tri-tert-butyl 2,2',2"-(10-(14-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-6-(2-(4-hydroxyphenyl)acetyl)-2,8,11-trioxo-3,6,9,12-tetraazatetradecyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetate | 1482496-76-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: tri-tert-butyl 2,2',2"-(10-(14-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-6-(2-(4-hydroxyphenyl)acetyl)-2,8,11-trioxo-3,6,9,12-tetraazatetradecyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetate
• 英文别名: tri-tert-butyl 2,2',2''-(10-(14-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-6-(2-(4-hydroxyphenyl)acetyl)-2,8,11-trioxo-3,6,9,12-tetraazatetradecyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetate；tert-butyl 2-[4-[2-[2-[[2-[[2-[2-(2,5-dioxopyrrol-1-yl)ethylamino]-2-oxoethyl]amino]-2-oxoethyl]-[2-(4-hydroxyphenyl)acetyl]amino]ethylamino]-2-oxoethyl]-7,10-bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,4,7,10-tetrazacyclododec-1-yl]acetate
• CAS: 1482496-76-3
• 化学式: C₄₈H₇₅N₉O₁₃
• 分子量: 986.176
• InChiKey: DPPPEQJMELKFCX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  70
• 可旋转键数：
  26
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  257
• 氢给体数：
  4
• 氢受体数：
  17

反应信息

• 作为反应物：
  描述：

  tri-tert-butyl 2,2',2"-(10-(14-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-6-(2-(4-hydroxyphenyl)acetyl)-2,8,11-trioxo-3,6,9,12-tetraazatetradecyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetate 在 sodium iodide 、 1,3,4,6-四氯-3α,6α-二苯基甘脲 、 溶剂黄146 、 sodium hydroxide 作用下， 以 氯仿 、 水 为溶剂， 反应 0.08h， 生成 tert-butyl 2-[4-[2-[2-[[2-[[2-[2-(2,5-dioxopyrrol-1-yl)ethylamino]-2-oxoethyl]amino]-2-oxoethyl]-[2-(4-hydroxy-3-(125I)iodanylphenyl)acetyl]amino]ethylamino]-2-oxoethyl]-7,10-bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,4,7,10-tetrazacyclododec-1-yl]acetate
  参考文献：
  名称：

  Enhanced Tumor Retention of a Radiohalogen Label for Site-Specific Modification of Antibodies

  摘要：

  A known limitation of iodine radionuclides for labeling and biological tracking of receptor targeted proteins is the tendency of iodotyrosine to rapidly diffuse from cells following endocytosis and lysosomal degradation. In contrast, radiometal-chelate complexes such as indium-111-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (In-111-DOTA) accumulate within target cells due to the residualizing properties of the polar, charged metal-chelate-amino acid adduct. Iodine radionuclides boast a diversity of nuclear properties and chemical means for incorporation, prompting efforts to covalently link radioiodine with residualizing molecules. Herein, we describe the Ugi-assisted synthesis of [I-125]HIP-DOTA, a 4-hydroxy-3-iodophenyl (HIP) derivative of DOTA, and demonstration of its residualizing properties in a murine xenograft model. Overall, this study displays the power of multicomponent synthesis to yield a versatile radioactive probe for antibodies across multiple therapeutic areas with potential applications in both preclinical biodistribution studies and clinical radioimmunotherapies.

  DOI：

  10.1021/jm401365h
• 作为产物：
  描述：

  tritert-butyl 2,2′,2″-(10-(6-(2-(4-hydroxyphenyl)acetyl)-2,8,11-trioxo-12-oxa-3,6,9-triazatetradecyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetate 在 甲酸 作用下， 以 乙醇 、 水 、 乙腈 为溶剂， 生成 tri-tert-butyl 2,2',2"-(10-(14-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-6-(2-(4-hydroxyphenyl)acetyl)-2,8,11-trioxo-3,6,9,12-tetraazatetradecyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetate
  参考文献：
  名称：

  METHODS AND COMPOSITIONS FOR RADIOHALOGEN PROTEIN LABELING

  摘要：

  提供了使用放射性卤素标记试剂标记蛋白质的方法和组合物。放射性卤素标记的蛋白质可用于成像研究、治疗和诊断测试。[125I] HIP-DOTA 标记试剂6通过高效便捷的过程制备。

  公开号：

  US20140170064A1

文献信息

• Methods and compositions for radiohalogen protein labeling
  申请人：Genentech, Inc.

  公开号：US09393327B2

  公开（公告）日：2016-07-19

  Methods and compositions are provided for labeling proteins with radiohalogen-label reagents. Radiohalogen-labeled proteins may be used for imaging studies, as therapeutics and in diagnostic tests. The [125I] HIP-DOTA label reagent 6 is prepared by an efficient and convenient process.

  提供了一种使用放射性卤素标签试剂对蛋白质进行标记的方法和组合物。放射性卤素标记的蛋白质可用于成像研究、治疗和诊断测试。[125I] HIP-DOTA标签试剂6通过高效便捷的过程制备。
• US9393327B2
  申请人：——

  公开号：US9393327B2

  公开（公告）日：2016-07-19
• US9486546B2
  申请人：——

  公开号：US9486546B2

  公开（公告）日：2016-11-08
• [EN] METHODS AND COMPOSITIONS FOR RADIOHALOGEN PROTEIN LABELING<br/>[FR] PROCÉDÉS ET COMPOSITIONS POUR LE MARQUAGE DE PROTÉINE PAR UN RADIOHALOGÈNE
  申请人：GENENTECH INC

  公开号：WO2014100095A1

  公开（公告）日：2014-06-26

  Methods and compositions are provided for labeling proteins with radiohalogen-label reagents. Radiohalogen-labeled proteins may be used for imaging studies, as therapeutics and in diagnostic tests. The [125I] HIP-DOTA label reagent 6 is prepared by an efficient and convenient process.