5-amino-2,4-difluoro-N-methylbenzamide | 639858-44-9

• 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: 5-amino-2,4-difluoro-N-methylbenzamide
• 英文别名: 5-amino-2,4-difluoro-N-methyl-benzamide
• CAS: 639858-44-9
• 化学式: C₈H₈F₂N₂O
• 分子量: 186.161
• InChiKey: YYPDETPSKQJSOB-UHFFFAOYSA-N

物化性质

• 沸点：
  257.6±40.0 °C(Predicted)
• 密度：
  1.325±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(pyridin-2-ylamino)thiazole-5-carbaldehyde 、 5-amino-2,4-difluoro-N-methylbenzamide 在 三乙基硅烷 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以75%的产率得到2,4-Difluoro-N-methyl-5-{[2-(Pyridin-2-ylamino)-thiazole-5-ylmethyl]-amino}-benzamide
  参考文献：
  名称：

  Heterocyclic inhibitors of kinases

  摘要：

  本发明提供了公式I的化合物 1 以及药用可接受的盐。 公式I化合物抑制生长因子受体如VEGFR-2、FGFR-1的酪氨酸激酶活性，从而使其作为抗癌剂具有用途。公式I化合物还用于治疗其他通过生长因子受体作用的信号转导通路相关的疾病。

  公开号：

  US20040077696A1
• 作为产物：
  描述：

  2,4-二氟-5-硝基苯甲酸 在 palladium on activated charcoal 氯化亚砜 、 氢气 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， -40.0~25.0 ℃ 、101.33 kPa 条件下， 反应 3.0h， 生成 5-amino-2,4-difluoro-N-methylbenzamide
  参考文献：
  名称：

  Discovery and Evaluation of N-Cyclopropyl- 2,4-difluoro-5-((2-(pyridin-2-ylamino)thiazol-5- ylmethyl)amino)benzamide (BMS-605541), a Selective and Orally Efficacious Inhibitor of Vascular Endothelial Growth Factor Receptor-2

  摘要：

  Substituted 3-((2-(pyridin-2-ylamino)thiazol-5-ylmethyl)-amino) benzamides were identified as potent and selective inhibitors of vascular endothelial growth factor receptor-2 (VEGFR-2) kinase activity. The enzyme kinetics associated with the VEGFR-2 inhibition of 14 (K-i=49 +/- 9 nM) confirmed that the aminothiazole-based analogues are competitive with ATP. Analogue 14 demonstrated excellent kinase selectivity, favorable pharmacokinetic properties in multiple species, and robust in vivo efficacy in human lung and colon carcinoma xenograft models.

  DOI：

  10.1021/jm060347y

文献信息

• Heterocyclic inhibitors of kinases
  申请人：——

  公开号：US20040077696A1

  公开（公告）日：2004-04-22

  The present invention provides compounds of formula I 1 and pharmaceutically acceptable salts thereof. The formula I compounds inhibit the tyrosine kinase activity of growth factor receptors such as VEGFR-2, FGFR-1, thereby making them useful as anti-cancer agents. The formula I compounds are also useful for the treatment of other diseases associated with signal transduction pathways operating through growth factor receptors.

  本发明提供了公式I的化合物 1 以及药用可接受的盐。 公式I化合物抑制生长因子受体如VEGFR-2、FGFR-1的酪氨酸激酶活性，从而使其作为抗癌剂具有用途。公式I化合物还用于治疗其他通过生长因子受体作用的信号转导通路相关的疾病。
• [EN] NEW SUBSTITUTED CYANOINDOLINE DERIVATIVES AS NIK INHIBITORS<br/>[FR] NOUVEAUX DÉRIVÉS DE CYANOINDOLINE UTILISÉS COMME INHIBITEURS DE NIK
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2017125530A1

  公开（公告）日：2017-07-27

  The present invention relates to pharmaceutical agents of formula (I) useful for therapy and/or prophylaxis in a mammal, and in particular to inhibitors of NF- KB-inducing kinase (NIK - also known as MAP3K14) useful for treating diseases such as cancer, inflammatory disorders, metabolic disorders and autoimmune disorders. The invention is also directed to pharmaceutical compositions comprising such compounds, and to the use of such compounds or pharmaceutical compositions for the prevention or treatment of diseases such as cancer, inflammatory disorders, metabolic disorders including obesity and diabetes, and autoimmune disorders.

