δ-Chlor-γ-oxo-DL-norvalin | 7444-55-5

• 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
• 英文名称: δ-Chlor-γ-oxo-DL-norvalin
• 英文别名: L-2-amino-4-oxo-5-chloropentoic acid；2-azaniumyl-5-chloro-4-oxopentanoate
• CAS: 7444-55-5
• 化学式: C₅H₈ClNO₃
• mdl: MFCD19232712
• 分子量: 165.576
• InChiKey: RAAUBRQLKXXMQK-UHFFFAOYSA-N

物化性质

• 沸点：
  329.2±37.0 °C(Predicted)
• 密度：
  1.400±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -3.1
• 重原子数：
  10
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  80.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-acetylamino-5-chloro-4-oxo-valeric acid ethyl ester 在 盐酸 作用下， 生成 δ-Chlor-γ-oxo-DL-norvalin
  参考文献：
  名称：

  Miyake,A., Chemical and pharmaceutical bulletin, 1960, vol. 8, p. 1079 - 1083

  摘要：

  DOI：

文献信息

• Methods and compositions for treating metabolic reprogramming disorders
  申请人：THE JOHNS HOPKINS UNIVERSITY

  公开号：US10568868B2

  公开（公告）日：2020-02-25

  The disclosure provides methods of treating a condition, disease, or disorder in a subject that involves metabolically reprogrammed cells whose activation, function, growth, proliferation, or survival depends on increased activity of at least one metabolic pathway selected from the group consisting of glutamine metabolism, glycolysis, and fatty acid synthesis, comprising administering to the subject a compound having formula (I): and the pharmaceutically acceptable salts thereof, wherein R1, R2, R2′, and X are as defined as set forth in the specification. Compounds having formula (I) are prodrugs that release glutamine analogs, e.g., 6-diazo-5-oxo-L-norleucine (DON).

  本公开提供了治疗受试者体内涉及代谢重编程细胞的病症、疾病或紊乱的方法，这些细胞的活化、功能、生长、增殖或存活依赖于至少一种选自由谷氨酰胺代谢、糖酵解和脂肪酸合成组成的组的代谢途径活性的增加，包括向受试者施用具有式（I）的化合物： 及其药学上可接受的盐，其中 R1、R2、R2′ 和 X 如说明书中所定义。具有式（I）的化合物是释放谷氨酰胺类似物的原药，例如 6-重氮-5-氧代-L-正亮氨酸（DON）。
• Methods for cancer and immunotherapy using prodrugs of glutamine analogs
  申请人：The Johns Hopkins University

  公开号：US10842763B2

  公开（公告）日：2020-11-24

  The disclosure provides methods of treating cancer in a subject or preventing a relapse or reducing the incidence of relapse of cancer in a subject in remission, comprising administering to the subject: (a) a therapeutically effective amount of an immunotherapeutic agent, e.g., an immune checkpoint blockade therapy, an adoptive cellular therapy, a marrow-infiltrating lymphocytes, an adenosine A2aR inhibitor, or an antibody; and (b) a compound having formula (I): and the pharmaceutically acceptable salts thereof, wherein R1, R2, R2′, and X are as defined as set forth in the specification. Compounds having formula (I) are prodrugs that release glutamine analogs, e.g., 6-diazo-5-oxo-L-norleucine (DON).

  本公开提供了治疗受试者癌症或预防缓解期受试者癌症复发或降低复发率的方法，包括向受试者施用：(a)治疗有效量的免疫治疗剂，如免疫检查点阻断疗法、收养细胞疗法、骨髓浸润淋巴细胞、腺苷A2aR抑制剂或抗体；和(b)具有式(I)的化合物： 及其药学上可接受的盐，其中 R1、R2、R2′ 和 X 如说明书中所定义。具有式（I）的化合物是释放谷氨酰胺类似物的原药，例如 6-重氮-5-氧代-L-正亮氨酸（DON）。
• Glutamine antagonists for the treatment of cognitive deficits and psychiatric disorders
  申请人：THE JOHNS HOPKINS UNIVERSITY

  公开号：US11110104B2

  公开（公告）日：2021-09-07

  The disclosure provides compounds having formula (I): and the pharmaceutically acceptable salts thereof, wherein R1, R2, R2′, and X are as defined as set forth in the specification, for use in treating cognitive deficits and/or psychiatric disorders, such as those associated with neurological or neurodegenerative disorders, psychiatric or mood disorders, and HIV-associated neurocognitive disorders (HAND). Compounds having formula (I) are prodrugs that release glutamine analogs, e.g., 6-diazo-5-oxo-L-norleucine (DON).

  本公开提供了具有式 (I) 的化合物： 及其药学上可接受的盐，其中R1、R2、R2′和X如说明书中所定义，用于治疗认知缺陷和/或精神障碍，例如与神经或神经退行性疾病、精神或情绪障碍以及HIV相关神经认知障碍（HAND）有关的认知缺陷和/或精神障碍。具有式（I）的化合物是释放谷氨酰胺类似物的原药，例如 6-重氮-5-氧代-L-正亮氨酸（DON）。
• SELECTIVE INHIBITION OF GLUTAMINASE BY BIS-THIADIAZOLES
  申请人：——

  公开号：US20020115698A1

  公开（公告）日：2002-08-22

  Compounds are disclosed which efficiently inhibit glutaminase but which have no effect, at higher levels, on various mechanistically and functionally related enzymes. The compounds, which are useful for neuroprotection and in treatment of hepatic encephalopathy, have the general formula I: 1 as defined further herein.

  已公开的化合物能有效抑制谷氨酰胺酶，但在较高水平上对各种机制和功能相关的酶没有影响。这些化合物可用于神经保护和肝性脑病的治疗，其通式为 I： 1 如本文进一步定义。
• Method of alleviating chronic pain via peripheral glutaminase regulation
  申请人：——

  公开号：US20030072746A1

  公开（公告）日：2003-04-17

  A composition having sustained pain-relieving properties such that the composition may be administered to a subject to alleviate chronic pain. The composition includes an effective amount of at least one glutaminase inhibitor. A method for alleviating chronic pain in a subject for an extended period of time is also disclosed, in which the compound is administered to a subject suffering from chronic pain at a site of inflammation such that the administration of the compound results in a reduction in at least one of thermal and mechanical pain responses at the site of inflammation for a period of at least two days without any resulting acute pain behavior. The composition may further include an effective amount of at least one compound having analgesic effects such that the composition also alleviates acute pain.

  一种具有持续止痛特性的组合物，可将该组合物施用给受试者以缓解慢性疼痛。该组合物包括有效量的至少一种谷氨酰胺酶抑制剂。还公开了一种在较长时间内减轻受试者慢性疼痛的方法，其中向患有炎症部位慢性疼痛的受试者施用该化合物，从而使该化合物的施用导致炎症部位的热痛和机械痛反应中的至少一种疼痛反应在至少两天的时间内减轻，而不会产生任何急性疼痛行为。该组合物可进一步包括有效量的至少一种具有镇痛作用的化合物，从而使该组合物也能减轻急性疼痛。