N-(6-aminoxyhexyl)maleimide hydrochloride | 1378306-38-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: N-(6-aminoxyhexyl)maleimide hydrochloride
• 英文别名: 1-(6-(aminooxy)hexyl)-1H-pyrrole-2,5-dione hydrochloride；1-(6-(Aminooxy)hexyl)-1H-pyrrole-2,5-dione hydrochloride；1-(6-aminooxyhexyl)pyrrole-2,5-dione;hydrochloride
• CAS: 1378306-38-7
• 化学式: C₁₀H₁₆N₂O₃*ClH
• 分子量: 248.71
• InChiKey: XVFUFIBSMKZNKF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.78
• 重原子数：
  16
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  72.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(6-aminoxyhexyl)maleimide hydrochloride 以 水 为溶剂， 反应 0.22h， 生成 N5-((2R)-1-((carboxymethyl)amino)-3-((1-(6-((((2S,3S,4S)-5-(fluoro-18F)-2,3,4-trihydroxypentylidene)amino)oxy)hexyl)-2,5-dioxopyrrolidin-3-yl)thio)-1-oxopropan-2-yl)-L-glutamine
  参考文献：
  名称：

  [18F] -5-氟-5-脱氧核糖，一种有效的肽生物共轭配体，用于正电子发射断层扫描（PET）成像。

  摘要：

  [（18）F] -5-氟-5-脱氧核糖（[（18）F] -FDR）在温和的肽反应条件下比[（18）F] -FDG缀合快得多，为轻度和轻度的降解提供了新的前景。快速生物共轭，用于PET成像中的氟18标记。

  DOI：

  10.1039/c2cc31262j
• 作为产物：
  描述：

  1,1-Dimethylethyl N-[[6-(2,5-dihydro-2,5-dioxo-1H-pyrrol-1-yl)hexyl]oxy]carbamate 在 盐酸 作用下， 以 水 、 乙酸乙酯 为溶剂， 反应 1.0h， 以87%的产率得到N-(6-aminoxyhexyl)maleimide hydrochloride
  参考文献：
  名称：

  [18F] -5-氟-5-脱氧核糖，一种有效的肽生物共轭配体，用于正电子发射断层扫描（PET）成像。

  摘要：

  [（18）F] -5-氟-5-脱氧核糖（[（18）F] -FDR）在温和的肽反应条件下比[（18）F] -FDG缀合快得多，为轻度和轻度的降解提供了新的前景。快速生物共轭，用于PET成像中的氟18标记。

  DOI：

  10.1039/c2cc31262j

文献信息

• Efficient bioconjugation of 5-fluoro-5-deoxy-ribose (FDR) to RGD peptides for positron emission tomography (PET) imaging of αvβ3 integrin receptor
  作者：Sergio Dall'Angelo、Qingzhi Zhang、Ian N. Fleming、Monica Piras、Lutz F. Schweiger、David O'Hagan、Matteo Zanda

  DOI：10.1039/c3ob40550h

  日期：——

  The utility of 5-fluoro-5-deoxyribose (FDR) as an efficient bioconjugation agent for radiolabelling of the RGD peptides c(RGDfK) and c(RGDfC) is demonstrated. The bioconjugation is significantly superior to that achieved with 2-fluoro-2-deoxyglucose (FDG) and benefits from the location of the fluorine at C-5, and that ribose is a 5-membered ring sugar rather than a 6-membered ring. Both features favour ring opening to the aldehydic form of the sugar to promote smooth oxime ligation with aminooxy ether functionalised peptides. [18F]FDR was prepared in this study by synthesis from fluoride-18 using an automated synthesis protocol adapting that used routinely for [18F]FDG. c(RGDfK) was functionalised with an aminooxyacetyl group (Aoa) via its lysine terminus, while c(RGDfC) was functionalised with an aminooxyhexylmaleimide (Ahm) through a cysteine–maleimide conjugation. Bioconjugation of [18F]FDR to c(RGDfC)-Ahm proved to be more efficient than c(RGDfK)-Aoa (92% versus 65%). The unlabelled (19F) bioconjugates c(RGDfK)-Aoa-FDR and c(RGDfC)-Ahm-FDR were prepared and their in vitro affinity to purified integrin αvβ3 was determined. c(RGDfK)-Aoa-FDR showed the greater affinity. Purified “hot” bioconjugates c(RGDfK)-Aoa-[18F]FDR and c(RGDfC)-Ahm-[18F]FDR were assayed by incubation with MCF7, LNCaP and PC3 cell lines. In both cases the conjugated RGD peptides showed selectivity for PC3 cells, which express αvβ3 integrin, with the c(RGDfK)-Aoa-[18F]FDR demonstrating better binding, consistent with its higher in vitro affinity. The study demonstrates that [18F]FDR is an efficient bioconjugation ligand for RGD bioactive peptides.

