pregn-4-ene-3,20-dione 3-O-(L-valine)-E-oxime | 1185297-01-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: pregn-4-ene-3,20-dione 3-O-(L-valine)-E-oxime
• 英文别名: 3-valine-E-oxime-progesterone；(3Z)-Pregn-4-ene-3,20-dione 3-[O-[(2S)-2-amino-3-methyl-1-oxobutyl]oxime]；[(E)-[(8S,9S,10R,13S,14S,17S)-17-acetyl-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-ylidene]amino] (2S)-2-amino-3-methylbutanoate
• CAS: 1185297-01-1
• 化学式: C₂₆H₄₀N₂O₃
• 分子量: 428.615
• InChiKey: JFIPYWOCXPCAFX-NPRMJFGVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  81.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  pregn-4-ene-3,20-dione 3-O-(L-valine)-E-oxime 在 盐酸 作用下， 以 乙醚 为溶剂， 生成 (S)-1-((E)-((8S,9S,10R,13S,14S,17S)-17-acetyl-10,13-dimethyl-7,8,9,11-tetrahydro-1H-cyclopenta[a]phenanthren-3(2H,6H,10H,12H,13H,14H,15H,16H,17H)-ylidene)aminooxy)-2-amino-3-methylbutan-1-one hydrochloride
  参考文献：
  名称：

  Development and Screening of Water-Soluble Analogues of Progesterone and Allopregnanolone in Models of Brain Injury

  摘要：

  Preclinical and clinical research findings have revealed that the hormone progesterone, when acutely administered, can dramatically reduce cerebral edema, inflammation, tissue necrosis, and programmed cell death following traumatic brain injury (TBI). The poor aqueous solubility of progesterone, however, limits its potential use as a therapeutic. Several chemically novel analogues of progesterone and its natural metabolite allopregnanolone have been synthesized and screened using both in vitro and whole animal models of TBI. The new derivatives demonstrated greatly improved solubility and select compounds have shown equivalent effectiveness to progesterone in reducing cerebral edema after TBI.

  DOI：

  10.1021/jm900712n
• 作为产物：
  描述：

  tert-butyl (S)-1-((E)-((8S,9S,10R,13S,14S,17S)-17-acetyl-10,13-dimethyl-7,8,9,11-tetrahydro-1H-cyclopenta[a]phenanthren-3 (2H,6H,10H,12H,13H,14H,15H,16H,17H)-ylidene)aminooxy)-3-methyl-1-oxobutan-2-ylcarbamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.25h， 生成 pregn-4-ene-3,20-dione 3-O-(L-valine)-E-oxime
  参考文献：
  名称：

  Water-Soluble Progesterone Analogues Are Effective, Injectable Treatments in Animal Models of Traumatic Brain Injury

  摘要：

  After more than 30 years of research and 30 failed clinical trials with as many different treatments, progesterone is the first agent to demonstrate robust clinical efficacy as a treatment for traumatic brain injuries. It is currently being investigated in two, independent phase III clinical trials in hospital settings; however, it presents a formidable solubility challenge that has so far prevented the identification of a formulation that would be suitable for emergency field response use or battlefield situations. Accordingly, we have designed and tested a novel series of water-soluble analogues that address this critical need. We report here the synthesis of C-20 oxime conjugates of progesterone as therapeutic agents for traumatic brain injuries with comparable efficacy in animal models of traumatic brain injury and improved solubility and pharmacokinetic profiles. Pharmacodynamic analysis reveals that a nonprogesterone steroidal analogue may be primarily responsible for the observed activity.

  DOI：

  10.1021/ml200303r

文献信息

• PROGESTERONE ANALOGS AND USES RELATED THERETO
  申请人：Emory University

  公开号：US20130210785A1

  公开（公告）日：2013-08-15

  This disclosure relates to progesterone derivatives and uses related thereto. In certain embodiments, the disclosure relates to compounds disclosed herein and uses for managing inflammation resulting from traumatic brain injury or stroke.

  该披露涉及孕酮衍生物及其相关用途。在某些实施例中，该披露涉及本文披露的化合物及其用途，用于管理由创伤性脑损伤或中风引起的炎症。
• METHODS OF NEUROPROTECTION USING NEUROPROTECTIVE STEROIDS AND A VITAMIN D
  申请人：Stein Donald G.

  公开号：US20110306579A1

  公开（公告）日：2011-12-15

  Described herein are compositions and methods for treating or preventing nervous system injury. In particular, the methods and compositions relate to the use of at least one neuroprotective steroid, such as progesterone, and vitamin D.

  本文描述了用于治疗或预防神经系统损伤的组合物和方法。具体而言，这些方法和组合物涉及使用至少一种神经保护类固醇，如孕激素，和维生素D。
• STEROID ANALOGUES FOR NEUROPROTECTION
  申请人：Macnevin Christopher

  公开号：US20110263553A1

  公开（公告）日：2011-10-27

  Provided are steroid analogues functionalized with polar substituents at the C3 and/or C20 positions of the steroid ring system that exhibit improved water solubility. Also provided are pharmaceutical compositions comprising the steroid analogues and methods using the novel steroid analogues for the treatment and prevention of neurodegeneration in a patient following injury to the central nervous system.

  提供的是具有带极性取代基的类固醇类似物，这些取代基位于类固醇环系统的C3和/或C20位置，具有改善的水溶性。还提供了包含这些类固醇类似物的药物组合物，以及使用新型类固醇类似物治疗和预防中枢神经系统损伤后患者的神经退行性疾病的方法。
• Progesterone Phosphate Analogs and Uses Related Thereto
  申请人：EMORY UNIVERSITY

  公开号：US20160194351A1

  公开（公告）日：2016-07-07

  This disclosure relates to progesterone phophate derivatives and uses related thereto. In certain embodiments, the disclosure relates to compounds disclosed herein and uses for managing inflammation such as those resulting from traumatic brain injury or stroke.

  本公开涉及孕酮磷酸酯衍生物及其相关用途。在某些实施例中，本公开涉及本文所披露的化合物及其用于管理炎症，例如由创伤性脑损伤或中风引起的炎症。
• Steroid analogues for neuroprotection
  申请人：Emory University

  公开号：US10716795B2

  公开（公告）日：2020-07-21

  Provided are steroid analogues functionalized with polar substituents at the C3 and/or C20 positions of the steroid ring system that exhibit improved water solubility. Also provided are pharmaceutical compositions comprising the steroid analogues and methods using the novel steroid analogues for the treatment and prevention of neurodegeneration in a patient following injury to the central nervous system.

  本发明提供了在类固醇环系统的 C3 和/或 C20 位上用极性取代基进行官能化的类固醇类似物，这些类固醇类似物具有更好的水溶性。还提供了包含这些类固醇类似物的药物组合物，以及使用这些新型类固醇类似物治疗和预防中枢神经系统损伤后患者神经变性的方法。