2-(3,4-dihydronaphth-2-yl)-1H-indole | 174349-62-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-(3,4-dihydronaphth-2-yl)-1H-indole
• 英文别名: 2-(3,4-dihydronaphthalen-2-yl)-1H-indole
• CAS: 174349-62-3
• 化学式: C₁₈H₁₅N
• 分子量: 245.324
• InChiKey: UISXPDDRBNEQBG-UHFFFAOYSA-N

物化性质

• 熔点：
  179-180 °C(Solv: methanol (67-56-1))
• 沸点：
  443.8±24.0 °C(Predicted)
• 密度：
  1.201±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  15.8
• 氢给体数：
  1
• 氢受体数：
  0

反应信息

• 作为反应物：
  描述：

  2-(3,4-dihydronaphth-2-yl)-1H-indole 在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 1,4-二氧六环 、 甲苯 为溶剂， 反应 18.5h， 生成 naphtho[2.1-α]pyrrolo[3,4-c]cabazole-5,7(6H,12H)-dione
  参考文献：
  名称：

  Synthesis and Mixed Lineage Kinase Activity of Pyrrolocarbazole and Isoindolone Analogs of (+)K-252a

  摘要：

  Structural modification of the indolecarbazole natural product (+)K-252a identified structural requirements for MLK activity and a novel series of potent fused pyrrolocarbazole MLK1/3 inhibitors. The SAR revealed that the lactam regiochemistry, the shape of the heterocycle, and aryl rings B and F are important to MLK activity. Heteroatom and alkyl replacement of the N-12 and/or N-13 indole nitrogen atoms identified the nonplanar dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-7-one (8) and corresponding 5,7-dione (7) as potent cell-permeable MLK1/3 family-selective leads with in vitro activity comparable to that of (+)K-252a and determined them to be 2- to 3-fold more potent than the aglycone natural product K-252c.

  DOI：

  10.1021/jm051074u
• 作为产物：
  描述：

  β-四氢萘酮 在 盐酸 作用下， 以 丙酮 为溶剂， 反应 1.0h， 生成 2-(3,4-dihydronaphth-2-yl)-1H-indole
  参考文献：
  名称：

  Synthesis and Mixed Lineage Kinase Activity of Pyrrolocarbazole and Isoindolone Analogs of (+)K-252a

  摘要：

  Structural modification of the indolecarbazole natural product (+)K-252a identified structural requirements for MLK activity and a novel series of potent fused pyrrolocarbazole MLK1/3 inhibitors. The SAR revealed that the lactam regiochemistry, the shape of the heterocycle, and aryl rings B and F are important to MLK activity. Heteroatom and alkyl replacement of the N-12 and/or N-13 indole nitrogen atoms identified the nonplanar dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-7-one (8) and corresponding 5,7-dione (7) as potent cell-permeable MLK1/3 family-selective leads with in vitro activity comparable to that of (+)K-252a and determined them to be 2- to 3-fold more potent than the aglycone natural product K-252c.

  DOI：

  10.1021/jm051074u

文献信息

• Fused pyrrolocarbazoles
  申请人：CEPHALON, INC.

  公开号：EP1088823A1

  公开（公告）日：2001-04-04

  Disclosed herein are compounds referred to as "fused pyrrolocarbazoles" which possess a variety of functional pharmacological activities including effect on the function and/or survival of trophic factor responsive cells; inhibition of enzymatic activity; inhibition of inflammation-associated responses; inhibition of cell growth associated with hyperproliferative states; and inhibition of developmentally programmed motoneuron death.. The disclosed compounds are represented by the following general formula: Methodologies for the synthetic production of fused pyrrolocarbazoles are also disclosed, as well as exemplary uses of the compounds.

  本文公开的化合物被称为 "融合吡咯并咔唑"，具有多种功能性药理活性，包括对营养因子反应细胞的功能和/或存活的影响；抑制酶活性；抑制炎症相关反应；抑制与过度增殖状态相关的细胞生长；以及抑制发育程序化的运动神经元死亡。所公开的化合物由以下通式表示： 还公开了合成生产融合吡咯并咔唑的方法以及化合物的示例用途。
• 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.
• FUSED PYRROLOCARBAZOLES
  申请人：CEPHALON, INC.

  公开号：EP0785938A1

  公开（公告）日：1997-07-30
• FUSED PYRROLO(2,3-C)CARBAZOLE-6-ONES WHICH POTENTIATE ACTIVITY OF GAMMA INTERFERON
  申请人：CEPHALON, INC.

  公开号：EP0885229A1

  公开（公告）日：1998-12-23
• US5591855A
  申请人：——

  公开号：US5591855A

  公开（公告）日：1997-01-07