tert-butyl (5-{3-[5-(2-chloro-5-fluorophenyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]isoxazol-5-yl}-2H-tetrazol-2-yl)acetate | 1246749-89-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tert-butyl (5-{3-[5-(2-chloro-5-fluorophenyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]isoxazol-5-yl}-2H-tetrazol-2-yl)acetate
• 英文别名: tert-Butyl (5-{3-[5-(2-chloro-5-fluorophenyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]isoxazol-5-yl}-2H-tetrazol-2-yl)acetate；tert-butyl 2-[5-[3-[2-(2-chloro-5-fluorophenyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]-1,2-oxazol-5-yl]tetrazol-2-yl]acetate
• CAS: 1246749-89-2
• 化学式: C₂₂H₂₅ClFN₇O₃
• 分子量: 489.937
• InChiKey: VQPMNJBVBDRHBQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  102
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  tert-butyl (5-{3-[5-(2-chloro-5-fluorophenyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]isoxazol-5-yl}-2H-tetrazol-2-yl)acetate 在 甲酸 作用下， 以 水 为溶剂， 反应 1.0h， 生成 (5-{3-[5-(2-chloro-5-fluorophenyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]isoxazol-5-yl}-2H-tetrazol-2-yl)acetic acid
  参考文献：
  名称：

  Discovery of potent and liver-targeted stearoyl-CoA desaturase (SCD) inhibitors in a bispyrrolidine series

  摘要：

  Inhibition of stearoyl-CoA desaturase (SCD) activity represents a potential novel mechanism for the treatment of metabolic disorders including obesity and type II diabetes. To circumvent skin and eye adverse events observed in rodents with systemically-distributed SCD inhibitors, our research efforts have been focused on the search for new and structurally diverse liver-targeted SCD inhibitors. This work has led to the discovery of novel, potent and structurally diverse liver-targeted bispyrrolidine SCD inhibitors. These compounds possess suitable cellular activity and pharmacokinetic properties to inhibit liver SCD activity in a mouse pharmacodynamic model. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.002
• 作为产物：
  描述：

  2-BOC-八氢吡咯基[3,4-C]吡咯 在 咪唑 、 盐酸 、 sodium azide 、 碘 、 palladium diacetate 、 sodium carbonate 、 氯化铵 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 三乙胺 、 三氟乙酸酐 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二甲基亚砜 、 甲苯 、 正丁醇 为溶剂， 反应 68.0h， 生成 tert-butyl (5-{3-[5-(2-chloro-5-fluorophenyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]isoxazol-5-yl}-2H-tetrazol-2-yl)acetate 、 tert-butyl 2-(5-(3-(5-(2-chloro-5-fluorophenyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)isoxazol-5-yl)-1H-tetrazol-1-yl)acetate
  参考文献：
  名称：

  Discovery of potent and liver-targeted stearoyl-CoA desaturase (SCD) inhibitors in a bispyrrolidine series

  摘要：

  Inhibition of stearoyl-CoA desaturase (SCD) activity represents a potential novel mechanism for the treatment of metabolic disorders including obesity and type II diabetes. To circumvent skin and eye adverse events observed in rodents with systemically-distributed SCD inhibitors, our research efforts have been focused on the search for new and structurally diverse liver-targeted SCD inhibitors. This work has led to the discovery of novel, potent and structurally diverse liver-targeted bispyrrolidine SCD inhibitors. These compounds possess suitable cellular activity and pharmacokinetic properties to inhibit liver SCD activity in a mouse pharmacodynamic model. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.002

文献信息

• [EN] HETEROCYCLIC COMPOUNDS AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES INHIBITEURS DE LA STÉAROYL-COENZYME A DELTA-9 DÉSATURASE
  申请人：MERCK FROSST CANADA LTD

  公开号：WO2010108268A1

  公开（公告）日：2010-09-30

  Heterocyclic 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; cancer, liver steatosis; and non-alcoholic steatohepatitis.

  结构式I的杂环化合物是硬脂酰辅酶A Δ-9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；癌症；肝脂肪变性；以及非酒精性脂肪性肝炎。
• HETEROCYCLIC COMPOUNDS AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE
  申请人：Lachance Nicolas

  公开号：US20120010186A1

  公开（公告）日：2012-01-12

  Heterocyclic 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; cancer, liver steatosis; and non-alcoholic steatohepatitis.

  结构式I的杂环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有关的疾病，包括心血管疾病；动脉粥样硬化；肥胖症；糖尿病；神经系统疾病；代谢综合征；胰岛素抵抗；癌症；肝脂肪变性和非酒精性脂肪性肝炎。
• Discovery of potent and liver-targeted stearoyl-CoA desaturase (SCD) inhibitors in a bispyrrolidine series
  作者：Nicolas Lachance、Yves Gareau、Sébastien Guiral、Zheng Huang、Elise Isabel、Jean-Philippe Leclerc、Serge Léger、Evelyn Martins、Christian Nadeau、Renata M. Oballa、Stéphane G. Ouellet、David A. Powell、Yeeman K. Ramtohul、Geoffrey K. Tranmer、Thao Trinh、Hao Wang、Lei Zhang

  DOI：10.1016/j.bmcl.2011.12.002

  日期：2012.1

  Inhibition of stearoyl-CoA desaturase (SCD) activity represents a potential novel mechanism for the treatment of metabolic disorders including obesity and type II diabetes. To circumvent skin and eye adverse events observed in rodents with systemically-distributed SCD inhibitors, our research efforts have been focused on the search for new and structurally diverse liver-targeted SCD inhibitors. This work has led to the discovery of novel, potent and structurally diverse liver-targeted bispyrrolidine SCD inhibitors. These compounds possess suitable cellular activity and pharmacokinetic properties to inhibit liver SCD activity in a mouse pharmacodynamic model. (C) 2011 Elsevier Ltd. All rights reserved.