3-Benzyloxycarbonylmethyl-6,9-bis(t-butoxycarbonylmethyl)-3,6,9-triazaundecanedicarboxylic acid-di-t-butyl ester | 180152-87-8

• 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: 3-Benzyloxycarbonylmethyl-6,9-bis(t-butoxycarbonylmethyl)-3,6,9-triazaundecanedicarboxylic acid-di-t-butyl ester
• 英文别名: 3-Oxa-6,9,12-triazatetradecan-14-oic acid, 6,9-bis[2-(1,1-dimethylethoxy)-2-oxoethyl]-2,2-dimethyl-4-oxo-12-[2-oxo-2-(phenylmethoxy)ethyl]-, 1,1-dimethylethyl ester；tert-butyl 2-[2-[bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]ethyl-[2-[[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-(2-oxo-2-phenylmethoxyethyl)amino]ethyl]amino]acetate
• CAS: 180152-87-8
• 化学式: C₃₇H₆₁N₃O₁₀
• 分子量: 707.905
• InChiKey: OZCTZCBWAICTEF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  50
• 可旋转键数：
  27
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  141
• 氢给体数：
  0
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  3-Benzyloxycarbonylmethyl-6,9-bis(t-butoxycarbonylmethyl)-3,6,9-triazaundecanedicarboxylic acid-di-t-butyl ester 在 palladium on activated charcoal 氢气 作用下， 以 乙酸乙酯 为溶剂， 反应 6.0h， 以98%的产率得到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 N,N-二甲基甲酰胺 、 乙腈 、 叔丁醇 为溶剂， 反应 3.5h， 生成 3-Benzyloxycarbonylmethyl-6,9-bis(t-butoxycarbonylmethyl)-3,6,9-triazaundecanedicarboxylic acid-di-t-butyl ester
  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

• [EN] PREPARATION OF DTPA ESTERS WITH DIFFERENT ESTER GROUPS<br/>[FR] PRÉPARATION D'ESTERS D'ACIDE DIÉTHYLÈNETRIAMINEPENTAACÉTIQUE (DPTA) À L'AIDE DE DIFFÉRENTS GROUPES ESTERS
  申请人：MALLINCKRODT INC

  公开号：WO2000058265A1

  公开（公告）日：2000-10-05

  The synthesis of compounds of formula (XI) wherein each R4 is a removable protecting group; R5 is a removable protecting group different from and removable separately from R4; each R6 and R8 is a linking moiety having 1 to 10 carbon atoms; and R9 is hydrogen or a C1 to C50 alkyl moiety, is disclosed. These compounds are useful intermediates in the synthesis of compounds of formula (X). These compounds are useful in the preparation of nuclear pharmaceuticals such as those used for tumor imaging or tumor therapy.
• [EN] ENHANCED SELECTIVITY IN THE SYNTHESIS OF DTPA ESTERS FOM DIETHYLENETRIAMINE<br/>[FR] RENFORCEMENT DE LA SELECTIVITE DANS LA SYNTHESE D'ESTERS D'ACIDE DIETHYLENE TRIAMINEPENTA ACETIQUE (DPTA) A PARTIR DE DIETHYLENETRIAMINE
  申请人：MALLINCKRODT INC

  公开号：WO2000058267A1

  公开（公告）日：2000-10-05

  The synthesis of compounds of formula (XI) is disclosed. These compounds are useful intermediates in the synthesis of compounds of formula (X). These compounds are useful in the preparation of nuclear pharmaceuticals such as those used for tumor imaging or tumor therapy.
• [EN] DTPA ESTERS WITH ORTHOGONAL REMOVABLE PROTECTING GROUPS<br/>[FR] ESTERS DTPA AVEC GROUPES DE PROTECTION AMOVIBLES ORTHOGONAUX
  申请人：MALLINCKRODT INC

  公开号：WO2000058269A1

  公开（公告）日：2000-10-05

  The synthesis of compounds of formula (XXXIII) wherein each R4 is a removable protecting group; R5 is a removable protecting group different from and removable separately from R4; each R6 and R8 is a linking moiety having 1 to 10 carbon atoms; and R9 is hydrogen or a C1 to C50 alkyl moiety; is disclosed. These compounds are useful intermediates in the synthesis of compounds of formula (X). These compounds are useful in the preparation of nuclear pharmaceuticals such as those used for tumor imaging or tumor therapy.
• [EN] VERSATILE METHOD FOR THE SYNTHESIS OF ISO-DTPA<br/>[FR] PROCEDE UNIVERSEL DE SYNTHESE D'ISO-DTPA
  申请人：MALLINCKRODT INC

  公开号：WO2001002339A1

  公开（公告）日：2001-01-11

  The synthesis of compounds of formula (XII) is disclosed. These compounds are useful intermediates in the synthesis of compounds of formulae (XI) and (X). These compounds are useful in the preparation of nuclear pharmaceuticals such as those used for tumor imaging or tumor therapy.
• Reassessment of Diethylenetriaminepentaacetic Acid (DTPA) as a Chelating Agent for Indium-111 Labeling of Polypeptides Using a Newly Synthesized Monoreactive DTPA Derivative
  作者：Yasushi Arano、Takashi Uezono、Hiromichi Akizawa、Masahiro Ono、Kouji Wakisaka、Morio Nakayama、Harumi Sakahara、Junji Konishi、Akira Yokoyama

  DOI：10.1021/jm950949+

  日期：1996.1.1

  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.