2-methoxy-13,14-dihydronaphtho[2,1-a]pyrrolo[3,4-c]carbazole-5-one | 856693-49-7

• 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: 2-methoxy-13,14-dihydronaphtho[2,1-a]pyrrolo[3,4-c]carbazole-5-one
• 英文别名: 20-Methoxy-3,13-diazahexacyclo[14.8.0.0^{2,10}.0^{4,9}.0^{11,15}.0^{17,22}]tetracosa-1(16),2(10),4(9),5,7,11(15),17(22),18,20-nonaen-14-one；20-methoxy-3,13-diazahexacyclo[14.8.0.02,10.04,9.011,15.017,22]tetracosa-1(16),2(10),4,6,8,11(15),17(22),18,20-nonaen-14-one
• CAS: 856693-49-7
• 化学式: C₂₃H₁₈N₂O₂
• 分子量: 354.408
• InChiKey: PKGQDPNUCJTZSZ-UHFFFAOYSA-N

物化性质

• 沸点：
  745.5±60.0 °C(Predicted)
• 密度：
  1.372±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  27
• 可旋转键数：
  1
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  54.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-methoxy-13,14-dihydronaphtho[2,1-a]pyrrolo[3,4-c]carbazole-5-one 在 aluminum (III) chloride 、 乙硫醇 、 盐酸 作用下， 以 1,2-二氯乙烷 、 乙二醇二乙醚 、 水 为溶剂， 反应 0.5h， 生成 2-hydroxy-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-2,13-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

文献信息

• Novel fused pyrrolocarbazoles
  申请人：Hudkins L. Robert

  公开号：US20050143442A1

  公开（公告）日：2005-06-30

  The present invention relates generally to selected fused pyrrolocarbazoles, including pharmaceutical compositions thereof and methods of treating diseases therewith. The present invention is also directed to intermediates and processes for making these fused pyrrolocarbazoles.

  本发明一般涉及选定的融合吡咯咯噻唑，包括其药物组合物以及用于治疗疾病的方法。本发明还涉及制备这些融合吡咯咯噻唑的中间体和方法。
• Novel Fused Pyrrolocarbazoles
  申请人：Becknell Nadine C.

  公开号：US20100152196A1

  公开（公告）日：2010-06-17

  The present invention relates generally to selected fused pyrrolocarbazoles, including pharmaceutical compositions thereof and methods of treating diseases therewith. The present invention is also directed to intermediates and processes for making these fused pyrrolocarbazoles.
• US7169802B2
  申请人：——

  公开号：US7169802B2

  公开（公告）日：2007-01-30
• US7671064B2
  申请人：——

  公开号：US7671064B2

  公开（公告）日：2010-03-02
• US8044064B2
  申请人：——

  公开号：US8044064B2

  公开（公告）日：2011-10-25