3-(4-fluoro-2-methoxyphenyl)-3-methylbutyronitrile | 609807-32-1

• 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-(4-fluoro-2-methoxyphenyl)-3-methylbutyronitrile
• 英文别名: 3-(4-fluoro-2-methoxyphenyl)-3-methylbutanenitrile
• CAS: 609807-32-1
• 化学式: C₁₂H₁₄FNO
• 分子量: 207.248
• InChiKey: SZIXKCOKIGPRBV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  33
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(4-fluoro-2-methoxyphenyl)-3-methylbutyronitrile 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 potassium tert-butylate 、 四丁基氟化铵 、 二异丁基氢化铝 、 戴斯-马丁氧化剂 、 三乙胺 、 氢化铝 、 mercury dichloride 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 53.5h， 生成 1,1,1-trifluoro-4-(3-fluoro-2-methoxyphenyl)-4-methyl-2-(5H-pyrrolo[3,2-d]pyrimidin-6-ylmethyl)pentan-2-ol
  参考文献：
  名称：

  Identification of Highly Efficacious Glucocorticoid Receptor Agonists with a Potential for Reduced Clinical Bone Side Effects

  摘要：

  Synthesis and structure-activity relationship (SAR) of a series of nonsteroidal glucocorticoid receptor (GR) agonists are described. These compounds contain "diazaindole" moieties and display different transcriptional regulatory profiles in vitro and are considered "dissociated" between gene transrepression and transactivation. The lead optimization effort described in this article focused in particular on limiting the transactivation of genes which result in bone side effects and these were assessed in vitro in MG-63 osteosarcoma cells, leading to the identification of (R)-18 and (R)-21. These compounds maintained anti-inflammatory activity in vivo in collagen induced arthritis studies in mouse but had reduced effects on bone relevant parameters compared to the widely used synthetic glucocorticoid prednisolone 2 in vivo. To our knowledge, we are the first to report on selective glucocorticoid ligands with reduced bone loss in a preclinical in vivo model.

  DOI：

  10.1021/jm4019178
• 作为产物：
  描述：

  4-氟-2-甲氧基苯乙酮 在 copper(l) iodide 、 溶剂黄146 、 苄胺 、 sodium chloride 作用下， 以 乙醚 、 水 、 二甲基亚砜 、 甲苯 为溶剂， 反应 22.75h， 生成 3-(4-fluoro-2-methoxyphenyl)-3-methylbutyronitrile
  参考文献：
  名称：

  Identification of Highly Efficacious Glucocorticoid Receptor Agonists with a Potential for Reduced Clinical Bone Side Effects

  摘要：

  Synthesis and structure-activity relationship (SAR) of a series of nonsteroidal glucocorticoid receptor (GR) agonists are described. These compounds contain "diazaindole" moieties and display different transcriptional regulatory profiles in vitro and are considered "dissociated" between gene transrepression and transactivation. The lead optimization effort described in this article focused in particular on limiting the transactivation of genes which result in bone side effects and these were assessed in vitro in MG-63 osteosarcoma cells, leading to the identification of (R)-18 and (R)-21. These compounds maintained anti-inflammatory activity in vivo in collagen induced arthritis studies in mouse but had reduced effects on bone relevant parameters compared to the widely used synthetic glucocorticoid prednisolone 2 in vivo. To our knowledge, we are the first to report on selective glucocorticoid ligands with reduced bone loss in a preclinical in vivo model.

  DOI：

  10.1021/jm4019178

文献信息

• [EN] GLUCOCORTICOID MIMETICS, METHODS OF MAKING THEM, PHARMACEUTICAL COMPOSITIONS, AND USES THEREOF<br/>[FR] MIMETIQUES DU GLUCOCORTICOIDE, PROCEDES DE FABRICATION DE CES MIMETIQUES, COMPOSITIONS PHARMACEUTIQUES ET LEURS UTILISATIONS
  申请人：BOEHRINGER INGELHEIM PHARMA

  公开号：WO2003082787A1

  公开（公告）日：2003-10-09

  Compounds of Formula (IA) and Formula (IB) wherein R1, R2, R3, R4, R5, and R6 are as defined herein for Formula (IA) or Formula (IB), or a tautomer, prodrug, solvate,or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.

  式（IA）和式（IB）的化合物，其中R1、R2、R3、R4、R5和R6如本说明所定义的适用于式（IA）或式（IB），或其互变异构体、前药、溶剂化合物或盐；含有这些化合物的药物组合物，以及利用这些化合物调节糖皮质激素受体功能的方法、治疗由糖皮质激素受体功能介导的疾病状态或病情特征或患者体内的炎症、过敏或增殖过程的方法。
• [EN] GLUCOCORTICOID MIMETICS, METHODS OF MAKING THEM, PHARMACEUTICAL COMPOSITIONS, AND USES THEREOF<br/>[FR] MIMETIQUES DE GLUCOCORTICOIQUES, PROCEDES DE FABRICATION, COMPOSITIONS PHARMACEUTIQUES, ET UTILISATIONS CORRESPONDANTS
  申请人：BOEHRINGER INGELHEIM PHARMA

  公开号：WO2003082280A1

  公开（公告）日：2003-10-09

  Compounds of Formula (IA) and Formula (IB) wherein R1, R2, R3, R4, R5 and R6 are as defined herein for Formula (IA) or Formula (IB), or a tautomer, prodrug, solvate, or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.

  该文段描述的是公式（IA）和公式（IB）的化合物，其中R1、R2、R3、R4、R5和R6的定义与公式（IA）或公式（IB）中所定义的相同，或其互变异构体、前药、溶剂化物或盐；包含这些化合物的药物组合物；以及使用这些化合物来调节糖皮质激素受体功能、治疗由糖皮质激素受体功能介导或以炎症、过敏或增生过程为特征的疾病状态或病情的方法。
• Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof
  申请人：Bekkali Younes

  公开号：US20050282881A1

  公开（公告）日：2005-12-22

  Compounds of Formula (IA) wherein R 1 , R 2 , R 3 , R 4 and R 5 are as defined herein for Formula (IA), or a tautomer, prodrug, solvate, or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.

  本发明涉及式（IA）的化合物，其中R1，R2，R3，R4和R5如式（IA）所定义，或其互变异构体，前药，溶剂化物或盐；包含这些化合物的制药组合物以及使用这些化合物调节糖皮质激素受体功能的方法，以及治疗由糖皮质激素受体功能介导或以炎性，过敏或增殖过程为特征的疾病状态或病情的方法。
• Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and thereof
  申请人：Bekkali Younes

  公开号：US20060189647A1

  公开（公告）日：2006-08-24

  Compounds of Formula (IA) wherein R 1 , R 2 , R 3 , R 4 and R 5 are as defined herein for Formula (IA), or a tautomer, prodrug, solvate, or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.

  本文描述了化学式（IA）的化合物，其中R1、R2、R3、R4和R5的定义如化学式（IA）中所述，或其互变异构体、前药、溶剂化物或盐；含有这些化合物的药物组合物；以及使用这些化合物调节糖皮质激素受体功能、治疗由糖皮质激素受体功能介导或以炎症、过敏或增殖过程为特征的疾病状态或病情的方法。
• GLUCOCORTICOID MIMETICS, METHODS OF MAKING THEM, PHARMACEUTICAL COMPOSITIONS, AND USES THEREOF
  申请人：Boehringer Ingelheim Pharmaceuticals Inc.

  公开号：EP1490062B1

  公开（公告）日：2007-12-19