(S)-2-cyclopropyl-N-(((R)-4-cyclopropyl-2,5-dioxoimidazolidin-4-yl)methyl)-3-(4-(trifluoromethyl)phenyl)propanamide | 1607004-34-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-2-cyclopropyl-N-(((R)-4-cyclopropyl-2,5-dioxoimidazolidin-4-yl)methyl)-3-(4-(trifluoromethyl)phenyl)propanamide
• 英文别名: (2S)-2-cyclopropyl-N-[[(4R)-4-cyclopropyl-2,5-dioxoimidazolidin-4-yl]methyl]-3-[4-(trifluoromethyl)phenyl]propanamide
• CAS: 1607004-34-1
• 化学式: C₂₀H₂₂F₃N₃O₃
• 分子量: 409.408
• InChiKey: JHOUEQAOHDTLPY-KXBFYZLASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  87.3
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  环丙烷乙酰氯 在 4-二甲氨基吡啶 、 双氧水 、 三乙胺 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 lithium hydroxide 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 50.0h， 生成 (S)-2-cyclopropyl-N-(((R)-4-cyclopropyl-2,5-dioxoimidazolidin-4-yl)methyl)-3-(4-(trifluoromethyl)phenyl)propanamide
  参考文献：
  名称：

  A Highly Selective Hydantoin Inhibitor of Aggrecanase-1 and Aggrecanase-2 with a Low Projected Human Dose

  摘要：

  Aggrecanase-1 and -2 (ADAMTS-4 and ADAMTS-5) are zinc metalloproteases involved in the degradation of aggrecan in cartilage. Inhibitors could provide a means of altering the progression of osteoarthritis. We report the identification of 7 which had good oral pharmacokinetics in rats and showed efficacy in a rat chemical model of osteoarthritis. The projected human dose required to achieve sustained plasma levels >= 10 times the hADAMTS-5 IC50 is 5 mg q.d.

  DOI：

  10.1021/acs.jmedchem.7b00650

文献信息

• [EN] AGGRECANASE INHIBITORS<br/>[FR] INHIBITEURS D'AGGRÉCANASE
  申请人：LILLY CO ELI

  公开号：WO2014066151A1

  公开（公告）日：2014-05-01

  The present invention provides compounds having the formula: wherein R1 is selected from methyl, ethyl, propyl, cyclopropyl, and dimethyl, or a pharmaceutically acceptable salt thereof, along with methods and intermediates for their preparation, and uses thereof.

  本发明提供具有以下结构的化合物：其中R1从甲基、乙基、丙基、环丙基和二甲基中选择，或其药学上可接受的盐，以及它们的制备方法和中间体，以及它们的用途。
• AGGRECANASE INHIBITORS
  申请人：Eli Lily and Company

  公开号：US20150218107A1

  公开（公告）日：2015-08-06

  The present invention provides compounds having the formula: wherein R 1 is selected from methyl, ethyl, propyl, cyclopropyl, and dimethyl, or a pharmaceutically acceptable salt thereof, along with methods and intermediates for their preparation, and uses thereof.

  本发明提供了具有以下式子的化合物：其中R1选自甲基、乙基、丙基、环丙基和二甲基，或其药学上可接受的盐，以及其制备方法和中间体，以及它们的用途。
• EP2912021B1
  申请人：——

  公开号：EP2912021B1

  公开（公告）日：2017-08-16
• US9206139B2
  申请人：——

  公开号：US9206139B2

  公开（公告）日：2015-12-08
• [EN] COMPOSITION AND METHODS FOR TREATING RESPIRATORY DISEASES<br/>[FR] COMPOSITIONS ET MÉTHODES POUR LE TRAITEMENT DE MALADIES RESPIRATOIRES
  申请人：ST JUDE CHILDRENS RES HOSPITAL

  公开号：WO2021214637A1

  公开（公告）日：2021-10-28

  Provided herein are compositions containing a therapeutically effective amount of at least one ADAMTS4 inhibitor, such as a specific ADAMTS4 inhibitor, and a therapeutically effective amount of at least one antibiotic, and the use of such compositions in treating an infection in a subject in need thereof. Also disclosed herein are methods for treating an infection in a subject in need thereof, by administering to the subject a therapeutically effective amount of at least one ADAMTS4 inhibitor, such as a specific ADAMTS4 inhibitor, and a therapeutically effective amount of at least one antibiotic.