Benzyl 3-(2,5-dioxo-1,3-oxazol-4-yl)propanoate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Benzyl 3-(2,5-dioxo-1,3-oxazol-4-yl)propanoate
• 英文别名: benzyl 3-(2,5-dioxo-1,3-oxazol-4-yl)propanoate
• 化学式: C₁₃H₁₁NO₅
• 分子量: 261.23
• InChiKey: ARZWXDBIWZGRAF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  82
• 氢给体数：
  0
• 氢受体数：
  5

文献信息

• Controlled Synthesis of Polyglutamates with Low Polydispersity and Versatile Architectures
  申请人：Fundacion de la Comunidad Valenciana "Centro De Investigaciones Principe Felipe

  公开号：US20150087788A1

  公开（公告）日：2015-03-26

  Polyglutamates are well known to be highly biocompatible, biodegradable and multifunctional polymers, which have been already used as building blocks in polymer drug conjugates and polymeric micelles. Those systems have been applied to various medical applications ranging from therapy to molecular imaging. Furthermore a polyglutamic acid (PGA) paclitaxel conjugate has already entered clinical studies (Opaxio™ PGA-PTX conjugate currently in phase III of Clinical trials). In this context, a synthetic pathway to a plethora functional polyglutamates (homopolymers, block-co-polymers, triblocks) with well-defined structure, adjustable molecular weight (Mw) and low dispersity (D=Mw/Mn<1.2) applying the ring opening polymerization (ROP) of N-carboxyanhydrides (NCA) has been developed. Additionally, the acid moieties of the polyglutamates can be activated with 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium (DMTMM) and various functionalities can be easily introduced by “post-polymerization modification” yielding a set orthogonal reactive attachment sides. The reactive moieties, such as azides, maleimides, thiols, alkynes (linear or cyclic) offer the opportunity of specific conjugation of the drugs, targeting moieties or markers. Besides introducing reactive groups the functionalization strategy was also used for PEGylation of PGA reducing charge induced interactions and therefore pharmacological properties, such as blood circulation time may be adjusted. In summary, a tool kit of various polyglutamates has been developed enabling the synthesis of a variety of polymer drug conjugates or polymer based imaging agents. The functional polymeric precursors developed will allow us to functionalize and therefore adjust the polymer properties to a desired application.

  多聚谷氨酸被广泛认为是高度生物相容性、可生物降解和多功能聚合物，已经被用作聚合物药物共轭物和聚合物微胞的构建模块。这些系统已被应用于从治疗到分子成像等各种医疗应用中。此外，一种聚谷氨酸（PGA）紫杉醇共轭物已经进入临床研究阶段（Opaxio™ PGA-PTX 共轭物目前处于临床试验的第三阶段）。在这种背景下，已经开发了一种合成途径，用于制备各种功能性多聚谷氨酸（同聚物、嵌段共聚物、三嵌段）具有明确定义的结构、可调节的分子量（Mw）和低分散度（D=Mw/Mn<1.2），应用 N-羧酸酐（NCA）的环开聚合（ROP）。此外，多聚谷氨酸的酸基团可以用 4-(4,6-二甲氧基-1,3,5-三嗪-2-基)-4-甲基吗啉（DMTMM）激活，并且各种功能基易于通过“后聚合物修饰”引入，产生一组正交反应附加侧。这些反应基团，如叠氮基、马来酰亚胺、硫醇、炔基（线性或环状），为药物、靶向基团或标记物的特异性共轭提供了机会。除了引入反应基团外，功能化策略还用于 PGA 的 PEG化，减少了电荷诱导的相互作用，从而可以调整药理学性质，例如血液循环时间。总之，已开发了各种多聚谷氨酸的工具包，使得能够合成各种聚合物药物共轭物或基于聚合物的成像试剂。开发的功能性聚合物前体将使我们能够对聚合物性质进行功能化调整，以适用于所需的应用。
• CONTROLLED SYNTHESIS OF POLYGLUTAMATES WITH LOW POLYDISPERSITY AND VERSATILE ARCHITECTURES
  申请人：Fundacion De La Comunidad Valenciana Centro De Investigacion Principe Felipe

  公开号：EP2772497A1

  公开（公告）日：2014-09-03

  The present invention relates to the control of the polymerization of N-carboxyanhydrides (NCAs) of alpha-amino acids via the use of non-nucleophilic salts in order to obtain highly versatile polymeric architectures with low polydispersity indexes (homopolymers, diblock polymers, triblock polymers or multiblock sustems), and also to processes for the preparation therof and the use thereof of pharmaceutical compositions. Reference is specifically made to the production of functional polyglutamates with a defined structure, adjustable molecular weight and low polydispersity (D = Ms / Mn < 1.3) by means of the ring-opening polymerization of N-carboxyanhydrides. Also, the acid groups of the polymeric chain of the polyglutamates may be activated with 4- (4,6-dimethoxy-1,3,5-trizin-2-yl)-4-methylmorpholine, which allows the incorporation of various functionalities by "post-polymerization modification", thereby forming different reactive groups in the side chains of the polymer. The remaining reagents, such as azides, maleimides, thiles or (linear or cyclic) alkynes offer the opportunity for specific conjugation and can be used for drugs, directing units or markers. Futhermore, this functionalization strategy has also been used as a polyglutamate PEGylation mechanism, which reduces possible interactions arising from the carboxyl group load and therefore allows adjustment of the pharmacological properties of each case to the use therof in drugs or molecular imaging agents with therapeutic and/or diagnostic applications.

  本发明涉及通过使用非亲核盐控制α-氨基酸的 N-羧基酸酐（NCA）的聚合，以获得具有低 分散指数的多功能聚合物结构（均聚物、二嵌段聚合物、三嵌段聚合物或多嵌段聚合 物），还涉及其制备工艺及其在药物组合物中的应用。特别要提到的是通过 N-羧基酸酐的开环聚合，生产出具有确定结构、可调分子量和低 分散性（D = Ms / Mn < 1.3）的功能性聚谷氨酸酯。此外，聚谷氨酸酯聚合物链上的酸基可以用 4-（4,6-二甲氧基-1,3,5-三嗪-2-基）-4-甲基吗啉活化，这样就可以通过 "聚合后改性 "加入各种官能团，从而在聚合物侧链中形成不同的活性基团。其余的试剂，如叠氮化物、马来酰亚胺、噻吩或（线性或环状）炔烃等，则为特定的共轭提供了机会，可用于药物、导向单元或标记。此外，这种功能化策略还被用作聚谷氨酸 PEG 化机制，可减少羧基负载可能产生的相互作用，从而调整每种情况的药理特性，使其用于具有治疗和/或诊断用途的药物或分子成像剂。
• US9623125B2
  申请人：——

  公开号：US9623125B2

  公开（公告）日：2017-04-18