1-(6-bromobenzo[d]thiazol-2-yl)-3-(2-(dimethylamino)ethyl)urea | 1103862-04-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 1-(6-bromobenzo[d]thiazol-2-yl)-3-(2-(dimethylamino)ethyl)urea
• 英文别名: 1-(6-bromo-benzothiazol-2-yl)-3-(2-dimethylamino-ethyl)-urea；1-(6-bromo-1,3-benzothiazol-2-yl)-3-[2-(dimethylamino)ethyl]urea
• CAS: 1103862-04-9
• 化学式: C₁₂H₁₅BrN₄OS
• 分子量: 343.247
• InChiKey: AUTBNJPTJKRPSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  85.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(6-bromobenzo[d]thiazol-2-yl)-3-(2-(dimethylamino)ethyl)urea 、 4-fluoro-N-(2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)benzenesulfonamide 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 2.0h， 以33%的产率得到1-(6-(6-methoxy-5-(4-fluorophenylsulfonamino)pyridin-3-yl)benzo[d]thiazol-2-yl)-3-(2-(dimethylamino)ethyl)urea
  参考文献：
  名称：

  Synthesis and anticancer effects evaluation of 1-alkyl-3-(6-(2-methoxy-3-sulfonylaminopyridin-5-yl)benzo[d]thiazol-2-yl)urea as anticancer agents with low toxicity

  摘要：

  As a PI3K and mTOR dual inhibitor, N-(2-chloro-5-(2-acetylaminobenzo[d]thiazol-6-yl)pyridin-3-yl)-4-fluorophenylsulfonamide displays toxicity when orally administrated. In the present study, alkylurea moiety replaced the acetamide group in the compound and a series of 1-alkyl-3-(6-(2,3-disubstituted pyridin-5-yl) benzo[d]thiazol-2-yl) urea derivatives were synthesized. The antiproliferative activities of the synthesized compounds in vitro were evaluated against HCT116, MCF-7, U87 MG and A549 cell lines. The compounds with potent antiproliferative activity were tested for their acute oral toxicity and inhibitory activity against PI3Ks and mTORC1. The results indicate that the compound attached a 2-(dialkylamino) ethylurea moiety at the 2-positeion of benzothiazole can retain the antiproliferative activity and inhibitory activity against PI3K and mTOR. In addition, their acute oral toxicity reduced dramatically. Moreover, compound 2f can effectively inhibit tumor growth in a mice S180 homograft model. These findings suggest that 1-(2-dialkylaminoethyl)-3-(6-(2-methoxy-3-sulfonylaminopyridin-5-yl) benzo[d] thiazol-2-yl) urea derivatives can serve as potent PI3K inhibitors and anticancer agents with low toxicity. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.08.013
• 作为产物：
  描述：

  2-氨基-6-溴苯并噻唑 、 N,N-二甲基乙二胺 、 N,N'-羰基二咪唑 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以77%的产率得到1-(6-bromobenzo[d]thiazol-2-yl)-3-(2-(dimethylamino)ethyl)urea
  参考文献：
  名称：

  Synthesis and anticancer effects evaluation of 1-alkyl-3-(6-(2-methoxy-3-sulfonylaminopyridin-5-yl)benzo[d]thiazol-2-yl)urea as anticancer agents with low toxicity

