N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-S-3-iodo-L-tyrosine | 564482-88-8

• 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: N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-S-3-iodo-L-tyrosine
• 英文别名: [121I]-DCIT；DCIT；[131I]-DCIT；(S)-2-(3-((S)-1-carboxy-2-(4-hydroxy-3-iodophenyl)ethyl)ureido)pentanedioic acid；N-{[(1s)-1-Carboxy-2-(4-Hydroxy-3-Iodophenyl)ethyl]carbamoyl}-L-Glutamic Acid；(2S)-2-[[(1S)-1-carboxy-2-(4-hydroxy-3-iodophenyl)ethyl]carbamoylamino]pentanedioic acid
• CAS: 564482-88-8
• 化学式: C₁₅H₁₇IN₂O₈
• 分子量: 480.213
• InChiKey: GUNPTUQXZIVQBT-UWVGGRQHSA-N

物化性质

• 沸点：
  744.7±60.0 °C(Predicted)
• 密度：
  1.863±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  173
• 氢给体数：
  6
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-S-3-iodo-L-tyrosine 在 sodium hydroxide 、 sodium iodide 作用下， 以 水 为溶剂， 反应 0.38h， 生成 [I-131]-DCIT
  参考文献：
  名称：

  HETERODIMERS OF GLUTAMIC ACID

  摘要：

  化合物的化学式（Ia），其中R是C6-C12取代或未取代的芳基，C6-C12取代或未取代的杂环芳基，C1-C6取代或未取代的烷基或-NR′R′，Q是C（O），O，NR′，S，S（O）2，C（O）2（CH2）p，Y是C（O），O，NR′，S，S（O）2，C（O）2（CH2）p，Z是H或C1-C4烷基，R′是H，C（O），S（O）2，C（O）2，C6-C12取代或未取代的芳基，C6-C12取代或未取代的杂环芳基或C1-C6取代或未取代的烷基，当取代时，芳基，杂环芳基和烷基取代为卤素，C6-C12杂环芳基，-NR′R′或COOZ，具有诊断和治疗特性，如治疗和管理前列腺癌和其他与NAALADase抑制相关的疾病。放射性标记可以通过连接到X氨基酸侧链的多种假体基团结构中。

  公开号：

  US20080193381A1
• 作为产物：
  描述：

  (S)-bis(4-methoxybenzyl)-2-(3-((S)-3-(4-hydroxy-3-iodophenyl)-1-(4-methoxybenzyloxy)-1-oxopropan-2-yl)ureido)pentanedioate 在 苯甲醚 、 三氟乙酸 作用下， 以78%的产率得到N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-S-3-iodo-L-tyrosine
  参考文献：
  名称：

  Interactions between Human Glutamate Carboxypeptidase II and Urea-Based Inhibitors: Structural Characterization

  摘要：

  Urea-based, low molecular weight ligands of glutamate carboxypeptidase II (GCPII) have demonstrated efficacy in various models of neurological disorders and can serve as imaging agents for prostate cancer. To enhance further development of such compounds, we determined X-ray structures of four complexes between human GCPII and urea-based inhibitors at high resolution. All ligands demonstrate an invariant glutarate moiety within the S1' pocket of the enzyme. The ureido linkage between P1 and P1' inhibitor sites interacts with the active-site Zn(1)(2+) ion and the side chains of Tyr552 and His553. Interactions within the S1 pocket are defined primarily by a network of hydrogen bonds between the P1 carboxylate group of the inhibitors and the side chains of Arg534, Arg536, and Asn519. Importantly, we have identified a hydrophobic pocket accessory to the S1 site that can be exploited for structure-based design of novel GCPII inhibitors with increased lipophilicity.

  DOI：

  10.1021/jm800765e

文献信息

• [EN] RADIOLABELED PROSTATE SPECIFIC MEMBRANE ANTIGEN INHIBITORS<br/>[FR] INHIBITEURS RADIOMARQUÉS D'ANTIGÈNE MEMBRANAIRE SPÉCIFIQUE DE LA PROSTATE
  申请人：MOLECULAR INSIGHT PHARM INC

  公开号：WO2013022797A1

  公开（公告）日：2013-02-14

  Compounds according to Formula I and Formula II are potent inhibitors of PSMA activity: The invention also provides pharmaceutical compositions of a complex of a radionuclide and a Formula I compound or a Formula II compound and methods of using the radionuclide complex of a Formula I compound or a Formula II compound for treating or diagnosis of a disease or a condition associated with PSMA activity.

  根据公式I和公式II合成物是PSMA活性的有效抑制剂：本发明还提供了一个放射性核素和公式I化合物或公式II化合物的复合物的药物组合物，以及使用公式I化合物或公式II化合物的放射性核素复合物用于治疗或诊断与PSMA活性相关的疾病或病况的方法。
• Structure–activity relationships of succinimidyl-Cys-C(O)-Glu derivatives with different near-infrared fluorophores as optical imaging probes for prostate-specific membrane antigen
  作者：Daiko Matsuoka、Hiroyuki Watanabe、Yoichi Shimizu、Hiroyuki Kimura、Yusuke Yagi、Ryoko Kawai、Masahiro Ono、Hideo Saji