  本发明涉及一种公式（I）的药物制剂，用于治疗和/或预防哺乳动物中的疾病，特别是用于治疗癌症、炎症性疾病、代谢性疾病和自身免疫性疾病的NF-KB诱导激酶（NIK，也称为MAP3K14）的抑制剂。该发明还涉及包含这些化合物的药物组合物，以及利用这些化合物或药物组合物预防或治疗癌症、炎症性疾病、包括肥胖和糖尿病在内的代谢性疾病以及自身免疫性疾病的用途。
• Quinazoline Derivatives as a Multiplex Inhibitor and Method For the Preparation Thereof
  申请人：Ahn Young-Gil

  公开号：US20080318950A1

  公开（公告）日：2008-12-25

  The present invention relates to a novel quinazoline derivative and a pharmaceutically acceptable salt thereof as a multiplex inhibitor, a method for the preparation thereof, and a pharmaceutical composition and a therapeutic composition comprising same as an active ingredient. The inventive quinazoline derivative as a multiplex inhibitor can selectively and effectively inhibit diseases caused by the overactivity of a tyrosine kinase.

  本发明涉及一种新型喹唑啉衍生物及其药学上可接受的盐，作为多重抑制剂，其制备方法，以及包含其作为活性成分的药物组合物和治疗组合物。发明的喹唑啉衍生物作为多重抑制剂可以选择性和有效地抑制由酪氨酸激酶过度活性引起的疾病。
• Quinazoline derivatives as a multiplex inhibitor and method for the preparation thereof
  申请人：Ahn Young-Gil

  公开号：US08846699B2

  公开（公告）日：2014-09-30

  The present invention relates to a novel quinazoline derivative compound having the formula (1) as follows: with the constituents defined in claim 1, and a pharmaceutically acceptable salt thereof as a multiplex inhibitor, a method for the preparation thereof, and a pharmaceutical composition and a therapeutic composition comprising same as an active ingredient. The inventive quinazoline derivative as a multiplex inhibitor can selectively and effectively inhibit diseases caused by the overactivity of a tyrosine kinase.

  本发明涉及一种具有以下式（1）的新型喹唑啉衍生物化合物：其中组分定义如权利要求书所述，以及其药学上可接受的盐作为多重抑制剂，其制备方法，以及包含其作为活性成分的药物组合物和治疗组合物。作为多重抑制剂的本发明喹唑啉衍生物可以选择性地和有效地抑制由酪氨酸激酶过度活化引起的疾病。
• Substituted cyanoindoline derivatives as NIK inhibitors
  申请人：Janssen Pharmaceutica NV

  公开号：US11180487B2

  公开（公告）日：2021-11-23

  The present invention relates to pharmaceutical agents of formula (I) useful for therapy and/or prophylaxis in a mammal, and in particular to inhibitors of NF-κB-inducing kinase (NIK—also known as MAP3K14) useful for treating diseases such as cancer, inflammatory disorders, metabolic disorders and autoimmune disorders. The invention is also directed to pharmaceutical compositions comprising such compounds, and to the use of such compounds or pharmaceutical compositions for the prevention or treatment of diseases such as cancer, inflammatory disorders, metabolic disorders including obesity and diabetes, and autoimmune disorders.

  本发明涉及用于哺乳动物治疗和/或预防的式(I)药物制剂，特别是用于治疗癌症、炎症性疾病、代谢性疾病和自身免疫性疾病等疾病的NF-κB诱导激酶（NIK-又称MAP3K14）抑制剂。本发明还涉及包含此类化合物的药物组合物，以及使用此类化合物或药物组合物预防或治疗癌症、炎症性疾病、代谢紊乱（包括肥胖和糖尿病）和自身免疫性疾病等疾病。