N-{3-[2-(2-{3-[2-(4,7,10-tris-tert-butoxycarbonylmethyl-1,4,7,10-tetraaza-cyclododec-1-yl)-acetylamino]-propoxy}-ethoxy)-ethoxy]-propyl}-succinamic acid | 1613332-71-0

• 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-{3-[2-(2-{3-[2-(4,7,10-tris-tert-butoxycarbonylmethyl-1,4,7,10-tetraaza-cyclododec-1-yl)-acetylamino]-propoxy}-ethoxy)-ethoxy]-propyl}-succinamic acid
• 英文别名: DOTA(tBu)₃-Ttds-OH；4-Oxo-4-[3-[2-[2-[3-[[2-[4,7,10-tris[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,4,7,10-tetrazacyclododec-1-yl]acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]butanoic acid；4-oxo-4-[3-[2-[2-[3-[[2-[4,7,10-tris[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,4,7,10-tetrazacyclododec-1-yl]acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]butanoic acid
• CAS: 1613332-71-0
• 化学式: C₄₂H₇₈N₆O₁₃
• 分子量: 875.114
• InChiKey: KLAHCJYPPHJUNE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  61
• 可旋转键数：
  31
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  215
• 氢给体数：
  3
• 氢受体数：
  17

反应信息

• 作为反应物：
  描述：

  2-({5-(2,6-dimethoxy-phenyl)-1-[2-isopropyl-4-(methyl-{3-[methyl-(3-methylamino-propyl)-amino]-propyl}-carbamoyl)-phenyl]-1H-pyrazole-3-carbonyl}-amino)-adamantane-2-carboxylic acid tert-butyl ester trityl resin 、 N-{3-[2-(2-{3-[2-(4,7,10-tris-tert-butoxycarbonylmethyl-1,4,7,10-tetraaza-cyclododec-1-yl)-acetylamino]-propoxy}-ethoxy)-ethoxy]-propyl}-succinamic acid 在 N-羟基-7-氮杂苯并三氮唑 、 N,N-二异丙基乙胺 、 N,N'-二异丙基碳二亚胺 、 三异丙基硅烷 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 、 水 、 苯酚 为溶剂， 反应 32.0h， 以15.8%的产率得到2-{[1-(4-{[3-({3-[(DOTA-Ttds)-methyl-amino]-propyl}-methyl-amino)-propyl]-methyl-carbamoyl}-2-isopropyl-phenyl)-5-(2,6-dimethoxy-phenyl)-1H-pyrazole-3-carbonyl]-amino}-adamantane-2-carboxylic acid
  参考文献：
  名称：

  [EN] NEUROTENSIN RECEPTOR LIGANDS
  [FR] LIGANDS DES RÉCEPTEURS DE LA NEUROTENSINE

  摘要：

  公开号：

  WO2014086499A8
• 作为产物：
  描述：

  1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸三叔丁酯 、 N-Fmoc-N''-琥珀酰-4,7,10-三氧-1,13-十三烷二胺 在 trityl chloride polystyrene resin 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 以45%的产率得到N-{3-[2-(2-{3-[2-(4,7,10-tris-tert-butoxycarbonylmethyl-1,4,7,10-tetraaza-cyclododec-1-yl)-acetylamino]-propoxy}-ethoxy)-ethoxy]-propyl}-succinamic acid
  参考文献：
  名称：

  [EN] NEUROTENSIN RECEPTOR LIGANDS
  [FR] LIGANDS DES RÉCEPTEURS DE LA NEUROTENSINE

  摘要：

  公开号：

  WO2014086499A8

文献信息

• Conjugate comprising a neurotensin receptor ligand and use thereof
  申请人：3B Pharmaceuticals GmbH

  公开号：EP2954934A1

  公开（公告）日：2015-12-16

  The present invention is related to a conjugate comprising a structure of general formula (1)         [TM1] - [AD1] - [LM] - [AD2] - [TM2]     (1), wherein TM1 is a first targeting moiety, wherein the first targeting moiety is capable of binding to a first target, AD1 is a first adapter moiety or is absent, LM is a linker moiety or is absent, AD2 is a second adapter moiety or is absent, and TM2 is a second targeting moiety, wherein the second targeting moiety is capable of binding to a second target; wherein the first targeting moiety and/or the second targeting moiety is a compound of formula (2): wherein R1 is selected from the group consisting of hydrogen, methyl and cyclopropylmethyl; AA-COOH is an amino acid selected from the group consisting of 2-amino-2-adamantane carboxylic acid, cyclohexylglycine and 9-amino-bicyclo[3.3.1]nonane-9-carboxylic acid; R2 is selected from the group consisting of (C1-C6)alkyl, (C3-C8)cycloalkyl, (C3C8)cycloalkylmethyl, halogen, nitro and trifluoromethyl; ALK is (C2-C5)alkylidene; R3, R4 and R5 are each and independently selected from the group consisting of hydrogen and (C1-C4)alkyl under the proviso that one of R3, R4 and R5 is of the following formula (3) wherein ALK' is (C2-C5)alkylidene; R6 is selected from the group consisting of hydrogen and (C1-C4)alkyl; and R7 is a bond; or a pharmacologically acceptable salt, solvate or hydrate thereof.

