4-chloro-N-(3',4',5',6',10,11-hexahydrospiro[dibenzo[a,d][7]annulene-5,2'-pyran]-5'-yl)benzenesulfonamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 二苯并环庚烯
• 英文名称: 4-chloro-N-(3',4',5',6',10,11-hexahydrospiro[dibenzo[a,d][7]annulene-5,2'-pyran]-5'-yl)benzenesulfonamide
• 英文别名: 4-chloro-N-spiro[oxane-6,2'-tricyclo[9.4.0.03,8]pentadeca-1(15),3,5,7,11,13-hexaene]-3-ylbenzenesulfonamide
• 化学式: C₂₅H₂₄ClNO₃S
• 分子量: 453.989
• InChiKey: WFVHWGFNHWUJKJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  63.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  10,11-二氢二苯并[a,b]环庚烯-5-酮 在 Grubbs catalyst first generation 、 硼烷四氢呋喃络合物 、 ammonium acetate 、 sodium hydride 、 sodium cyanoborohydride 、 三乙胺 、 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 78.28h， 生成 4-chloro-N-(3',4',5',6',10,11-hexahydrospiro[dibenzo[a,d][7]annulene-5,2'-pyran]-5'-yl)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

• 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.