  DOI：10.1016/j.bmc.2018.03.015

  日期：2018.5

  target for imaging and therapy of PCa. We previously reported a PSMA imaging probe, 800CW-SCE, based on succinimidyl-Cys-C(O)-Glu (SCE) for optical imaging of PCa. In this study, we investigated the structure–activity relationships of novel SCE derivatives with five different near-infrared (NIR) fluorophores (IRDye 680LT, IRDye 750, Indocyanine Green, Cyanine 5.5, and Cyanine 7) as optical imaging probes

  在恶性前列腺癌（PCa）中过表达的前列腺特异性膜抗原（PSMA）是PCa成像和治疗的理想靶标。我们以前曾报道过一种基于琥珀酰亚胺基-Cys-C（O）-Glu（SCE）的PSMA成像探头800CW-SCE，用于PCa的光学成像。在这项研究中，我们研究了具有五个不同近红外（NIR）荧光团（IRDye 680LT，IRDye 750，吲哚菁绿，花菁5.5和花菁7）作为针对PSMA的光学成像探针的新型SCE衍生物的结构-活性关系。一种在体外结合测定显示800CW-SCE，680LT-SCE和750-SCE的结合亲和力比2-PMPA（称为PSMA抑制剂）的结合亲和力高。这三种SCE衍生物被内在化为PSMA阳性细胞（LNCaP细胞），而不是内化为PSMA阴性细胞（PC-3细胞）。在体内成像研究中，LNCaP肿瘤中高度积累了800CW-SCE和750-SCE，而PC-3肿瘤中却没有积累800CW-SCE和800CW-SCE的LNCaP
• Heterodimers of Glutamic Acid
  申请人：Babich John W.

  公开号：US20120269726A1

  公开（公告）日：2012-10-25

  Compounds of Formula (Ia) wherein R is a C 6 -C 12 substituted or unsubstituted aryl, a C 6 -C 12 substituted or unsubstituted heteroaryl, a C 1 -C 6 substituted or unsubstituted alkyl or —NR′R′, Q is C(O), O, NR′, S, S(O) 2 , C(O) 2 (CH2)p Y is C(O), O, NR′, S, S(O) 2 , C(O) 2 (CH2)p Z is H or C 1 -C 4 alkyl, R′ is H, C(O), S(O) 2 , C(O) 2 , a C 6 -C 12 substituted or unsubstituted aryl, a C 6 -C 12 substituted or unsubstituted heteroaryl or a C 1 -C 6 substituted or unsubstituted alkyl, when substituted, aryl, heteroaryl and alkyl are substituted with halogen, C 1 -C 12 heteroaryl, —NR′R′ or COOZ, which have diagnostic and therapeutic properties, such as the treatment and management of prostate cancer and other diseases related to NAALADase inhibition. Radiolabels can be incorporated into the structure through a variety of prosthetic groups attached at the X amino acid side chain via a carbon or hetero atom linkage.

  化合物的式子(Ia)，其中R是C6-C12取代或未取代芳基，C6-C12取代或未取代杂芳基，C1-C6取代或未取代烷基或—NR′R′，Q是C(O)，O，NR′，S，S(O)2，C(O)2(CH2)p，Y是C(O)，O，NR′，S，S(O)2，C(O)2( )p，Z是H或C1-C4烷基，R′是H，C(O)，S(O)2，C(O)2，C6-C12取代或未取代芳基，C6-C12取代或未取代杂芳基或C1-C6取代或未取代烷基，当取代时，芳基，杂芳基和烷基被卤素，C1-C12杂芳基，—NR′R′或COOZ取代，具有诊断和治疗性能，例如治疗和管理前列腺癌和其他与NAALADase抑制有关的疾病。可以通过连接到X氨基酸侧链的碳或杂原子连接处的各种假体团将放射性标记纳入结构中。
• TECHNETIUM- AND RHENIUM-BIS(HETEROARYL) COMPLEXES AND METHODS OF USE THEREOF FOR INHIBITING PSMA
  申请人：Babich John W.

  公开号：US20100178246A1

  公开（公告）日：2010-07-15

  A compound of Formula I, a pharmaceutically acceptable salt, or solvate thereof: complexes with metals such as rhenium, technetium, and others to provide a complex for imaging tissues or treating disease, particularly where the metal is radioactive. Such complexes are specific to PSMA protein and can therefore be used in imaging or treating cancer of the prostate and other tissue where the protein is expressed.

  公式I的化合物，其药学上可接受的盐或溶剂化物：与金属如铼、锝等形成络合物，以提供成像组织或治疗疾病的复合物，特别是当金属具有放射性时。这些复合物针对PSMA蛋白质具有特异性，因此可以用于成像或治疗前列腺癌和其他表达该蛋白质的组织。
• RADIOLABELED PROSTATE SPECIFIC MEMBRANE ANTIGEN INHIBITORS
  申请人：BABICH John W.

  公开号：US20130034494A1

  公开（公告）日：2013-02-07

  Compounds according to Formula I and Formula II are potent inhibitors of PSMA activity: The invention also provides pharmaceutical compositions of a complex of a radionuclide and a Formula I compound or a Formula II compound and methods of using the radionuclide complex of a Formula I compound or a Formula II compound for treating or diagnosis of a disease or a condition associated with PSMA activity.

  公式I和公式II所描述的化合物是PSMA活性的有效抑制剂：本发明还提供了一个由放射性核素和公式I化合物或公式II化合物组成的复合物的药物组合物，以及使用公式I化合物或公式II化合物的放射性核素复合物来治疗或诊断与PSMA活性相关的疾病或病况的方法。