6-(5-chloro-2,3-dihydrobenzofuran-7-yl)-6-methyl-4-trifluoromethylhept-1-yn-4-ol | 849354-09-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 香豆素
• 英文名称: 6-(5-chloro-2,3-dihydrobenzofuran-7-yl)-6-methyl-4-trifluoromethylhept-1-yn-4-ol
• 英文别名: 6-(5-chloro-2,3-dihydro-1-benzofuran-7-yl)-6-methyl-4-(trifluoromethyl)hept-1-yn-4-ol
• CAS: 849354-09-2
• 化学式: C₁₇H₁₈ClF₃O₂
• 分子量: 346.777
• InChiKey: JQTWVZJTXXOCPM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-(5-chloro-2,3-dihydrobenzofuran-7-yl)-6-methyl-4-trifluoromethylhept-1-yn-4-ol 、 叔-丁基-7-氨基-3,4-二氢异喹啉-2(1H)-甲酸 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 以73%的产率得到{4-[6-(5-chloro-2,3-dihydrobenzofuran-7-yl)-4-hydroxy-6-methyl-4-trifluoromethylhept-1-ynyl]pyridin-3-yl}carbamic acid tert-butyl ester
  参考文献：
  名称：

  Nonsteroidal Dissociated Glucocorticoid Agonists Containing Azaindoles as Steroid A-Ring Mimetics

  摘要：

  Syntheses and structure activity relationships (SA R) of nonsteroidal glucocorticoid receptor (GR) agonists are described. These compounds contain azaindole moieties as A-ring mimetics and display various degrees of in vitro dissociation between gene transrepression and transactivation. Collagen induced arthritis studies in mouse have demonstrated that in vitro dissociated compounds (R)-16 and (R)-37 have steroid-like anti-inflammatory properties with improved metabolic side effect profiles, such as a reduced increase in body fat and scrum insulin levels, compared to steroids.

  DOI：

  10.1021/jm100751q
• 作为产物：
  描述：

  1,1,1-trifluoro-4-(5-chloro-2,3-dihydrobenzofuran-7-yl)-4-methylpentan-2-one 、 3-溴丙炔 在 氢化铝 、 mercury dichloride 作用下， 以 四氢呋喃 、 甲苯 、 乙醚 为溶剂， 反应 1.0h， 以64%的产率得到6-(5-chloro-2,3-dihydrobenzofuran-7-yl)-6-methyl-4-trifluoromethylhept-1-yn-4-ol
  参考文献：
  名称：

  Nonsteroidal Dissociated Glucocorticoid Agonists Containing Azaindoles as Steroid A-Ring Mimetics

  摘要：

  Syntheses and structure activity relationships (SA R) of nonsteroidal glucocorticoid receptor (GR) agonists are described. These compounds contain azaindole moieties as A-ring mimetics and display various degrees of in vitro dissociation between gene transrepression and transactivation. Collagen induced arthritis studies in mouse have demonstrated that in vitro dissociated compounds (R)-16 and (R)-37 have steroid-like anti-inflammatory properties with improved metabolic side effect profiles, such as a reduced increase in body fat and scrum insulin levels, compared to steroids.

  DOI：

  10.1021/jm100751q

文献信息

• [EN] 1,1,1-TRIFLUORO-4-PHENYL-4-METHYL-2-(1H-PYRROLO<br/>[FR] DERIVES DE 1,1,1-TRIFLUORO-4-PHENYL-4-METHYL-2-(1H-PYRROLO-2,3-C PYRIDIN-2-YLMETHYL)PENTAN-2-OLE ET COMPOSES ASSOCIES EN TANT QUE LIGANDS DE GLUCOCORTICOIDES POUR LE TRAITEMENT DE MALADIES INFLAMMATOIRES ET DE DIABETE
  申请人：BOEHRINGER INGELHEIM PHARMA

  公开号：WO2005030213A1

  公开（公告）日：2005-04-07

  Compounds of Formula (IA), IB), IC), and (ID) wherein R1, R2, R3, R4, R5, and R6 are as respectively defined herein for Formula (IA), (IB), (IC), and (ID), 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(I A)、(IB)、(IC)和(ID)的化合物，其中R1、R2、R3、R4、R5和R6分别如本文所定义的式(I A)、(IB)、(IC)和(ID)，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，以及利用这些化合物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：Bekkali Younes

  公开号：US20050176706A1

  公开（公告）日：2005-08-11

  Compounds of Formula (IA), (IB), (IC), and (ID) wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are as respectively defined herein for Formula (IA), (IB), (IC), and (ID), 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.

  化合物的公式为（IA），（IB），（IC）和（ID），其中R1，R2，R3，R4，R5和R6分别定义为公式（IA），（IB），（IC）和（ID）中所述，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调节糖皮质激素受体功能的方法和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：Harcken Christian

  公开号：US20090325988A1

  公开（公告）日：2009-12-31

  Compounds of Formula (I) wherein R 1 , R 2 , X, and Y are as defined herein, or a tautomer, optical isomer, prodrug, co-crystal, 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.

  化合物的公式（I），其中R1，R2，X和Y的定义如本文所述，或其互变异构体，光学异构体，前药，共晶体或盐；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的方法，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。
• Identification of Highly Efficacious Glucocorticoid Receptor Agonists with a Potential for Reduced Clinical Bone Side Effects
  作者：Christian Harcken、Doris Riether、Daniel Kuzmich、Pingrong Liu、Raj Betageri、Mark Ralph、Michel Emmanuel、Jonathan T. Reeves、Angela Berry、Donald Souza、Richard M. Nelson、Alison Kukulka、Tazmeen N. Fadra、Ljiljana Zuvela-Jelaska、Roger Dinallo、Jörg Bentzien、Gerald H. Nabozny、David S. Thomson

  DOI：10.1021/jm4019178

  日期：2014.2.27

  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.
• GLUCOCORTICOID MIMETICS, METHODS OF MAKING THEM, PHARMACEUTICAL COMPOSITIONS, AND USES THEREOF
  申请人：Boehringer Ingelheim International GmbH

  公开号：EP2300472A1

  公开（公告）日：2011-03-30