4'-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenylamino)-3,6'-biquinoline-3'-carboxylic acid | 1223003-29-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4'-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenylamino)-3,6'-biquinoline-3'-carboxylic acid
• 英文别名: 4'-(4-(4-Propionylpiperazin-1-yl)-3(trifluoromethyl)phenylamino)-3,6'-biquinoline-3'-carboxylic acid；4-[4-(4-propanoylpiperazin-1-yl)-3-(trifluoromethyl)anilino]-6-quinolin-3-ylquinoline-3-carboxylic acid
• CAS: 1223003-29-9
• 化学式: C₃₃H₂₈F₃N₅O₃
• 分子量: 599.612
• InChiKey: UIZHBOBBSHEZBV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  44
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  98.7
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  4'-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenylamino)-3,6'-biquinoline-3'-carboxylic acid 、 N-甲基-N-甲氧基胺盐酸盐 在 三乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 N-methoxy-N-methyl-4-[4-(4-propanoylpiperazin-1-yl)-3-(trifluoromethyl)anilino]-6-quinolin-3-ylquinoline-3-carboxamide
  参考文献：
  名称：

  Discovery of 1-(4-(4-Propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo[h][1,6]naphthyridin-2(1H)-one as a Highly Potent, Selective Mammalian Target of Rapamycin (mTOR) Inhibitor for the Treatment of Cancer

  摘要：

  The mTOR It protein is a master regulator of cell growth and proliferation, and inhibitors of its kinase activity have the potential to become new class of anticancer drugs. Starting from quinoline I, which was identified in a biochemical mTOR assay, we developed a tricyclic benzonaphthyridinone inhibitor 37 (Torin 1), which inhibited phosphorylation of mTORC1 and mTORC2 substrates in cells at concentrations of 2 and 10 nM, respectively. Moreover, Torin I exhibits 1000-fold selectivity for mTOR over P13K (EC50 = 1800 nM) and exhibits 100-fold binding selectivity relative to 450 other protein kinases. Torin was efficacious at a dose of 20 mg/kg in a U87MG xenograft model and demonstrated good pharmacodynamic inhibition of downstream effectors of mTOR in tumor and per tissues. These results demonstrate that Torin I is a useful probe of mTOR-dependent phenomena and that benzo-naphthridinones represent a promising scaffold for the further development of mTOR-specific inhibitors with the potential for clinical utility.

  DOI：

  10.1021/jm101144f
• 作为产物：
  描述：

  ethyl 4-(3-(trifluoromethyl)-4-(4-propionylpiperazin-1-yl)phenylamino)-6-(quinolin-3-yl)quinoline-3-carboxylate 在 水 、 sodium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 生成 4'-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenylamino)-3,6'-biquinoline-3'-carboxylic acid
  参考文献：
  名称：

  [EN] SOLUBLE MTOR COMPLEXES AND MODULATORS THEREOF
  [FR] COMPLEXES MTOR SOLUBLES ET MODULATEURS ASSOCIÉS

  摘要：

  公开号：

  WO2010044885A3

文献信息

• SOLUBLE MTOR COMPLEXES AND MODULATORS THEREOF
  申请人：Gray Nathanael

  公开号：US20110288091A1

  公开（公告）日：2011-11-24

  The present invention relates to small molecule modulators of mTORC1 and mTORC2, syntheses thereof, and intermediates thereto. Such small molecule modulators are useful in the treatment of proliferative diseases (e.g., benign neoplasms, cancers, inflammatory diseases, autoimmune diseases, diabetic retinopathy) and metabolic diseases. Novel small molecules are provided that inhibit one or more of mTORC1, mTORC2, and PI3K-related proteins. Novel methods of providing soluble mTORC1 and mTORC2 complexes are discussed, as well as methods of using the soluble complexes in a high-throughput manner to screen for inhibitory compounds.

  本发明涉及mTORC1和mTORC2的小分子调节剂，其合成和中间体。这些小分子调节剂在治疗增生性疾病（例如良性肿瘤、癌症、炎症性疾病、自身免疫性疾病、糖尿病性视网膜病变）和代谢性疾病方面有用。提供了新的小分子，其抑制mTORC1、mTORC2和PI3K相关蛋白质中的一个或多个。讨论了提供可溶性mTORC1和mTORC2复合物的新方法，以及使用可溶性复合物以高通量方式筛选抑制性化合物的方法。
• Soluble mTOR complexes and modulators thereof
  申请人：Gray Nathanael

  公开号：US08394818B2

  公开（公告）日：2013-03-12

  The present invention relates to small molecule modulators of mTORC1 and mTORC2, syntheses thereof, and intermediates thereto. Such small molecule modulators are useful in the treatment of proliferative diseases (e.g., benign neoplasms, cancers, inflammatory diseases, autoimmune diseases, diabetic retinopathy) and metabolic diseases. Novel small molecules are provided that inhibit one or more of mTORC1, mTORC2, and PI3K-related proteins. Novel methods of providing soluble mTORC1 and mTORC2 complexes are discussed, as well as methods of using the soluble complexes in a high-throughput manner to screen for inhibitory compounds.

  本发明涉及mTORC1和mTORC2的小分子调节剂、其合成以及中间体。这样的小分子调节剂在治疗增生性疾病（如良性肿瘤、癌症、炎症性疾病、自身免疫疾病、糖尿病性视网膜病变）和代谢性疾病方面非常有用。提供了新的小分子，它们抑制mTORC1、mTORC2和PI3K相关蛋白中的一个或多个。讨论了提供可溶性mTORC1和mTORC2复合物的新方法，以及使用可溶性复合物进行高通量筛选抑制剂的方法。
• [EN] SOLUBLE MTOR COMPLEXES AND MODULATORS THEREOF<br/>[FR] COMPLEXES MTOR SOLUBLES ET MODULATEURS ASSOCIÉS
  申请人：WHITEHEAD BIOMEDICAL INST

  公开号：WO2010044885A3

  公开（公告）日：2010-09-02
• Modulators of MTOR Complexes
  申请人：Whitehead Institute For Biomedical Research

  公开号：EP2350053B1

  公开（公告）日：2013-12-11
• US8394818B2
  申请人：——

  公开号：US8394818B2

  公开（公告）日：2013-03-12