6-diazo-5-oxonorleucine

• 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: 6-diazo-5-oxonorleucine
• 英文别名: (+/-)-6-Diazo-5-oxo-norleucin；DON；Diazo-oxo-L-norleucine；(6Z)-2-amino-6-diazo-5-oxohexanoic acid
• 化学式: C₆H₉N₃O₃
• mdl: MFCD19301326
• 分子量: 171.156
• InChiKey: YCWQAMGASJSUIP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.5
• 重原子数：
  12
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  82.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-邻苯二甲酰-L-谷氨酸酐 在 甲醇 作用下， 生成 6-diazo-5-oxonorleucine
  参考文献：
  名称：

  6-Diazo-5-oxo-L-norleucine, a New Tumor-inhibitory Substance.^1a Preparation of L-, D- and DL-Forms^1b

  摘要：

  DOI：

  10.1021/ja01548a036

文献信息

• [EN] NOVEL GLUTAMINE ANTAGONISTS AND USES THEREOF<br/>[FR] NOUVEAUX ANTAGONISTES DE LA GLUTAMINE ET LEURS UTILISATIONS
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2019071110A1

  公开（公告）日：2019-04-11

  Glutamine antagonists and their use for treating oncological, immunological, and neurological diseases are disclosed. Also disclosed are methods for treating an oncological, immunological, infectious or neurological disease or disorder, the method comprising administering to a subject in need of treatment thereof a therapeutically effective amount of a glutamine antagonist of the disclosure or the pharmaceutical composition thereof. Also disclosed are methods of enhancing the effects of an immune checkpoint inhibitor, enabling a subject to respond to an immune checkpoint inhibitor, or enabling the toxicity or the dose or number of treatments with an immune checkpoint inhibitor to be reduced, comprising administering to a subject in need of treatment thereof a therapeutically effective amount of a glutamine antagonist of the disclosure or the pharmaceutical composition thereof, and an immune checkpoint inhibitor. Also disclosed are methods for treating an oncological, immunological, infectious or neurological disease or disorder that is refractory to checkpoint inhibitor therapy, the method comprising administering to a subject in need thereof, and having the refractory disease or disorder, a therapeutically effective amount of a glutamine antagonist of the disclosure or the pharmaceutical composition thereof.

  谷氨酰胺拮抗剂及其用于治疗肿瘤、免疫和神经系统疾病的方法已被披露。还披露了治疗肿瘤、免疫、传染性或神经系统疾病或紊乱的方法，该方法包括向需要治疗的受试者施用本公开的谷氨酰胺拮抗剂或其药物组成的治疗有效量。还披露了增强免疫检查点抑制剂效果的方法，使受试者对免疫检查点抑制剂产生反应，或减少免疫检查点抑制剂的毒性或剂量或治疗次数的方法，包括向需要治疗的受试者施用本公开的谷氨酰胺拮抗剂或其药物组成的治疗有效量，以及免疫检查点抑制剂。还披露了治疗对检查点抑制剂疗法无效的肿瘤、免疫、传染性或神经系统疾病或紊乱的方法，该方法包括向需要治疗的受试者施用本公开的谷氨酰胺拮抗剂或其药物组成的治疗有效量。
• INHIBITORS OF TRANSGLUTAMINASES
  申请人：Zedira GmbH

  公开号：EP3342779A1

  公开（公告）日：2018-07-04

  The invention relates to the compound of general formula (I) as novel inhibitors of transglutaminases, to methods for producing the inventive compounds, to pharmaceutical compositions containing said inventive compounds and to their use for the prophylaxis and treatment of diseases associated with transglutaminases.

  这项发明涉及通式（I）的化合物作为新型转谷氨酰胺酶抑制剂，以及生产这些创新化合物的方法，含有这些创新化合物的药物组合物，以及它们用于预防和治疗与转谷氨酰胺酶相关疾病的用途。
• [EN] METHOD OF PREPARING A DON PRODRUG FROM L-GLUTAMIC ACID<br/>[FR] PROCÉDÉ DE PRÉPARATION D'UN PROMÉDICAMENT DON À PARTIR D'ACIDE L-GLUTAMIQUE
  申请人：DRACEN PHARMACEUTICALS INC

  公开号：WO2020167831A1

  公开（公告）日：2020-08-20

  The present disclosure provides methods of preparing a compound of Formula (1): wherein R1, R2, and R3 are as defined as set forth in the application. In one embodiment, a compound of Formula (1) is prepared in >95% chemical purity and >95% enantiomeric excess.

  本公开提供了制备化合物式（1）的方法：其中R1、R2和R3如申请中所定义。在一种实施例中，化合物式（1）以>95%的化学纯度和>95%的对映体过量制备。
• [EN] SMALL MOLECULE INHIBITORS OF NEUTRAL SPHINGOMYELINASE 2 (nSMase2) FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES<br/>[FR] INHIBITEURS À PETITES MOLÉCULES DE SPHINGOMYÉLINASE 2 NEUTRE (NSMASE2) POUR TRAITER DES MALADIES NEURODÉGÉNÉRATIVES
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2018129405A1

  公开（公告）日：2018-07-12

  Small molecule inhibitors of neutral sphingomyelinase 2 (nSMase2) and their use for treating neurodegenerative diseases, such as, neurodegenerative diseases associated with high levels of ceramide, including, but not limited to Alzheimer's disease (AD), HIV-associated neurocognitive disorder (HAND), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS), and, in other aspects, for treating cancer, are provided.

  提供了针对中性鞘磷脂酶2（nSMase2）的小分子抑制剂以及它们用于治疗神经退行性疾病的方法，例如与高水平神经鞘磷脂酰胺相关的神经退行性疾病，包括但不限于阿尔茨海默病（AD）、HIV相关神经认知障碍（HAND）、多发性硬化（MS）和肌萎缩侧索硬化症（ALS），以及在其他方面用于治疗癌症。
• [EN] METHOD OF PREPARING A DON PRODRUG FROM L-PYROGLUTAMIC ACID<br/>[FR] PROCÉDÉ DE PRÉPARATION D'UN PROMÉDICAMENT DE DON À PARTIR D'ACIDE L-PYROGLUTAMIQUE
  申请人：DRACEN PHARMACEUTICALS INC

  公开号：WO2020167829A1

  公开（公告）日：2020-08-20

  The present disclosure provides a method of preparing a compound of Formula I, wherein R1 is C1-C4 alkyl; R2 is C1-C4 alkyl; and R3 is selected from the group consisting of C1-C6 alkyl, (aryl)alkyl, and (heteroaryl)alkyl in >95% chemical purity and >95% enantiomeric excess.

  本公开提供了一种制备化合物I的方法，其中R1为C1-C4烷基；R2为C1-C4烷基；R3从C1-C6烷基、(芳基)烷基和(杂环芳基)烷基组成的群体中选择，在>95%的化学纯度和>95%的对映体过量下。