1-(4-氟-苯基)-2,5-二甲基-1H-吡咯-3-甲酸 | 519151-74-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 中文名称: 1-(4-氟-苯基)-2,5-二甲基-1H-吡咯-3-甲酸
• 中文别名: 1-(4-氟苯基)-2,5-二甲基-1H-吡咯-3-羧酸
• 英文名称: 2,5-dimethyl-1-(4-fluorophenyl)-1H-pyrrole-3-carboxylic acid
• 英文别名: 1-(4-fluorophenyl)-2,5-dimethyl-pyrrole-3-carboxylic acid；1-(4-Fluorophenyl)-2,5-dimethyl-1H-pyrrole-3-carboxylic acid；1-(4-fluorophenyl)-2,5-dimethylpyrrole-3-carboxylic acid
• CAS: 519151-74-7
• 化学式: C₁₃H₁₂FNO₂
• mdl: MFCD03479904
• 分子量: 233.242
• InChiKey: UHSNGSYVRLIXCX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.153
• 拓扑面积：
  42.2
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  对氰基苄胺 、 1-(4-氟-苯基)-2,5-二甲基-1H-吡咯-3-甲酸 在 草酰氯 、 三乙胺 、 盐酸羟胺 作用下， 以 二氯甲烷 、 乙醇 为溶剂， 反应 6.0h， 生成 1-(4-fluorophenyl)-N-[[4-(N'-hydroxycarbamimidoyl)phenyl]methyl]-2,5-dimethyl-pyrrole-3-carboxamide
  参考文献：
  名称：

  PRODRUGS OF INHIBITORS OF PLASMA KALLIKREIN

  摘要：

  这项发明提供了一些新的药物化合物，它们是血浆卡利肌酶抑制剂的前药，以及预防或治疗血浆卡利肌酶依赖性疾病或病况的方法和组合物，例如糖尿病黄斑水肿或出血性中风，通过给予下列公式的前药：

  公开号：

  US20120264798A1
• 作为产物：
  描述：

  tert-butyl 2-acetyl-4-oxopentanoate 、 4-氟苯胺 在 水 、 对甲苯磺酸 作用下， 以 二甲基亚砜 为溶剂， 反应 0.5h， 以55%的产率得到1-(4-氟-苯基)-2,5-二甲基-1H-吡咯-3-甲酸
  参考文献：
  名称：

  Screening of a Custom-Designed Acid Fragment Library Identifies 1-Phenylpyrroles and 1-Phenylpyrrolidines as Inhibitors of Notum Carboxylesterase Activity

  摘要：

  The Wnt family of proteins are secreted signaling proteins that play key roles in regulating cellular functions. Recently, carboxylesterase Notum was shown to act as a negative regulator of Wnt signaling by mediating the removal of an essential palmitoleate. Here we disclose two new chemical scaffolds that inhibit Notum enzymatic activity. Our approach was to create a fragment library of 250 acids for screening against Notum in a biochemical assay followed by structure determination by X-ray crystallography. Twenty fragments were identified as hits for Notum inhibition, and 14 of these fragments were shown to bind in the palmitoleate pocket of Notum. Optimization of 1-phenylpyrrole 20, guided by structure-based drug design, identified 20z as the most potent compound from this series. Similarly, the optimization of 1-phenylpyrrolidine 8 gave acid 26. This work demonstrates that inhibition of Notum activity can be achieved by small, drug-like molecules possessing favorable in vitro ADME profiles.

  DOI：

  10.1021/acs.jmedchem.0c00660

文献信息

• PRODRUGS OF INHIBITORS OF PLASMA KALLIKRIEN
  申请人：Sinha Sukanto

  公开号：US20110152533A1

  公开（公告）日：2011-06-23

  The present invention provides prodrugs of compounds that inhibit the activity of plasma kallikrein (PK) and methods of preventing and treating plasma kallikrein dependent diseases or conditions, for example, diabetic macular edema, with the prodrugs having the formula:

  该发明提供了抑制血浆激肽酶（PK）活性的化合物的前体药物，以及预防和治疗血浆激肽酶依赖性疾病或病况的方法，例如糖尿病黄斑水肿，这些前体药物具有以下结构式：
• Prodrugs of inhibitors of plasma kallikrein
  申请人：Sinha Sukanto

  公开号：US08691861B2

  公开（公告）日：2014-04-08

  This invention provides new pharmaceutically useful compounds that are prodrugs of inhibitors of plasma kallikrein and methods and compositions for preventing or treating plasma kallikrein dependent diseases or conditions, such as diabetic macular edema or hemorrhagic stroke, by administering prodrugs of the formula:

  这项发明提供了新的药物化合物，它们是血浆卡利肌酶抑制剂的前药，并提供了预防或治疗血浆卡利肌酶依赖性疾病或状况的方法和组合物，例如糖尿病黄斑水肿或出血性中风，通过给予公式的前药：
• US8609866B2
  申请人：——

  公开号：US8609866B2

  公开（公告）日：2013-12-17
• US9206123B2
  申请人：——

  公开号：US9206123B2

  公开（公告）日：2015-12-08
• [EN] PRODRUGS OF INHIBITORS OF PLASMA KALLIKREIN<br/>[FR] PROMÉDICAMENTS D'INHIBITEURS DE LA KALLICRÉINE PLASMATIQUE
  申请人：ACTIVESITE PHARMACEUTICALS INC

  公开号：WO2011075684A1

  公开（公告）日：2011-06-23

  The present invention provides prodrugs of compounds that inhibit the activity of plasma kallikrein (PK) and methods of preventing and treating plasma kallikrein dependent diseases or conditions, for example, diabetic macular edema, with the prodrugs having the formula (I).