3-(4-bromo-2-(trifluoromethyl)-phenoxy)propan-1-ol | 1104381-01-2

• 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-bromo-2-(trifluoromethyl)-phenoxy)propan-1-ol
• 英文别名: 3-[4-bromo-2-(trifluoromethyl)phenoxy]propan-1-ol
• CAS: 1104381-01-2
• 化学式: C₁₀H₁₀BrF₃O₂
• 分子量: 299.087
• InChiKey: CKSHJPUXJCBREM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 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：

  3-(4-bromo-2-(trifluoromethyl)-phenoxy)propan-1-ol 、 对甲苯磺酸一水合物 在 3,4-dihydro-2H-puran 、 乙酸乙酯 、 Sodium sulfate-III 作用下， 以 四氢呋喃 、 disodium;carbonate 为溶剂， 反应 1.0h， 以to give expected product (15 g)的产率得到2-[3-(4-bromo-2-(trifluoromethyl)-phenoxy)-propoxy]-tetrahydro-2H-pyran
  参考文献：
  名称：

  6-PHENYL-1H-IMIDAZO[4,5-c]PYRIDINE-4-CARBONITRILE DERIVATIVES

  摘要：

  本发明涉及具有通式I的6-苯基-1H-咪唑[4,5-c]吡啶-4-碳腈衍生物的制药组合物，以及利用这些衍生物制备用于治疗与蛋白酶S相关的疾病的药物，例如动脉硬化、肥胖症、炎症和免疫紊乱，例如类风湿性关节炎、银屑病、癌症和慢性疼痛，例如神经病理性疼痛。

  公开号：

  US20100184761A1
• 作为产物：
  描述：

  3-碘丙醇 、 4-溴-2-三氟甲基苯酚 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 4.0h， 生成 3-(4-bromo-2-(trifluoromethyl)-phenoxy)propan-1-ol
  参考文献：
  名称：

  6-PHENYL-1H-IMIDAZO[4,5-c]PYRIDINE-4-CARBONITRILE DERIVATIVES

  摘要：

  本发明涉及具有通式I的6-苯基-1H-咪唑[4,5-c]吡啶-4-碳腈衍生物，以及包含它们的药物组合物，以及利用这些衍生物制备用于治疗与S蛋白酶相关疾病的药物，如动脉粥样硬化、肥胖、炎症和免疫紊乱，如类风湿性关节炎、牛皮癣、癌症和慢性疼痛，如神经病性疼痛。

  公开号：

  US20100184761A1

文献信息

• [EN] 6-PHENYL-1H-IMIDAZO[4,5-C]PYRIDINE-4-CARBONITRILE DERIVATIVES AS CATHEPSIN INHIBITORS<br/>[FR] DÉRIVÉS DE 6-PHÉNYL-1H-IMIDAZO[4,5-C]PYRIDINE-4-CARBONITRILE COMME INHIBITEUR DE LA CATHEPSINE
  申请人：ORGANON NV

  公开号：WO2009010491A1

  公开（公告）日：2009-01-22

  The present invention relates to 6-phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile derivatives having the general Formula (I), to pharmaceutical compositions comprising the same as well as to the use of these derivatives for the preparation of a medicament for the treatment of cathepsin S related diseases such asatherosclerosis,obesity, inflammation and immune disorders, such as rheumatoid arthritis, psoriasis, cancer,and chronic pain, such as neuropathic pain.

  本发明涉及具有通式（I）的6-苯基-1H-咪唑[4,5-c]吡啶-4-碳腈衍生物，以及包含相同的药物组合物，以及利用这些衍生物制备用于治疗与S蛋白酶相关疾病的药物，如动脉粥样硬化、肥胖、炎症和免疫紊乱，如类风湿性关节炎、牛皮癣、癌症和慢性疼痛，如神经病性疼痛。
• [EN] 6-PHENYL-LH-IMIDAZO [4, 5-C] PYRIDINE-4-CARBONITRILE DERIVATIVES AS CATHEPSIN S AND/OR CATHEPSIN K INHIBITORS<br/>[FR] DÉRIVÉS DE 6-PHÉNYL-1H-IMIDAZO[4,5-C]PYRIDINE-4-CARBONITRILE EN TANT QU'INHIBITEURS DE LA CATHEPSINE S ET/OU DE LA CATHEPSINE K
  申请人：ORGANON NV

  公开号：WO2010081859A1

  公开（公告）日：2010-07-22

  The present invention relates to 6-phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile derivatives having the general Formula (I) to pharmaceutical compositions comprising the same as well as to the use of these derivatives for the preparation of a medicament for the treatment of cathepsin S related diseases such as atherosclerosis, obesity, inflammation and immune disorders, such as rheumatoid arthritis, psoriasis, cancer, and chronic pain, such as neuropathic pain.

