ethyl 6-cyano-12,13-dihydro-11H-naphtho[2,1-a]carbazole-5-carboxylate | 174349-69-0

• 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 6-cyano-12,13-dihydro-11H-naphtho[2,1-a]carbazole-5-carboxylate
• CAS: 174349-69-0
• 化学式: C₂₄H₁₈N₂O₂
• 分子量: 366.419
• InChiKey: XNSJTJPZEXLOKH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  65.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 6-cyano-12,13-dihydro-11H-naphtho[2,1-a]carbazole-5-carboxylate 、 苄基2-溴乙基醚 在 sodium hydroxide 作用下， 以 水 、 丙酮 为溶剂， 生成
  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 6-cyano-5,6,11,11b,12,13-hexahydro-4bH-naphtho[2,1-a]carbazole-5-carboxylate 在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 甲苯 为溶剂， 生成 ethyl 6-cyano-12,13-dihydro-11H-naphtho[2,1-a]carbazole-5-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

文献信息

• 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
  作者：Robert L. Hudkins、James L. Diebold、Ming Tao、Kurt A. Josef、Chung Ho Park、Thelma S. Angeles、Lisa D. Aimone、Jean Husten、Mark A. Ator、Sheryl L. Meyer、Beverly P. Holskin、John T. Durkin、Alexander A. Fedorov、Elena V. Fedorov、Steven C. Almo、Joanne R. Mathiasen、Donna Bozyczko-Coyne、Michael S. Saporito、Richard W. Scott、John P. Mallamo

  DOI：10.1021/jm8005838

  日期：2008.9.25

  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.