2-hydroxy-5-[N-[(2,5-dihydroxyphenyl)methyl] amino]-benzoic acid 3-phenylpropyl ester

• 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: 2-hydroxy-5-[N-[(2,5-dihydroxyphenyl)methyl] amino]-benzoic acid 3-phenylpropyl ester
• 英文别名: 3-phenylpropyl 5-[(2,5-dihydroxyphenyl)methylamino]-2-hydroxybenzoate
• 化学式: C₂₃H₂₃NO₅
• 分子量: 393.439
• InChiKey: WEZNDVHCINCVNY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  99
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2,5-二羟基苯甲醛 在 镍 氢气 、 三乙胺 作用下， 以 甲醇 为溶剂， 60.0 ℃ 、101.33 kPa 条件下， 反应 18.0h， 生成 2-hydroxy-5-[N-[(2,5-dihydroxyphenyl)methyl] amino]-benzoic acid 3-phenylpropyl ester
  参考文献：
  名称：

  Structure-Activity Relationships in a Series of 5-[(2,5-Dihydroxybenzyl)amino]salicylate Inhibitors of EGF-Receptor-Associated Tyrosine Kinase: Importance of Additional Hydrophobic Aromatic Interactions

  摘要：

  Potent inhibitors of EGF-dependent protein tyrosine kinase (PTK) activity were synthesized in a series of 5-[(2,5-dihydroxybenzyl)amino]salicylates. Several of these compounds inhibited EGF-dependent DNA synthesis in ER 22 cells with IC50 < 1 muM. In this series of PTK inhibitors, the role of the salicylate moiety as a potential divalent ion chelator was tested and found to be nonessential in all cases. The length and ramification of the substituting carboxyl group were investigated to improve cellular bioavailability, and this analysis provided compounds with increased inhibitory effect on EGF-induced DNA synthesis. Salicylates esterified with long hydrophobic chains were shown to be noncompetitive inhibitors of ATP, in contrast to the free acid and methyl salicylate. Moreover, all the tested inhibitors were shown to be noncompetitive inhibitors of the peptide substrate. Structure-activity relationships allowed us to suspect a hydrophobic pocket in the tyrosine kinase domain, preferentially interacting with aromatic rings. Finally, the selectivity of the best inhibitors was tested against other kinases, and they were found to be selective for tyrosine kinase. They were also shown to be good inhibitors of EGF-receptor autophosphorylation.

  DOI：

  10.1021/jm00032a020

文献信息

• Methods for treating inflammatory bowel disease
  申请人：Nogra Pharma Limited

  公开号：US10473669B2

  公开（公告）日：2019-11-12

  Methods of treating a subject with IBD with an anti-SMAD7 therapy, such as a SMAD7 antisense oligonucleotide, to reduce CRP levels are disclosed. Methods of treating and managing IBD in a subject using an anti-SMAD7 therapy, such as a SMAD7 antisense oligonucleotide, based on CRP levels are also disclosed. Also disclosed are methods of determining whether a subject with IBD is responsive or likely to be responsive to treatment an anti-SMAD7 therapy. Reduction of CRP levels may correlated with IBD remission or decreases in CDAI score. The present invention also relates to treatment of IBD using an anti-SMAD7 therapy (e.g., an antisense oligonucleotide) in combination with an additional agent. The invention also features related pharmaceutical compositions and kits.

  公开了用抗SMAD7疗法（如SMAD7反义寡核苷酸）治疗IBD患者以降低CRP水平的方法。还公开了基于CRP水平使用抗SMAD7疗法（如SMAD7反义寡核苷酸）治疗和管理受试者IBD的方法。还公开了确定IBD患者是否对抗SMAD7疗法有反应或可能有反应的方法。CRP水平的降低可能与IBD缓解或CDAI评分的降低相关。本发明还涉及使用抗SMAD7疗法（如反义寡核苷酸）与附加药剂联合治疗IBD。本发明还涉及相关药物组合物和试剂盒。
• METHODS FOR TREATING INFLAMMATORY BOWEL DISEASE
  申请人：Nogra Pharma Limited

  公开号：EP3140658A2

  公开（公告）日：2017-03-15
• METHODS OF USING SMAD7 ANTISENSE OLIGONUCLEOTIDES
  申请人：Celgene Alpine Investment Company II, LLC

  公开号：EP3237018A1

  公开（公告）日：2017-11-01
• METHODS OF USING SMAD7 ANTISENSE OLIGONUCLEOTIDES BASED ON BIOMARKER EXPRESSION
  申请人：Nogra Pharma Limited

  公开号：EP3355896A2

  公开（公告）日：2018-08-08
• [EN] METHODS FOR TREATING INFLAMMATORY BOWEL DISEASE<br/>[FR] MÉTHODES DE TRAITEMENT D'UNE MALADIE INFLAMMATOIRE CHRONIQUE DE L'INTESTIN
  申请人：NOGRA PHARMA LTD

  公开号：WO2015169966A2

  公开（公告）日：2015-11-12

  Methods of treating a subject with IBD with an anti-SMAD7 therapy,such as a SMAD7 antisense oligonucleotide, to reduce CRP levels are disclosed. Methods of treating and managing IBD in a subject using an anti-SMAD7 therapy, such as a SMAD7 antisense oligonucleotide, based on CRP levels are also disclosed. Also disclosed are methods of determining whether a subject with IBD is responsive or likely to be responsive to treatment an anti-SMAD7 therapy. Reduction of CRP levels may correlated with IBD remission or decreases in CDAI score.The present invention also relates to treatment of IBD using an anti-SMAD7 therapy (e.g., an antisense oligonucleotide) in combination with an additional agent. The invention also features related pharmaceutical compositions and kits.