AMXT1501 | 441022-64-6

• 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: AMXT1501
• 英文别名: D-lys-ε-(palmitoyl)-N¹-spermine；C3Zum5A33F；N-[(5R)-5-amino-6-[3-[4-(3-aminopropylamino)butylamino]propylamino]-6-oxohexyl]hexadecanamide
• CAS: 441022-64-6
• 化学式: C₃₂H₆₈N₆O₂
• 分子量: 568.931
• InChiKey: USNCWPSRPOWEBG-SSEXGKCCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  40
• 可旋转键数：
  32
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  134
• 氢给体数：
  6
• 氢受体数：
  6

制备方法与用途

AMXT-1501（包括AMXT 1501和AMXT1501）是一种新型有效的多胺转运抑制剂，与DFMO联合使用可协同降低神经母细胞瘤（NB）细胞的活力；能够完全阻断多种NB细胞系中放射性标记的亚精胺摄取，并且AMXT-1501和DFMO的组合可以协同减少BE(2)-C和KELLY等细胞系中的集落形成。联合治疗导致视网膜母细胞瘤蛋白（Rb）的低磷酸化，表明通过神经母细胞瘤中G1期细胞周期停滞实现生长抑制；同时能够抑制多胺合成和摄取，从而减少肿瘤进展并延长与DFMO组合的小鼠模型中的存活时间。此外，AMXT-1501已进入实体瘤的I期临床试验阶段。

反应信息

• 作为反应物：
  描述：

  AMXT1501 、 正癸酸 以 甲醇 为溶剂， 反应 0.01h， 以0.97%的产率得到AMXT 1501 dicaprate
  参考文献：
  名称：

  生物可用多胺

  摘要：

  本文公开阳离子质子化多胺医药剂和阴离子有机羧酸酯的医药盐，所述阴离子有机羧酸酯在呈质子化形式时具有疏水性，所述医药盐尤其适于口服给予，其中这些盐的固体剂型具有良好的生物可用性并且可以用于治疗癌症以及所述医药剂所预期用于的其它医学病状。

  公开号：

  CN109069594B
• 作为产物：
  描述：

  {(R)-1-[3-(tert-Butoxycarbonyl-{4-[tert-butoxycarbonyl-(3-tert-butoxycarbonylamino-propyl)-amino]-butyl}-amino)-propylcarbamoyl]-5-hexadecanoylamino-pentyl}-carbamic acid tert-butyl ester 在 盐酸 作用下， 以 甲醇 为溶剂， 生成 AMXT1501
  参考文献：
  名称：

  Lysine–spermine conjugates: hydrophobic polyamine amides as potent lipopolysaccharide sequestrants

  摘要：

  Lipopolysaccharides (LPS), otherwise termed `endotoxins' are outer-membrane constituents of Gram-negative bacteria. Lipopolysaccharides play a key role in the pathogenesis of `Septic Shock', a major cause of mortality in the critically ill patient. Therapeutic options aimed at limiting downstream systemic inflammatory processes by targeting lipopolysaccharide do not exist at the present time. We have defined the pharmacophore necessary for small molecules to specifically bind and neutralize LPS and, using animal models of sepsis, have shown that the sequestration of circulatory LPS by small molecules is a therapeutically viable strategy. In this paper, the interactions of a focused library of lysine-spermine conjugates with lipopolysaccharide (LPS) have been characterized. Lysine-spermine conjugates with the epsilon-amino terminus of the lysinyl moiety derivatized with long-chain aliphatic hydrophobic substituents in acyl or alkyl linkage bind and neutralize bacterial lipopolysaccharides, and may be of use in the prevention or treatment of endotoxic shock states. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.01.038

文献信息

• MITOGUAZONE FOR PREVENTING THE RELAPSE OR THE PROGRESSION OF MULTIPLE SCLEROSIS
  申请人：Pathologica LLC

  公开号：EP3831372A1

  公开（公告）日：2021-06-09

  Disclosed herein are new oral pharmaceutical compositions of SAMDC inhibitors, polyamine analogs, and polyamine biosynthesis inhibitors, and their application for the treatment of conditions including demyelinating diseases, autoimmune disorders affecting the nervous system, and other neurodegenerative conditions.

  本文公开了SAMDC抑制剂、多胺类似物和多胺生物合成抑制剂的新型口服药物组合物，以及它们在治疗脱髓鞘疾病、影响神经系统的自身免疫性疾病和其他神经退行性疾病等疾病中的应用。
• Methods and compositions for treatment of demyelinating diseases
  申请人：Pathologica LLC

  公开号：US10350178B2

  公开（公告）日：2019-07-16

  Disclosed herein is a method of prevention of progression of a multiple sclerosis in a patient, comprising the administration of methylglyoxal bis(guanylhydrazone) (MGBG) to the patient in need thereof. Also disclosed herein is a method of prevention or reduction in severity of the initiation phase of autoimmune response in a patient having multiple sclerosis, comprising the administration of MGBG to the patient in need thereof.

  本文公开了一种预防多发性硬化症患者病情恶化的方法，包括向有需要的患者施用甲基乙二醛双（鸟苷酸腙）（MGBG）。本文还公开了一种预防多发性硬化症患者自身免疫反应起始阶段或减轻其严重程度的方法，包括对有需要的患者施用 MGBG。
• Bioavailable polyamines
  申请人：AMINEX THERAPEUTICS INC.

  公开号：US10632145B2

  公开（公告）日：2020-04-28

  Disclosed herein are pharmaceutical salts of a cationic protonated polyamine pharmaceutical agent and an anionic organic carboxylate which is hydrophobic when in protonated form, particularly suited for oral administration, where these salts have good bioavailability in solid dosage forms and may be used in the treatment of cancer and other medical conditions for which the pharmaceutical agent is intended.

  本文公开了阳离子质子化多胺药剂和阴离子有机羧酸盐的药剂盐，后者在质子化形式时具有疏水性，特别适合口服给药，这些盐在固体剂型中具有良好的生物利用度，可用于治疗癌症和药剂所针对的其他病症。
• BIOAVAILABLE POLYAMINES
  申请人：Aminex Therapeutics, Inc.

  公开号：EP3432914B1

  公开（公告）日：2020-09-23
• PHARMACEUTICAL FOR ORAL DELIVERY COMPRISING MGBG AND METHODS OF TREATING DISEASE
  申请人：McKearn John

  公开号：US20110112199A1

  公开（公告）日：2011-05-12

  Disclosed herein are new oral pharmaceutical compositions of MGBG and related polyamine analogs, polyamine biosynthesis inhibitors, polyamine inhibitors of AMD-I and regulators of osteopontin, and their application for the treatment of disease.