3-chloro-4-(2-chloropyridin-4-yloxy)benzenamine | 1225278-52-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-chloro-4-(2-chloropyridin-4-yloxy)benzenamine
• 英文别名: 3-chloro-4-((2-chloropyridin-4-yl)oxy)aniline；3-Chloro-4-(2-chloropyridin-4-yloxy)benzenamine；3-chloro-4-(2-chloropyridin-4-yl)oxyaniline
• CAS: 1225278-52-3
• 化学式: C₁₁H₈Cl₂N₂O
• 分子量: 255.103
• InChiKey: KSPIMVUELMKZGI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  48.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-chloro-4-(2-chloropyridin-4-yloxy)benzenamine 在 四(三苯基膦)钯 、 potassium carbonate 、 三乙胺 作用下， 以 乙二醇二甲醚 、 二氯甲烷 、 水 为溶剂， 反应 1.0h， 生成 N-(3-chloro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide
  参考文献：
  名称：

  IMIDAZOLIDINONES AND ANALOGS EXHIBITING ANTI-CANCER AND ANTI-PROLIFERATIVE ACTIVITIES

  摘要：

  描述了一种化合物，其化学式为I，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。这些化合物还在治疗其他由c-FMS、c-KIT或PDGFR激酶介导的哺乳动物疾病中发挥作用。

  公开号：

  US20140315917A1
• 作为产物：
  描述：

  2,4-二氯吡啶 、 2-氯-4-氨基苯酚 在 potassium tert-butylate 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 4.5h， 以97%的产率得到3-chloro-4-(2-chloropyridin-4-yloxy)benzenamine
  参考文献：
  名称：

  发现嘧啶二酮衍生物作为有效且口服生物可利用的 Axl 抑制剂

  摘要：

  受体酪氨酸激酶 Axl 在促进癌症进展、转移和耐药性中发挥重要作用，并已被确定为抗癌治疗的有希望的靶点。我们从低微摩尔效力化合物9开始，使用分子建模辅助结构优化来发现化合物13c ，这是一种高效且可口服生物利用的 Axl 抑制剂。选择性分析表明， 13c可以抑制众所周知的致癌激酶 Met，其抑制 Axl 超家族激酶的效力相同。化合物13c显着抑制细胞Axl和Met信号传导，抑制Axl和Met驱动的细胞增殖，并抑制Gas6/Axl介导的癌细胞迁移或侵袭。此外， 13c在 Axl 驱动和 Met 驱动的肿瘤异种移植模型中表现出显着的抗肿瘤功效，在耐受良好的剂量下导致肿瘤停滞或消退。所有这些有利的数据使13c成为癌症治疗的有前途的候选药物。

  DOI：

  10.1021/acs.jmedchem.0c02093

文献信息

• [EN] CYCLOPROPANE AMIDES AND ANALOGS EXHIBITING ANTI-CANCER AND ANTI-PROLIFERATIVE ACTIVITIES<br/>[FR] AMIDES DE CYCLOPROPANE ET ANALOGUES PRÉSENTANT DES ACTIVITÉS ANTICANCÉREUSES ET ANTIPROLIFÉRATIVES
  申请人：DECIPHERA PHARMACEUTICALS LLC

  公开号：WO2010051373A1

  公开（公告）日：2010-05-06

  Compounds of the present invention find utility in the treatment of mammalian cancers and especially human cancers including, but not limited to, malignant melanomas, solid tumors, glioblastomas, ovarian cancer, pancreatic cancer, prostate cancer, lung cancers, breast cancers, kidney cancers, hepatic cancers, cervical carcinomas, metastasis of primary tumor sites, myeloproliferative diseases, chronic myelogenous leukemia, leukemias, papillary thyroid carcinoma, non-small cell lung cancer, mesothelioma, hypereosinophilic syndrome, gastrointestinal stromal tumors, colonic cancers, ocular diseases characterized by hyperproliferation leading to blindness including various retinopathies, diabetic retinopathy, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, mastocytosis, mast cell leukemia, and diseases caused by PDGFR-α kinase, PDGFR-β kinase, c-KIT kinase, cFMS kinase, c-MET kinase, and oncogenic forms, aberrant fusion proteins and polymorphs of any of the foregoing kinases.

