9-(bis(pyridin-2-ylmethyl)amino)nonanoic acid | 1045709-82-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 9-(bis(pyridin-2-ylmethyl)amino)nonanoic acid
• 英文别名: 8-(bis-pyridin-2-ylmethylamino)octanoic acid；8-[Bis(pyridin-2-ylmethyl)amino]octanoic acid
• CAS: 1045709-82-7
• 化学式: C₂₀H₂₇N₃O₂
• 分子量: 341.453
• InChiKey: NUBHRRRBXXCAPB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  25
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  66.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-羟基丁二酰亚胺 、 9-(bis(pyridin-2-ylmethyl)amino)nonanoic acid 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以65%的产率得到2,5-dioxopyrrolidin-1-yl 8-(bis(pyridin-2-ylmethyl)amino)octanoate
  参考文献：
  名称：

  Synthesis and Evaluation of Technetium-99m- and Rhenium-Labeled Inhibitors of the Prostate-Specific Membrane Antigen (PSMA)

  摘要：

  The prostate- specific membrane antigen (PSMA) is increasingly recognized as a viable target for imaging and therapy of cancer. We prepared seven 99'Tc/Re-labeled compounds by attaching known Tc/Re chelating agents to an amino-functionalized PSMA inhibitor (lys-NHCONH-glu) with or without a variable length linker moiety. Ki values ranged from 0.17 to 199 nM. Ex vivo biodistribution and in vivo imaging demonstrated the degree of specific binding to engineered PSMA+ PC3 PIP tumors. PC3-PIP cells are derived from PO that have been transduced with the gene for PSMA. Despite demonstrating nearly the lowest PSMA inhibitory potency of this series, [99`Tc(COXLI)]+ (LI = (2-pyridylmethVI)2N(CH,,)4CH(COH)NHCO-(CH2)6CO-NH-lys-NHCONH-glu) showed the highest, most selective PIP tumor uptake, at 7.9 4.0% injected dose per gram of tissue at 30 min postinjection. Radioactivity cleared from nontarget tissues to produce a PIP to flu (PSMA-PC3) ratio of 44:1 at 120 min postinjection. PSMA can accommodate the steric requirements of 99"Tc/Re complexes within PSMA inhibitors, the best results achieved with a linker moiety between the e amine of the urea lysine and the chelator.

  DOI：

  10.1021/jm800111u
• 作为产物：
  描述：

  BOC-8-氨基辛酸 在 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 9-(bis(pyridin-2-ylmethyl)amino)nonanoic acid
  参考文献：
  名称：

  Single Modification at the N‐Terminus of Norvancomycin to Combat Drug‐Resistant Gram‐Positive Bacteria

  摘要：

  AbstractIn the arsenal of glycopeptide antibiotics, norvancomycin, which differs from vancomycin by a single methyl group, has received much less attention. Facing the risks of serious antibiotic resistance and even the collapse of last‐line defenses, we designed and synthesized 40 novel norvancomycin derivatives to combat the threat. 32 compounds are single N‐terminally modified derivatives generated through simple and efficient methods. Diversity at the N‐terminus was greatly enriched, mainly by lipophilic attachment and strategies for the introduction of lipo‐sulfonium moieties for extensive structure–activity relationship analysis. The first incorporation of a sulfonium moiety into the norvancomycin structure gave rise to compounds that exhibited 4‐ to 2048‐fold higher activity against vancomycin‐resistant bacteria VISA and VRE. This N‐terminal modification for norvancomycin provides an alternatively useful and promising strategy to restore the antibacterial activity of glycopeptide antibiotics against resistant bacteria, highlighting the same importance of the N‐terminal site as well as the vancosamine position, which is worth further study and development.

  DOI：

  10.1002/cmdc.202200708

文献信息

• Alkyl linker effects on the coordination topology of ditopic di(2-pyridylmethyl)amine carboxylate ligands with Zn^IIand Cu^II: polymers<i>vs.</i>macrocycles
  作者：Kiattipoom Rodpun、Allan G. Blackman、Michael G. Gardiner、Eng Wui Tan、Carla J. Meledandri、Nigel T. Lucas

  DOI：10.1039/c5ce00375j

  日期：——

  [Zn(C3COO)(H2O)](ClO4)·3.5H2O}n (1), [Zn(C4COO)(H2O)]4(ClO4)4·1.5H2O}n (2), [Zn(C5COO)(H2O)](ClO4)}n (3), [Cu(C3COO)](ClO4)·MeOH}n (4), [Cu(C4COO)(H2O)]2(ClO4)2·2H2O}n (5) and [Cu(C5COO)(H2O)](ClO4)·2H2O}n (6). In contrast, the ligands with longer alkyl chains (n ≥ 7) participate in Zn2L2 metallomacrocyclic structures [Zn(C7COO)(H2O)](ClO4)}2 (7), [Zn2(C10COO)2(H2O)2](ClO4)2·2H2O·MeOH (8) and [Z