  研究表明，5-氟-5-脱氧核糖（FDR）作为RGD肽c(RGDfK)和c(RGDfC)的放射标记高效生物偶联剂具有实用性。与2-氟-2-脱氧葡萄糖（FDG）相比，生物偶联效果显著优越，这得益于氟原子位于C-5位置，以及核糖是五元环糖而非六元环糖的特点。这两个特性有利于糖环开环形成醛式，促进与氨基氧乙基功能化肽的顺利肟连接。在本研究中，[18F]FDR通过从氟-18开始，采用适应常规[18F]FDG合成方法的自动化合成协议制备。c(RGDfK)通过其赖氨酸末端与氨基氧乙酰基（Aoa）功能化，而c(RGDfC)通过半胱氨酸-马来酰亚胺连接与氨基氧己基马来酰亚胺（Ahm）功能化。[18F]FDR与c(RGDfC)-Ahm的生物偶联证明比c(RGDfK)-Aoa更高效（92%对65%）。制备了未标记的（19F）生物偶联物c(RGDfK)-Aoa-FDR和c(RGDfC)-Ahm-FDR，并测定了它们对纯化整合素αvβ3的体外亲和力。c(RGDfK)-Aoa-FDR显示出更高的亲和力。纯化的“热”生物偶联物c(RGDfK)-Aoa-[18F]FDR和c(RGDfC)-Ahm-[18F]FDR通过与MCF7、LNCaP和PC3细胞系共孵育进行检测。两种情况下，结合的RGD肽均显示出对表达αvβ3整合素的PC3细胞的选择性，其中c(RGDfK)-Aoa-[18F]FDR显示出更好的结合效果，与其更高的体外亲和力一致。该研究表明，[18F]FDR是RGD生物活性肽的高效生物偶联配体。
• [EN] TRIOXACARCINS, TRIOXACARCIN-ANTIBODY CONJUGATES, AND USES THEREOF<br/>[FR] TRIOXACARCINES, CONJUGUÉS TRIOXACARCINE-ANTICORPS, ET LEURS UTILISATIONS
  申请人：HARVARD COLLEGE

  公开号：WO2014082065A1

  公开（公告）日：2014-05-30

  Provided herein are trioxacarcin-antibody drug conjugates of Formula (A): and pharmaceutically acceptable salts thereof, comprising at least one instance of the group - L1 -(A-L2 )a-B attached thereto, wherein a is an integer between 1 and 10, inclusive, L1 is absent or is a linking group, A is a moiety formed from the reaction of two complimentary groups (X and Y), L2 is absent or is another linking group, and B is an antibody or antibody fragment. Also provided are methods of preparing these antibody-drug conjugates, pharmaceutically acceptable compositions thereof, and methods of their use and treatment. Further provided are precursors to the trioxacarcin-antibody drug conjugates, novel trioxacarcins without an antibody conjugated thereto, pharmaceutical compositions thereof, and methods of their use and treatment.

  本文提供的是Formula（A）的三氧卡西青霉素-抗体药物偶联物及其药学上可接受的盐，其中至少包括一个-L1-（A-L2）a-B的组合，其中a是1到10之间的整数，L1不存在或是一个连接基团，A是由两个互补基团（X和Y）反应形成的基团，L2不存在或是另一个连接基团，B是抗体或抗体片段。还提供了制备这些抗体药物偶联物的方法，其药学上可接受的组成物，以及其使用和治疗的方法。此外，还提供了三氧卡西青霉素-抗体药物偶联物的前体，未与抗体偶联的新型三氧卡西青霉素，其药学上可接受的组成物，以及其使用和治疗的方法。
• Rapid synthesis of maleimide functionalized fluorine-18 labeled prosthetic group using “radio-fluorination on the Sep-Pak” method
  作者：Falguni Basuli、Xiang Zhang、Elaine M. Jagoda、Peter L. Choyke、Rolf E. Swenson

