N-[5-bromo-2-methyloxy-3-pyridinyl]-4-methylphenylsulfonamide | 1425046-30-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-[5-bromo-2-methyloxy-3-pyridinyl]-4-methylphenylsulfonamide
• 英文别名: N-(5-bromo-2-methoxypyridin-3-yl)-4-methylbenzenesulfonamide
• CAS: 1425046-30-5
• 化学式: C₁₃H₁₃BrN₂O₃S
• 分子量: 357.228
• InChiKey: PVJDSBUDGTZIQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  76.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-[5-bromo-2-methyloxy-3-pyridinyl]-4-methylphenylsulfonamide 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 乙醇 、 水 为溶剂， 反应 5.0h， 生成 N-(7-(6-methoxy-5-(4-methylphenylsulfonamido)pyridin-3-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)acetamide
  参考文献：
  名称：

  Synthesis and anticancer activity evaluation of a series of [1,2,4]triazolo[1,5-a]pyridinylpyridines in vitro and in vivo

  摘要：

  A series of [1,2,4]triazolo[1,5-a]pyridinylpyridines were synthesized and characterized. Their antiproliferative activities in vitro were evaluated by MTT against three human cancer cell lines including HCT-116, U-87 MG and MCF-7 cell lines. The SAR of target compounds was preliminarily discussed. The compounds 1c and 2d with potent antiproliferative activities were tested for their effects on the AKT and p-AKT(473). The anticancer effect of 1c was evaluated in mice bearing sarcoma S-180 model. The results suggest that the title compounds are potent anticancer agents. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.06.052
• 作为产物：
  描述：

  5-溴-2-氯-3-硝基吡啶 在 吡啶 、 tin(II) chloride dihdyrate 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 39.0h， 生成 N-[5-bromo-2-methyloxy-3-pyridinyl]-4-methylphenylsulfonamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation of novel 4-alkynyl-quinoline derivatives as PI3K/mTOR dual inhibitors

  摘要：

  A novel series of 4-alkynyl-quinoline derivatives were designed, synthesized and biologically evaluated for their PI3K alpha inhibitory activities and anti-proliferative effects against two cancer cell lines PC-3 and HCT-116. Most of them showed potent PI3K alpha inhibitory activities with IC50 values at low nanomolar level and good to excellent anti-proliferative effects against both cell lines. Among them, compound 15d, the most potent one, was selected for further biological evaluation. As a result, 15d displayed strong inhibitory activity against other class I PI3K isoforms (PI3K beta, PI3K gamma and PI3K delta) and mTOR with an acceptable kinase selectivity profile. Moreover, the western blot assay indicated that the phosphorylation of Akt, another downstream effector of PI3K, can be remarkably suppressed by 15d at cellular level. All these experimental results suggested that 15d is a potent PI3K/mTOR dual inhibitor and could serve as a promising lead compound for the development of anticancer agents. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.05.025

文献信息

• Synthesis and antitumor activity evaluation of PI3K inhibitors containing 3-substituted quinazolin-4(3H)-one moiety
  作者：Hao Zhang、Min-Hang Xin、Xiao-Xiao Xie、Shuai Mao、Sai-Jie Zuo、She-Min Lu、San-Qi Zhang

  DOI：10.1016/j.bmc.2015.11.027

  日期：2015.12

  In present study, a series of N-(2-methoxy-5-(3-substituted quinazolin-4(3H)-one-6-yl)-pyridin-3-yl) phenylsulfonamide were synthesized. Their antiproliferative activities in vitro were evaluated via MTT assay against HCT116 and MCF-7 cancer cell lines. The SAR of title compounds was discussed. The compounds (S)-C5 and (S)-C8 displayed potent inhibitory activity against PI3Ks and mTOR, especially against PI3K alpha. In addition, compound (S)-C5 can efficaciously inhibit tumor growth in a mice S-180 model. These findings suggest that our designed compounds can serve as potent PI3K inhibitors and effective anticancer agents. (c) 2015 Published by Elsevier Ltd.
• Modification of N -(6-(2-methoxy-3-(4-fluorophenylsulfonamido)pyridin-5-yl)-[1,2,4]triazolo[1,5- a ]pyridin-2-yl)acetamide as PI3Ks inhibitor by replacement of the acetamide group with alkylurea
  作者：Xiao-Meng Wang、Shuai Mao、Lei Cao、Xiao-Xiao Xie、Min-Hang Xin、Jia-Fang Lian、Yong-Xiao Cao、San-Qi Zhang

  DOI：10.1016/j.bmc.2015.07.017

  日期：2015.9

  N-(6-(2-Methoxy-3-(4-fluorophenylsulfonamido)pyridin-5-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)acetamide exhibits remarkable anticancer effects and toxicity when orally administrated. In present study, alkylurea moiety replaced the acetamide group in the compound and a series of 1-alkyl-3-(6-(2-methoxy-3-sulfonylaminopyridin-5-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl) urea derivatives were synthesized. The antiproliferative activities of the synthesized compounds in vitro were evaluated against four human cancer cell lines. Several compounds with potent antiproliferative activities were tested for their acute oral toxicity and their inhibitory activity against PI3Ks and mTOR. The results indicate that the compound attached a alkylurea or 2-(dialkylamino)ethylurea moiety at the 2-position of [1,2,4]triazolo[1,5-a]pyridine can retain the antiproliferative activity and the inhibitory activity against PI3Ks and mTOR. In addition, their acute oral toxicity reduced dramatically. Moreover, the results also indicate that compound 1e can efficaciously inhibit tumor growth in a mice S180 model. These findings suggest that title compounds can serve as potent PI3K inhibitors and effective anticancer agents with low toxicity. (C) 2015 Elsevier Ltd. All rights reserved.
• 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.