(5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl-6-((tert-butoxycarbonyl)amino)hexanoate | 138559-82-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl-6-((tert-butoxycarbonyl)amino)hexanoate
• 英文别名: T-Boc 5-fluoro-1N-(methyl-6-aminocaprolate)uracil；(5-Fluoro-2,4-dioxopyrimidin-1-yl)methyl 6-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoate
• CAS: 138559-82-7
• 化学式: C₁₆H₂₄FN₃O₆
• 分子量: 373.381
• InChiKey: ZTUHJUCDUDDXSI-UHFFFAOYSA-N

物化性质

• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  26
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  114
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl-6-((tert-butoxycarbonyl)amino)hexanoate 在 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 9.5h， 生成 (5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl-6-((S)-2-((2S,3R)-3-amino-2-hydroxy-4-phenylbutanamido)-4-methylpentanamido)hexanoate hydrochloride
  参考文献：
  名称：

  Synthesis and biological characterization of ubenimex-fluorouracil conjugates for anti-cancer therapy

  摘要：

  Previously a novel ubenimex-fluorouracil (5-FU) conjugate, BC-01 was identified and validated as a potent CD13 inhibitor with marked in vitro and in vivo antitumor potency. Herein, further structural modifications of the linker part of BC-01 was carried out to get more potent and stable ubenimex -fluorouracil conjugates. It was striking that most of these conjugates showed even more potent CD13 inhibitory activities than BC-01 and the approved CD13 inhibitor ubenimex. One representative compound 12a displayed significant in vitro anti-proliferation, pro-apoptosis, anti-metastasis, anti-angiogenesis and CD13(+) cell elimination effects. In vitro stability and in vivo pharmacokinetic study revealed that compound 12a could release ubenimex and 5-FU slowly, which could act as a mutual prodrug of ubenimex and 5-FU. Compared with 5-FU or 5-FU plus ubenimex, 12a exhibited superior in vivo antitumor growth efficiency, even in our mice model of 5-FU-resistant liver cancer. Moreover, 12a exhibited more potent in vivo anti-metastasis and lifespan extension effects compared to the approved 5-FU prodrug capecitabine. Collectively, these results suggest that further optimization and evaluation of 12a as a promising anticancer candidate are warranted to develop effective therapeutic agents for human liver cancer. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.11.074
• 作为产物：
  描述：

  叔丁氧羰酰基6-氨基己酸 在 四丁基硫酸氢铵 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl-6-((tert-butoxycarbonyl)amino)hexanoate
  参考文献：
  名称：

  [EN] METHODS OF TREATING A SUBJECT AND RELATED PARTICLES, POLYMERS AND COMPOSITIONS
  [FR] MÉTHODES DE TRAITEMENT D'UN SUJET ET PARTICULES, POLYMÈRES ET COMPOSITIONS À CET EFFET

  摘要：

  本文描述了一种利用聚合物-药剂颗粒和环糊精聚合物药剂共轭物组合治疗受试者的方法。本文中的方法可用于治疗被诊断患有癌症、心血管疾病、自身免疫性疾病或炎症性疾病的受试者。本文还描述了包含聚合物-药剂颗粒和环糊精聚合物药剂共轭物的组合物、剂型和配套工具。

  公开号：

  WO2012044832A1

文献信息

• CYCLODEXTRIN-BASED POLYMERS FOR THERAPEUTIC DELIVERY
  申请人：Cerulean Pharma Inc.

  公开号：US20130196906A1

  公开（公告）日：2013-08-01

  Provided are methods relating to the use of CDP-therapeutic agent conjugates for the treatment of a disease or disorder, e.g., autoimmune disease, inflammatory disease, central nervous system disorder, cardiovascular disease, or metabolic disorder. Also provided are CDP-therapeutic agent conjugates, particles comprising CDP-therapeutic agent conjugates, and compositions comprising CDP-therapeutic agent conjugates.

  提供了关于使用CDP-治疗剂偶联物治疗疾病或紊乱的方法，例如自身免疫疾病、炎症性疾病、中枢神经系统紊乱、心血管疾病或代谢紊乱。还提供了CDP-治疗剂偶联物、包含CDP-治疗剂偶联物的颗粒以及包含CDP-治疗剂偶联物的组合物。
• COMPOSITIONS AND METHODS FOR TREATMENT OF AUTOIMMUNE AND OTHER DISEASE
  申请人：CERULEAN PHARMA INC.

  公开号：US20180193486A1

  公开（公告）日：2018-07-12

  Provided are methods relating to the use of CDP-therapeutic agent conjugates for the treatment of autoimmune disease, inflammatory disease, or cancer. Also provided are CDP-therapeutic agent conjugates, particles comprising CDP-therapeutic agent conjugates, and compositions comprising CDP-therapeutic agent conjugates.

  提供了关于使用CDP-治疗剂偶联物治疗自身免疫疾病、炎症性疾病或癌症的方法。还提供了CDP-治疗剂偶联物、包含CDP-治疗剂偶联物的颗粒以及包含CDP-治疗剂偶联物的组合物。
• METHODS OF TREATING A SUBJECT AND RELATED PARTICLES, POLYMERS AND COMPOSITIONS
  申请人：Fetzer Oliver S.

  公开号：US20120213854A1

  公开（公告）日：2012-08-23

  Described herein are methods for treating a subject with combinations of polymer-agent particles and cyclodextrin polymer agent conjugates. The methods herein may be used to treat subjects identified with cancer, cardiovascular disorders, autoimmune disorders, or inflammatory disorders. Also described herein are compositions, dosage forms, and kits comprising polymer-agent particles and cyclodextrin polymer agent conjugates.

  本文介绍了使用聚合物-药剂颗粒和环糊精聚合物药剂共轭物的组合治疗方法来治疗患有癌症、心血管疾病、自身免疫性疾病或炎症性疾病的受试者。本文还描述了包含聚合物-药剂颗粒和环糊精聚合物药剂共轭物的组合物、剂型和套装。
• COMPOSITIONS AND METHODS FOR TREATMENT OF AUTOIMMUNE AND OTHER DISEASES
  申请人：Cerulean Pharma Inc.

  公开号：EP3566719A1

  公开（公告）日：2019-11-13

  Provided are methods relating to the use of CDP-therapeutic agent conjugates for the treatment of autoimmune disease, inflammatory disease, or cancer. Also provided are CDP-therapeutic agent conjugates, particles comprising CDP-therapeutic agent conjugates, and compositions comprising CDP-therapeutic agent conjugates.

  本文提供了有关使用 CDP-治疗剂共轭物治疗自身免疫性疾病、炎症性疾病或癌症的方法。还提供了 CDP-治疗剂共轭物、包含 CDP-治疗剂共轭物的颗粒和包含 CDP-治疗剂共轭物的组合物。
• US20140255374A1
  申请人：——

  公开号：US20140255374A1

  公开（公告）日：2014-09-11