5-chloro-1'-(4-chlorobenzyl)-1-methyl-5',7'-dihydrospiro[indoline-3,4'-pyrazolo[3,4-b]pyridine]-2,6'(1'H)-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5-chloro-1'-(4-chlorobenzyl)-1-methyl-5',7'-dihydrospiro[indoline-3,4'-pyrazolo[3,4-b]pyridine]-2,6'(1'H)-dione
• 英文别名: 5'-chloro-1-[(4-chlorophenyl)methyl]-1'-methylspiro[5,7-dihydropyrazolo[3,4-b]pyridine-4,3'-indole]-2',6-dione
• 化学式: C₂₁H₁₆Cl₂N₄O₂
• 分子量: 427.29
• InChiKey: DQUNEBLYBSKGGA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  29
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  67.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-chloro-1'-(4-chlorobenzyl)-1-methyl-5',7'-dihydrospiro[indoline-3,4'-pyrazolo[3,4-b]pyridine]-2,6'(1'H)-dione 在 Chiralpak IA (4.6x250mm) 5μ 作用下， 生成 (R)-5-chloro-1'-(4-chlorobenzyl)-1-methyl-5',7'-dihydrospiro[indoline-3,4'-pyrazolo[3,4-b]pyridine]-2,6'(1'H)-dione 、 (4S)-5'-chloro-1-[(4-chlorophenyl)methyl]-1'-methylspiro[5,7-dihydropyrazolo[3,4-b]pyridine-4,3'-indole]-2',6-dione
  参考文献：
  名称：

  Lead Optimization of Spiropyrazolopyridones: A New and Potent Class of Dengue Virus Inhibitors

  摘要：

  Spiropyrazolopyridone 1 was identified, as a novel dengue virus (DENY) inhibitor, from a DENV serotype 2 (DENV-2) high throughput phenotypic screen. As a general trend within this chemical class, chiral resolution of the racemate revealed that R enantiomer was significantly more potent than the S. Cell based lead optimization of the spiropyrazolopyridones focusing on improving the physico-chemical properties is described. As a result, an optimal compound 14a, with balanced in vitro potency and pharmacokinetic profile, achieved about 1.9 log viremia reduction at 3 X 50 mg/kg (bid) or 3 X 100 mg/kg (QD) oral doses in the dengue in vivo mouse efficacy model.

  DOI：

  10.1021/ml500521r
• 作为产物：
  描述：

  ethyl 5-amino-1-(4-chlorobenzyl)-1H-pyrazole-4-carboxylate 在 sodium hydroxide 作用下， 以 乙醇 、 水 、 溶剂黄146 为溶剂， 反应 6.0h， 生成 5-chloro-1'-(4-chlorobenzyl)-1-methyl-5',7'-dihydrospiro[indoline-3,4'-pyrazolo[3,4-b]pyridine]-2,6'(1'H)-dione
  参考文献：
  名称：

  Lead Optimization of Spiropyrazolopyridones: A New and Potent Class of Dengue Virus Inhibitors

  摘要：

  Spiropyrazolopyridone 1 was identified, as a novel dengue virus (DENY) inhibitor, from a DENV serotype 2 (DENV-2) high throughput phenotypic screen. As a general trend within this chemical class, chiral resolution of the racemate revealed that R enantiomer was significantly more potent than the S. Cell based lead optimization of the spiropyrazolopyridones focusing on improving the physico-chemical properties is described. As a result, an optimal compound 14a, with balanced in vitro potency and pharmacokinetic profile, achieved about 1.9 log viremia reduction at 3 X 50 mg/kg (bid) or 3 X 100 mg/kg (QD) oral doses in the dengue in vivo mouse efficacy model.

  DOI：

  10.1021/ml500521r