3-methyl-4-fluoro-5-chloroaniline | 187929-77-7

• 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: 3-methyl-4-fluoro-5-chloroaniline
• 英文别名: 3-Chloro-4-fluoro-5-methylaniline；3-chloro-4-fluoro-5-methylaniline
• CAS: 187929-77-7
• 化学式: C₇H₇ClFN
• 分子量: 159.591
• InChiKey: UMUINZLEGJRKGN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  26
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-methyl-4-fluoro-5-chloroaniline 、 7-methoxy-4-chloro-6-nitroquinoline-3-methyl 以 异丙醇 为溶剂， 反应 4.0h， 以32.1 g的产率得到4-(3-methyl-4-fluoro-5-chlorophenylamino)-7-methoxy-6-nitroquinoline-3-methyl hydrochloride
  参考文献：
  名称：

  Redesigning Kinase Inhibitors to Enhance Specificity

  摘要：

  Kinases are important targets in molecular cancer therapy. However, the evolutionary relatedness and structural conservation of these proteins often lead to unforeseen cross reactivity, yielding unexpected side effects. Thus, the use of promiscuous drugs is likely to introduce dangerous clinical uncertainties. Here, we show how to rationally redesign two promiscuous kinase inhibitors, staurosporine (7) and EKB-569 (8), with the goal of turning, them into more selective ligands. This problem is addressed by exploiting a structure-based selectivity filter for specificity: the pattern of packing defects in the target. These singularities, called dehydrons, are solvent-exposed intramolecular hydrogen bonds that may be protected by drugs upon association and are not conserved across protein families. Our redesigned compounds possess a significantly focused activity, as experimentally corroborated in high-throughput screening assays. Thus, our design strategy proves to be operative to reduce the inhibitory impact of promiscuous kinase ligands, enhancing their safety as therapeutic agents.

  DOI：

  10.1021/jm800453a

文献信息

• [EN] AMIDE DERIVATIVES USEFUL IN THE TREATMENT OF HBV INFECTION OR HBV-INDUCED DISEASES<br/>[FR] DÉRIVÉS D'AMIDE UTILES DANS LE TRAITEMENT D'UNE INFECTION PAR LE VIRUS DE L'HÉPATITE B OU DE MALADIES INDUITES PAR LE VIRUS DE L'HÉPATITE B
  申请人：JANSSEN SCIENCES IRELAND UNLIMITED CO

  公开号：WO2020225230A1

  公开（公告）日：2020-11-12

  The application relates to amide derivatives, processes for their preparation, pharmaceutical compositions, and their uses, more particularly their uses in treating chronic hepatitis B virus (HBV) infection.

  该申请涉及酰胺衍生物，其制备方法，药物组合物以及它们的用途，更具体地说，它们在治疗慢性乙型肝炎病毒（HBV）感染中的用途。
• AMIDE DERIVATIVES USEFUL IN THE TREATMENT OF HBV INFECTION OR HBV-INDUCED DISEASES
  申请人：Janssen Sciences Ireland Unlimited Company

  公开号：US20200352925A1

  公开（公告）日：2020-11-12

  The application relates to amide derivatives, processes for their preparation, pharmaceutical compositions, and their uses, more particularly their uses in treating chronic hepatitis B virus (HBV) infection.
• Redesigning Kinase Inhibitors to Enhance Specificity
  作者：Alejandro Crespo、Xi Zhang、Ariel Fernández

  DOI：10.1021/jm800453a

  日期：2008.8.1

  Kinases are important targets in molecular cancer therapy. However, the evolutionary relatedness and structural conservation of these proteins often lead to unforeseen cross reactivity, yielding unexpected side effects. Thus, the use of promiscuous drugs is likely to introduce dangerous clinical uncertainties. Here, we show how to rationally redesign two promiscuous kinase inhibitors, staurosporine (7) and EKB-569 (8), with the goal of turning, them into more selective ligands. This problem is addressed by exploiting a structure-based selectivity filter for specificity: the pattern of packing defects in the target. These singularities, called dehydrons, are solvent-exposed intramolecular hydrogen bonds that may be protected by drugs upon association and are not conserved across protein families. Our redesigned compounds possess a significantly focused activity, as experimentally corroborated in high-throughput screening assays. Thus, our design strategy proves to be operative to reduce the inhibitory impact of promiscuous kinase ligands, enhancing their safety as therapeutic agents.