6-chloro-2-(isopropylthio)-3-nitropyridine

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 6-chloro-2-(isopropylthio)-3-nitropyridine
• 英文别名: 6-Chloro-3-nitro-2-propan-2-ylsulfanylpyridine
• 化学式: C₈H₉ClN₂O₂S
• 分子量: 232.691
• InChiKey: LCARJBKTJRIDEG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  84
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-chloro-2-(isopropylthio)-3-nitropyridine 在 盐酸 、 铁粉 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 3.0h， 生成 2-(isopropylthio)-6-morpholinopyridin-3-amine
  参考文献：
  名称：

  Design, synthesis and biological evaluation N2-(2-alkyoxy-6-aliphatic aminopyridin-3-yl)-2,4-diaminepyrimidine derivatives bearing acylamino or DBTD ‘head’ as potential ALK inhibitors

  摘要：

  Aiming to develop promising ALK inhibitors, two series of N-2-(2-alkyoxy-6-aliphatic aminopyridin-3-yl)-2,4-diaminepyrimidine derivatives (22a-x and 23a-d) were designed according to scaffold hopping and bioisosterism principles. All compounds were efficiently synthesized by concise reactions and anti-proliferative activities on ALK-addicted H2228, Karpas299 cells and EGFR-expressive A549 cell were evaluated by MTT assay. Several compounds exhibited potential cytotoxic activities with IC50 values below 0.10 mu M. Five compounds (22g, 22h, 22l, 22s and 23a) were selected for further enzymatic determination, resulting in the discovery of 22l against ALK and ALK(L1196M) with IC50 values of 2.1 nM and 3.8 nM. Particularly, western blot and cell apoptosis assays identified 22l as a promising ALK inhibitor, which was capable of obviously inhibiting cellular ALK activity and inducing cell apoptosis. Eventually, molecular docking modes of 22l with ALK confirmed structural basis in accordance with the SARs analysis.

  DOI：

  10.1016/j.bioorg.2018.09.019
• 作为产物：
  描述：

  2,6-二氯-3-硝基吡啶 、 异丙硫醇 在 sodium hydride 作用下， 以 甲苯 为溶剂， 生成 6-chloro-2-(isopropylthio)-3-nitropyridine
  参考文献：
  名称：

  Synthesis and Insecticidal Activity of Novel Nitropyridyl-Based Dichloropropene Ethers

  摘要：

  Dihalopropene ether insecticides are known for good features such as no cross-resistance to other insecticide classes and safety for mammals. Pyridalyl is the only currently commercialized dichloropropene ether insecticide; however, it contains a trifluoromethyl group, the synthesis of which requires harsh reagents and reaction conditions. To search for novel dihalopropene ethers with unique biological activities but without trifluoromethyl groups, a series of nitropyridyl-based dichloropropene ether analogues were synthesized by reacting nitro-based halopyridine with 2,6-dichloro-4-(3,3-dichloroallyloxy)phenol or 2,6-dichloro-4-(3,3-dichloroallyloxy)phenyl 3-hydroxypropyl ether. Bioassay showed that the compounds exhibited potent insecticidal activities against various lepidopteran pests. Particularly, 2,6-dichloro-4-(3,3-dichloroallyloxy)phenyl 3-(5-nitro-2-pyridyloxy)propyl ether (8e) was active against major agricultural pests, and its insecticidal potency was comparable to that of Pyridalyl. Besides the trifluoromethyl group in Pyridalyl, a nitro group on the 5-position of the pyridyl ring is also viable for the development of optimal insecticidal activity.

  DOI：

  10.1021/acs.jafc.5b02279

文献信息

• 二氯烯丙醚类化合物及其制备方法与应用
  申请人：湖南化工研究院有限公司

  公开号：CN105254558A

  公开（公告）日：2016-01-20

  本发明公开了式(I)所示的二氯烯丙醚类化合物及其制备方法与应用。式中Q、R1、R2、R3、R4、R5、R6、R7、n、X、Y、Z具有说明书中所给定义。本发明式(I)化合物具有杀虫和/或杀螨、杀菌生物活性，尤其是对粘虫、小菜蛾等害虫具有很高的活性。
• Dual potent ALK and ROS1 inhibitors combating drug-resistant mutants: Synthesis and biological evaluation of aminopyridine-containing diarylaminopyrimidine derivatives
  作者：Ming Guo、Daiying Zuo、Junlong Zhang、Lingyun Xing、Wenfeng Gou、Feng Jiang、Nan Jiang、Dajun Zhang、Xin Zhai

