6-氯-4-(苯基氨基)烟酸乙酯 | 1012878-94-2

• 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
• 中文名称: 6-氯-4-(苯基氨基)烟酸乙酯
• 英文名称: ethyl 6-chloro-4-(phenylamino)nicotinate
• 英文别名: ethyl 4-anilino-6-chloropyridine-3-carboxylate
• CAS: 1012878-94-2
• 化学式: C₁₄H₁₃ClN₂O₂
• 分子量: 276.722
• InChiKey: HFZNNKRDKQNPAK-UHFFFAOYSA-N

物化性质

• 沸点：
  393.7±42.0 °C(Predicted)
• 密度：
  1.286±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-氯-4-(苯基氨基)烟酸乙酯 在 水 、 palladium diacetate 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 64.5h， 生成 6-(3-ethylureido)-4-(phenylamino)nicotinic acid
  参考文献：
  名称：

  [EN] HETEROCYCLIC UREA COMPOUNDS
  [FR] COMPOSÉS HÉTÉROCYCLIQUES D'URÉE

  摘要：

  本发明提供了以下式的化合物，它们的外消旋体、对映体和盐。还提供了这些化合物作为抗菌剂的用途，包括它们的组合物和制造过程。

  公开号：

  WO2013091011A1
• 作为产物：
  描述：

  4,6-二羟基烟酸乙酯 在 盐酸 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 2.5h， 生成 6-氯-4-(苯基氨基)烟酸乙酯
  参考文献：
  名称：

  [EN] HETEROCYCLIC UREA COMPOUNDS
  [FR] COMPOSÉS HÉTÉROCYCLIQUES D'URÉE

  摘要：

  本发明提供了以下式的化合物，它们的外消旋体、对映体和盐。还提供了这些化合物作为抗菌剂的用途，包括它们的组合物和制造过程。

  公开号：

  WO2013091011A1

文献信息

• Optimization and biological evaluation of nicotinamide derivatives as Aurora kinase inhibitors
  作者：Baohui Qi、Xingwei Xu、Ying Yang、Huan He、Xupeng Yue

  DOI：10.1016/j.bmc.2019.07.016

  日期：2019.9

  Aurora kinases are known to be overexpressed in various solid tumors and implicated in oncogenesis and tumor progression. A series of nicotinamide derivatives were synthesized and their biological activities were evaluated, including kinase inhibitory activity against Aur A and Aur B and in vitro antitumor activity against SW620, HT-29, NCI-H1975 and Hela cancer cell lines. In addition, the study of

  已知极光激酶在各种实体瘤中过表达，并且与肿瘤发生和肿瘤进展有关。合成了一系列烟酰胺衍生物，并评估了它们的生物学活性，包括对Aur A和Aur B的激酶抑制活性以及对SW620，HT-29，NCI-H1975和Hela癌细胞系的体外抗肿瘤活性。此外，还进行了抗增殖，细胞毒性和凋亡的研究。作为Aur A的最强抑制剂，4-（（3-溴-4-氟苯基）氨基）-6-氯-N-（4-（（6,7-二甲氧基喹啉-4-基）氧基] -3-氟苯基）烟酰胺（10升）对SW620和NCI-H1975具有优异的抗肿瘤活性，IC50值为0.61和1.06μM，而参考化合物的IC50值分别为3.37和6.67μM。此外，
• Kinase inhibitors useful for the treatment of proliferative diseases
  申请人：Flynn L. Daniel

  公开号：US20080114006A1

  公开（公告）日：2008-05-15

  The present invention relates to novel kinase inhibitors and modulator compounds useful for the treatment of various diseases. More particularly, the invention is concerned with such compounds, kinase/compound adducts, methods of treating diseases, and methods of synthesis of the compounds. Preferrably, the compounds are useful for the modulation of kinase activity of Raf kinases and disease polymorphs thereof. Compounds of the present invention find utility in the treatment of mammalian cancers and especially human cancers including but not limited to malignant melanoma, colorectal cancer, ovarian cancer, papillary thyroid carcinoma, non small cell lung cancer, and mesothelioma. Compounds of the present invention also find utility in the treatment of rheumatoid arthritis and retinopathies including diabetic retinal neuropathy and macular degeneration.

  本发明涉及一种新型激酶抑制剂和调节剂化合物，用于治疗各种疾病。更具体地说，本发明涉及这样的化合物、激酶/化合物加合物、治疗疾病的方法以及合成化合物的方法。优选地，这些化合物对Raf激酶及其疾病多态性的激酶活性调节是有用的。本发明的化合物在哺乳动物癌症，特别是人类癌症，包括但不限于恶性黑色素瘤、结肠直肠癌、卵巢癌、乳头状甲状腺癌、非小细胞肺癌和间皮瘤的治疗中发挥作用。本发明的化合物也在治疗类风湿性关节炎和视网膜病变，包括糖尿病性视网膜神经病变和黄斑变性方面发挥作用。
• COMPOSITIONS AND METHODS FOR MODULATING C-KIT AND PDGFR RECEPTORS
  申请人：Chianelli Donatella

