N-[3-(2-chloro-phenothiazin-10-yl)-propyl]-phthalimide | 180388-71-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻嗪类
• 英文名称: N-[3-(2-chloro-phenothiazin-10-yl)-propyl]-phthalimide
• 英文别名: N-[3-(2-Chlor-phenothiazin-10-yl)-propyl]-phthalimid；10-(3-(Phthalimido)propyl)-2-chloro-10H-phenothiazine；2-[3-(2-chlorophenothiazin-10-yl)propyl]isoindole-1,3-dione
• CAS: 180388-71-0
• 化学式: C₂₃H₁₇ClN₂O₂S
• 分子量: 420.919
• InChiKey: MXHGUJMFTXTEAV-UHFFFAOYSA-N

物化性质

• 沸点：
  608.2±55.0 °C(Predicted)
• 密度：
  1.397±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  65.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-[3-(2-chloro-phenothiazin-10-yl)-propyl]-phthalimide 在 sodium carbonate 、 一水合肼 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 6.0h， 生成 methyl (3-(2-chloro-10H-phenothiazin-10-yl)propyl)carbamate
  参考文献：
  名称：

  Motohashi, Noboru; Kawase, Masami; Molnar, Joseph, Arzneimittel-Forschung/Drug Research, 2003, vol. 53, # 8, p. 590 - 599

  摘要：

  DOI：
• 作为产物：
  描述：

  N-(3-溴丙基)苯二胺 、 2-氯吩噻嗪 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 以73%的产率得到N-[3-(2-chloro-phenothiazin-10-yl)-propyl]-phthalimide
  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

• DE1012915
  申请人：——

  公开号：——

  公开（公告）日：——
• 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.
• Motohashi, Noboru; Kawase, Masami; Molnar, Joseph, Arzneimittel-Forschung/Drug Research, 2003, vol. 53, # 8, p. 590 - 599
  作者：Motohashi, Noboru、Kawase, Masami、Molnar, Joseph、Ferenczy, Lajos、Wesolowska, Olga、Hendrich, Andrzej B.、Bobrowska-Haegerstrand, Malgorzata、Haegerstrand, Henry、Michalak, Krystyna

  DOI：——

  日期：——