2-(5-氟戊基)-2-甲基丙二酸 | 1216897-16-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: 2-(5-氟戊基)-2-甲基丙二酸
• 英文名称: (5-fluoropentyl)(methyl)propanedioic acid
• 英文别名: 2-(5-fluoropentyl)-2-methylmalonic acid；5-fluoropentyl-2-methyl-malonic acid；ML-10；2-(5-fluoropentyl)-2-methylpropanedioic acid
• CAS: 1216897-16-3
• 化学式: C₉H₁₅FO₄
• 分子量: 206.214
• InChiKey: BOYGOAXVKOOCKN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  14
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  74.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  di-tert-butyl 2-(5-hydroxypentyl)-2-methylmalonate 在 水 、 triethylamine tris(hydrogen fluoride) 、 三乙胺 、 ethanaminium,N-(difluoro-λ⁴-sulfanylidene)-N-ethyl-,tetrafluoroborate 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 24.5h， 生成 2-(5-氟戊基)-2-甲基丙二酸
  参考文献：
  名称：

  Detection of apoptosis by PET/CT with the diethyl ester of [18F]ML-10 and fluorescence imaging with a dansyl analogue

  摘要：

  The diethyl ester of [F-18]ML-10 is a small molecule apoptotic PET probe for cancer studies. Here we report a novel multi-step synthesis of the diethyl ester of ML-10 in excellent yields via fluorination using Xtal-Fluor-E. In addition, a one-pot radiosynthesis of the diethyl ester of [F-18]ML-10 from nucleophilic [F-18]fluoride was completed in 23% radiochemical yield (decay corrected). The radiochemical purity of the product was >= 99%. The diethyl ester of [F-18]ML-10 was used in vivo to detect apoptosis in the testes of mice. In parallel studies, the dansyl-ML-10 diethyl ester was prepared and used to detect apoptotic cells in an in vitro cell based assay. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.11.019

文献信息

• [EN] NOVEL TARGETING AGENTS FOR DIAGNOSTIC AND THERAPEUTIC INDICATIONS<br/>[FR] NOUVEAUX AGENTS DE CIBLAGE POUR INDICATIONS DIAGNOSTIQUES ET THÉRAPEUTIQUES
  申请人：APOSENSE LTD

  公开号：WO2013150534A1

  公开（公告）日：2013-10-10

  The invention relates to compounds and use thereof in the diagnosis and/or in treatment of medical disorders. In some embodiments, the compounds may be used for detecting a cancer. The compound may include a di-acid moiety. In some embodiments the di-acid moiety comprises a di-carboxylic acid and in some embodiments the di- acid moiety comprises a di-tetrazole.

  该发明涉及化合物及其在诊断和/或治疗医疗疾病中的用途。在某些实施例中，这些化合物可用于检测癌症。该化合物可能包括二酸基团。在某些实施例中，二酸基团包括二羧酸，而在某些实施例中，二酸基团包括二四唑。
• Microfluidic radiosynthesis and biodistribution of [¹⁸F] 2-(5-fluoro-pentyl)-2-methyl malonic acid
  作者：Gajanan K. Dewkar、Gobalakrishnan Sundaresan、Narottam Lamichhane、Jerry Hirsch、Celina Thadigiri、Thomas Collier、Matthew C. T. Hartman、Ganesan Vaidyanthan、Jamal Zweit

  DOI：10.1002/jlcr.3016

  日期：2013.5.15

  Microfluidics technology has emerged as a powerful tool for the radiosynthesis of positron emission tomography (PET) and single-photon emission computed tomography radiolabeled compounds. In this work, we have exploited a continuous flow microfluidic system (Advion, Inc., USA) for the [18F]-fluorine radiolabeling of the malonic acid derivative, [18F] 2-(5-fluoro-pentyl)-2-methyl malonic acid ([18F]-FPMA), also known as [18F]-ML-10, a radiotracer proposed as a potential apoptosis PET imaging agent. The radiosynthesis was developed using a new tosylated precursor. Radiofluorination was initially optimized by manual synthesis and served as a basis to optimize reaction parameters for the microfluidic radiosynthesis. Under optimized conditions, radio-thin-layer chromatography analysis showed 79% [18F]-fluorine incorporation prior to hydrolysis and purification. Following hydrolysis, the [18F]-FPMA was purified by C18 Sep-Pak, and the final product was analyzed by radio-HPLC (high-performance liquid chromatography). This resulted in a decay-corrected 60% radiochemical yield and ≥98% radiochemical purity. Biodistribution data demonstrated rapid blood clearance with less than 2% of intact [18F]-FPMA radioactivity remaining in the circulation 60 min post-injection. Most organs showed low accumulation of the radiotracer, and radioactivity was predominately cleared through kidneys (95% in 1 h). Radio-HPLC analysis of plasma and urine samples showed a stable radiotracer at least up to 60 min post-injection.

