4-oxo-7-(trifluoromethoxy)-1,4-dihydroquinoline-3-carbonitrile

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-oxo-7-(trifluoromethoxy)-1,4-dihydroquinoline-3-carbonitrile
• 英文别名: 4-oxo-7-(trifluoromethoxy)-1H-quinoline-3-carbonitrile
• 化学式: C₁₁H₅F₃N₂O₂
• 分子量: 254.168
• InChiKey: LAWSFFMFCYRZDH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  62.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-oxo-7-(trifluoromethoxy)-1,4-dihydroquinoline-3-carbonitrile 在 亚硝酸铵 、 三氟乙酸酐 作用下， 以30%的产率得到4-羟基-6-硝基-7-(三氟甲氧基)-3-喹啉甲腈
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of 6,7-Disubstituted 4-Anilinoquinoline-3-carbonitriles. The Design of an Orally Active, Irreversible Inhibitor of the Tyrosine Kinase Activity of the Epidermal Growth Factor Receptor (EGFR) and the Human Epidermal Growth Factor Receptor-2 (HER-2)

  摘要：

  A series of of 6,7-disubstituted-4-anilinoquinoline-3-carbonitrile derivatives that function as irreversible inhibitors of EGFR and HER-2 kinases have been prepared. These inhibitors have, at the 6-position, butynamide, crotonamide, and methacrylamide Michael acceptors bearing water-solublilizing substituents. These compounds were prepared by acylation of 6-amino-4-(arylamino)quinoline-3-carbonitriles with unsaturated acid chlorides or mixed anhydrides. We performed competitive reactivity studies showing that attaching a dialkylamino group onto the end of the Michael acceptor results in compounds with greater reactivity due to intramolecular catalysis of the Michael addition. This, along with improved water-solubility results in compounds with enhanced biological properties. We present molecular modeling results consistent with the proposed mechanism of inhibition. One compound, 5 (EKB-569), which shows excellent oral in vivo activity, was selected for further studies and is currently in phase I clinical trials for the treatment of cancer.

  DOI：

  10.1021/jm020241c
• 作为产物：
  描述：

  ethyl 2-cyano-3-[3-(trifluoromethoxy)anilino]prop-2-enoate 在 二苯醚 作用下， 反应 5.0h， 以7%的产率得到4-oxo-7-(trifluoromethoxy)-1,4-dihydroquinoline-3-carbonitrile
  参考文献：
  名称：

  三氟甲氧基-4-喹诺酮类衍生物新核苷的合成及生物学评价

  摘要：

  描述了由6-和7-三氟甲氧基-4-喹诺酮合成新的核苷衍生物。目前的合成方法是Gould-Jacobs反应（用于制备4-喹诺酮）和改良的Vorbrüggen反应（用于构建核苷衍生物）的组合。测试了针对鼠类γ疱疹病毒MHV-68型的目标化合物。

  DOI：

  10.1016/j.tetlet.2015.07.031

文献信息

• [EN] COMPOUNDS USEFUL FOR ALTERING THE LEVELS OF BILE ACIDS FOR THE TREATMENT OF DIABETES AND CARDIOMETABOLIC DISEASE<br/>[FR] COMPOSÉS UTILES POUR MODIFIER LES TAUX D'ACIDES BILIAIRES POUR LE TRAITEMENT DU DIABÈTE ET DE MALADIES CARDIOMÉTABOLIQUES.
  申请人：MERCK SHARP & DOHME

  公开号：WO2018034918A1

  公开（公告）日：2018-02-22

  Described herein are compounds of Formula (I) or a pharmaceutically acceptable salt thereof. The compounds of Formula I act as Cyp8b1 inhibitors and can be useful in preventing, treating or acting as a remedial agent for diabetes and cardiovascular disease.

  本文描述了式（I）的化合物或其药用可接受的盐。式（I）的化合物作为Cyp8b1抑制剂，可用于预防、治疗或作为糖尿病和心血管疾病的治疗剂。
• Compound useful for altering the levels of bile acids for the treatment of diabetes and cardiometabolc disease
  申请人：Merck Sharp & Dohme Corp.

  公开号：US10414774B2

  公开（公告）日：2019-09-17

  Described herein are compounds of Formula (I) or a pharmaceutically acceptable salt thereof. The compounds of Formula I act as Cyp8b1 inhibitors and can be useful in preventing, treating or acting as a remedial agent for diabetes and cardiovascular disease.

  本文描述的是式（I）化合物或其药学上可接受的盐。式 I 的化合物作为 Cyp8b1 抑制剂，可用于预防、治疗或作为糖尿病和心血管疾病的补救药物。
• COMPOUNDS USEFUL FOR ALTERING THE LEVELS OF BILE ACIDS FOR THE TREATMENT OF DIABETES AND CARDIOMETABOLIC DISEASE
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP3496716A1

  公开（公告）日：2019-06-19
• COMPOUNDS USEFUL FOR ALTERING THE LEVELS OF BILE ACIDS FOR THE TREATMENT OF DIABETES AND CARDIOMETABOLC DISEASE
  申请人：CUMMING Jared N.

  公开号：US20190218223A1

  公开（公告）日：2019-07-18

  Described herein are compounds of Formula (I) or a pharmaceutically acceptable salt thereof. The compounds of Formula I act as Cyp8b1 inhibitors and can be useful in preventing, treating or acting as a remedial agent for diabetes and cardiovascular disease.
• Synthesis and biological evaluation of new nucleosides derived from trifluoromethoxy-4-quinolones
  作者：Kristína Plevová、Katarína Briestenská、Françoise Colobert、Jela Mistríková、Viktor Milata、Frédéric R. Leroux

  DOI：10.1016/j.tetlet.2015.07.031

  日期：2015.9

  The synthesis of new nucleoside derivatives from 6- and 7-trifluoromethoxy-4-quinolones is described. The present synthesis is a combination of the Gould–Jacobs reaction for the preparation of 4-quinolones and a modified Vorbrüggen reaction for the construction of nucleoside derivatives. The target compounds were tested against murine gammaherpesvirus MHV-68 type.

  描述了由6-和7-三氟甲氧基-4-喹诺酮合成新的核苷衍生物。目前的合成方法是Gould-Jacobs反应（用于制备4-喹诺酮）和改良的Vorbrüggen反应（用于构建核苷衍生物）的组合。测试了针对鼠类γ疱疹病毒MHV-68型的目标化合物。