4-chloro-N-cyclopropylpicolinamide | 1090815-16-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-chloro-N-cyclopropylpicolinamide
• 英文别名: N-Cyclopropyl 4-chloropicolinamide；4-chloro-N-cyclopropylpyridine-2-carboxamide
• CAS: 1090815-16-9
• 化学式: C₉H₉ClN₂O
• mdl: MFCD10663418
• 分子量: 196.636
• InChiKey: BIBWPAZILMLFNO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  42
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-chloro-N-cyclopropylpicolinamide 在 potassium tert-butylate 、 potassium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 N-cyclopropyl-4-(3-(3-(3-(trifluoromethyl)phenyl)thioureido)phenoxy)picolinamide
  参考文献：
  名称：

  Design, synthesis and biological activities of sorafenib derivatives as antitumor agents

  摘要：

  A series of novel sorafenib derivatives, 9a-w, was designed and synthesized in high yields using various substituted anilines, and their antiproliferative activities against HCT116, PC-3 and MDA-MB-231 cell lines were also evaluated and described. All compounds exhibited potent antiproliferative activity against HCT116 and PC-3 cells with IC50 = 2.8-52.0 and 2.2-45.6 mu M; compounds 9p and 9q demonstrated competitive antiproliferative activities to sorafenib against all three cancer cell lines, the cytotoxicity of compound 9r is more potent than that of sorafenib. Compounds (9g, 9p, 9q and 9r) were chosen for further evaluation of the anti-angiogenesis activity, and showed the inhibition of sprout formation from aortic ring ex vivo. The structures of all the newly synthesized compounds were determined by H-1 NMR, C-13 NMR and HRMS. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.09.031
• 作为产物：
  描述：

  4-氯-吡啶-2-酰氯 以 四氢呋喃 、 甲醇 为溶剂， 反应 2.0h， 生成 4-chloro-N-cyclopropylpicolinamide
  参考文献：
  名称：

  含有索拉非尼类似物作为抗肿瘤剂的硫脲的设计，合成和生物学活性

  摘要：

  设计并合成了一系列新型的含有索拉非尼衍生物9a – t的二芳基硫脲。所有新合成的化合物的结构均通过1 H NMR，13 C NMR和HRMS确定。评估并描述了它们对HCT116和MDA-MB-231细胞系的抗增殖活性，以及​​对VEGFR磷酸化的抑制活性。一些化合物对细胞系和VEGFR均显示出显着活性。化合物9g，9m，9o和9p对参考标准索拉非尼具有竞争性抗增殖活性，而化合物9d，9m和9p显示出对VEGFR的磷酸化的显着抑制活性。

  DOI：

  10.1016/j.bmc.2012.03.018

文献信息

• Design, synthesis and biological evaluation of novel 4-phenoxypyridine based 3-oxo-3,4-dihydroquinoxaline-2-carboxamide derivatives as potential c-Met kinase inhibitors
  作者：Zhen Wang、Jiantao Shi、Xianglong Zhu、Wenwen Zhao、Yilin Gong、Xuechen Hao、Yunlei Hou、Yajing Liu、Shi Ding、Ju Liu、Ye Chen

  DOI：10.1016/j.bioorg.2020.104371

  日期：2020.12

  Blocking c-Met kinase activity by small-molecule inhibitors has been identified as a promising approach for the treatment of cancers. Herein, we described the design, synthesis, and biological evaluation of a series of 4-phenoxypyridine-based 3-oxo-3,4-dihydroquinoxaline derivatives as c-Met kinase inhibitors. Inhibitory activitives against c-Met kinase evaluation indicated that most of compounds showed