  公开号：US20080176846A1

  公开（公告）日：2008-07-24

  The invention provides compounds and pharmaceutical compositions thereof, which are useful as protein kinase inhibitors, as well as methods for using such compounds to treat, ameliorate or prevent a condition associated with abnormal or deregulated kinase activity. In some embodiments, the invention provides methods for using such compounds to treat, ameliorate or prevent diseases or disorders that involve abnormal activation of c-kit, PDGFRα, PDGFRβ, CSF1R, Abl, BCR-Abl, CSK, JNK1, JNK2, p38, p70S6K, TGFβ, SRC, EGFR, trkB, FGFR3, FLT3, Fes, Lck, Syk, RAF, MKK4, MKK6, SAPK2β, BRK, KDR, c-raf or b-raf kinase, or mutant forms thereof.

  该发明提供了化合物及其制药组合物，其作为蛋白激酶抑制剂有用，以及使用这些化合物的方法来治疗、改善或预防与异常或失调的激酶活性相关的疾病或症状。在某些实施例中，该发明提供了使用这些化合物来治疗、改善或预防涉及c-kit、PDGFRα、PDGFRβ、CSF1R、Abl、BCR-Abl、CSK、JNK1、JNK2、p38、p70S6K、TGFβ、SRC、EGFR、trkB、FGFR3、FLT3、Fes、Lck、Syk、RAF、MKK4、MKK6、SAPK2β、BRK、KDR、c-raf或b-raf激酶或其突变形式的疾病或紊乱的方法。
• Dihydropyridopyrimidinyl, dihydronaphthyidinyl and related compounds useful as kinase inhibitors for the treatment of proliferative diseases
  申请人：Deciphera Pharmaceuticals, Inc.

  公开号：US08188113B2

  公开（公告）日：2012-05-29

  The present invention relates to novel dihydropyridopyrimidinyl, dihydronaphthyridinyl, and related compounds which are kinase inhibitors and modulator useful for the treatment of various diseases. More particularly, the invention is concerned with such compounds, kinase/compound adducts, methods of treating diseases, and methods of synthesis of the compounds. Preferably, the compounds are useful for the modulation of kinase activity of Raf kinases and disease polymorphs thereof. Compounds of the present invention find utility in the treatment of mammalian cancers and especially human cancers including but not limited to malignant melanoma, colorectal cancer, ovarian cancer, papillary thyroid carcinoma, non small cell lung cancer, and mesothelioma. Compounds of the present invention also find utility in the treatment of rheumatoid arthritis and retinopathies including diabetic retinal neuropathy and macular degeneration.

  本发明涉及一种新型的二氢吡啶吡嗪基，二氢萘嗪基和相关化合物，这些化合物是激酶抑制剂和调节剂，可用于治疗各种疾病。更具体地说，本发明涉及这些化合物，激酶/化合物加合物，治疗疾病的方法以及合成这些化合物的方法。优选地，这些化合物对Raf激酶及其疾病多态体的激酶活性的调节具有用处。本发明的化合物在哺乳动物癌症治疗中，特别是人类癌症治疗中，包括但不限于恶性黑色素瘤、结肠直肠癌、卵巢癌、乳头状甲状腺癌、非小细胞肺癌和间皮瘤中具有用处。本发明的化合物在类风湿性关节炎和视网膜病变治疗中也具有用处，包括糖尿病性视网膜神经病变和黄斑变性。
• Compositions and methods for modulating c-kit and PDGFR receptors
  申请人：IRM LLC

  公开号：US08106068B2

  公开（公告）日：2012-01-31

  The invention provides compounds of Formula (2), and pharmaceutical compositions thereof, wherein R1, R2, R3, R4 and L are as described herein; as well as methods for using such compounds to treat, ameliorate or prevent a condition associated with abnormal or deregulated kinase activity. In some embodiments, the invention provides methods for using such compounds to treat, ameliorate or prevent diseases or disorders that involve abnormal activation of c-kit, PDGFRα, PDGFRβ, CSF1R, Abl, BCR-Abl, CSK, JNK1, JNK2, p38, p70S6K, TGFβ, SRC, EGFR, trkB, FGFR3, FLT3, Fes, Lck, Syk, RAF, MKK4, MKK6, SAPK2β, BRK, KDR, c-raf or b-raf kinase, or mutant forms thereof.

  本发明提供了公式（2）的化合物及其制药组合物，其中R1、R2、R3、R4和L如本文所述；以及使用这些化合物来治疗、改善或预防与异常或非规则激酶活性相关的疾病或症状的方法。在某些实施例中，本发明提供使用这些化合物来治疗、改善或预防涉及c-kit、PDGFRα、PDGFRβ、CSF1R、Abl、BCR-Abl、CSK、JNK1、JNK2、p38、p70S6K、TGFβ、SRC、EGFR、trkB、FGFR3、FLT3、Fes、Lck、Syk、RAF、MKK4、MKK6、SAPK2β、BRK、KDR、c-raf或b-raf激酶或其突变形式的疾病或疾病的方法。