10-{3-[4-(2-morpholin-4-yl-ethyl)-piperazin-1-yl]-propyl}-2-trifluoromethyl-10H-phenothiazine | 66421-99-6

• 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: 10-{3-[4-(2-morpholin-4-yl-ethyl)-piperazin-1-yl]-propyl}-2-trifluoromethyl-10H-phenothiazine
• 英文别名: 4-[2-[4-[3-[2-(Trifluoromethyl)phenothiazin-10-yl]propyl]piperazin-1-yl]ethyl]morpholine
• CAS: 66421-99-6
• 化学式: C₂₆H₃₃F₃N₄OS
• 分子量: 506.635
• InChiKey: KXYSYSJXECFHRI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  47.5
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  10-(3-氯丙基)-2-(三氟甲基)-10H-吩噻嗪 在 盐酸 、 氯化亚砜 、 sodium iodide 作用下， 以 氯仿 、 丁酮 为溶剂， 反应 27.0h， 生成 10-{3-[4-(2-morpholin-4-yl-ethyl)-piperazin-1-yl]-propyl}-2-trifluoromethyl-10H-phenothiazine
  参考文献：
  名称：

  潜在的中枢神经系统抗肿瘤药-吩噻嗪II：氟吩嗪类似物。

  摘要：

  发现氟奋乃静对腹膜内L-1210和P-388白血病小鼠肿瘤模型具有中等程度的可再现活性。在腹膜内L-1210，P-388和B16黑色素瘤系统以及脑内L-1210中制备了氟奋乃静的7种醚衍生物和8种化合物，其中末端侧链羟基被胺官能团取代。和上皮细胞母细胞瘤脑肿瘤模型。虽然没有观察到实质性的脑内活性，但七种衍生物在腹膜内L-1210或P-388系统中具有可再现的活性。几个给出的T / C值为150％。没有观察到B16黑色素瘤活性。还测试了这些化合物在培养过程中针对L-1210，P-388和KB细胞的细胞毒性。胺类等排体虽然几乎没有体内活性，

  DOI：

  10.1002/jps.2600670209

文献信息

• NUPR1 INHIBITION FOR TREATING CANCER
  申请人：INSTITUT NATIONAL DE SANTE ET DE LA RECHERCHE MEDICALE (INSERM)

  公开号：US20210137938A1

  公开（公告）日：2021-05-13

  The present invention relates to the treatment of a tumor selected from the group consisting of pancreatic cancer, liver cancer, melanoma, colon cancer, glioblastoma, osteosarcoma, prostate cancer and breast cancer, more particularly pancreatic cancer. The inventors found a novel family compounds of formula (I) able to treat a variety of cancers by inhibiting NUPR1, a stress-inducible 82-amino-acid-long, intrinsically disordered member of the AT-hook family of chromatin proteins. Thus, the present invention relates to a compound of formula (I) for its use in the treatment of a tumor selected from the group consisting of pancreatic cancer, liver cancer, melanoma, colon cancer, glioblastoma, osteosarcoma, prostate cancer and breast cancer. In particular, the inventors tested compounds of formula (I) on four well characterized primary pancreatic cancer-derived cells 02.063 and LIPC (Basal subtype), Foic8b (derived from a liver metastasis) and HN14 (Classical subtype), as well as on other cellular lines derived from different tumors, i.e. U87 (glioblastoma), A375 and B16 (melanoma), U20S and SaOS (osteosarcoma), HT29, SK-CO-1 and LS174T (colon cancer), HepG2 (hepatocarcinoma), PC3 (prostate) and MDA-MB-231 (breast cancer). The compounds per se are also claimed.
• Potential CNS Antitumor Agents—Phenothiazines II: Fluphenazine Analogs
  作者：Tadashi Hirata、Geoffrey Peng、John S. Driscoll

  DOI：10.1002/jps.2600670209

  日期：1978.2

  Fluphenazine was found to possess moderate reproducible activity against the intraperitoneal L-1210 and P-388 leukemia murine tumor models. Seven ether derivatives of fluphenazine and eight compounds in which the terminal side-chain hydroxyl group was replaced by an amine function were prepared and evaluated in the intraperitoneal L-1210, P-388, and B16 melanoma systems as well as the intracerebral

  发现氟奋乃静对腹膜内L-1210和P-388白血病小鼠肿瘤模型具有中等程度的可再现活性。在腹膜内L-1210，P-388和B16黑色素瘤系统以及脑内L-1210中制备了氟奋乃静的7种醚衍生物和8种化合物，其中末端侧链羟基被胺官能团取代。和上皮细胞母细胞瘤脑肿瘤模型。虽然没有观察到实质性的脑内活性，但七种衍生物在腹膜内L-1210或P-388系统中具有可再现的活性。几个给出的T / C值为150％。没有观察到B16黑色素瘤活性。还测试了这些化合物在培养过程中针对L-1210，P-388和KB细胞的细胞毒性。胺类等排体虽然几乎没有体内活性，