3-[6-[[2-[4,7,10-Tris[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,4,7,10-tetrazacyclododec-1-yl]acetyl]amino]hexanoylamino]pentanedioic acid | 1128109-44-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3-[6-[[2-[4,7,10-Tris[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,4,7,10-tetrazacyclododec-1-yl]acetyl]amino]hexanoylamino]pentanedioic acid
• CAS: 1128109-44-3
• 化学式: C₃₉H₇₀N₆O₁₂
• 分子量: 815.018
• InChiKey: RCOPVDSBQDJRGA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3
• 重原子数：
  57
• 可旋转键数：
  25
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  225
• 氢给体数：
  4
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  pentixather 、 3-[6-[[2-[4,7,10-Tris[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,4,7,10-tetrazacyclododec-1-yl]acetyl]amino]hexanoylamino]pentanedioic acid 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成
  参考文献：
  名称：

  Design, Synthesis, and Functionalization of Dimeric Peptides Targeting Chemokine Receptor CXCR4

  摘要：

  The chemokine receptor CXCR4 is a critical regulator of inflammation and immune surveillance, and it is specifically implicated in cancer metastasis and HIV-1 infection. On the basis of the observation that several of the known antagonists remarkably share a C-2 symmetry element, we constructed symmetric dimers with excellent antagonistic activity using a derivative of a cyclic pentapeptide as monomer. To optimize the binding affinity, we investigated the influence of the distance between the monomers and the pharmacophoric sites in the synthesized constructs. The affinity studies in combination with docking computations support a two-site binding model. In a final step, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was introduced as chelator for (radio-)metals, thus allowing to exploit these compounds as a new group of CXCR4-binding peptidic probes for molecular imaging and endoradiotherapeutic purposes. Both the DOTA conjugates and some of their corresponding metal complexes retain good CXCR4 affinity, and one Ga-68 labeled compound was studied as PET tracer.

  DOI：

  10.1021/jm2009716

文献信息

• CANCER IMAGING AND TREATMENT
  申请人：Technische Universitat Munchen

  公开号：US20140039153A1

  公开（公告）日：2014-02-06

  A compound, or a pharmaceutically acceptable salt or ester thereof, comprises the structure: [(P1-S1 j ) p -L-(S2 q -P2) r ] t wherein: P1 and P2, which may be the same or different, are cyclic oligopeptide moieties, at least one of P1 and P2 having the motif B-Arg or B-(Me)Arg within the cyclic moiety, wherein B is a basic amino acid, a derivative thereof, or phenylalanine or a derivative thereof; S1 and S2 are spacer groups, which may be the same or different; L is a linker moiety containing at least two functional groups for attachment of the cyclic oligopeptides or spacer groups; n and q are independently 0 or 1; p and r are independently integers of 1 or more; and t is an integer of 1 or more, provided that, when t, p or r is greater than 1, the cyclic oligopeptide moiety, spacer group and/or the value of j or q may be the same or different between the multiple (P1-S1 j ) moieties or multiple (S2 q -P2) moieties.

  一种化合物，或其药用可接受的盐或酯，包括结构：[(P1-S1j)p-L-(S2q-P2)r]t其中：P1和P2，可能相同或不同，是环状寡肽基团，P1和P2中至少一个具有环状基团内的B-Arg或B-(Me)Arg基序，其中B是一种碱性氨基酸，其衍生物，苯丙氨酸或其衍生物；S1和S2是间隔基团，可能相同或不同；L是一个连接基团，含有至少两个功能基团，用于连接环状寡肽基团或间隔基团；n和q独立地为0或1；p和r独立地为1或更多的整数；t是1或更多的整数，但当t、p或r大于1时，环状寡肽基团、间隔基团和/或j或q的值在多个(P1-S1j)基团或多个(S2q-P2)基团之间可能相同或不同。
• Cancer Imaging and Treatment
  申请人：Wester Hans Jürgen

  公开号：US20100240072A1

  公开（公告）日：2010-09-23

  A compound, or a pharmaceutically acceptable salt or ester thereof, comprises the structure: [(P1-S1 j ) p -L-(S2 q -P2) r ] t wherein: P1 and P2, which may be the same or different, are cyclic oligopeptide moieties, at least one of P1 and P2 having the motif B-Arg or B-(Me) Arg within the cyclic moiety, wherein B is a basic amino acid, a derivative thereof, or phenylalanine or a derivative thereof; S1 and S2 are spacer groups, which may be the same or different; L is a linker moiety containing at least two functional groups for attachment of the cyclic oligopeptides or spacer groups; n and q are independently 0 or 1; p and r are independently integers of 1 or more; and t is an integer of 1 or more, provided that, when t, p or r is greater than 1, the cyclic oligopeptide moiety, spacer group and/or the value of j or q may be the same or different between the multiple (P1-S1 j ) moieties or multiple (S2 q -P2) moieties.

  该化合物或其药学上可接受的盐或酯包括结构：[(P1-S1j)p-L-(S2q-P2)r]t，其中：P1和P2可以相同也可以不同，是环状寡肽基团，其中至少一个P1和P2在环状基团内具有B-Arg或B-(Me) Arg基序，其中B是一种碱性氨基酸，其衍生物，苯丙氨酸或其衍生物；S1和S2是间隔基团，可以相同也可以不同；L是一个连接基团，含有至少两个功能基团，用于连接环状寡肽或间隔基团；n和q独立地为0或1；p和r独立地为1或更多的整数；t是1或更多的整数，但当t，p或r大于1时，环状寡肽基团，间隔基团和/或j或q的值可能在多个（P1-S1j）基团或多个（S2q-P2）基团之间相同或不同。
• Design, Synthesis, and Functionalization of Dimeric Peptides Targeting Chemokine Receptor CXCR4
  作者：Oliver Demmer、Ingrid Dijkgraaf、Udo Schumacher、Luciana Marinelli、Sandro Cosconati、Eleni Gourni、Hans-Jürgen Wester、Horst Kessler

  DOI：10.1021/jm2009716

  日期：2011.11.10

  The chemokine receptor CXCR4 is a critical regulator of inflammation and immune surveillance, and it is specifically implicated in cancer metastasis and HIV-1 infection. On the basis of the observation that several of the known antagonists remarkably share a C-2 symmetry element, we constructed symmetric dimers with excellent antagonistic activity using a derivative of a cyclic pentapeptide as monomer. To optimize the binding affinity, we investigated the influence of the distance between the monomers and the pharmacophoric sites in the synthesized constructs. The affinity studies in combination with docking computations support a two-site binding model. In a final step, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was introduced as chelator for (radio-)metals, thus allowing to exploit these compounds as a new group of CXCR4-binding peptidic probes for molecular imaging and endoradiotherapeutic purposes. Both the DOTA conjugates and some of their corresponding metal complexes retain good CXCR4 affinity, and one Ga-68 labeled compound was studied as PET tracer.