卡非佐米杂质14 | 1396006-47-5

• 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
• 中文名称: 卡非佐米杂质14
• 英文名称: PR-413
• 英文别名: Carfilzomib Impurity 14；(2S)-4-methyl-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]-4-phenylbutanoyl]amino]pentanoic acid
• CAS: 1396006-47-5
• 化学式: C₂₂H₃₃N₃O₅
• 分子量: 419.521
• InChiKey: WKTVUOBKTNVUSS-OALUTQOASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  卡非佐米杂质14 、 在 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 作用下， 生成 (S)-4-methyl-N-((S,E)-4-(methylsulfonyl)-1-(p-tolyl)but-3-en-2-yl)-2-((S)-2-(2-morpholinoacetamido)-4-phenylbutanamido)pentanamide
  参考文献：
  名称：

  Defining the Determinants of Specificity of Plasmodium Proteasome Inhibitors

  摘要：

  The Plasmodium proteasome is an emerging antimalarial target due to its essential role in all the major life cycle stages of the parasite and its contribution to the establishment of resistance to artemisinin (ART)-based therapies. However, because of a similarly essential role for the host proteasome, the key property of any antiproteasome therapeutic is selectivity. Several parasite-specific proteasome inhibitors have recently been reported, however, their selectivity must be improved to enable clinical development. Here we describe screening of diverse libraries of non-natural synthetic fluorogenic substrates to identify determinants at multiple positions on the substrate that produce enhanced selectivity. We find that selection of an optimal electrophilic "warhead" is essential to enable high selectivity that is driven by the peptide binding elements on the inhibitor. We also find that host cell toxicity is dictated by the extent of coinhibition of the human beta\2 and beta 5 subunits. Using this information, we identify compounds with over 3 orders of magnitude selectivity for the parasite enzyme. Optimization of the pharmacological properties resulted in molecules that retained high potency and selectivity, were soluble, sufficiently metabolically stable and orally bioavailable. These molecules are highly synergistic with ART and can clear parasites in a mouse model of infection, making them promising leads as antimalarial drugs.

  DOI：

  10.1021/jacs.8b06656
• 作为产物：
  描述：

  Boc-L-高苯丙氨酸 在 水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 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 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 卡非佐米杂质14
  参考文献：
  名称：

  [EN] EPOXYKETONE COMPOUNDS FOR ENZYME INHIBITION
  [FR] COMPOSÉS D'ÉPOXYCÉTONE POUR L'INHIBITION D'ENZYMES

  摘要：

  公开号：

  WO2016011088A3

文献信息

• METHODS OF MAKING CARFILZOMIB AND INTERMEDIATES THEREOF
  申请人：Apicore US LLC

  公开号：US20160115198A1

  公开（公告）日：2016-04-28

  Racemization-free methods are disclosed for the synthesis of carfilzomib. Novel intermediates and methods of making carfilzomib employing fragment condensation using the novel intermediates are disclosed. Amorphous carfilzomib and methods of making same are disclosed.

  无光学异构体的方法被揭示用于合成卡菲索米。揭示了使用新型中间体进行片段缩合的方法以制备卡菲索米的新颖中间体和方法。揭示了非晶态卡菲索米和制备该物质的方法。
• [EN] AN IMPROVED PROCESSES FOR THE PREPARATION OF CARFILZOMIB OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF<br/>[FR] PROCÉDÉ PERFECTIONNÉ DE PRÉPARATION DE CARFILZOMIB OU DE SELS PHARMACEUTIQUEMENT ACCEPTABLES DE CELUI-CI
  申请人：LAURUS LABS PRIVATE LTD

  公开号：WO2016185450A1

  公开（公告）日：2016-11-24

  The present invention relates to an improved process for the preparation of carfilzomib or a pharmaceutically acceptable salt thereof. The present invention also relates to a process for the preparation of amorphous form of carfilzomib.

  本发明涉及一种改进的制备卡菲唑胺或其药学上可接受的盐的工艺。本发明还涉及一种制备卡菲唑胺非晶态形式的工艺。
• PROCESSES FOR THE PREPARATION OF CARFILZOMIB OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
  申请人：LAURUS LABS LIMITED

  公开号：US20190284231A1

  公开（公告）日：2019-09-19

  The present invention relates to an improved process for the preparation of carfilzomib or a pharmaceutically acceptable salt thereof. The present invention also relates to a process for the preparation of amorphous form of carfilzomib.

  本发明涉及一种改进的制备卡非索米或其药学上可接受的盐的方法。本发明还涉及一种制备卡非索米非晶态的方法。
• Processes for the preparation of carfilzomib or pharmaceutically acceptable salts thereof
  申请人：LAURUS LABS PRIVATE LIMITED

  公开号：US10364269B2

  公开（公告）日：2019-07-30

  The present invention relates to an improved process for the preparation of carfilzomib or a pharmaceutically acceptable salt thereof. The present invention also relates to a process for the preparation of amorphous form of carfilzomib.

  本发明涉及一种制备卡非佐米或其药学上可接受的盐的改进工艺。本发明还涉及一种制备无定形卡非佐米的工艺。
• Epoxyketone compounds for enzyme inhibition
  申请人：CENTRAX INTERNATIONAL, INC.

  公开号：US10787482B2

  公开（公告）日：2020-09-29

  The present disclosure relates to novel compounds and pharmaceutical compositions thereof which are useful as inhibitors of proteasomes. The compounds provided herein have improved proteasome potency and selectivity, and increased aqueous solubility, and are useful in treating various conditions or diseases associated with proteasomes.

  本公开涉及可用作蛋白酶体抑制剂的新型化合物及其药物组合物。本文所提供的化合物具有更好的蛋白酶体效力和选择性，以及更高的水溶性，可用于治疗与蛋白酶体相关的各种病症或疾病。