N-hydroxy-3-(trifluoromethoxy)benzimidoyl chloride | 677728-60-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: N-hydroxy-3-(trifluoromethoxy)benzimidoyl chloride
• 英文别名: N-hydroxy-3-(trifluoromethoxy)benzimidoylchloride；N-hydroxy-3-(trifluoromethoxy)benzenecarboximidoyl chloride
• CAS: 677728-60-8
• 化学式: C₈H₅ClF₃NO₂
• 分子量: 239.581
• InChiKey: KBXSWBJOSXKJSH-UHFFFAOYSA-N

物化性质

• 沸点：
  280.2±50.0 °C(Predicted)
• 密度：
  1.45±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  41.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-hydroxy-3-(trifluoromethoxy)benzimidoyl chloride 在 lithium aluminium tetrahydride 、 18-冠醚-6 、 四溴化碳 、 potassium tert-butylate 、 三乙胺 、 三苯基膦 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 28.16h， 生成
  参考文献：
  名称：

  Discovery and Optimization of Non-bile Acid FXR Agonists as Preclinical Candidates for the Treatment of Nonalcoholic Steatohepatitis

  摘要：

  Farnesoid X receptor (FXR) plays a key role in bile acid homeostasis, inflammation, fibrosis, and metabolism of lipid and glucose and becomes a promising therapeutic target for nonalcoholic steatohepatitis (NASH) or other FXR-dependent diseases. The phase III trial results of obeticholic acid demonstrate that the FXR agonists emerge as a promising intervention in patients with NASH and fibrosis, but this bile acid-derived FXR agonist brings severe pruritus and an elevated risk of cardiovascular disease for patients. Herein, we reported our efforts in the discovery of a series of non-bile acid FXR agonists, and 36 compounds were designed and synthesized based on the structure-based drug design and structural optimization strategies. Particularly, compound 42 is a highly potent and selective FXR agonist, along with good pharmacokinetic profiles, high liver distribution, and preferable in vivo efficacy, indicating that it is a potential candidate for the treatment of NASH or other FXR-dependent diseases.

  DOI：

  10.1021/acs.jmedchem.0c01065
• 作为产物：
  描述：

  3-(三氟甲氧基)苯甲醛 在 N-氯代丁二酰亚胺 、 盐酸羟胺 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 N-hydroxy-3-(trifluoromethoxy)benzimidoyl chloride
  参考文献：
  名称：

  Discovery and Optimization of Non-bile Acid FXR Agonists as Preclinical Candidates for the Treatment of Nonalcoholic Steatohepatitis

  摘要：

  Farnesoid X receptor (FXR) plays a key role in bile acid homeostasis, inflammation, fibrosis, and metabolism of lipid and glucose and becomes a promising therapeutic target for nonalcoholic steatohepatitis (NASH) or other FXR-dependent diseases. The phase III trial results of obeticholic acid demonstrate that the FXR agonists emerge as a promising intervention in patients with NASH and fibrosis, but this bile acid-derived FXR agonist brings severe pruritus and an elevated risk of cardiovascular disease for patients. Herein, we reported our efforts in the discovery of a series of non-bile acid FXR agonists, and 36 compounds were designed and synthesized based on the structure-based drug design and structural optimization strategies. Particularly, compound 42 is a highly potent and selective FXR agonist, along with good pharmacokinetic profiles, high liver distribution, and preferable in vivo efficacy, indicating that it is a potential candidate for the treatment of NASH or other FXR-dependent diseases.

  DOI：

  10.1021/acs.jmedchem.0c01065

文献信息

• Stereospecific 1,4‐Metallate Shift Enables Stereoconvergent Synthesis of Ketoximes
  作者：Kai Yang、Feng Zhang、Tongchang Fang、Guan Zhang、Qiuling Song

  DOI：10.1002/anie.201906057

  日期：2019.9.16

  Reported herein is a stereospecific 1,4-metallate rearrangement for single-geometry ketoxime synthesis from oxime chlorides and arylboronic acids. This strategy exhibits broad substrate scope with excellent stereoselectivity under mild reaction conditions. In comparison with the conventional approaches, each configuration of unsymmetric diaryl oximes, as well as the thermodynamically less stable Z isomer

  本文报道了用于由肟氯化物和芳基硼​​酸合成单几何型酮肟的立体有规的1,4-金属盐重排。该策略在温和的反应条件下具有宽泛的底物范围和出色的立体选择性。与常规方法相比，可以选择性地并且排他地获得不对称二芳基肟的每种构型以及芳基烷基酮肟的热力学上较不稳定的Z异构体。一类未开发的分子，不对称二芳基肟和芳基烷基肟的Z异构体的反应性使得能够有效地获得具有单一构型的相应异喹啉，异喹啉N-氧化物和酰胺。
• PHENYL-ISOXAZOL DERIVATIVES AND PREPARATION PROCESS THEREOF
  申请人：Kim Dong Yeon

  公开号：US20140031364A1

  公开（公告）日：2014-01-30

  Disclosed are a phenyl-isoxazol derivative compound, which is useful as a treatment material for virus infection, especially, infection of an influenza virus, or its pharmaceutically acceptable derivative, a preparation method thereof, and an illness treatment pharmaceutical composition including the compound as an active ingredient.

  本发明涉及一种苯基异噁唑衍生物化合物，其可用作治疗病毒感染的治疗材料，特别是流感病毒感染，或其药学上可接受的衍生物，其制备方法，以及包含该化合物作为活性成分的疾病治疗药物组合物。
• Phenyl-isoxazole derivatives and preparation process thereof
  申请人：Kim Dong Yeon

  公开号：US09132126B2

  公开（公告）日：2015-09-15

  Disclosed are a phenyl-isoxazol derivative compound, which is useful as a treatment material for virus infection, especially, infection of an influenza virus, or its pharmaceutically acceptable derivative, a preparation method thereof, and an illness treatment pharmaceutical composition including the compound as an active ingredient.

  本发明涉及一种苯基异噁唑衍生物化合物，其可用作治疗病毒感染的治疗材料，特别是治疗流感病毒感染，或其药学上可接受的衍生物，以及其制备方法和包括该化合物作为活性成分的疾病治疗药物组合物。
• Discovery and Optimization of Non-bile Acid FXR Agonists as Preclinical Candidates for the Treatment of Nonalcoholic Steatohepatitis
  作者：Junyou Li、Mengqi Liu、Yazhou Li、Dan-dan Sun、Zhihao Shu、Qian Tan、Shimeng Guo、Rongrong Xie、Lixin Gao、Hongbo Ru、Yi Zang、Hong Liu、Jia Li、Yu Zhou

  DOI：10.1021/acs.jmedchem.0c01065

  日期：2020.11.12

  Farnesoid X receptor (FXR) plays a key role in bile acid homeostasis, inflammation, fibrosis, and metabolism of lipid and glucose and becomes a promising therapeutic target for nonalcoholic steatohepatitis (NASH) or other FXR-dependent diseases. The phase III trial results of obeticholic acid demonstrate that the FXR agonists emerge as a promising intervention in patients with NASH and fibrosis, but this bile acid-derived FXR agonist brings severe pruritus and an elevated risk of cardiovascular disease for patients. Herein, we reported our efforts in the discovery of a series of non-bile acid FXR agonists, and 36 compounds were designed and synthesized based on the structure-based drug design and structural optimization strategies. Particularly, compound 42 is a highly potent and selective FXR agonist, along with good pharmacokinetic profiles, high liver distribution, and preferable in vivo efficacy, indicating that it is a potential candidate for the treatment of NASH or other FXR-dependent diseases.