bis(tert-butyl) 3,6-bis[(tert-butoxycarbonyl)methyl]-3,6,9-triazaundecanedioate | 180152-86-7

• 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: bis(tert-butyl) 3,6-bis[(tert-butoxycarbonyl)methyl]-3,6,9-triazaundecanedioate
• 英文别名: 6,9-Bis(t-butoxycarbonylmethyl)-3,6,9-triazaundecanedicarboxylic acid-di-t-butyl ester；Tert-butyl 2-[2-[2-[bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]ethyl-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]ethylamino]acetate
• CAS: 180152-86-7
• 化学式: C₂₈H₅₃N₃O₈
• 分子量: 559.744
• InChiKey: MTKDMPHUIXUTFV-UHFFFAOYSA-N

物化性质

• 沸点：
  573.7±50.0 °C(Predicted)
• 密度：
  1.059±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  39
• 可旋转键数：
  22
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  124
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  bis(tert-butyl) 3,6-bis[(tert-butoxycarbonyl)methyl]-3,6,9-triazaundecanedioate 在 palladium on activated charcoal 氢气 、 N,N-二异丙基乙胺 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 3,6,9-tris(2-(tert-butoxy)-2-oxoethyl)-13,13-dimethyl-11-oxo-12-oxa-3,6,9-triazatetradecan-1-oic acid
  参考文献：
  名称：

  Reassessment of Diethylenetriaminepentaacetic Acid (DTPA) as a Chelating Agent for Indium-111 Labeling of Polypeptides Using a Newly Synthesized Monoreactive DTPA Derivative

  摘要：

  Previous studies on indium-111 (In-111) labeling of polypeptides and peptides using cyclic diethylenetriaminepentaacetic dianhydride (cDTPA) as a bifunctional chelating agent (BCA) have indicated that DTPA might be a useful BCA for In-111 labeling of polypeptides at high specific activities when DTPA can be incorporated without inducing intra- or intermolecular cross-linking. To investigate this hypothesis, a monoreactive DTPA derivative with a maleimide group as the peptide binding site (MDTPA) was designed and synthesized. A monoclonal antibody (OST7, IgG(1)) was used as a model polypeptide, and conjugation of MDTPA with OST7, In-111 radiolabeling of MDTPA-OST7, and the stability of In-111-MDTPA-OST7 were investigated using cDTPA and benzyl-EDTA derivatives as references. SDS-PAGE analysis demonstrated that while cDTPA induced intramolecular cross-linking, no such undesirable side reactions were observed with MDTPA. MDTPA generated In-111-labeled OST7 with high radiochemical yields at higher specific activities than those produced using cDTPA and benzyl-EDTA derivatives as the BCAs. incubation of each In-111-labeled OST7 in human serum indicated that MDTPA generated In-111-labeled OST7 of much higher and a little lower stability than those derived from cDTPA and benzyl-EDTA derivatives, respectively. These findings indicated that the low in vivo stability of cDTPA-conjugated antibody reported previously is not attributable to low stability of In-111-DTPA but to formation of intramolecular cross-linking during cDTPA conjugation reactions. The present study also indicated that MDTPA and its precursor, the tetra-tert-butyl derivative of DTPA, would be useful BCAs for In-111 radiolabeling of polypeptides that have rapid blood clearance with high specific activities.

  DOI：

  10.1021/jm950949+
• 作为产物：
  描述：

  1-Trifluoroacetyl-1,4,7-triazaheptane 在 sodium hydride 、 N,N-二异丙基乙胺 、 肼 作用下， 以 乙腈 、 叔丁醇 为溶剂， 反应 3.5h， 生成 bis(tert-butyl) 3,6-bis[(tert-butoxycarbonyl)methyl]-3,6,9-triazaundecanedioate
  参考文献：
  名称：

  Reassessment of Diethylenetriaminepentaacetic Acid (DTPA) as a Chelating Agent for Indium-111 Labeling of Polypeptides Using a Newly Synthesized Monoreactive DTPA Derivative