  本发明的化合物在治疗哺乳动物癌症，尤其是人类癌症方面具有实用性，包括但不限于恶性黑色素瘤、实体肿瘤、胶质母细胞瘤、卵巢癌、胰腺癌、前列腺癌、肺癌、乳腺癌、肾癌、肝癌、宫颈癌、原发肿瘤部位的转移、骨髓增生性疾病、慢性髓细胞白血病、白血病、乳头状甲状腺癌、非小细胞肺癌、间皮瘤、高嗜酸性综合征、胃肠道间质瘤、结肠癌、由高增殖导致失明的眼部疾病，包括各种视网膜病变、糖尿病视网膜病变、类风湿性关节炎、哮喘、慢性阻塞性肺病、肥大细胞增多症、肥大细胞白血病，以及由PDGFR-α激酶、PDGFR-β激酶、c-KIT激酶、cFMS激酶、c-MET激酶和致癌形式、异常融合蛋白和任何上述激酶的多态体引起的疾病。
• CYCLOPROPANE AMIDES AND ANALOGS EXHIBITING ANTI-CANCER AND ANTI-PROLIFERATIVE ACTIVITIES
  申请人：Flynn Daniel L.

  公开号：US20100120806A1

  公开（公告）日：2010-05-13

  Compounds of the present invention find utility in the treatment of mammalian cancers and especially human cancers including, but not limited to, malignant melanomas, solid tumors, glioblastomas, ovarian cancer, pancreatic cancer, prostate cancer, lung cancers, breast cancers, kidney cancers, hepatic cancers, cervical carcinomas, metastasis of primary tumor sites, myeloproliferative diseases, chronic myelogenous leukemia, leukemias, papillary thyroid carcinoma, non-small cell lung cancer, mesothelioma, hypereosinophilic syndrome, gastrointestinal stromal tumors, colonic cancers, ocular diseases characterized by hyperproliferation leading to blindness including various retinopathies, diabetic retinopathy, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, mastocytosis, mast cell leukemia, and diseases caused by PDGFR-α kinase, PDGFR-β kinase, c-KIT kinase, cFMS kinase, c-MET kinase, and oncogenic forms, aberrant fusion proteins and polymorphs of any of the foregoing kinases.

  本发明的化合物在哺乳动物癌症治疗中具有实用性，特别是人类癌症，包括但不限于恶性黑色素瘤、实体肿瘤、胶质母细胞瘤、卵巢癌、胰腺癌、前列腺癌、肺癌、乳腺癌、肾癌、肝癌、宫颈癌、原发肿瘤部位的转移、骨髓增生性疾病、慢性髓性白血病、白血病、乳头状甲状腺癌、非小细胞肺癌、间皮瘤、高嗜酸性综合症、胃肠道间质瘤、结肠癌、眼部疾病，其特征为细胞过度增殖导致失明，包括各种视网膜病变、糖尿病视网膜病变、类风湿性关节炎、哮喘、慢性阻塞性肺疾病、肥大细胞增多症、肥大细胞白血病以及由PDGFR-α激酶、PDGFR-β激酶、c-KIT激酶、cFMS激酶、c-MET激酶和任何上述激酶的癌变形式、异常融合蛋白和多态性引起的疾病。
• N-acyl ureas exhibiting anti-cancer and anti-proliferative activities
  申请人：Deciphera Pharmaceuticals, LLC

  公开号：US08278331B2

  公开（公告）日：2012-10-02

  Compounds of the present invention find utility in the treatment of mammalian cancers and especially human cancers including, but not limited to, malignant melanomas, solid tumors, glioblastomas, ovarian cancer, pancreatic cancer, prostate cancer, lung cancers, breast cancers, kidney cancers, hepatic cancers, cervical carcinomas, metastasis of primary tumor sites, myeloproliferative diseases, chronic myelogenous leukemia, leukemias, papillary thyroid carcinoma, non-small cell lung cancer, mesothelioma, hypereosinophilic syndrome, gastrointestinal stromal tumors, colonic cancers, ocular diseases characterized by hyperproliferation leading to blindness including various retinopathies, diabetic retinopathy, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, mastocytosis, mast cell leukemia, and diseases caused by PDGFR-α kinase, PDGFR-β kinase, c-KIT kinase, cFMS kinase, c-MET kinase, and oncogenic forms, aberrant fusion proteins and polymorphs of any of the foregoing kinases.

