(1H-benzo[d]imidazol-2-yl)(4-(2-(trifluoromethyl)phenyl)piperidin-1-yl)methanone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (1H-benzo[d]imidazol-2-yl)(4-(2-(trifluoromethyl)phenyl)piperidin-1-yl)methanone
• 英文别名: 1H-benzimidazol-2-yl-[4-[2-(trifluoromethyl)phenyl]piperidin-1-yl]methanone
• 化学式: C₂₀H₁₈F₃N₃O
• 分子量: 373.378
• InChiKey: XDWWBAXVDRKVQA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  49
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  邻溴三氟甲苯 在 盐酸 、 正丁基锂 、 氯化亚砜 、 palladium 10% on activated carbon 、 甲酸铵 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 24.92h， 生成 (1H-benzo[d]imidazol-2-yl)(4-(2-(trifluoromethyl)phenyl)piperidin-1-yl)methanone
  参考文献：
  名称：

  Design, Synthesis, and Preclinical Efficacy of Novel Nonretinoid Antagonists of Retinol-Binding Protein 4 in the Mouse Model of Hepatic Steatosis

  摘要：

  Retinol-binding protein 4 (RBP4) serves as a transporter for all-trans-retinol (1) in the blood, and it has been proposed to act as an adipokine. Elevated plasma levels of the protein have been linked to diabetes, obesity, cardiovascular diseases, and nonalcoholic fatty liver disease (NAFLD). Recently, adipocyte-specific overexpression of RBP4 was reported to cause hepatic steatosis in mice. We previously identified an orally bioavailable RBP4 antagonist that significantly lowered RBP4 serum levels in Abca4(-/-) knockout mice with concomitant normalization of complement system protein expression and reduction of bisretinoid formation within the retinal pigment epithelium. We describe herein the discovery of novel RBP4 antagonists 48 and 59, which reduce serum RBP4 levels by >80% in mice upon acute oral dosing. Furthermore, 59 demonstrated efficacy in the transgenic adi-hRBP4 murine model of hepatic steatosis, suggesting that RBP4 antagonists may also have therapeutic utility for the treatment of NAFLD.

  DOI：

  10.1021/acs.jmedchem.9b00352

文献信息

• 4-PHENYLPIPERIDINES, THEIR PREPARATION AND USE
  申请人：PETRUKHIN Konstantin

  公开号：US20160046648A1

  公开（公告）日：2016-02-18

  The present invention provides a compound having the structure: (structurally represented) wherein R 1 , R 2 , R 3 , R 4 , and R 5 are each independently H, halogen, CF 3 or C 1 -C 4 alkyl; R 6 is H, OH, or halogen; B is a substituted or unsubstituted heterobicycle, pyridazine, pyrazole, pyrazine, thiadiazole, or triazole, wherein the heterobicycle is other than chloro substituted indole; and the pyrazole, when substituted, is substituted with other than trifluoromethyl, or a pharmaceutically acceptable salt thereof.

  本发明提供了一种化合物，其结构为：（结构式表示），其中R1、R2、R3、R4和R5各自独立地为H、卤素、CF3或C1-C4烷基；R6为H、OH或卤素；B为取代或未取代杂环、吡嗪、吡唑、吡嗪、噻二唑或三唑，其中杂环不是氯取代的吲哚；当吡唑取代时，取代基不是三氟甲基，或其药学上可接受的盐。
• 4-phenylpiperidines, their preparation and use
  申请人：The Trustees of Columbia University in the City of New York

  公开号：US10273243B2

  公开（公告）日：2019-04-30

  The present invention provides a compound having the structure: (structurally represented) wherein R1, R2, R3, R4, and R5 are each independently H, halogen, CF3 or C1-C4 alkyl; R6 is H, OH, or halogen; B is a substituted or unsubstituted heterobicycle, pyridazine, pyrazole, pyrazine, thiadiazole, or triazole, wherein the heterobicycle is other than chloro substituted indole; and the pyrazole, when substituted, is substituted with other than trifluoromethyl, or a pharmaceutically acceptable salt thereof.

  本发明提供了一种具有以下结构的化合物：(结构表示），其中 R1、R2、R3、R4 和 R5 各自独立地为 H、卤素、CF3 或 C1-C4 烷基；R6 为 H、OH 或卤素；B 为取代或未取代的杂环、哒嗪、吡唑、吡嗪、噻二唑或三唑，其中杂环为氯取代的吲哚以外的杂环；吡唑取代时为三氟甲基以外的取代基，或其药学上可接受的盐。
• Methods of treating metabolic diseases with fused bicyclic pyrazoles
  申请人：BELITE BIO, INC

  公开号：US11389444B2

  公开（公告）日：2022-07-19

  Provided herein are heterocyclic derivative compounds and pharmaceutical compositions comprising said compounds that are useful for the treatment of retinal binding protein (RBP4) related diseases, such as obesity and the like.

  本文提供了可用于治疗视网膜结合蛋白（RBP4）相关疾病（如肥胖症等）的杂环衍生物化合物和包含上述化合物的药物组合物。
• FORMULATIONS OF RBP4 INHIBITORS AND METHODS OF USE
  申请人：Belite Bio, LLC

  公开号：EP3996714A1

  公开（公告）日：2022-05-18
• METHODS OF TREATING METABOLIC DISEASES WITH FUSED BICYCLIC PYRAZOLES
  申请人：BELITE BIO, INC

  公开号：US20200197390A1

  公开（公告）日：2020-06-25

  Provided herein are heterocyclic derivative compounds and pharmaceutical compositions comprising said compounds that are useful for the treatment of retinal binding protein (RBP4) related diseases, such as obesity and the like.