  通过小分子抑制剂阻断c-Met激酶活性已被认为是治疗癌症的有前途的方法。在这里，我们描述了一系列基于4-苯氧吡啶的3-氧代-3,4-二氢喹喔啉衍生物作为c-Met激酶抑制剂的设计，合成和生物学评估。对c-Met激酶的抑制活性评估表明，大多数化合物在体外均表现出出色的c-Met激酶活性，十种化合物（23a，23e，23f，23l，23r，23s，23v，23w，23x和23y）的IC 50值）小于10.00 nM。值得注意的是，它们中的三个（23v，23w和23y）显示出显着的效价，IC 50值分别为2.31 nM，1.91 nM和2.44 nM，因此它们比阳性对照药物foretinib（c-Met，IC 50  = 2.53 nM）。细胞毒性评估表明，最有希望的化合物23w对A549，H460和HT-29细胞系表现出显着的细胞毒性，IC 50值分别为1.57μM，0.94μM和0.65μM
• Synthesis and evaluation of new thiourea derivatives as antitumor and antiangiogenic agents
  作者：Wenjing Bai、Jianxin Ji、Qiang Huang、Wei Wei

  DOI：10.1016/j.tetlet.2020.152366

  日期：2020.10

  A series of novel thiourea derivatives were synthesized and evaluated by biological activities. Among them, compound 10e containing 3,5-bis(trifluoromethyl)phenyl moiety (R1) at the terminal thiourea and phenylamino (R2) at the terminal acyl position showed the best cytotoxic activities against seven cancer cell lines (NCI-H460, Colo-205, HCT116, MDA-MB-231, MCF-7, HepG2, PLC/PRF/5) and HUVECs. Moreover

  合成了一系列新型硫脲衍生物，并通过生物学活性对其进行了评估。其中，在末端硫脲处含有3,5-双（三氟甲基）苯基部分（R 1）在酰基末端具有苯氨基（R 2）的化合物10e对7种癌细胞系（NCI-H460， Colo-205，HCT116，MDA-MB-231，MCF-7，HepG2，PLC / PRF / 5）和HUVEC。此外，化合物10e适度抑制各种RTK，例如VEGFR2，VEGFR3和PDGFRβ。值得注意的是，在相同浓度下，10e对肿瘤形成和抗血管生成活性的抑制作用比索拉非尼和Regorafenib好得多。进一步的对接研究表明10e 可以作为癌症治疗的潜在候选人。
• Discovery of novel picolinamide-based derivatives as novel VEGFR-2 kinase inhibitors: synthesis,<i>in vitro</i>biological evaluation and molecular docking
  作者：Wuji Sun、Shubiao Fang、Hong Yan

  DOI：10.1039/c8md00057c

  日期：——

  Vascular endothelial growth factor receptor-2 (VEGFR-2) plays a crucial role in tumor angiogenesis, and inhibition of the VEGFR-2 signaling pathway has emerged as an attractive target for cancer therapy. In our effort, a novel series of picolinamide-based derivatives were designed and synthesized as potent and effective VEGFR-2 inhibitors. All the newly prepared compounds were evaluated in vitro for

  血管内皮生长因子受体2（VEGFR-2）在肿瘤血管生成中起着至关重要的作用，而对VEGFR-2信号通路的抑制已成为癌症治疗的诱人靶标。在我们的努力中，设计并合成了一系列新的基于吡啶啉酰胺的衍生物，它们是有效且有效的VEGFR-2抑制剂。在体外评估所有新制备的化合物对A549和HepG2细胞系的抗增殖活性。在新化合物中，8j和8l对A549和HepG2细胞系均表现出更好的活性。进行分子对接以研究与VEGFR-2（PDB代码：4ASD）的结合能力和结合方式。
• N-acyl-N′-(pyridin-2-yl) ureas and analogs exhibiting anti-cancer and anti-proliferative activities
  申请人：Deciphera Pharmaceuticals, LLC

  公开号：US09309224B2

  公开（公告）日：2016-04-12

  Described are compounds of Formula 1 which find utility in the treatment of cancer, autoimmune diseases and metabolic bone disorders through inhibition of c-FMS (CSF-1R), c-KIT, and/or PDGFR kinases. These compounds also find utility in the treatment of other mammalian diseases mediated by c-FMS, c-KIT, or PDGFR kinases.

  描述了一种化合物，其化学式为1，通过抑制c-FMS（CSF-1R），c-KIT和/或PDGFR激酶，在治疗癌症，自身免疫疾病和代谢性骨疾病方面具有用途。这些化合物还可用于治疗其他由c-FMS，c-KIT或PDGFR激酶介导的哺乳动物疾病。
• US2014/275016
  申请人：——

  公开号：——

  公开（公告）日：——