trans-4-((1-(5-(5-(trifluoromethyl)-1Hbenzo[d]imidazol-2-yl)pyridin-2-yl)piperidin-4-yl)oxy)cyclohexanecarboxylic acid | 1415571-46-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: trans-4-((1-(5-(5-(trifluoromethyl)-1Hbenzo[d]imidazol-2-yl)pyridin-2-yl)piperidin-4-yl)oxy)cyclohexanecarboxylic acid
• 英文别名: trans-4-[(1-{5-[5-(trifluoromethyl)-1H-benzimidazol-2-yl]pyridin-2-yl}piperidin-4-yl)oxy]cyclohexanecarboxylic acid
• CAS: 1415571-46-8
• 化学式: C₂₅H₂₇F₃N₄O₃
• 分子量: 488.51
• InChiKey: MCFBUIIRFZBRCU-RZDIXWSQSA-N

物化性质

• 沸点：
  692.0±65.0 °C(Predicted)
• 密度：
  1.41±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.27
• 重原子数：
  35.0
• 可旋转键数：
  5.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  91.34
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  2-氟吡啶-5-甲醛 在 Oxone 、 碳酸氢钠 、 lithium hydroxide 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 N,N-二甲基乙酰胺 、 水 为溶剂， 生成 trans-4-((1-(5-(5-(trifluoromethyl)-1Hbenzo[d]imidazol-2-yl)pyridin-2-yl)piperidin-4-yl)oxy)cyclohexanecarboxylic acid
  参考文献：
  名称：

  Discovery of a Potent and Selective DGAT1 Inhibitor with a Piperidinyl-oxy-cyclohexanecarboxylic Acid Moiety

  摘要：

  We report the discovery of a novel series of DGAT1 inhibitors in the benzimidazole class with a piperdinyl-oxy-cyclohexanecarboxylic acid moiety. This novel series possesses significantly improved selectivity against the A(2A) receptor, no ACAT1 off-target activity at 10 mu M, and higher aqueous solubility and free fraction in plasma as compared to the previously reported pyridyl-oxy-cyclohexanecarboxylic acid series. In particular, 5B was shown to possess an excellent selectivity profile by screening it against a panel of more than 100 biological targets. Compound 5B significantly reduces lipid excursion in LTT in mouse and rat, demonstrates DGAT1 mediated reduction of food intake and body weight in mice, is negative in a 3-strain Ames test, and appears to distribute preferentially in the liver and the intestine in mice. We believe this lead series possesses significant potential to identify optimized compounds for clinical development.

  DOI：

  10.1021/ml5003426

文献信息

• [EN] IMIDAZOLE DERIVATIVES<br/>[FR] DÉRIVÉS D'IMIDAZOLE
  申请人：INTERVET INT BV

  公开号：WO2012164071A1

  公开（公告）日：2012-12-06

  Described herein are compounds of formula (I), The compounds of formula I act as DGAT1 inhibitors and can be useful in preventing, treating or acting as a remedial agent for hyperlipidemia, diabetes mellitus and obesity.

  本文描述了式(I)的化合物。式(I)的化合物作为DGAT1抑制剂，可用于预防、治疗或作为高脂血症、糖尿病和肥胖的治疗药物。
• IMIDAZOLE DERIVATIVES
  申请人：DeVita Robert J.

  公开号：US20140088124A1

  公开（公告）日：2014-03-27

  Described herein are compounds of formula (I), The compounds of formula I act as DGAT1 inhibitors and can be useful in preventing, treating or acting as a remedial agent for hyperlipidemia, diabetes mellitus and obesity.

  本文描述了化学式（I）的化合物。化合物I的作用是DGAT1抑制剂，可以用于预防，治疗或作为治疗高脂血症，糖尿病和肥胖症的药物。
• Method for Stimulating Axonal Regeneration
  申请人：The Hong Kong University of Science and Technology

  公开号：US20220160897A1

  公开（公告）日：2022-05-26

  A method of promoting axonal regeneration can include directing neuronal lipid synthesis away from triglyceride synthesis and toward phospholipid synthesis. The method can include administering to the patient a therapeutically effective amount of an inhibitor compound selected from the group consisting of a Lipin-1 inhibitor, a diglyceride acyltransferase inhibitor, and combinations thereof or administering a gene editing therapy to the patient that reduces expression of LIPIN1 or a diglyceride acyltransferase gene.
• Discovery of a Potent and Selective DGAT1 Inhibitor with a Piperidinyl-oxy-cyclohexanecarboxylic Acid Moiety
  作者：Shuwen He、Qingmei Hong、Zhong Lai、David X. Yang、Pauline C. Ting、Jeffrey T. Kuethe、Timothy A. Cernak、Kevin D. Dykstra、Donald M. Sperbeck、Zhicai Wu、Yang Yu、Ginger X. Yang、Tianying Jian、Jian Liu、Deodial Guiadeen、Arto D. Krikorian、Lisa M. Sonatore、Judyann Wiltsie、Jinqi Liu、Judith N. Gorski、Christine C. Chung、Jack T. Gibson、JeanMarie Lisnock、Jianying Xiao、Michael Wolff、Sharon X. Tong、Maria Madeira、Bindhu V. Karanam、Dong-Ming Shen、James M. Balkovec、Shirly Pinto、Ravi P. Nargund、Robert J. DeVita

  DOI：10.1021/ml5003426

  日期：2014.10.9

  We report the discovery of a novel series of DGAT1 inhibitors in the benzimidazole class with a piperdinyl-oxy-cyclohexanecarboxylic acid moiety. This novel series possesses significantly improved selectivity against the A(2A) receptor, no ACAT1 off-target activity at 10 mu M, and higher aqueous solubility and free fraction in plasma as compared to the previously reported pyridyl-oxy-cyclohexanecarboxylic acid series. In particular, 5B was shown to possess an excellent selectivity profile by screening it against a panel of more than 100 biological targets. Compound 5B significantly reduces lipid excursion in LTT in mouse and rat, demonstrates DGAT1 mediated reduction of food intake and body weight in mice, is negative in a 3-strain Ames test, and appears to distribute preferentially in the liver and the intestine in mice. We believe this lead series possesses significant potential to identify optimized compounds for clinical development.