({5-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl][1,3]thiazolo[5,4-d]pyrimidin-2-yl}oxy)acetic acid | 1108199-48-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 1,3-噻唑并[5,4-d]嘧啶
• 英文名称: ({5-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl][1,3]thiazolo[5,4-d]pyrimidin-2-yl}oxy)acetic acid
• 英文别名: 2-[[5-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]-[1,3]thiazolo[5,4-d]pyrimidin-2-yl]oxy]acetic acid
• CAS: 1108199-48-9
• 化学式: C₁₈H₁₆BrFN₄O₄S
• 分子量: 483.318
• InChiKey: NXLAQFZWXQNOCF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  126
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  4-(2-溴-5-氟苯氧基)哌啶盐酸盐 在 甲醇 、 亚硝酸特丁酯 、 sodium hydride 、 三乙胺 、 sodium hydroxide 、 copper(ll) bromide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 ({5-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl][1,3]thiazolo[5,4-d]pyrimidin-2-yl}oxy)acetic acid
  参考文献：
  名称：

  Bicyclic heteroaryl inhibitors of stearoyl-CoA desaturase: From systemic to liver-targeting inhibitors

  摘要：

  Optimization of a lead thiazole amide MF-152 led to the identification of potent bicyclic heteroaryl SCD1 inhibitors with good mouse pharmacokinetic profiles. In a view to target the liver for efficacy and to avoid SCD1 inhibition in the skin and eyes where adverse effects were previously observed in rodents, representative systemically-distributed SCD1 inhibitors were converted into liver-targeting SCD1 inhibitors. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.08.037

文献信息

• [EN] BICYCLIC HETEROAROMATIC COMPOUNDS AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE<br/>[FR] COMPOSÉS HÉTÉROAROMATIQUES BICYCLIQUES EN TANT QU'INHIBITEURS DE LA STÉAROYL-COENZYME A DELTA-9 DÉSATURASE
  申请人：MERCK FROSST CANADA LTD

  公开号：WO2009012573A1

  公开（公告）日：2009-01-29

  Bicyclic heteroaromatic compounds of structural formula I are inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD). The compounds of the present invention are useful for the prevention and treatment of conditions related to abnormal lipid synthesis and metabolism, including cardiovascular disease; atherosclerosis; obesity; diabetes; neurological disease; metabolic syndrome; insulin resistance; liver steatosis; and non-alcoholic steatohepatitis.

  结构式I的双环杂芳化合物是硬脂酰辅酶A 9-脱饱和酶（SCD）的抑制剂。本发明的化合物对预防和治疗与异常脂质合成和代谢相关的疾病有用，包括心血管疾病；动脉粥样硬化；肥胖；糖尿病；神经系统疾病；代谢综合征；胰岛素抵抗；肝脂肪变性；以及非酒精性脂肪肝。
• BICYCLIC HETEROAROMATIC COMPOUNDS AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE
  申请人：Ramtohul Yeeman K.

  公开号：US20100197692A1

  公开（公告）日：2010-08-05

  Bicyclic heteroaromatic compounds of structural formula I are inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD). The compounds of the present invention are useful for the prevention and treatment of conditions related to abnormal lipid synthesis and metabolism, including cardiovascular disease; atherosclerosis; obesity; diabetes; neurological disease; metabolic syndrome; insulin resistance; liver steatosis; and non-alcoholic steatohepatitis.

  结构式I的双环杂环芳香化合物是硬脂酰辅酶A 三十九号去饱和酶(SCD)的抑制剂。本发明的化合物对于预防和治疗与异常脂质合成和代谢相关的疾病非常有用，包括心血管疾病、动脉粥样硬化、肥胖、糖尿病、神经系统疾病、代谢综合征、胰岛素抵抗、肝脂肪变性和非酒精性脂肪性肝炎。
• NOVEL INHIBITORS OF STEAROYL-CoA-DESATURASE-1 AND THEIR USES
  申请人：Fajas Lluis

  公开号：US20130012709A1

  公开（公告）日：2013-01-10

  An inhibitor of the activity of stearoyl-CoA-desaturase-1 (SCD-1) enzyme for use in the treatment of prostate cancer as well as novel inhibitors of formula (IIa).

  一种用于治疗前列腺癌的硬脂酰辅酶A去饱和酶1（SCD-1）酶活性的抑制剂，以及化学式（IIa）的新型抑制剂。
• Bicyclic heteroaryl inhibitors of stearoyl-CoA desaturase: From systemic to liver-targeting inhibitors
  作者：Yeeman K. Ramtohul、David Powell、Jean-Philippe Leclerc、Serge Leger、Renata Oballa、Cameron Black、Elise Isabel、Chun Sing Li、Sheldon Crane、Joel Robichaud、Jocelyne Guay、Sébastien Guiral、Lei Zhang、Zheng Huang

  DOI：10.1016/j.bmcl.2011.08.037

  日期：2011.10

  Optimization of a lead thiazole amide MF-152 led to the identification of potent bicyclic heteroaryl SCD1 inhibitors with good mouse pharmacokinetic profiles. In a view to target the liver for efficacy and to avoid SCD1 inhibition in the skin and eyes where adverse effects were previously observed in rodents, representative systemically-distributed SCD1 inhibitors were converted into liver-targeting SCD1 inhibitors. (C) 2011 Elsevier Ltd. All rights reserved.