3-amino-2-benzyl-7-nitro-4-(2-quinolyl)-1,2-dihydroisoquinolin-1-one | 147642-50-0

• 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
• 英文名称: 3-amino-2-benzyl-7-nitro-4-(2-quinolyl)-1,2-dihydroisoquinolin-1-one
• 英文别名: 3-Amino-2-benzyl-7-nitro-4-quinolin-2-ylisoquinolin-1-one
• CAS: 147642-50-0
• 化学式: C₂₅H₁₈N₄O₃
• 分子量: 422.443
• InChiKey: UUGOHBJAEUZKAI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  32
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-(喹啉-2-基)乙腈 、 N-苄基-2-氯-5-硝基苯甲酰胺 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 以86%的产率得到3-amino-2-benzyl-7-nitro-4-(2-quinolyl)-1,2-dihydroisoquinolin-1-one
  参考文献：
  名称：

  Synthesis and structure of 3-amino-4-hetaryl-1-(2H)-isoquinolones

  摘要：

  DOI：

  10.1007/bf00472292

文献信息

• COMPOSITIONS FOR THE TREATMENT OF HYPERPHENYLALANINEMIA
  申请人：Pey Rodríguez Ángel

  公开号：US20100286166A1

  公开（公告）日：2010-11-11

  The present invention relates to the use of specific types of compounds acting as pharmacological chaperones having a stabilizing activity on the phenylalanine hydroxylase (PAH) enzyme for the prophylaxis and/or treatment of hyperphenylalaninemia (HPA) and phenylketonuria PKU) and diseases, disorders and conditions related thereto. Further, the present invention relates to pharmaceutical compositions containing the compounds according to the present invention as well as to methods of treatment of HPA, in particular, PKU and diseases, disorders and conditions related thereto.

  本发明涉及使用具有稳定苯丙氨酸羟化酶（PAH）酶活性的特定化合物作为药理伴侣，用于预防和/或治疗高苯丙氨酸血症（HPA）和苯丙酮尿症（PKU）以及相关疾病、障碍和病况。此外，本发明还涉及含有本发明化合物的药物组合物，以及治疗HPA，特别是PKU以及相关疾病、障碍和病况的方法。
• Compositions for the treatment of hyperphenylalaninemia
  申请人：Bergen Teknologioverforing AS

  公开号：EP2008656A1

  公开（公告）日：2008-12-31

  The present invention relates to the use of specific types of compounds acting as pharmacological chaperones having a stabilizing activity on the phenylalanine hydroxylase (PAH) enzyme for the prophylaxis and/or treatment of hyperphenylalaninemia (HPA) and phenylketonuria (PKU) and diseases, disorders and conditions related thereto. Further, the present invention relates to pharmaceutical compositions containing the compounds according to the present invention as well as to methods of treatment of HPA, in particular, PKU and diseases, disorders and conditions related thereto.

  本发明涉及作为对苯丙氨酸羟化酶（PAH）酶具有稳定活性的药理伴侣的特定类型化合物在预防和/或治疗高苯丙氨酸血症（HPA）和苯丙酮尿症（PKU）以及与之相关的疾病、紊乱和病症方面的用途。此外，本发明还涉及含有根据本发明的化合物的药物组合物，以及治疗高苯丙氨酸血症（HPA），尤其是高苯丙氨酸尿症（PKU）和与之相关的疾病、失调和病症的方法。
• Allosteric activators for treatment of phenylketonuria
  申请人：MCMASTER UNIVERSITY

  公开号：US10426751B2

  公开（公告）日：2019-10-01

  A method of restoring activity in phenylalanine hydroxylase is provided. The method comprises exposing the phenylalanine hydroxylase to shikimic acid, a functionally equivalent analog thereof, a pharmaceutically acceptable salt of shikimic acid or analog thereof, or combinations thereof. A method of screening for allosteric activators for a target enzyme is also provided comprising the steps of: denaturing the target enzyme with a first chaotropic agent to yield denatured enzyme, incubating the denatured enzyme with a candidate compound under denaturing conditions to allow enzyme refolding, and assaying enzyme activity in the presence of enzyme substrate and a candidate compound; and if enzyme activity of the denatured enzyme was restored in step i) by at least about 10% of residual enzyme activity, denaturing the target enzyme with a second chaotropic agent to yield denatured enzyme, incubating the denatured enzyme with the candidate compound under non-denaturing conditions to allow enzyme refolding, and assaying enzyme activity in the presence of enzyme substrate and the candidate compound, wherein an increase in enzyme activity of at least about 10% of residual enzyme activity indicates that the candidate compound is an allosteric activator of the target enzyme.

  提供了一种恢复苯丙氨酸羟化酶活性的方法。该方法包括将苯丙氨酸羟化酶暴露于莽草酸、其功能等同的类似物、莽草酸或其类似物的药学上可接受的盐或其组合。还提供了一种筛选目标酶的异位激活剂的方法，包括以下步骤：用第一种混沌剂使目标酶变性以产生变性酶，在变性条件下将变性酶与候选化合物孵育以允许酶重折叠，在酶底物和候选化合物存在下测定酶活性；如果变性酶的酶活性在步骤 i）中恢复了至少约 10%的残余酶活性，则用第二种混沌剂对目标酶进行变性以产生变性酶，在非变性条件下将变性酶与候选化合物孵育以允许酶重折叠、在酶底物和候选化合物存在下测定酶活性，其中酶活性至少增加残余酶活性的约 10%表明候选化合物是目标酶的异位激活剂。
• Synthesis of 3-amino-4-hetaryl-1(2H)-isoquinolones from condensed isoquinolones with a bridgehead nitrogen atom
  作者：A. G. Nemazanyi、Yu. M. Volovenko、T. A. Silaeva、M. Yu. Kornilov、F. S. Babichev

  DOI：10.1007/bf00529484

  日期：1992.1
• NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE (NMPRTase) INHIBITOR FOR GLIOMA THERAPY
  申请人：Council of Scientific & Industrial Research

  公开号：EP2552444A1

  公开（公告）日：2013-02-06