N'-hydroxy-2-{4-[2-(trifluoromethyl)phenoxy]piperidin-1-yl}-1,3-thiazole-5-carboximidamide | 916889-28-6

• 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: N'-hydroxy-2-{4-[2-(trifluoromethyl)phenoxy]piperidin-1-yl}-1,3-thiazole-5-carboximidamide
• 英文别名: N'-hydroxy-2-[4-[2-(trifluoromethyl)phenoxy]piperidin-1-yl]-1,3-thiazole-5-carboximidamide
• CAS: 916889-28-6
• 化学式: C₁₆H₁₇F₃N₄O₂S
• 分子量: 386.398
• InChiKey: SPCWZMKOCVPDKX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  乙醇酸乙酯 、 N'-hydroxy-2-{4-[2-(trifluoromethyl)phenoxy]piperidin-1-yl}-1,3-thiazole-5-carboximidamide 在 sodium 作用下， 以 乙醇 为溶剂， 生成 [3-(2-{4-[2-(trifluoromethyl)benzoyl]piperazin-1-yl}-1,3-thiazol-5-yl)-1,2,4-oxadiazol-5-yl]methanol
  参考文献：
  名称：

  SAR and optimization of thiazole analogs as potent stearoyl-CoA desaturase inhibitors

  摘要：

  Elevated stearoyl-CoA desaturase (SCD) activity has been linked to a number of metabolic disorders including obesity and type II diabetes. Compound 3j, a potent SCD inhibitor (human HepG2 IC(50) = 1 nM) was identified from the optimization of a lead thiazole compound MF-152 with over 100-fold improvement in potency. In a 4-week chronic oral dosing at 0.2 mg/ kg, 3j gave a robust 24% prevention of body weight gain in mice fed on a high fat diet accompanied with an improved metabolic profile on insulin and glucose levels. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.01.083
• 作为产物：
  描述：

  1-(5-bromo-1,3-thiazol-2-yl)-4-[2-(trifluoromethyl)phenoxy]piperidine 在 盐酸羟胺 、 水 、 sodium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 N'-hydroxy-2-{4-[2-(trifluoromethyl)phenoxy]piperidin-1-yl}-1,3-thiazole-5-carboximidamide
  参考文献：
  名称：

  WO2006/130986

  摘要：

  公开号：

文献信息

• Azacyclohexane derivatives as inhibitors of stearoyl-coenzyme a delta-9 desaturase
  申请人：Li Chun Sing

  公开号：US20090099200A1

  公开（公告）日：2009-04-16

  Azacyclohexane derivatives of structural formula I are selective inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD1) relative to other known stearoyl-coenzyme A desaturases. 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; and liver steatosis.

  结构式I的脂环己基衍生物是选择性抑制硬脂酰辅酶A delta-9去饱和酶（SCD1）相对于其他已知的硬脂酰辅酶A去饱和酶的化合物。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、胰岛素抵抗和肝脂肪变性。
• AZACYCLOHEXANE DERIVATIVES AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE
  申请人：Merck Frosst Canada Ltd.

  公开号：EP1902051A1

  公开（公告）日：2008-03-26
• [EN] AZACYCLOHEXANE DERIVATIVES AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE<br/>[FR] DERIVES D'AZACYCLOHEXANE COMME INHIBITEURS DE LA STEAROYL-COENZYME A DELTA-9 DESATURASE
  申请人：MERCK FROSST CANADA LTD

  公开号：WO2006130986A1

  公开（公告）日：2006-12-14

  [EN] Azacyclohexane derivatives of structural formula I are selective inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD1) relative to other known stearoyl-coenzyme A desaturases. 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; and liver steatosis.
  [FR] Les dérivés d'azacyclohexane de formule structurelle I sont des inhibiteurs sélectifs de la stéaroyl-coenzyme A delta-9 désaturase (SCD1) par rapport à d'autres stéaroyl-coenzyme A désaturases connues. Les composés de la présente invention sont utiles pour la prévention et le traitement de pathologies liées à la synthèse et au métabolisme anormaux de lipides, y compris les maladies cardiovasculaires; l'athérosclérose; l'obésité; le diabète; les maladies neurologiques; le syndrome métabolique; la résistance à l'insuline; et la stéatose du foie.
• WO2006/130986
  申请人：——

  公开号：——

  公开（公告）日：——
• SAR and optimization of thiazole analogs as potent stearoyl-CoA desaturase inhibitors
  作者：Yeeman K. Ramtohul、Cameron Black、Chi-Chung Chan、Sheldon Crane、Jocelyne Guay、Sébastien Guiral、Zheng Huang、Renata Oballa、Li-Jing Xu、Lei Zhang、Chun Sing Li

  DOI：10.1016/j.bmcl.2010.01.083

  日期：2010.3

  Elevated stearoyl-CoA desaturase (SCD) activity has been linked to a number of metabolic disorders including obesity and type II diabetes. Compound 3j, a potent SCD inhibitor (human HepG2 IC(50) = 1 nM) was identified from the optimization of a lead thiazole compound MF-152 with over 100-fold improvement in potency. In a 4-week chronic oral dosing at 0.2 mg/ kg, 3j gave a robust 24% prevention of body weight gain in mice fed on a high fat diet accompanied with an improved metabolic profile on insulin and glucose levels. (C) 2010 Elsevier Ltd. All rights reserved.