  摘要：

  Previous studies on indium-111 (In-111) labeling of polypeptides and peptides using cyclic diethylenetriaminepentaacetic dianhydride (cDTPA) as a bifunctional chelating agent (BCA) have indicated that DTPA might be a useful BCA for In-111 labeling of polypeptides at high specific activities when DTPA can be incorporated without inducing intra- or intermolecular cross-linking. To investigate this hypothesis, a monoreactive DTPA derivative with a maleimide group as the peptide binding site (MDTPA) was designed and synthesized. A monoclonal antibody (OST7, IgG(1)) was used as a model polypeptide, and conjugation of MDTPA with OST7, In-111 radiolabeling of MDTPA-OST7, and the stability of In-111-MDTPA-OST7 were investigated using cDTPA and benzyl-EDTA derivatives as references. SDS-PAGE analysis demonstrated that while cDTPA induced intramolecular cross-linking, no such undesirable side reactions were observed with MDTPA. MDTPA generated In-111-labeled OST7 with high radiochemical yields at higher specific activities than those produced using cDTPA and benzyl-EDTA derivatives as the BCAs. incubation of each In-111-labeled OST7 in human serum indicated that MDTPA generated In-111-labeled OST7 of much higher and a little lower stability than those derived from cDTPA and benzyl-EDTA derivatives, respectively. These findings indicated that the low in vivo stability of cDTPA-conjugated antibody reported previously is not attributable to low stability of In-111-DTPA but to formation of intramolecular cross-linking during cDTPA conjugation reactions. The present study also indicated that MDTPA and its precursor, the tetra-tert-butyl derivative of DTPA, would be useful BCAs for In-111 radiolabeling of polypeptides that have rapid blood clearance with high specific activities.

  DOI：

  10.1021/jm950949+

文献信息

• Concise site-specific synthesis of DTPA–peptide conjugates: Application to imaging probes for the chemokine receptor CXCR4
  作者：Ryo Masuda、Shinya Oishi、Hiroaki Ohno、Hiroyuki Kimura、Hideo Saji、Nobutaka Fujii

  DOI：10.1016/j.bmc.2011.03.059

  日期：2011.5

  Diethylenetriaminepentaacetic acid (DTPA) is a useful chelating agent for radionuclides such as (68)Ga, (99m)Tc and (111)In, which are applicable to nuclear medicine imaging. In this study, we established a facile synthetic protocol for the production of mono-DTPA-conjugated peptide probes. A novel monoreactive DTPA precursor reagent was synthesized in two steps using the chemistry of the o-nitrobenzenesulfonyl (Ns) protecting group, and under mild conditions this DTPA precursor was incorporated onto an N(epsilon)-bromoacetylated Lys of a protected peptide resin. The site-specific DTPA conjugation was facilitated by using a highly acid-labile 4-methyltrityl (Mtt) protecting group for the target site of the bioactive peptide during the solid-phase synthesis. A combination of both techniques yielded peptides with disulfide bonds, such as octreotide and polyphemusin II-derived CXCR4 antagonists. DTPA-peptide conjugates were purified in a single step following cleavage from the resin and disulfide bond formation. This site-specific on-resin construction strategy was used for the design and synthesis of a novel In-DTPA-labeled CXCR4 antagonist, which exhibited highly potent inhibitory activity against SDF-1-CXCR4 binding. (C) 2011 Elsevier Ltd. All rights reserved.
• THERAPEUTIC AND DIAGNOSTIC CONJUGATES FOR USE WITH MULTISPECIFIC ANTIBODIES
  申请人：Immunomedics Inc.

  公开号：EP1720575B1

  公开（公告）日：2015-05-20
• Therapeutic and diagnostic conjugates for use with multispecific antibodies
  申请人：McBride J. William

  公开号：US20050002945A1

  公开（公告）日：2005-01-06

  Disclosed are compounds that include two or more haptens conjugated by a spacer or a carrier. The haptens may include diethylenetriaminepentaacetate (DTPA), histimine-succinyl-glutamine (HSG), or combinations of DTPA and HSG. The compound also includes an effector molecule which may be conjugated to one or more of the haptens, the spacer/carrier, or both. The effector molecule may be conjugated by a number of linkages including an ester linkage, an imino linkage, an amino linkage, a sulfide linkage, a thiosemicarbazone linkage, a semicarbazone linkage, an oxime linkage, an ether linkage, or combinations of these linkages. Also disclosed are methods of synthesizing the compounds and/or precursors of the compounds.
• US7405320B2
  申请人：——

  公开号：US7405320B2

  公开（公告）日：2008-07-29
• US8158573B2
  申请人：——

  公开号：US8158573B2

  公开（公告）日：2012-04-17