ethyl 8-cyano-4-methoxy-2,13-dihydro-1H-naphtho[2,1-a]carbazole-7-carboxylate | 263141-91-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: ethyl 8-cyano-4-methoxy-2,13-dihydro-1H-naphtho[2,1-a]carbazole-7-carboxylate
• CAS: 263141-91-9
• 化学式: C₂₅H₂₀N₂O₃
• 分子量: 396.445
• InChiKey: MMRVAMRHYWRPRI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.14
• 重原子数：
  30.0
• 可旋转键数：
  3.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  75.11
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  ethyl 8-cyano-4-methoxy-2,13-dihydro-1H-naphtho[2,1-a]carbazole-7-carboxylate 在 氢气 、 镍 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 2-methoxy-13,14-dihydronaphtho[2,1-a]pyrrolo[3,4-c]carbazole-5-one
  参考文献：
  名称：

  Mixed-Lineage Kinase 1 and Mixed-Lineage Kinase 3 Subtype-Selective Dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5-ones: Optimization, Mixed-Lineage Kinase 1 Crystallography, and Oral in Vivo Activity in 1-Methyl-4-phenyltetrahydropyridine Models

  摘要：

  The optimization of the dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5-one R(2) and R(12) positions led to the identification of the first MLK1 and MLK3 subtype-selective inhibitors within the MLK family. Compounds 14 (CEP-5104) and 16 (CEP-6331) displayed good potency for MLK1 and MLK3 inhibition with a greater than 30- to 100-fold selectivity for related family members MLK2 and DLK. Compounds 14 and 16 were orally active in vivo in a mouse MPTP biochemical efficacy model that was comparable to the first-generation pan-MLK inhibitor 1 (CEP-1347). The MLK1 structure-activity relationships were supported by the first-reported X-ray crystal structure of MLK1 bound with 16.

  DOI：

  10.1021/jm8005838
• 作为产物：
  描述：

  ethyl 8-cyano-4-methoxy-2,6b,7,8,13,13b-hexahydro-1H-naphtho[2,1-a]carbazole-7-carboxylate 在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 甲苯 为溶剂， 反应 1.0h， 以99%的产率得到ethyl 8-cyano-4-methoxy-2,13-dihydro-1H-naphtho[2,1-a]carbazole-7-carboxylate
  参考文献：
  名称：

  Mixed-Lineage Kinase 1 and Mixed-Lineage Kinase 3 Subtype-Selective Dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5-ones: Optimization, Mixed-Lineage Kinase 1 Crystallography, and Oral in Vivo Activity in 1-Methyl-4-phenyltetrahydropyridine Models

  摘要：

  The optimization of the dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5-one R(2) and R(12) positions led to the identification of the first MLK1 and MLK3 subtype-selective inhibitors within the MLK family. Compounds 14 (CEP-5104) and 16 (CEP-6331) displayed good potency for MLK1 and MLK3 inhibition with a greater than 30- to 100-fold selectivity for related family members MLK2 and DLK. Compounds 14 and 16 were orally active in vivo in a mouse MPTP biochemical efficacy model that was comparable to the first-generation pan-MLK inhibitor 1 (CEP-1347). The MLK1 structure-activity relationships were supported by the first-reported X-ray crystal structure of MLK1 bound with 16.

  DOI：

  10.1021/jm8005838