  DOI：10.1002/jlcr.3623

  日期：2018.6.30

  Following our recently published fluorine-18 labeling method, “Radio-fluorination on the Sep-Pak”, we have successfully synthesized 6-[18F]fluoronicotinaldehyde by passing a solution (1:4 acetonitrile: t-butanol) of its quaternary ammonium salt precursor, 6-(N,N,N-trimethylamino)nicotinaldehyde trifluoromethanesulfonate (2), through a fluorine-18 containing anion exchange cartridge (PS-HCO3). Over 80% radiochemical conversion was observed using 10 mg of precursor within 1 minute. The [18F]fluoronicotinaldehyde ([18F]5) was then conjugated with 1-(6-(aminooxy)hexyl)-1H-pyrrole-2,5-dione to prepare the fluorine-18 labeled maleimide functionalized prosthetic group, 6-[18F]fluoronicotinaldehyde O-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexyl) oxime, 6-[18F]FPyMHO ([18F]6). The current Sep-Pak method not only improves the overall radiochemical yield (50 ± 9%, decay-corrected, n = 9) but also significantly reduces the synthesis time (from 60-90 minutes to 30 minutes) when compared with literature methods for the synthesis of similar prosthetic groups.

  遵循我们最近发布的氟 18 标记方法“Sep-Pak 上的放射氟化”，我们通过季铵盐溶液（1:4 乙腈：叔丁醇）成功合成了 6-[18F]氟烟醛前体 6-(N,N,N-三甲氨基)烟醛三氟甲磺酸盐 (2)，通过含氟 18 的阴离子交换柱 (PS-HCO3)。使用 10 毫克前体在 1 分钟内观察到超过 80% 的放射化学转化。然后将[18F]氟烟醛([18F]5)与1-(6-(氨基氧基)己基)-1H-吡咯-2,5-二酮缀合以制备氟18标记的马来酰亚胺官能化辅基6-[ 18F]氟烟醛O-(6-(2,5-二氧代-2,5-二氢-1H-吡咯-1-基)己基)肟，6-[18F]FPyMHO ([18F]6)。与文献方法相比，当前的 Sep-Pak 方法不仅提高了总体放射化学产率（50 ± 9%，衰减校正，n = 9），而且还显着缩短了合成时间（从 60-90 分钟缩短到 30 分钟）。相似辅基的合成。
• Trioxacarcins, trioxacarcin#antibody conjugates, and uses thereof
  申请人：President and Fellows of Harvard College

  公开号：US10639381B2

  公开（公告）日：2020-05-05

  Provided herein are trioxacarcin-antibody drug conjugates of Formula (A): and pharmaceutically acceptable salts thereof, comprising at least one instance of the group -L1-(A-L2)a-B attached thereto, wherein a is an integer between 1 and 10, inclusive, L1 is absent or is a linking group, A is a moiety formed from the reaction of two complimentary groups (X and Y), L2 is absent or is another linking group, and B is an antibody or antibody fragment. Also provided are methods of preparing these antibody-drug conjugates, pharmaceutically acceptable compositions thereof, and methods of their use and treatment. Further provided are precursors to the trioxacarcin-antibody drug conjugates, novel trioxacarcins without an antibody conjugated thereto, pharmaceutical compositions thereof, and methods of their use and treatment.

  本文提供的是式 (A) 的三氧羰基霉素-抗体药物共轭物： 及其药学上可接受的盐，包含至少一个连接在其上的基团-L1-(A-L2)a-B 的实例，其中 a 是 1 至 10（包括 10）之间的整数，L1 不存在或为连接基团，A 是由两个互补基团（X 和 Y）反应形成的分子，L2 不存在或为另一个连接基团，B 是抗体或抗体片段。此外，还提供了制备这些抗体-药物共轭物的方法、其药学上可接受的组合物及其使用和治疗方法。此外，还提供了三氧嘧啶-抗体药物共轭物的前体、不含抗体的新型三氧嘧啶、其药用组合物及其使用和治疗方法。
• TRIOXACARCINS, TRIOXACARCIN-ANTIBODY CONJUGATES, AND USES THEREOF
  申请人：President and Fellows of Harvard College

  公开号：EP2922575A1

  公开（公告）日：2015-09-30