(E)-2-(6-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-7-methoxy-1,1-dimethyl-3,4-dihydronaphthalen-2(1H)-ylidene)hydrazine-1-carboxamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (E)-2-(6-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-7-methoxy-1,1-dimethyl-3,4-dihydronaphthalen-2(1H)-ylidene)hydrazine-1-carboxamide
• 英文别名: (E)-2-(6-(5-chloro-4-(2-(isopropylsulfonyl)phenylamino)pyrimidine-2-ylamino)-7-methoxy-1,1-dimethyl-3,4-dihydronaphthalene-2(1H)-yladene)hydrogencarboxamide；[(E)-[6-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]-7-methoxy-1,1-dimethyl-3,4-dihydronaphthalen-2-ylidene]amino]urea
• 化学式: C₂₇H₃₂ClN₇O₄S
• 分子量: 586.115
• InChiKey: GHSPDHNQBYYRPD-PPFNPFNJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  40
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  169
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  7-甲氧基-1,1-二甲基-3,4-二氢萘-2(1H)-酮 在 盐酸 、 硫酸 、 potassium nitrate 作用下， 以 乙二醇乙醚 、 乙醇 、 三氟乙酸 为溶剂， 100.0 ℃ 、101.33 kPa 条件下， 反应 23.0h， 生成 (E)-2-(6-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-7-methoxy-1,1-dimethyl-3,4-dihydronaphthalen-2(1H)-ylidene)hydrazine-1-carboxamide
  参考文献：
  名称：

  Novel 2,4-diaminopyrimidines bearing tetrahydronaphthalenyl moiety against anaplastic lymphoma kinase (ALK): Synthesis, in vitro, ex vivo, and in vivo efficacy studies

  摘要：

  A series of novel 2,4-diaminopyrimidines bearing tetrahydronaphthalenyl moiety were synthesized and evaluated for their anti-anaplastic lymphoma kinase (ALK) activities using enzymatic and cell-based assays. Among the compounds synthesized, compound 17b showed promising pharmacological results in in vitro, ex vivo, and pharmacokinetic studies. An in vivo efficacy study with compound 17b demonstrated highly potent inhibitory activity in H3122 tumor xenograft model mice. A series of kinase assays showed that compound 17b inhibited various kinases including FAK, ACK1, FGFR, RSK1, IGF-1R, among others, thus demonstrating its potential for synergistic anti-tumor activity and development as a multi-targeted non-small cell lung cancer (NSCLC) therapy. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.02.052

文献信息

• 4-(2-AMINO-TETRAHYDRONAPHTHALENYL)PYRIMIDINE DERIVATIVE, PREPARATION METHOD THEREFOR, AND PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING CANCER, CONTAINING SAME AS ACTIVE INGREDIENT
  申请人：KOREA RESEARCH INSTITUTE OF CHEMICAL TECHNOLOGY

  公开号：US20180104242A1

  公开（公告）日：2018-04-19

  The present invention relates to a 4-(2-amino-tetrahydronaphthaleneyl)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 4-(2-amino-tetrahydronaphthaleneyl)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4-(2-氨基-四氢萘基)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4-(2-氨基-四氢萘基)嘧啶衍生物及其光学异构体或其药用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，因此可以有效地作为预防或治疗癌症的药物组合物使用。
• 4-(2-amino-tetrahydronaphthalenyl)pyrimidine derivative, preparation method therefor, and pharmaceutical composition for preventing or treating cancer, containing same as active ingredient
  申请人：KOREA RESEARCH INSTITUTE OF CHEMICAL TECHNOLOGY

  公开号：US10369149B2

  公开（公告）日：2019-08-06

  The present invention relates to a 4-(2-amino-tetrahydronaphthaleneyl)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 4-(2-amino-tetrahydronaphthaleneyl)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 4-(2-氨基-四氢萘基)嘧啶衍生物、其制备方法和一种预防或治疗癌症的药物组合物，其有效成分包括 4-(2-氨基-四氢萘基)嘧啶衍生物。本发明的 4-(2-氨基-四氢萘基)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。
• Novel 2,4-diaminopyrimidines bearing tetrahydronaphthalenyl moiety against anaplastic lymphoma kinase (ALK): Synthesis, in vitro, ex vivo, and in vivo efficacy studies
  作者：Dawn Song、Minji Lee、Chi Hoon Park、Sunjoo Ahn、Chang Soo Yun、Chong Ock Lee、Hyoung Rae Kim、Jong Yeon Hwang

  DOI：10.1016/j.bmcl.2016.02.052

  日期：2016.4

  A series of novel 2,4-diaminopyrimidines bearing tetrahydronaphthalenyl moiety were synthesized and evaluated for their anti-anaplastic lymphoma kinase (ALK) activities using enzymatic and cell-based assays. Among the compounds synthesized, compound 17b showed promising pharmacological results in in vitro, ex vivo, and pharmacokinetic studies. An in vivo efficacy study with compound 17b demonstrated highly potent inhibitory activity in H3122 tumor xenograft model mice. A series of kinase assays showed that compound 17b inhibited various kinases including FAK, ACK1, FGFR, RSK1, IGF-1R, among others, thus demonstrating its potential for synergistic anti-tumor activity and development as a multi-targeted non-small cell lung cancer (NSCLC) therapy. (C) 2016 Elsevier Ltd. All rights reserved.