N-[(R)-2-amino-3-(p-aminophenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-N,N,N',N'',N''-penta-tert-butyl acetate | 880644-84-8

• 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: N-[(R)-2-amino-3-(p-aminophenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-N,N,N',N'',N''-penta-tert-butyl acetate
• 英文别名: tert-butyl 2-[[(2R)-3-(4-aminophenyl)-2-[bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]propyl]-[(1S,2S)-2-[bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]cyclohexyl]amino]acetate
• CAS: 880644-84-8
• 化学式: C₄₅H₇₆N₄O₁₀
• 分子量: 833.119
• InChiKey: RDMLHTCIZUNOJF-PLJDCMBSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  59
• 可旋转键数：
  27
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  167
• 氢给体数：
  1
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  N-[(R)-2-amino-3-(p-aminophenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-N,N,N',N'',N''-penta-tert-butyl acetate 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 生成 N-[(R)-2-amino-3-(p-5-[(2,5-dioxopyrrolidin-1-yl)oxy]-5-oxo-N-phenylpentanamide)-propyl]-trans-(S,S)-cyclohexane-1,2-diamine-N,N,N',N'',N''-penta-tert-butyl acetate
  参考文献：
  名称：

  Validation of a Novel CHX-A‘ ‘ Derivative Suitable for Peptide Conjugation:  Small Animal PET/CT Imaging Using Yttrium-86-CHX-A‘ ‘-Octreotide

  摘要：

  A versatile bifunctional chelating reagent based on a preorganized cyclohexyl derivative of DTPA (CHX-A ") has been developed for the convenient N-terminal labeling of peptides with metal ion radionuclides of Bi(III), In(III), Lu(III), or Y(III). This was achieved via the synthesis of a mono-N-hydroxysuccinimidyl penta-tert-butyl ester derivative of CHX-A" (trans-cyclohexyldiethylenetriaminepenta-acetic acid) featuring a glutaric acid spacer. Commercially obtained octreotide was modified at its N-terminus by this reagent in the solution phase, and its subsequent radiolabeling with In-111 (T-1/2 = 2.8 d) and Y-86 (T-1/2 = 14.7 h) demonstrated. Small animal PET/CT imaging results of Y-86-CHX-A"-octreotide in a somatostatin receptor-positive tumor-bearing rat model are presented for the validation of the novel agent.

  DOI：

  10.1021/jm060317v
• 作为产物：
  描述：

  溴乙酸叔丁酯 在 palladium on activated charcoal K₂O₃ 、 氢气 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 80.0h， 生成 N-[(R)-2-amino-3-(p-aminophenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-N,N,N',N'',N''-penta-tert-butyl acetate
  参考文献：
  名称：

  Validation of a Novel CHX-A‘ ‘ Derivative Suitable for Peptide Conjugation:  Small Animal PET/CT Imaging Using Yttrium-86-CHX-A‘ ‘-Octreotide

  摘要：

  A versatile bifunctional chelating reagent based on a preorganized cyclohexyl derivative of DTPA (CHX-A ") has been developed for the convenient N-terminal labeling of peptides with metal ion radionuclides of Bi(III), In(III), Lu(III), or Y(III). This was achieved via the synthesis of a mono-N-hydroxysuccinimidyl penta-tert-butyl ester derivative of CHX-A" (trans-cyclohexyldiethylenetriaminepenta-acetic acid) featuring a glutaric acid spacer. Commercially obtained octreotide was modified at its N-terminus by this reagent in the solution phase, and its subsequent radiolabeling with In-111 (T-1/2 = 2.8 d) and Y-86 (T-1/2 = 14.7 h) demonstrated. Small animal PET/CT imaging results of Y-86-CHX-A"-octreotide in a somatostatin receptor-positive tumor-bearing rat model are presented for the validation of the novel agent.

  DOI：

  10.1021/jm060317v

文献信息

• [EN] METAL CHELATORS AND METHODS OF THEIR USE<br/>[FR] CHELATEURS METALLIQUES ET LEURS PROCEDES D'UTILISATION
  申请人：US GOV HEALTH & HUMAN SERV

  公开号：WO2006033714A3

  公开（公告）日：2006-05-04
• Design, Synthesis, and Characterization of a Dual Modality Positron Emission Tomography and Fluorescence Imaging Agent for Monoclonal Antibody Tumor-Targeted Imaging
  作者：Heng Xu、Kwamena Baidoo、Andrew J. Gunn、C. Andrew Boswell、Diane E. Milenic、Peter L. Choyke、Martin W. Brechbiel

  DOI：10.1021/jm070657w

  日期：2007.9.1

  A novel lysine-based trifunctional chelate 3 was designed, synthesized, and characterized and bears both a chelating moiety (CHX-A '') for sequestering radiometals (Y-86 or In-111) and the near-infrared dye Cy5.5 for dual modality PET (or SPECT) and fluorescence imaging, respectively. Successful conjugation of 3 to the monoclonal antibody trastuzumab (Herceptin) was achieved by efficient thiol-maleimide chemistry, thereby yielding immunoconjugate 2. Analysis of 2 by flow cytometry and competitive binding assay demonstrates that immunoconjugate 2 binds to SKOV3 tumor cells comparably to native trastuzumab and, thus, may be used as a tumor-targeted monoclonal antibody probe for multimodality imaging.
• A novel bifunctional maleimido CHX-A″ chelator for conjugation to thiol-containing biomolecules
  作者：Heng Xu、Kwamena E. Baidoo、Karen J. Wong、Martin W. Brechbiel

  DOI：10.1016/j.bmcl.2008.03.022

  日期：2008.4

  A novel bifunctional maleimido CHX-A '' DTPA chelator 5 was developed and conjugated to the monoclonal antibody trastuzumab (Herceptin) and subsequently radiolabeled with In-111. The resulting In-111 labeled immunoconjugate 2 was demonstrated to bind to SKOV-3 ovarian cancer cells comparably to an isothiocyanato CHX-A '' DTPA modified native trastuzumab, 1. Through efficient thiol-maleimide chemistry, antibodies, peptides or other targeting vectors can now be modified with an established radioactive metal chelating agent CHX-A '' DTPA for imaging and/or therapies of cancer. Published by Elsevier Ltd.
• Metal Chelators and Methods of Their Use
  申请人：Brechbiel Martin Wade

  公开号：US20080152588A1

  公开（公告）日：2008-06-26

  Metal chelators of formula (I) and formula (II) are disclosed or a farmaceutically acceptable salt thereof. Also disclosed are metal chelator-targeting moiety complexes, metal chelator-targeting moiety-metal conjugates, kits, and methods of their preparation and use in diagnosis and/or treatment of diseases and conditions, including, inter alia, cancer and thrombosis.
• METAL CHELATORS AND METHODS OF THEIR USE
  申请人：Brechbiel Martin Wade

  公开号：US20100189645A1

  公开（公告）日：2010-07-29

  Metal chelators of Formula I and Formula II are disclosed: or a pharmaceutically acceptable salt thereof. Also disclosed are metal chelator-targeting moiety complexes, metal chelator-targeting moiety-metal conjugates, kits, and methods of their preparation and use in diagnosis and/or treatment of diseases and conditions, including, inter alia, cancer and thrombosis.