2-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-methoxy-2-methylphenyl)acetonitrile

• 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: 2-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-methoxy-2-methylphenyl)acetonitrile
• 英文别名: US10100019, Example 53；2-[4-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]-5-methoxy-2-methylphenyl]acetonitrile
• 化学式: C₂₃H₂₄ClN₅O₃S
• 分子量: 485.994
• InChiKey: CKOFEFWHTQQMLF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  125
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-methoxy-2-methylphenyl)acetonitrile 在 硼烷四氢呋喃络合物 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 以45%的产率得到N²-(4-(2-aminoethyl)-2-methoxy-5-methylphenyl)-5-chloro-N⁴-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine
  参考文献：
  名称：

  N2-(2-METHOXYPHENYL)PYRIMIDINE DERIVATIVE, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL COMPOSITION FOR CANCER PREVENTION OR TREATMENT CONTAINING SAME AS ACTIVE INGREDIENT

  摘要：

  本发明涉及一种N2-(2-甲氧基苯基)嘧啶衍生物，其制备方法，以及包含其作为活性成分的用于预防或治疗癌症的药物组合物。本发明的N2-(2-甲氧基苯基)嘧啶衍生物，其光学异构体，或其药学上可接受的盐对抑制间变性淋巴瘤激酶（ALK）活性非常有效，从而可以提高对具有间变性淋巴瘤激酶（ALK）融合蛋白如EML4-ALK和NPM-ALK的癌细胞的治疗效果，因此可以有效地用作预防或治疗癌症的药物组合物。

  公开号：

  US20180111905A1
• 作为产物：
  描述：

  2-(异丙基磺酰基)苯胺 在 sodium hydride 、 对甲苯磺酸 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 4.5h， 生成 2-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-methoxy-2-methylphenyl)acetonitrile
  参考文献：
  名称：

  [EN] POTENT AND SELECTIVE DEGRADERS OF ALK
  [FR] AGENTS DE DÉGRADATION D'ALK PUISSANTS ET SÉLECTIFS

  摘要：

  揭示了针对ALK或ALK和FAK进行降解的双特异性化合物（降解剂）。还揭示了含有这些降解剂的药物组合物，以及使用这些双特异性化合物治疗由异常ALK或ALK和FAK活性特征或介导的疾病和紊乱的方法。

  公开号：

  WO2021173677A1

文献信息

• N2-(2-METHOXYPHENYL)PYRIMIDINE DERIVATIVE, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL COMPOSITION FOR CANCER PREVENTION OR TREATMENT CONTAINING SAME AS ACTIVE INGREDIENT
  申请人：KOREA RESEARCH INSTITUTE OF CHEMICAL TECHNOLOGY

  公开号：US20180111905A1

  公开（公告）日：2018-04-26

  The present invention relates to a N2-(2-methoxyphenyl)pyrimidine derivative, a preparation method thereof, and a pharmaceutical composition for the prevention or treatment of cancer comprising the same as an active ingredient. The N2-(2-methoxyphenyl)pyrimidine derivative, the optical isomer thereof, or the pharmaceutically acceptable salt thereof of the present invention is very effective in suppressing anaplastic lymphoma kinase (ALK) activity and as a result it can improve the effectiveness of treatment on cancer cells having anaplastic lymphoma kinase (ALK) fusion proteins such as EML4-ALK and NPM-ALK, so that it can be effectively used as a pharmaceutical composition for preventing or treating cancer.

  本发明涉及一种N2-(2-甲氧基苯基)嘧啶衍生物，其制备方法，以及包含其作为活性成分的用于预防或治疗癌症的药物组合物。本发明的N2-(2-甲氧基苯基)嘧啶衍生物，其光学异构体，或其药学上可接受的盐对抑制间变性淋巴瘤激酶（ALK）活性非常有效，从而可以提高对具有间变性淋巴瘤激酶（ALK）融合蛋白如EML4-ALK和NPM-ALK的癌细胞的治疗效果，因此可以有效地用作预防或治疗癌症的药物组合物。
• N2-(2-methoxyphenyl)pyrimidine derivative, method for preparing same, and pharmaceutical composition for cancer prevention or treatment containing same as active ingredient
  申请人：KOREA RESEARCH INSTITUTE OF CHEMICAL TECHNOLOGY

  公开号：US10100019B2

  公开（公告）日：2018-10-16

  The present invention relates to a N2-(2-methoxyphenyl)pyrimidine derivative, a preparation method thereof, and a pharmaceutical composition for the prevention or treatment of cancer comprising the same as an active ingredient. The N2-(2-methoxyphenyl)pyrimidine derivative, the optical isomer thereof, or the pharmaceutically acceptable salt thereof of the present invention is very effective in suppressing anaplastic lymphoma kinase (ALK) activity and as a result it can improve the effectiveness of treatment on cancer cells having anaplastic lymphoma kinase (ALK) fusion proteins such as EML4-ALK and NPM-ALK, so that it can be effectively used as a pharmaceutical composition for preventing or treating cancer.

  本发明涉及一种N2-(2-甲氧基苯基)嘧啶衍生物、其制备方法以及一种预防或治疗癌症的药物组合物，该药物组合物以N2-(2-甲氧基苯基)嘧啶衍生物为有效成分。本发明的N2-(2-甲氧基苯基)嘧啶衍生物、其光学异构体或其药学上可接受的盐在抑制无性淋巴瘤激酶（ALK）活性方面非常有效，因此可以提高对具有无性淋巴瘤激酶（ALK）融合蛋白（如EML4-ALK和NPM-ALK）的癌细胞的治疗效果，从而可以有效地用作预防或治疗癌症的药物组合物。
• [EN] POTENT AND SELECTIVE DEGRADERS OF ALK<br/>[FR] AGENTS DE DÉGRADATION D'ALK PUISSANTS ET SÉLECTIFS
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2021173677A1

  公开（公告）日：2021-09-02

  Disclosed are bispecific compounds (degraders) that target ALK or ALK and FAK for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the bispecific compounds to treat diseases and disorders characterized or mediated by aberrant ALK or ALK and FAK activity.

  揭示了针对ALK或ALK和FAK进行降解的双特异性化合物（降解剂）。还揭示了含有这些降解剂的药物组合物，以及使用这些双特异性化合物治疗由异常ALK或ALK和FAK活性特征或介导的疾病和紊乱的方法。
• Replacing the terminal piperidine in ceritinib with aliphatic amines confers activities against crizotinib-resistant mutants including G1202R
  作者：Gangadhar Rao Mathi、Chung Hyo Kang、Heung Kyoung Lee、Raghavendra Achary、Ha-Yeon Lee、Joo-Youn Lee、Jae Du Ha、Sunjoo Ahn、Chi Hoon Park、Chong Ock Lee、Jong Yeon Hwang、Chang-Soo Yun、Hee Jung Jung、Sung Yun Cho、Hyoung Rae Kim、Pilho Kim

  DOI：10.1016/j.ejmech.2016.11.046

  日期：2017.1

  The piperidine fragment in ceritinib was replaced with diverse aliphatic amines to improve inherent resistance issues of ceritinib. While most of the prepared compounds exhibit as similar in vitro activities as ceritinib, compound 10 shows encouraging activities against wild-type ALK as well as crizotinibresistant mutants including extremely resistant G1202R mutant with an IC50 of 1.8 nM. Furthermore, pharmacokinetic profiles of 10 is apparently better than that of ceritinib. In murine xenograft studies, compound 10 turns out to be as active as ceritinib, suggesting that further optimization of 10 may lead to clinical candidates overcoming ALK mutant issues. (C) 2016 Elsevier Masson SAS. All rights reserved.