  本发明的化合物在哺乳动物癌症的治疗中具有实用性，特别是人类癌症，包括但不限于恶性黑色素瘤、实体肿瘤、胶质母细胞瘤、卵巢癌、胰腺癌、前列腺癌、肺癌、乳腺癌、肾癌、肝癌、宫颈癌、原发性肿瘤部位的转移、骨髓增生性疾病、慢性髓细胞白血病、白血病、乳头状甲状腺癌、非小细胞肺癌、间皮瘤、高嗜酸性综合征、胃肠间质肿瘤、结肠癌、眼部疾病，其特征为过度增殖导致失明，包括各种视网膜病变、糖尿病视网膜病变、类风湿性关节炎、哮喘、慢性阻塞性肺疾病、肥大细胞增多症、肥大细胞白血病，以及由PDGFR-α激酶、PDGFR-β激酶、c-KIT激酶、cFMS激酶、c-MET激酶和任何上述激酶的癌变形式、异常融合蛋白和多态性引起的疾病。
• Cyclopropane amides and analogs exhibiting anti-cancer and anti-proliferative activities
  申请人：Flynn Daniel L.

  公开号：US08486951B2

  公开（公告）日：2013-07-16

  Compounds of the present invention find utility in the treatment of mammalian cancers and especially human cancers including, but not limited to, malignant melanomas, solid tumors, glioblastomas, ovarian cancer, pancreatic cancer, prostate cancer, lung cancers, breast cancers, kidney cancers, hepatic cancers, cervical carcinomas, metastasis of primary tumor sites, myeloproliferative diseases, chronic myelogenous leukemia, leukemias, papillary thyroid carcinoma, non-small cell lung cancer, mesothelioma, hypereosinophilia syndrome, gastrointestinal stromal tumors, colonic cancers, ocular diseases characterized by hyperproliferation leading to blindness including various retinopathies, diabetic retinopathy, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, mastocytosis, mast cell leukemia, and diseases caused by PDGFR-α kinase, PDGFR-β kinase, c-KIT kinase, cFMS kinase, c-MET kinase, and oncogenic forms, aberrant fusion proteins and polymorphs of any of the foregoing kinases.

  本发明的化合物在哺乳动物癌症，特别是人类癌症的治疗中具有实用性，包括但不限于恶性黑色素瘤、实体肿瘤、胶质母细胞瘤、卵巢癌、胰腺癌、前列腺癌、肺癌、乳腺癌、肾癌、肝癌、宫颈癌、原发肿瘤部位的转移、骨髓增生性疾病、慢性髓细胞白血病、白血病、乳头状甲状腺癌、非小细胞肺癌、间皮瘤、高嗜酸性综合症、胃肠道间质瘤、结肠癌、眼部疾病（包括各种视网膜病变、糖尿病性视网膜病变）、类风湿性关节炎、哮喘、慢性阻塞性肺疾病、肥大细胞增多症、肥大细胞白血病，以及由PDGFR-α激酶、PDGFR-β激酶、c-KIT激酶、cFMS激酶、c-MET激酶和任何上述激酶的癌变形式、异常融合蛋白和多态体引起的疾病中具有实用性。
• Imidazolidinones and analogs exhibiting anti-cancer and anti-proliferative activities
  申请人：Deciphera Pharmaceuticals, LLC

  公开号：US09133183B2

  公开（公告）日：2015-09-15

  Described are compounds of Formula I 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.

  本文描述的是I式化合物，可通过抑制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发挥作用。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。