2-bromo-8-(trifluoromethoxy)naphthalene | 870822-75-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-bromo-8-(trifluoromethoxy)naphthalene
• 英文别名: 7-bromo-1-(trifluoromethoxy)naphthalene
• CAS: 870822-75-6
• 化学式: C₁₁H₆BrF₃O
• 分子量: 291.067
• InChiKey: JGHPMNAWKSVLHD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-bromo-8-(trifluoromethoxy)naphthalene 在 四(三苯基膦)钯 、 三甲基氯硅烷 、 三乙胺 、 三氟乙酸 、 sodium iodide 作用下， 以 乙二醇二甲醚 、 二氯甲烷 、 乙腈 为溶剂， 反应 2.67h， 生成 N-{[4-({3-(3,5-dichlorophenyl)-5-[8-(trifluoromethoxy)naphthalen-2-yl]-1H-pyrazol-1-yl}methyl)phenyl]carbonyl}-β-alanine
  参考文献：
  名称：

  Discovery of a Novel Glucagon Receptor Antagonist N-[(4-{(1S)-1-[3-(3, 5-Dichlorophenyl)-5-(6-methoxynaphthalen-2-yl)-1H-pyrazol-1-yl]ethyl}phenyl)carbonyl]-β-alanine (MK-0893) for the Treatment of Type II Diabetes

  摘要：

  A potent, selective glucagon receptor antagonist 9m, N-[(4-{(1S)-1-[3-(3,5-dichlorophenyl) -5-(6-methoxynaphthalen-2-yl)-1H-pyrazol-1-yl]ethyl}phenyl)-carbonyl]-beta-alanine, was discovered by optimization of a previously identified lead. Compound 9m is a reversible and competitive antagonist with high binding affinity (IC50 of 6.6 nM) and functional cAMP activity (IC50 of 15.7 nM). It is selective for glucagon receptor relative to other family B GPCRs, showing IC50 values of 1020 nM for GIPR, 9200 nM for PAC1, and >10000 nM for GLP-1R, VPAC1, and VPAC2. Compound 9m blunted glucagon-induced glucose elevation in hGCGR mice and rhesus monkeys. It also lowered ambient glucose levels in both acute and chronic mouse models: in hGCGR ob/ob mice it reduced glucose (AUC 0-6 h) by 32% and 39% at 3 and 10 mpk single doses, respectively. In hGCGR mice on a high fat diet, compound 9m at 3, and 10 mpk po in feed lowered blood glucose levels by 89% and 94% at day 10, respectively, relative to the difference between the vehicle control and lean hGCGR mice. On the basis of its favorable biological and DMPK properties, compound 9m (MK-0893) was selected for further preclinical and clinical evaluations.

  DOI：

  10.1021/jm300579z

文献信息

• Pyrazole derivatives, compositions containing such compounds and methods of use
  申请人：Parmee R. Emma

  公开号：US20050272794A1

  公开（公告）日：2005-12-08

  Pyrazoles having a naphthyl group attached are disclosed. The compounds are useful for treating type 2 diabetes and related conditions. Pharmaceutical compositions and methods of treatment are also included.

  揭示了附有萘基团的吡唑类化合物。这些化合物可用于治疗2型糖尿病及相关疾病。还包括药物组合物和治疗方法。
• PYRAZOLE DERIVATIVES, COMPOSITIONS CONTAINING SUCH COMPOUNDS AND METHODS OF USE
  申请人：Parmee Emma R.

  公开号：US20090176854A1

  公开（公告）日：2009-07-09

  Pyrazoles having a naphthyl group attached are disclosed. The compounds are useful for treating type 2 diabetes and related conditions. Pharmaceutical compositions and methods of treatment are also included.

  本发明揭示了连接有萘基团的吡唑类化合物。这些化合物可用于治疗2型糖尿病及相关疾病。还包括制药组合物和治疗方法。
• US7598285B2
  申请人：——

  公开号：US7598285B2

  公开（公告）日：2009-10-06
• US7799818B2
  申请人：——

  公开号：US7799818B2

  公开（公告）日：2010-09-21
• [EN] PYRAZOLE DERIVATIVES, COMPOSITIONS CONTAINING SUCH COMPOUNDS AND METHODS OF USE<br/>[FR] DERIVES DE PYRAZOLE, COMPOSITIONS CONTENANT LESDITS COMPOSES ET METHODES D'UTILISATION
  申请人：MERCK & CO INC

  公开号：WO2005121097A2

  公开（公告）日：2005-12-22

  Pyrazoles having a naphthyl group attached are disclosed. The compounds are useful for treating type 2 diabetes and related conditions. Pharmaceutical compositions and methods of treatment are also included.