  本发明涉及一种包含通式（1）结构的共轭物 [TM1] - [AD1] - [LM] - [AD2] - [TM2] (1)、 其中 TM1 是第一靶向分子，其中第一靶向分子能够与第一靶点结合、 AD1 是第一适配基团或不存在、 LM 是连接分子或不存在、 AD2 是第二适配基团或不存在，以及 TM2 是第二靶向分子，其中第二靶向分子能与第二靶点结合； 其中第一靶向分子和/或第二靶向分子为式（2）化合物： 其中 R1 选自由氢、甲基和环丙基甲基组成的组； AA-COOH 是一种氨基酸，选自由 2-氨基-2-金刚烷羧酸、环己基甘氨酸和 9-氨基-双环[3.3.1]壬烷-9-羧酸组成的组； R2 选自(C1-C6)烷基、(C3-C8)环烷基、(C3C8)环烷基甲基、卤素、硝基和三氟甲基组成的组； ALK 是（C2-C5）亚烷基； R3、R4 和 R5 各自独立地选自氢和(C1-C4)烷基组成的组，但 R3、R4 和 R5 中的一个必须符合下式 (3) 其中 ALK' 是 (C2-C5) 亚烷基； R6 选自氢和（C1-C4）烷基组成的组；以及 R7 是键； 或其药理学上可接受的盐、溶液或水合物。
• Neurotensin receptor ligands
  申请人：3B Pharmaceuticals GmbH

  公开号：US10961199B2

  公开（公告）日：2021-03-30

  The present invention is related to a compound of formula (I) wherein R1 is selected from the group consisting of hydrogen, methyl and cyclopropylmethyl; AA-COOH is an amino acid selected from the group consisting of 2-amino-2-adamantane carboxylic acid, cyclohexylglycine and 9-amino-bicyclo[3.3.1]nonane-9-carboxylic acid; R2 is selected from the group consisting of (C1-C6)alkyl, (C3-C8)cycloalkyl, (C3-C5)cycloalkylmethyl, halogen, nitro and trifluoromethyl; ALK is (C2-C5)alkylidene; R3, R4 and R5 are each and independently selected from the group consisting of hydrogen and (C1-C4)alkyl under the proviso that one of R3, R4 and R5 is of the formula (II) wherein ALK′ is (C2-C5)alkylidene; R6 is selected from the group consisting of hydrogen and (C1-C4)alkyl; and R7 is selected from the group consisting of H and an Effector moiety; or a pharmacologically acceptable salt, solvate or hydrate thereof.

  本发明涉及式(I)化合物 其中 R1 选自氢、甲基和环丙基甲基组成的组；AA-COOH 是选自 2-氨基-2-金刚烷羧酸、环己基甘氨酸和 9-氨基-双环[3.3.1]壬烷-9-羧酸组成的组的氨基酸；R2 选自(C1-C6)烷基、(C3-C8)环烷基、(C3-C5)环烷基组成的组。R2选自由(C1-C6)烷基、(C3-C8)环烷基、(C3-C5)环烷基甲基、卤素、硝基和三氟甲基组成的组；ALK为(C2-C5)亚烷基；R3、R4和R5各自独立地选自由氢和(C1-C4)烷基组成的组，但R3、R4和R5中的一个为式(II)，其中ALK′为(C2-C5)亚烷基；R6 选自由氢和（C1-C4）烷基组成的组；以及 R7 选自由 H 和效应分子组成的组；或其药理学上可接受的盐、溶液或水合物。
• NEUROTENSIN RECEPTOR LIGANDS
  申请人：3B Pharmaceuticals GmbH

  公开号：EP2928870A1

  公开（公告）日：2015-10-14
• CONJUGATE COMPRISING A NEUROTENSIN RECEPTOR LIGAND AND USE THEREOF
  申请人：3B Pharmaceuticals GmbH

  公开号：EP3154638A1

  公开（公告）日：2017-04-19
• [EN] CONJUGATE COMPRISING A NEUROTENSIN RECEPTOR LIGAND AND USE THEREOF<br/>[FR] CONJUGUÉ COMPRENANT UN LIGAND DE RÉCEPTEUR DE NEUROTENSINE ET SON UTILISATION
  申请人：3B PHARMACEUTICALS GMBH

  公开号：WO2015188934A1

  公开（公告）日：2015-12-17

  The present invention is related to a conjugate comprising a structure of general formula (1) [TM1] - [AD1] - [LM] - [AD2] - [TM2] (1), wherein TM1 is a first targeting moiety, wherein the first targeting moiety is capable of binding to a first target, AD1 is a first adapter moiety or is absent, LM is a linker moiety or is absent, AD2 is a second adapter moiety or is absent, and TM2 is a second targeting moiety, wherein the second targeting moiety is capable of binding to a second target; wherein the first targeting moiety and/or the second targeting moiety is a compound of formula (2): wherein R1 is selected from the group consisting of hydrogen, methyl and cyclopropylmethyl; AA-COOH is an amino acid selected from the group consisting of 2-amino-2 adamantane carboxylic acid, cyclohexylglycine and 9-amino-bicyclo[3.3.1]nonane-9 carboxylic acid; R2 is selected from the group consisting of (C1-C6)alkyl, (C3-C8)cycloalkyl, (C3C8)cycloalkylmethyl, halogen, nitro and trifluoromethyl; ALK' is (C2-C5)alkylidene; R3, R4 and R5 are each and independently selected from the group consisting of hydrogen and (C1-C4)alkyl under the proviso that one of R3, R4 and R5 is of the following formula (3) wherein ALK' is (C2-C5)alkylidene; R6 is selected from the group consisting of hydrogen and (C1-C4)alkyl; and R7 is a bond; or a pharmacologically acceptable salt, solvate or hydrate thereof.