  微流体技术已成为正电子发射断层扫描（PET）和单光子发射计算机断层扫描放射性标记化合物放射合成的强大工具。在这项工作中，我们利用连续流动微流体系统（Advion, Inc., USA）对马来酸衍生物[18F] 2-(5-氟戊基)-2-甲基马来酸（[18F]-FPMA），即[18F]-ML-10的[18F]氟标记进行了探索，这是一种被提议作为潜在凋亡PET成像剂的放射性示踪剂。放射合成采用了一种新的磷酸酯前体进行开发。通过手动合成初步优化了氟化反应，并作为优化微流体放射合成反应参数的基础。在优化条件下，放射薄层色谱分析显示在水解和纯化之前的[18F]-氟掺入率为79%。水解后，通过C18 Sep-Pak对[18F]-FPMA进行了纯化，最终产品通过放射性高效液相色谱（radio-HPLC）进行了分析，得到了校正后的60%放射化学产率和≥98%的放射化学纯度。生物分布数据显示，注射后60分钟内血液中剩余完整[18F]-FPMA放射性不足2%，表明快速清除。大多数器官对放射性示踪剂的积累较低，放射性主要通过肾脏排除（1小时内清除率为95%）。对血浆和尿液样品的放射性HPLC分析显示，放射性示踪剂在注射后至少稳定存在60分钟。
• METHOD FOR PRODUCTION OF SUBSTITUTED ALKYL MALONIC ESTERS AND DERIVATIVES THEREOF
  申请人：Friedman Gad

  公开号：US20120029223A1

  公开（公告）日：2012-02-02

  Substituted alkyl methyl malonate compounds are produced in an essentially one step method, the method suitable for large scale production of alkyl malonate compounds. According to one embodiment the method comprises reacting a methyl malonate with a di-functional, doubly tosylated, alkyl chain.

  取代烷基甲基丙二酸酯化合物是通过基本上一步法制备的，该方法适用于大规模生产烷基丙二酸酯化合物。根据一种实施方式，该方法包括将甲基丙二酸酯与双官能团、双甲苯磺酸酯化的烷基链反应。
• [EN] METHOD FOR PRODUCTION OF SUBSTITUTED ALKYL MALONIC ESTERS AND DERIVATIVES THEREOF<br/>[FR] PROCÉDÉ POUR LA PRODUCTION D'ESTERS ALKYLIQUES DE L'ACIDE MALONIQUE SUBSTITUÉS ET DE DÉRIVÉS DE CEUX-CI
  申请人：APOSENSE LTD

  公开号：WO2012014195A1

  公开（公告）日：2012-02-02

  Substituted alkyl methyl malonate compounds are produced in an essentially one step method, the method suitable for large scale production of alkyl malonate compounds. According to one embodiment the method comprises reacting a methyl malonate with a di-functional, doubly tosylated, alkyl chain.

  替代烷基甲基丙二酸酯化合物是在基本上一步法中生产的，该方法适用于大规模生产烷基丙二酸酯化合物。根据一种实施例，该方法包括将甲基丙二酸酯与双官能团、双重对甲苯磺酸酯化的烷基链反应。
• NOVEL TARGETING AGENTS FOR DIAGNOSTIC AND THERAPEUTIC INDICATIONS
  申请人：APOSENSE LTD.

  公开号：US20150064111A1

  公开（公告）日：2015-03-05

  The invention relates to compounds and use thereof in the diagnosis and/or in treatment of medical disorders. In some embodiments, the compounds may be used for detecting a cancer. The compound may include a di-acid moiety. In some embodiments the di-acid moiety comprises a di-carboxylic acid and in some embodiments the di-acid moiety comprises a di-tetrazole.

  本发明涉及化合物及其在诊断和/或治疗医学疾病中的用途。在某些实施例中，该化合物可以用于检测癌症。该化合物可以包括二酸基团。在某些实施例中，二酸基团包括二羧酸基团，在某些实施例中，二酸基团包括二四氮唑基团。