  合成了一系列结合了一系列正烷基连接基的二位ω-二（2-吡啶基甲基）胺羧酸配体（C n COOH，n = 3-5、7、10和11）。固溶相研究表明，在所有情况下，配体与M（ClO 4）2 ·6H 2 O（M = Zn II或Cu II）之间为1：1配位化学计量。锌II和铜II配合物随后通过液-液扩散而结晶，并通过X射线晶体学研究了固态结构。所获得的晶体结构与溶液相加合物的金属配体比为1：1完全一致。然而，配位几何形状和复杂的拓扑结构取决于配体C n COOH的烷基链长。锌II和Cu II的短链烷基配位体的复合物（Ñ ≤5）表现出1D协调与[锌（有点不同的构象聚合结构Ç 3 COO）（H 2 O）]（CLO 4）·3.5H 2 O} n（1），[Zn（C 4 COO）（H 2 O）] 4（ClO 4）4 ·1.5H 2 O} n（2），[Zn（C 5 COO）（H 2 O）]（ ClO 4）}
• LABELED INHIBITORS OF PROSTATE SPECIFIC MEMBRANE ANTIGEN (PSMA) BIOLOGICAL EVALUATION, AND USE OF IMAGING AGENTS
  申请人：THE JOHNS HOPKINS UNIVERSITY

  公开号：US20150246144A1

  公开（公告）日：2015-09-03

  The prostate-specific membrane antigen (PSMA) is increasingly recognized as a viable target for imaging and therapy of cancer. Various 99mTc/Re-labeled compounds were prepared by attaching known Tc/Re chelating agents to an amino-functionalized PSMA inhibitor with or without a variable length linker moiety. Ex vivo biodistribution and in vivo imaging demonstrated the degree of specific binding to engineered PSMA+PC3 PIP tumors.

  前列腺特异性膜抗原（PSMA）越来越被认为是癌症成像和治疗的可行靶点。通过将已知的Tc/Re螯合剂附着在具有可变长度连接单元的氨基功能化PSMA抑制剂上，制备了各种99mTc/Re标记化合物。外体分布和体内成像证明了对工程PSMA+PC3 PIP肿瘤的特异性结合程度。
• LABELED INHIBITORS OF PROSTATE SPECIFIC MEMBRANE ANTIGEN (PSMA), BIOLOGICAL EVALUATION, AND USE AS IMAGING AGENTS
  申请人：Pomper Martin Gilbert

  公开号：US20110064657A1

  公开（公告）日：2011-03-17

  The prostate-specific membrane antigen (PSMA) is increasingly recognized as a viable target for imaging and therapy of cancer. Various 99mTc/Re-labeled compounds were prepared by attaching known Tc/Re chelating agents to an amino-functionalized PSMA inhibitor with or without a variable length linker moiety. Ex vivo biodistribution and in vivo imaging demonstrated the degree of specific binding to engineered PSMA+ PC3 PIP tumors.

  前列腺特异性膜抗原（PSMA）越来越被认为是癌症影像和治疗的可行靶点。通过将已知的Tc/Re螯合剂连接到具有或不具有可变长度连接单元的氨基功能化PSMA抑制剂上，制备了各种99mTc/Re标记的化合物。外体分布和体内成像证明了对工程PSMA+ PC3 PIP肿瘤的特异性结合程度。
• Labeled inhibitors of prostate-specific membrane antigen (PSMA), biological evaluation, and use as imaging agents
  申请人：The Johns Hopkins University

  公开号：EP2921482A2

  公开（公告）日：2015-09-23

  The present invention provides radiolabeled compounds of formulae (VII) and (VIII) comprising a urea derivative, a linker, a metal chelating group, and a radiolabeled or isotopically labelled metal, pharmaceutical compositions comprising such radiolabeled compounds and methods of detecting PSMA expressing tumors. The compounds of the invention are useful for providing diagnosis of cancer.

  本发明提供了式(VII)和(VIII)的放射性标记化合物，包括脲衍生物、连接体、金属螯合基团和放射性标记或同位素标记的金属；提供了包含这种放射性标记化合物的药物组合物和检测表达 PSMA 的肿瘤的方法。本发明的化合物可用于癌症诊断。
• Labeled inhibitors of prostate specific membrane antigen (PSMA) biological evaluation, and use of imaging agents
  申请人：THE JOHNS HOPKINS UNIVERSITY

  公开号：US10039845B2

  公开（公告）日：2018-08-07

  The prostate-specific membrane antigen (PSMA) is increasingly recognized as a viable target for imaging and therapy of cancer. Various 99mTc/Re-labeled compounds were prepared by attaching known Tc/Re chelating agents to an amino-functionalized PSMA inhibitor with or without a variable length linker moiety. Ex vivo biodistribution and in vivo imaging demonstrated the degree of specific binding to engineered PSMA+ PC3 PIP tumors.

  前列腺特异性膜抗原（PSMA）越来越被认为是癌症成像和治疗的可行靶点。通过将已知的锝/铼螯合剂连接到带有或不带有可变长度连接分子的氨基功能化 PSMA 抑制剂上，制备出了各种 99mTc/Re 标记化合物。体内外生物分布和体内成像显示了与PSMA+ PC3 PIP肿瘤的特异性结合程度。