1-[4-Oxo-4-[4,8,11-tris[4-(2,5-dioxopyrrol-1-yl)butanoyl]-1,4,8,11-tetrazacyclotetradec-1-yl]butyl]pyrrole-2,5-dione | 1613477-13-6

• 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: 1-[4-Oxo-4-[4,8,11-tris[4-(2,5-dioxopyrrol-1-yl)butanoyl]-1,4,8,11-tetrazacyclotetradec-1-yl]butyl]pyrrole-2,5-dione
• 英文别名: 1-[4-oxo-4-[4,8,11-tris[4-(2,5-dioxopyrrol-1-yl)butanoyl]-1,4,8,11-tetrazacyclotetradec-1-yl]butyl]pyrrole-2,5-dione
• CAS: 1613477-13-6
• 化学式: C₄₂H₅₂N₈O₁₂
• 分子量: 860.921
• InChiKey: PKESRTBHFSBVTR-UHFFFAOYSA-N

物化性质

• 沸点：
  1109.6±65.0 °C(predicted)
• 密度：
  1.349±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -3.1
• 重原子数：
  62
• 可旋转键数：
  16
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  231
• 氢给体数：
  0
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  1,4,8,11-四氮杂环十四烷 、 4-马来酰亚胺丁酸 在 N-甲基吗啉 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.17h， 以48%的产率得到1-[4-Oxo-4-[4,8,11-tris[4-(2,5-dioxopyrrol-1-yl)butanoyl]-1,4,8,11-tetrazacyclotetradec-1-yl]butyl]pyrrole-2,5-dione
  参考文献：
  名称：

  A novel and facile synthesis of tetra branched derivatives of nociceptin/orphanin FQ

  摘要：

  Branched peptides have been found to be useful in several research fields however their synthesis and purification is complicated. Here we present a novel and facile synthesis of tetra branched derivatives of nociceptin/orphanin FQ (N/OFQ). Three N/OFQ tetra branched derivatives were prepared using novel cores (PWT1, PWT2 and PWT3) containing a maleimido moiety. [Cys(18)]N/OFQ-NH2 was linked to the cores via thiol-Michael reaction characterized by high yield and purity of the desired final product. In the electrically stimulated mouse vas deferens PWT-N/OFQ derivatives mimicked the inhibitory action of the natural sequence showing similar maximal effects and 3 fold higher potencies. The NOP selective antagonist SB-612111 antagonized the effects of N/OFQ and PWT derivatives with similar pKB values (8.02-8.48). In vivo after supraspinal administration PWT2-N/OFQ stimulated food intake in mice mimicking the action of N/OFQ. Compared to the natural peptide PWT2-N/OFQ was 40 fold more potent and elicited larger effects. These findings suggest that the PWT chemical strategy can be successfully applied to biologically active peptides to generate, with unprecedented high purity and yield, tetra branched derivatives displaying an in vitro pharmacological profile similar to that of the natural sequence associated, in vivo, to increased potency and effectiveness.

  DOI：

  10.1016/j.bmc.2014.05.005

文献信息

• Supramolecular aggregates comprising maleimido cores
  申请人：Ufpeptides S.r.l.

  公开号：EP2786766A1

  公开（公告）日：2014-10-08

  The invention relates to a supramolecular aggregate of formula (I) wherein A is an active substance, n is an integer from 4 to 16 and X is a core having at least four binding amino group. In a preferred embodiment the maleimido-funzionalized core X is selected from PWT1, PWT2 and PWT3. The supramolecular aggregates can be used in the field of drugs, vaccines, as ligands for GPCR, i.e. agonists as well as antagonist, as antibiotics and as diagnostics eventually in complex with radionuclides.

  本发明涉及式（I）的超分子聚合体，其中 A 是活性物质，n 是 4 至 16 的整数，X 是至少具有四个结合氨基的核心。在一个优选的实施方案中，马来酰亚胺化核心 X 选自 PWT1、PWT2 和 PWT3。超分子聚合体可用于药物、疫苗、GPCR 配体（即激动剂和拮抗剂）、抗生素以及最终与放射性核素复合的诊断。
• [EN] SUPRAMOLECULAR AGGREGATES COMPRISING MALEIMIDO CORES<br/>[FR] AGRÉGATS SUPRAMOLÉCULAIRES COMPRENANT DES NOYAUX MALÉIMIDO
  申请人：UFPEPTIDES S R L

  公开号：WO2014161926A9

  公开（公告）日：2015-12-23
• US9962447B2
  申请人：——

  公开号：US9962447B2

  公开（公告）日：2018-05-08
• A novel and facile synthesis of tetra branched derivatives of nociceptin/orphanin FQ
  作者：Remo Guerrini、Erika Marzola、Claudio Trapella、Michela Pela’、Stefano Molinari、Maria Camilla Cerlesi、Davide Malfacini、Anna Rizzi、Severo Salvadori、Girolamo Calo’

  DOI：10.1016/j.bmc.2014.05.005

  日期：2014.7

  Branched peptides have been found to be useful in several research fields however their synthesis and purification is complicated. Here we present a novel and facile synthesis of tetra branched derivatives of nociceptin/orphanin FQ (N/OFQ). Three N/OFQ tetra branched derivatives were prepared using novel cores (PWT1, PWT2 and PWT3) containing a maleimido moiety. [Cys(18)]N/OFQ-NH2 was linked to the cores via thiol-Michael reaction characterized by high yield and purity of the desired final product. In the electrically stimulated mouse vas deferens PWT-N/OFQ derivatives mimicked the inhibitory action of the natural sequence showing similar maximal effects and 3 fold higher potencies. The NOP selective antagonist SB-612111 antagonized the effects of N/OFQ and PWT derivatives with similar pKB values (8.02-8.48). In vivo after supraspinal administration PWT2-N/OFQ stimulated food intake in mice mimicking the action of N/OFQ. Compared to the natural peptide PWT2-N/OFQ was 40 fold more potent and elicited larger effects. These findings suggest that the PWT chemical strategy can be successfully applied to biologically active peptides to generate, with unprecedented high purity and yield, tetra branched derivatives displaying an in vitro pharmacological profile similar to that of the natural sequence associated, in vivo, to increased potency and effectiveness.