tert-butyl 4-(3-(4-(trifluoromethyl)phenyl)-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylate | 1001467-35-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: tert-butyl 4-(3-(4-(trifluoromethyl)phenyl)-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylate
• 英文别名: Tert-butyl 4-[3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl]piperidine-1-carboxylate
• CAS: 1001467-35-1
• 化学式: C₁₉H₂₂F₃N₃O₃
• 分子量: 397.397
• InChiKey: KOSBFHPEULSJLR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  68.5
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(3-(4-(trifluoromethyl)phenyl)-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 10.0h， 生成 5-(piperidin-4-yl)-3-(4-(trifluoromethyl)phenyl)-1,2,4-oxadiazole
  参考文献：
  名称：

  Discovery of highly potent triazoleantifungal agents with piperidine-oxadiazole side chains

  摘要：

  一系列含有哌啶-噁二唑侧链的新型三唑类抗真菌药物被设计并合成。化合物11b 对白念珠菌表现出高活性，最小抑菌浓度（MIC）值为0.016 μg/mL。

  DOI：

  10.1039/c4md00505h
• 作为产物：
  描述：

  对三氟甲基苯腈 在 盐酸羟胺 、 potassium carbonate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 tert-butyl 4-(3-(4-(trifluoromethyl)phenyl)-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylate
  参考文献：
  名称：

  在新型强效和选择性FXR拮抗剂化学型的发现中对恶二唑核的研究

  摘要：

  最近的发现表明，法尼醇X受体（FXR）拮抗剂可能在胆汁淤积症和相关代谢紊乱的治疗中有用。在本文中，我们报告了以3,5-二取代的恶二唑核心为特征的新型FXR拮抗剂化学型的发现。总共设计并合成了35种新的衍生物，尤其是含有哌啶环的化合物3f和13对FXR表现出最佳的拮抗活性，并具有有希望的细胞效价（IC 50分别为0.58±0.27和0.127±0.02μM） 。优异的药代动力学特性使化合物3f成为本研究中鉴定出的最有希望的先导。

  DOI：

  10.1021/acsmedchemlett.8b00534

文献信息

• COMPOUNDS HAVING A POTENTIATING EFFECT ON THE ACTIVITY OF ETHIONAMIDE AND USES THEREOF
  申请人：Deprez Benôit

  公开号：US20110136823A1

  公开（公告）日：2011-06-09

  The present invention relates to the use of compounds with a potentiating effect on the activity of antibiotics that are activatable via the EthA enzymatic pathway, for the preparation of a medicament for preventing and/or treating mycobacterial infections such as tuberculosis and leprosy, to pharmaceutical compositions comprising them in combination with an antibiotic that is activatable via the EthA pathway, to compounds having a potentiating effect on the activity of antibiotics that are activatable via the EthA enzymatic pathway, to pharmaceutical compositions comprising them and to their use as medicaments, especially medicaments for preventing and/or treating mycobacterial infections such as tuberculosis and leprosy.

  本发明涉及具有增强抗生素活性的化合物，这些抗生素通过EthA酶途径可激活，用于制备预防和/或治疗如结核病和麻风病等分枝杆菌感染的药物；涉及包含这些化合物与通过EthA途径可激活的抗生素组合的药物组合物；涉及具有增强通过EthA酶途径可激活抗生素活性的化合物；涉及包含这些化合物的药物组合物；以及涉及它们作为药物，特别是用于预防和/或治疗如结核病和麻风病等分枝杆菌感染的药物的使用。
• Ethionamide Boosters. 2. Combining Bioisosteric Replacement and Structure-Based Drug Design To Solve Pharmacokinetic Issues in a Series of Potent 1,2,4-Oxadiazole EthR Inhibitors
  作者：Marion Flipo、Matthieu Desroses、Nathalie Lecat-Guillet、Baptiste Villemagne、Nicolas Blondiaux、Florence Leroux、Catherine Piveteau、Vanessa Mathys、Marie-Pierre Flament、Juergen Siepmann、Vincent Villeret、Alexandre Wohlkönig、René Wintjens、Sameh H. Soror、Thierry Christophe、Hee Kyoung Jeon、Camille Locht、Priscille Brodin、Benoit Déprez、Alain R. Baulard、Nicolas Willand

  DOI：10.1021/jm200825u

  日期：2012.1.12

  Mycobacterial transcriptional repressor EthR controls the expression of EthA, the bacterial monooxygenase activating ethionamide, and is thus largely responsible for the low sensitivity of the human pathogen Mycobacterium tuberculosis to this antibiotic. We recently reported structure-activity relationships of a series of 1,2,4-oxadiazole EthR inhibitors leading to the discovery of potent ethionamide boosters. Despite high metabolic stability, pharmacokinetic evaluation revealed poor mice exposure; therefore, a second phase of optimization was required. Herein a structure-property relationship study is reported according to the replacement of the two aromatic heterocycles: 2-thienyl and 1,2,4-oxadiazolyl moieties. This work was done using a combination of structure-based drug design and in vitro/ex vivo evaluations of ethionamide boosters on the targeted protein EthR and on the human pathogen Mycobacterium tuberculosis. Thanks to this process, we identified compound 42 (BDM41906), which displays improved efficacy in addition to high exposure to mice after oral administration.
• US8338599B2
  申请人：——

  公开号：US8338599B2

  公开（公告）日：2012-12-25
• WO2023/275744
  申请人：——

  公开号：——

  公开（公告）日：——