  DOI：10.1016/j.ejmech.2018.09.012

  日期：2018.10

  To identify ALK and ROS1 dual inhibitors conferring resistance to ALK secondary mutations, especially 'gatekeeper' L1196 M and the most predominant ceritinib-resistant G1202R mutations, a series of novel 2,4-diarylaminopyrimidine analogues were designed and synthesized by incorporating 2-alkoxy-6-alicyclic aminopyridinyl motifs. The biological evaluations on cellular and enzymatic assays led to identification of compound F-1, which turned out to be effective against ALK(WT), ROS1(WT), ALK(L1196M) and ALK(G1202R) kinases with IC50 of 2.1 nM, 2.3 nM, 1.3 nM and 3.9 nM, respectively, superior to crizotinib and ceritinib. Moreover, F-1 exhibited significant cytotoxicity on ALK-addicted Karpas299, H2228, and Ba/F3 cell expressing G1202R mutant, as well as ROS1-positive HCC78 cell with IC50 values ranging from 10 nM to 43 nM. Notably, F-1 was capable of suppressing phospho-ALK and its relative downstream signaling pathways, and eventually, inducing cell apoptosis in a dose-dependent manner in Karpas-299 cell. Together, F-1 is validated as a promising ALK/ROS1 dual inhibitor great potential for G1202R ALK mutation cancers. (C) 2018 Elsevier Masson SAS. All rights reserved.
• Synthesis and Insecticidal Activity of Novel Nitropyridyl-Based Dichloropropene Ethers
  作者：Aiping Liu、Wanqi Yu、Minhua Liu、Jianjun Bai、Weidong Liu、Xingping Liu、Hui Pei、Li Hu、Mingzhi Huang、Xiaoguang Wang

  DOI：10.1021/acs.jafc.5b02279

  日期：2015.9.2

  Dihalopropene ether insecticides are known for good features such as no cross-resistance to other insecticide classes and safety for mammals. Pyridalyl is the only currently commercialized dichloropropene ether insecticide; however, it contains a trifluoromethyl group, the synthesis of which requires harsh reagents and reaction conditions. To search for novel dihalopropene ethers with unique biological activities but without trifluoromethyl groups, a series of nitropyridyl-based dichloropropene ether analogues were synthesized by reacting nitro-based halopyridine with 2,6-dichloro-4-(3,3-dichloroallyloxy)phenol or 2,6-dichloro-4-(3,3-dichloroallyloxy)phenyl 3-hydroxypropyl ether. Bioassay showed that the compounds exhibited potent insecticidal activities against various lepidopteran pests. Particularly, 2,6-dichloro-4-(3,3-dichloroallyloxy)phenyl 3-(5-nitro-2-pyridyloxy)propyl ether (8e) was active against major agricultural pests, and its insecticidal potency was comparable to that of Pyridalyl. Besides the trifluoromethyl group in Pyridalyl, a nitro group on the 5-position of the pyridyl ring is also viable for the development of optimal insecticidal activity.
• Design, synthesis and biological evaluation N2-(2-alkyoxy-6-aliphatic aminopyridin-3-yl)-2,4-diaminepyrimidine derivatives bearing acylamino or DBTD ‘head’ as potential ALK inhibitors
  作者：Lingyun Xing、Tongfei Jing、Junlong Zhang、Ming Guo、Xiuqi Miao、Feng Jiang、Xin Zhai

  DOI：10.1016/j.bioorg.2018.09.019

  日期：2018.12

  Aiming to develop promising ALK inhibitors, two series of N-2-(2-alkyoxy-6-aliphatic aminopyridin-3-yl)-2,4-diaminepyrimidine derivatives (22a-x and 23a-d) were designed according to scaffold hopping and bioisosterism principles. All compounds were efficiently synthesized by concise reactions and anti-proliferative activities on ALK-addicted H2228, Karpas299 cells and EGFR-expressive A549 cell were evaluated by MTT assay. Several compounds exhibited potential cytotoxic activities with IC50 values below 0.10 mu M. Five compounds (22g, 22h, 22l, 22s and 23a) were selected for further enzymatic determination, resulting in the discovery of 22l against ALK and ALK(L1196M) with IC50 values of 2.1 nM and 3.8 nM. Particularly, western blot and cell apoptosis assays identified 22l as a promising ALK inhibitor, which was capable of obviously inhibiting cellular ALK activity and inducing cell apoptosis. Eventually, molecular docking modes of 22l with ALK confirmed structural basis in accordance with the SARs analysis.