  本发明涉及具有通式（I）的6-苯基-1H-咪唑[4,5-c]吡啶-4-碳腈衍生物，以及包含它们的药物组合物，以及利用这些衍生物制备用于治疗与S蛋白酶相关疾病的药物，如动脉粥样硬化、肥胖、炎症和免疫紊乱，如类风湿性关节炎、牛皮癣、癌症和慢性疼痛，如神经病性疼痛。
• 6-phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile derivatives
  申请人：N.V. Organon

  公开号：US08026236B2

  公开（公告）日：2011-09-27

  The present invention relates to 6-phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile derivatives having the general Formula I to pharmaceutical compositions comprising the same as well as to the use of these derivatives for the preparation of a medicament for the treatment of cathepsin S related diseases such as atherosclerosis, obesity, inflammation and immune disorders, such as rheumatoid arthritis, psoriasis, cancer, and chronic pain, such as neuropathic pain.

  本发明涉及具有一般式I的6-苯基-1H-咪唑[4,5-c]吡啶-4-碳腈衍生物，以及包含它们的制药组合物，以及使用这些衍生物制备用于治疗与卡特普辛S相关的疾病的药物，例如动脉粥样硬化、肥胖症、炎症和免疫紊乱，例如类风湿性关节炎、牛皮癣、癌症和慢性疼痛，例如神经病性疼痛。
• 6-Phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile as cathepsin S inhibitors
  作者：Jiaqiang Cai、Mark Baugh、Darcey Black、Clive Long、D. Jonathan Bennett、Maureen Dempster、Xavier Fradera、Jonathan Gillespie、Fiona Andrews、Sylviane Boucharens、John Bruin、Kenneth S. Cameron、Iain Cumming、William Hamilton、Philip S. Jones、Allard Kaptein、Emma Kinghorn、Maurice Maidment、Iain Martin、Ann Mitchell、Zoran Rankovic、John Robinson、Paul Scullion、Joost C.M. Uitdehaag、Paul Vink、Paul Westwood、Mario van Zeeland、Leon van Berkom、Martijn Bastiani、Tommi Meulemans

  DOI：10.1016/j.bmcl.2010.06.072

  日期：2010.8

  6-Phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile analogues were identified as potent and selective cathepsin S inhibitor against both purified enzyme and in human JY cell based cellular assays. This core has a very stable thio-trapping nitrile war-head in comparison with the well reported pyrimidine-2-carbonitrile cysteine cathepsin inhibitors. Compound 47 is also very potent in in vivo mouse spleenic Lip10 accumulation assays. (C) 2010 Elsevier Ltd. All rights reserved.
• 4-(3-Trifluoromethylphenyl)-pyrimidine-2-carbonitrile as cathepsin S inhibitors: N3, not N1 is critically important
  作者：Jiaqiang Cai、Xavier Fradera、Mario van Zeeland、Maureen Dempster、Kenneth S. Cameron、D. Jonathan Bennett、John Robinson、Lucy Popplestone、Mark Baugh、Paul Westwood、John Bruin、William Hamilton、Emma Kinghorn、Clive Long、Joost C.M. Uitdehaag

  DOI：10.1016/j.bmcl.2010.06.043

  日期：2010.8

  Using computer aided modelling studies, a new extended P2/S2 interaction was identified. This extended region can accommodate a variety of functional groups, such as aryls and basic amines. It was discovered that the N3 nitrogen of the pyrimidine-2-carbonitrile is critical for its cathepsin cysteine protease inhibition. N1 nitrogen also contributes to the inhibitory activity, but to a very limited degree. An 'in situ double activation' mechanism was proposed to explain these results. (C) 2010 Elsevier Ltd. All rights reserved.