1-bromo-3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)benzene

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-bromo-3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)benzene
• 化学式: C₈H₄BrF₅O
• 分子量: 291.015
• InChiKey: LPCLDMZUPDUXRN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-bromo-3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)benzene 在 盐酸 、 titanium(IV) tetraethanolate 、 正丁基锂 、 三氟化硼乙醚 、 三溴化硼 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醚 、 正己烷 、 二氯甲烷 为溶剂， 反应 59.59h， 生成 4-fluoro-N-[(1R)-1-(4-fluoro-3-hydroxyphenyl)-1-[3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl]-2-phenylethyl]-3-(trifluoromethyl)benzamide
  参考文献：
  名称：

  Triphenylethanamine Derivatives as Cholesteryl Ester Transfer Protein Inhibitors: Discovery of N-[(1R)-1-(3-Cyclopropoxy-4-fluorophenyl)-1-[3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl]-2-phenylethyl]-4-fluoro-3-(trifluoromethyl)benzamide (BMS-795311)

  摘要：

  Cholesteryl ester transfer protein (CETP) inhibitors raise HDL-C in animals and humans and may be antiatherosclerotic by enhancing reverse cholesterol transport (RCT). In this article, we describe the lead optimization efforts resulting in the discovery of a series of triphenylethanamine (TPE) ureas and amides as potent and orally available CETP inhibitors. Compound 10g is a potent CETP inhibitor that maximally inhibited cholesteryl ester (CE) transfer activity at an oral dose of 1 mg/kg in human CETP/apoB-100 dual transgenic mice and increased HDL cholesterol content and size comparable to torcetrapib (1) in moderately-fat fed hamsters. In contrast to the off-target liabilities with 1, no blood pressure increase was observed with 10g in rat telemetry studies and no increase of aldosterone synthase (CYP11B2) was detected in H295R cells. On the basis of its preclinical profile, compound 10g was advanced into preclinical safety studies.

  DOI：

  10.1021/acs.jmedchem.5b01363
• 作为产物：
  描述：

  1-溴-3,5-二氟苯 在 potassium trimethylsilonate 、 caesium carbonate 作用下， 以 二乙二醇二甲醚 、 二甲基亚砜 为溶剂， 反应 11.0h， 生成 1-bromo-3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)benzene
  参考文献：
  名称：

  Triphenylethanamine Derivatives as Cholesteryl Ester Transfer Protein Inhibitors: Discovery of N-[(1R)-1-(3-Cyclopropoxy-4-fluorophenyl)-1-[3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl]-2-phenylethyl]-4-fluoro-3-(trifluoromethyl)benzamide (BMS-795311)

  摘要：

  Cholesteryl ester transfer protein (CETP) inhibitors raise HDL-C in animals and humans and may be antiatherosclerotic by enhancing reverse cholesterol transport (RCT). In this article, we describe the lead optimization efforts resulting in the discovery of a series of triphenylethanamine (TPE) ureas and amides as potent and orally available CETP inhibitors. Compound 10g is a potent CETP inhibitor that maximally inhibited cholesteryl ester (CE) transfer activity at an oral dose of 1 mg/kg in human CETP/apoB-100 dual transgenic mice and increased HDL cholesterol content and size comparable to torcetrapib (1) in moderately-fat fed hamsters. In contrast to the off-target liabilities with 1, no blood pressure increase was observed with 10g in rat telemetry studies and no increase of aldosterone synthase (CYP11B2) was detected in H295R cells. On the basis of its preclinical profile, compound 10g was advanced into preclinical safety studies.

  DOI：

  10.1021/acs.jmedchem.5b01363

文献信息

• HETEROCYCLIC CETP INHIBITORS
  申请人：Salvati E. Mark

  公开号：US20070161685A1

  公开（公告）日：2007-07-12

  Compounds of formula Ia and Ib wherein A, B, C and R 1 are described herein.

  式Ia和Ib的化合物 其中A、B、C和R1 如本文所述。
• N-((3-BENZYL)-2,2-(BIS-PHENYL)-PROPAN-1-AMINE DERIVATIVES AS CETP INHIBITORS FOR THE TREATMENT OF ATHEROSCLEROSIS AND CARDIOVASCULAR DISEASES
  申请人：Salvati Mark E.

  公开号：US20100041717A1

  公开（公告）日：2010-02-18

  Compounds of formula (Ia) and (Ib), wherein A, B, C, R 1 and R 14 are described herein.

  式(Ia)和(Ib)的化合物，其中A、B、C、R1和R14如本文所述。
• A practical synthesis of aryl tetrafluoroethyl ethers via the improved reaction of phenols with 1,2-dibromotetrafluoroethane
  作者：Jianqing Li、Jennifer X. Qiao、Daniel Smith、Bang-Chi Chen、Mark E. Salvati、Jacques Y. Roberge、Balu N. Balasubramanian

  DOI：10.1016/j.tetlet.2007.08.065

  日期：2007.10

  An efficient and practical synthesis of various aryl tetrafluoroethyl ethers by the reaction of phenols with 1,2-dibromotetrafluoroethane and the subsequent reduction with zinc dust was described. The nucleophilic substitution of 1,2-dibromotetrafluoroethane with phenols initiated by bromophilic attack was improved by using Cs2CO3 as a base and DMSO as a solvent.

  描述了通过苯酚与1，2-二溴四氟乙烷反应并随后用锌粉还原而有效和实用地合成各种芳基四氟乙基醚的方法。通过使用Cs 2 CO 3作为碱和DMSO作为溶剂，改善了由亲油性攻击引发的苯酚对1,2-二溴四氟乙烷的亲核取代。
• Heterocyclic CETP inhibitors
  申请人：Bristol-Myers Squibb Company

  公开号：US07888376B2

  公开（公告）日：2011-02-15

  Compounds of formula Ia and Ib wherein A, B, C and R1 are described herein.

  化合物Ia和Ib的公式如下，其中A、B、C和R1的描述如下。
• N-((3-benzyl)-2,2-(bis-phenyl)-propan-1-amine derivatives as CETP inhibitors for the treatment of atherosclerosis and cardiovascular diseases
  申请人：Salvati Mark E.

  公开号：US08404896B2

  公开（公告）日：2013-03-26

  Compounds of formula (Ia) and (Ib), wherein A, B, C, R1and R14 are described herein.

  式(Ia)和(Ib)的化合物，其中A、B、C、R1和R14的描述如下。