3-{2-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]-7-oxo-6,7-dihydro[1,3]thiazolo-[4,5-d]pyrimidin-5-yl}propanoic acid | 1085784-01-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-{2-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]-7-oxo-6,7-dihydro[1,3]thiazolo-[4,5-d]pyrimidin-5-yl}propanoic acid
• 英文别名: 3-[2-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]-7-oxo-6H-[1,3]thiazolo[4,5-d]pyrimidin-5-yl]propanoic acid
• CAS: 1085784-01-5
• 化学式: C₁₉H₁₈BrFN₄O₄S
• 分子量: 497.345
• InChiKey: ZMNCGKQJUYNKMG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  132
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  3-{2-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]-7-oxo-6,7-dihydro[1,3]thiazolo-[4,5-d]pyrimidin-5-yl}propanoic acid 在 氨 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 3-{2-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]-7-oxo-6,7-dihydro[1,3]thiazolo[4,5-d]pyrimidin-5-yl}propanamide
  参考文献：
  名称：

  WO2008/141455

  摘要：

  公开号：
• 作为产物：
  描述：

  1-[5-(3-methoxy-3-oxopropyl)-7-oxo-6,7-dihydro[1,3]thiazolo[4,5-d]pyrimidin-2-yl]piperidin-4-yl methyl succinate 在 甲醇 、 sodium methylate 、 三苯基膦 、 lithium hydroxide 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 生成 3-{2-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]-7-oxo-6,7-dihydro[1,3]thiazolo-[4,5-d]pyrimidin-5-yl}propanoic 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

• BICYCLIC HETEROAROMATIC COMPOUNDS AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE
  申请人：Leger Serge

  公开号：US20100152208A1

  公开（公告）日：2010-06-17

  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, such as atherosclerosis; obesity; Type 2 diabetes; insulin resistance; hyperglycemia; Metabolic Syndrome; neurological disease; cancer; and liver steatosis. Formula (I).

  结构式为I的双环杂环芳香化合物是硬脂酰辅酶A delta-9去饱和酶（SCD）的抑制剂。本发明的化合物可用于预防和治疗与异常脂质合成和代谢相关的疾病，包括心血管疾病，如动脉粥样硬化; 肥胖症; 第2型糖尿病; 胰岛素抵抗; 高血糖; 代谢综合征; 神经系统疾病; 癌症; 和脂肪肝。公式（I）。
• [EN] BICYCLIC HETEROAROMATIC COMPOUNDS AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE<br/>[FR] COMPOSÉS HÉTÉROAROMATIQUES BICYCLIQUES UTILISÉS EN TANT QU'INHIBITEURS DE LA STÉAROYL-COENZYME A DELTA-9 DÉSATURASE
  申请人：MERCK FROSST CANADA LTD

  公开号：WO2008141455A1

  公开（公告）日：2008-11-27

  [EN] 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, such as atherosclerosis; obesity; Type 2 diabetes; insulin resistance; hyperglycemia; Metabolic Syndrome; neurological disease; cancer; and liver steatosis. Formula (I).
  [FR] La présente invention concerne des composés hétéroaromatiques bicycliques de formule générale I qui sont des inhibiteurs de la stéaroyl-coenzyme A delta-9 désaturase (SCD). Les composés de la présente invention sont utilisables en vue de la prévention et du traitement des affections associées à une synthèse et à un métabolisme anormaux des lipides, ce qui comprend les maladies cardiovasculaires, comme l'athérosclérose ; l'obésité ; le diabète de type 2 ; la résistance à l'insuline ; l'hyperglycémie ; le syndrome métabolique ; les affections neurologiques ; le cancer ; et la stéatose hépatique. Formule (I).
• WO2008/141455
  申请人：——

  公开号：——

  公开（公告）日：——
• 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.