  71.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-甲基-5-苯基-2H-吡唑-3-甲酸 、 2-[4-(1-Aminoethyl)phenyl]-1lambda6,2-thiazolidine-1,1-dione 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 二甲基亚砜 为溶剂， 反应 1.58h， 以92%的产率得到N-{1-[4-(1,1-dioxo-1λ⁶,2-thiazolidin-2-yl)phenyl]ethyl}-1-methyl-3-phenyl-1H-pyrazole-5-carboxamide
  参考文献：
  名称：

  Intracellular Trapping of the Selective Phosphoglycerate Dehydrogenase (PHGDH) Inhibitor BI-4924 Disrupts Serine Biosynthesis

  摘要：

  Phosphoglycerate dehydrogenase (PHGDH) is known to be the rate-limiting enzyme in the serine synthesis pathway in humans. It converts glycolysis-derived 3-phosphoglycerate to 3-phosphopyruvate in a co-factor-dependent oxidation reaction. Herein, we report the discovery of BI-4916, a prodrug of the co-factor nicotinamide adenine dinucleotide (NADH/NAD(+))-competitive PHGDH inhibitor BI-4924, which has shown high selectivity against the majority of other dehydrogenase targets. Starting with a fragment-based screening, a subsequent hit optimization using structure-based drug design was conducted to deliver a single-digit nanomolar lead series and to improve potency by 6 orders of magnitude. To this end, an intracellular ester cleavage mechanism of the ester prodrug was utilized to achieve intracellular enrichment of the actual carboxylic acid based drug and thus overcome high cytosolic levels of the competitive cofactors NADH/NAD(+).

  DOI：

  10.1021/acs.jmedchem.9b00718