MIP-1129 | 1025796-57-9

• 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: MIP-1129
• 英文别名: (S)-2-(3-((S)-1-carboxy-5-(3-(4-bromophenyl)ureido)pentyl)ureido)pentanedioic acid；2-(3-{1-carboxy-5-[3-(4-bromo-phenyl)-ureido]-pentyl}-ureido)-pentanedioic acid；(2S)-2-[[(1S)-5-[(4-bromophenyl)carbamoylamino]-1-carboxypentyl]carbamoylamino]pentanedioic acid
• CAS: 1025796-57-9
• 化学式: C₁₉H₂₅BrN₄O₈
• 分子量: 517.333
• InChiKey: KRBIFVSYVYPEFJ-KBPBESRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  32
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  194
• 氢给体数：
  7
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  ditert-butyl (2S)-2-[[(2S)-6-[(4-bromophenyl)carbamoylamino]-1-[(2-methylpropan-2-yl)oxy]-1-oxohexan-2-yl]carbamoylamino]pentanedioate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 MIP-1129
  参考文献：
  名称：

  A Series of Halogenated Heterodimeric Inhibitors of Prostate Specific Membrane Antigen (PSMA) as Radiolabeled Probes for Targeting Prostate Cancer

  摘要：

  Prostate specific membrane antigen (PSMA) is a validated molecular marker for prostate cancer. A series of glutamate-urea (Glu-urea-X) heterodimeric inhibitors of PSMA were designed and synthesized where X = epsilon-N-(o-I, m-I, p-I, p-Br, o-C1, m-C1, p-C1, p-F, H)-benzyl-Lys and epsilon-(p-I, p-Br, p-C1, p-F, H)-phenylureido-Lys. The affinities for PSMA were determined by screening in a competitive binding assay. PSMA binding of the benzyllysine series was significantly affected by the nature of the halogen substituent (IC50 values, Cl < I = Br << F = H) and the ring position of the halogen atom (IC50 values, p-I < o-I << m-I). The halogen atom had little affect oil the binding affinity in the para substituted phenylureido-Lys series. Two lead iodine compounds were radiolabeled with I-123 and I-131 and demonstrated specific PSMA binding on human prostate cancer cells, warranting evaluation as radioligands for the detection, staging, and monitoring of prostate cancer.

  DOI：

  10.1021/jm800994j

文献信息

• HETERODIMERS OF GLUTAMIC ACID
  申请人：Babich John W.

  公开号：US20080193381A1

  公开（公告）日：2008-08-14

  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 6 -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（ ）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。
• 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。
• Heterodimers of glutamic acid
  申请人：Molecular Insight Pharmaceuticals, Inc.

  公开号：US10640461B2

  公开（公告）日：2020-05-05

  Compounds of Formula (Ia) wherein R is a C6-C12 substituted or unsubstituted aryl, a C6-C12 substituted or unsubstituted heteroaryl, a C1-C6 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 C1-C4 alkyl, R′ is H, C(O), S(O)2, C(O)2, a C6-C12 substituted or unsubstituted aryl, a C6-C12 substituted or unsubstituted heteroaryl or a C1-C6 substituted or unsubstituted alkyl, when substituted, aryl, heteroaryl and alkyl are substituted with halogen, C6-C12 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.

  式（Ia）化合物 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 ( )p Z 是 H 或 C1-C4 烷基、 R′ 是 H、C(O)、S(O)2、C(O)2、取代或未取代的 C6-C12 芳基、取代或未取代的 C6-C12 杂芳基或取代或未取代的 C1-C6 烷基，当芳基、杂芳基和烷基被卤素取代时、C6-C12杂芳基、-NR′R′或 COOZ，它们具有诊断和治疗特性，如治疗和控制前列腺癌以及与 NAALADase 抑制有关的其他疾病。放射性标记可通过碳原子或杂原子连接在 X 氨基酸侧链上的各种人工基团掺入结构中。
• US8487129B2
  申请人：——

  公开号：US8487129B2

  公开（公告）日：2013-07-16
• US9309193B2
  申请人：——

  公开号：US9309193B2

  公开（公告）日：2016-04-12