cis-N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)cyclohexyl)-4-(trifluoromethoxy)benzenesulfonamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: cis-N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)cyclohexyl)-4-(trifluoromethoxy)benzenesulfonamide
• 英文别名: N-((1S,3R)-3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)cyclohexyl)-4-(trifluoromethoxy)benzenesulfonamide；N-[(1S,3R)-3-(5,6-dihydrobenzo[b][1]benzazepin-11-yl)cyclohexyl]-4-(trifluoromethoxy)benzenesulfonamide
• 化学式: C₂₇H₂₇F₃N₂O₃S
• 分子量: 516.584
• InChiKey: WDTHSVMFQZAFNG-FCHUYYIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  36
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  67
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  亚氨基芪 在 palladium 10% on activated carbon 、 氢气 、 三乙酰氧基硼氢化钠 、 溶剂黄146 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 溶剂黄146 、 乙酸乙酯 、 1,2-二氯乙烷 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 30.5h， 生成 cis-N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)cyclohexyl)-4-(trifluoromethoxy)benzenesulfonamide
  参考文献：
  名称：

  Reengineered tricyclic anti-cancer agents

  摘要：

  The phenothiazine and dibenzazepine tricyclics are potent neurotropic drugs with a documented but underutilized anti-cancer side effect. Reengineering these agents (TFP, CPZ, CIP) by replacing the basic amine with a neutral polar functional group (e.g., RTC-1, RTC-2) abrogated their CNS effects as demonstrated by in vitro pharmacological assays and in vivo behavioral models. Further optimization generated several phenothiazines and dibenzazepines with improved anti-cancer potency, exemplified by RTC-5. This new lead demonstrated efficacy against a xenograft model of an EGFR driven cancer without the neurotropic effects exhibited by the parent molecules. Its effects were attributed to concomitant negative regulation of PI3K-AKT and RAS-ERK signaling. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.07.007

文献信息

• [EN] TRICYCLIC COMPOUNDS AS ANTICANCER AGENTS<br/>[FR] COMPOSÉS TRICYCLIQUES EN TANT QU'AGENTS ANTICANCÉREUX
  申请人：MT SINAI SCHOOL OF MEDICINE

  公开号：WO2013025882A3

  公开（公告）日：2013-04-25
• Reengineered tricyclic anti-cancer agents
  作者：David B. Kastrinsky、Jaya Sangodkar、Nilesh Zaware、Sudeh Izadmehr、Neil S. Dhawan、Goutham Narla、Michael Ohlmeyer

  DOI：10.1016/j.bmc.2015.07.007

  日期：2015.10

  The phenothiazine and dibenzazepine tricyclics are potent neurotropic drugs with a documented but underutilized anti-cancer side effect. Reengineering these agents (TFP, CPZ, CIP) by replacing the basic amine with a neutral polar functional group (e.g., RTC-1, RTC-2) abrogated their CNS effects as demonstrated by in vitro pharmacological assays and in vivo behavioral models. Further optimization generated several phenothiazines and dibenzazepines with improved anti-cancer potency, exemplified by RTC-5. This new lead demonstrated efficacy against a xenograft model of an EGFR driven cancer without the neurotropic effects exhibited by the parent molecules. Its effects were attributed to concomitant negative regulation of PI3K-AKT and RAS-ERK signaling. (C) 2015 Elsevier Ltd. All rights reserved.