  摘要：

  As a PI3K and mTOR dual inhibitor, N-(2-chloro-5-(2-acetylaminobenzo[d]thiazol-6-yl)pyridin-3-yl)-4-fluorophenylsulfonamide displays toxicity when orally administrated. In the present study, alkylurea moiety replaced the acetamide group in the compound and a series of 1-alkyl-3-(6-(2,3-disubstituted pyridin-5-yl) benzo[d]thiazol-2-yl) urea derivatives were synthesized. The antiproliferative activities of the synthesized compounds in vitro were evaluated against HCT116, MCF-7, U87 MG and A549 cell lines. The compounds with potent antiproliferative activity were tested for their acute oral toxicity and inhibitory activity against PI3Ks and mTORC1. The results indicate that the compound attached a 2-(dialkylamino) ethylurea moiety at the 2-positeion of benzothiazole can retain the antiproliferative activity and inhibitory activity against PI3K and mTOR. In addition, their acute oral toxicity reduced dramatically. Moreover, compound 2f can effectively inhibit tumor growth in a mice S180 homograft model. These findings suggest that 1-(2-dialkylaminoethyl)-3-(6-(2-methoxy-3-sulfonylaminopyridin-5-yl) benzo[d] thiazol-2-yl) urea derivatives can serve as potent PI3K inhibitors and anticancer agents with low toxicity. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.08.013

文献信息

• Organic Compounds
  申请人：Bruce Ian

  公开号：US20100197682A1

  公开（公告）日：2010-08-05

  Phosphatidylinositol (PI) 3-kinase inhibitor compounds, their pharmaceutically acceptable salts, and prodrugs thereof; compositions of the new compounds, either alone or in combination with at least one additional therapeutic agent, with a pharmaceutically acceptable carrier; and uses of the new compounds, either alone or in combination with at least one additional therapeutic agent, in the prophylaxis or treatment of proliferative diseases characterized by the abnormal activity of growth factors, protein serine/threonine kinases, and phospholipid kinases.

  磷脂酰肌醇（PI）3-激酶抑制剂化合物及其药学上可接受的盐和前药；新化合物的组合物，可以单独使用或与至少一种额外治疗剂联合使用，与药学上可接受的载体；以及新化合物的用途，可以单独使用或与至少一种额外治疗剂联合使用，用于预防或治疗由生长因子、蛋白质丝氨酸/苏氨酸激酶和磷脂酰肌醇激酶异常活性所特征的增殖性疾病。
• US8053574B2
  申请人：——

  公开号：US8053574B2

  公开（公告）日：2011-11-08
• Synthesis and anticancer effects evaluation of 1-alkyl-3-(6-(2-methoxy-3-sulfonylaminopyridin-5-yl)benzo[d]thiazol-2-yl)urea as anticancer agents with low toxicity
  作者：Xiao-Xiao Xie、Huan Li、Juan Wang、Shuai Mao、Min-Hang Xin、She-Min Lu、Qi-Bing Mei、San-Qi Zhang

  DOI：10.1016/j.bmc.2015.08.013

  日期：2015.10

  As a PI3K and mTOR dual inhibitor, N-(2-chloro-5-(2-acetylaminobenzo[d]thiazol-6-yl)pyridin-3-yl)-4-fluorophenylsulfonamide displays toxicity when orally administrated. In the present study, alkylurea moiety replaced the acetamide group in the compound and a series of 1-alkyl-3-(6-(2,3-disubstituted pyridin-5-yl) benzo[d]thiazol-2-yl) urea derivatives were synthesized. The antiproliferative activities of the synthesized compounds in vitro were evaluated against HCT116, MCF-7, U87 MG and A549 cell lines. The compounds with potent antiproliferative activity were tested for their acute oral toxicity and inhibitory activity against PI3Ks and mTORC1. The results indicate that the compound attached a 2-(dialkylamino) ethylurea moiety at the 2-positeion of benzothiazole can retain the antiproliferative activity and inhibitory activity against PI3K and mTOR. In addition, their acute oral toxicity reduced dramatically. Moreover, compound 2f can effectively inhibit tumor growth in a mice S180 homograft model. These findings suggest that 1-(2-dialkylaminoethyl)-3-(6-(2-methoxy-3-sulfonylaminopyridin-5-yl) benzo[d] thiazol-2-yl) urea derivatives can serve as potent PI3K inhibitors and anticancer agents with low toxicity. (C) 2015 Elsevier Ltd. All rights reserved.