2-methyl-1-phenyl-1H-pyrrole-3-carboxylic acid | 93001-77-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 2-methyl-1-phenyl-1H-pyrrole-3-carboxylic acid
• 英文别名: 2-methyl-1-phenyl-pyrrole-3-carboxylic acid；2-Methyl-1-phenylpyrrole-3-carboxylic acid
• CAS: 93001-77-5
• 化学式: C₁₂H₁₁NO₂
• 分子量: 201.225
• InChiKey: ZEPJBJJWMZRTFB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  42.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  ethyl 2-methyl-1-phenyl-1H-pyrrole-3-carboxylate 在 lithium hydroxide monohydrate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 24.0h， 以33.4 mg的产率得到2-methyl-1-phenyl-1H-pyrrole-3-carboxylic acid
  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

• PYRROLE BASED INHIBITORS OF GLYCOGEN SYNTHASE KINASE 3
  申请人：Desai C. Manoj

  公开号：US20070244109A1

  公开（公告）日：2007-10-18

  New pyrrole based compounds, compositions and methods of inhibiting the activity of glycogen synthase kinase (GSK3) in vitro and of treatment of GSK3 mediated disorders in vivo are provided. The methods, compounds and compositions of the invention may be employed alone, or in combination with other pharmacologically active agents in the treatment of disorders mediated by GSK3 activity, such as diabetes, Alzheimer's disease and other neurodegenerative disorders, obesity, atherosclerotic cardiovascular disease, essential hypertension, polycystic ovary syndrome, syndrome X, ischemia, traumatic brain injury, bipolar disorder, immunodeficiency or cancer.

  提供了基于新的吡咯基化合物、组合物和方法，用于体外抑制糖原合成酶激酶(GSK3)的活性和治疗GSK3介导的疾病。该发明的方法、化合物和组合物可单独应用，或与其他药理活性剂联合治疗GSK3活性介导的疾病，如糖尿病、阿尔茨海默病和其他神经退行性疾病、肥胖症、动脉粥样硬化性心血管疾病、原发性高血压、多囊卵巢综合征、X综合征、缺血、创伤性脑损伤、双相情感障碍、免疫缺陷或癌症。
• PYRROLO- AND THIAZOLO-PYRIDINE COMPOUNDS AS HIF MODULATORS
  申请人：FIBROGEN, INC.

  公开号：EP2016078A2

  公开（公告）日：2009-01-21
• US7250443B2
  申请人：——

  公开号：US7250443B2

  公开（公告）日：2007-07-31
• US7671049B2
  申请人：——

  公开号：US7671049B2

  公开（公告）日：2010-03-02
• [EN] PYRROLO- AND THIAZOLO-PYRIDINE COMPOUNDS, AND METHODS OF USE THEREOF<br/>[FR] COMPOSÉS DE PYRROLO- ET DE THIAZOLOPYRIDINE ET PROCÉDÉS D'UTILISATION
  申请人：FIBROGEN INC

  公开号：WO2007115315A2

  公开（公告）日：2007-10-11

  [EN] The present invention relates to novel compounds capable of modulating the stability and/or activity of hypoxia inducible factor (HIF).
  [FR] La présente invention concerne de nouveaux composés capables de moduler la stabilité et/ou l'activité du facteur inductible par hypoxie (HIF).