4-(2-carboxy-5-(hydroxyamino)-5-oxopentyl)benzoic acid

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: 4-(2-carboxy-5-(hydroxyamino)-5-oxopentyl)benzoic acid
• 英文别名: 4-carboxy-α-[3-(hydroxyamino)-3-oxopropyl]benzenepropanoic acid；4-carboxy-alpha-[3-(hydroxyamino)-3-oxopropyl]-benzenepropanoic acid；4-[2-Carboxy-5-(hydroxyamino)-5-oxopentyl]benzoic acid
• 化学式: C₁₃H₁₅NO₆
• 分子量: 281.265
• InChiKey: VUDGMYIWOPKVSL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  124
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  benzyl 4-(5-((benzyloxy)amino)-2-((benzyloxy)carbonyl)-5-oxopentyl)benzoate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 以98%的产率得到4-(2-carboxy-5-(hydroxyamino)-5-oxopentyl)benzoic acid
  参考文献：
  名称：

  谷氨酸羧肽酶的基于异羟肟酸酯的抑制剂的前所未有的结合模式：结构表征和生物活性。

  摘要：

  在与谷氨酸能系统过度激活有关的神经系统疾病的临床前模型中，谷氨酸羧肽酶II（GCPII）的抑制作用是有效的。在这里，我们报告合成，结构表征和具有纳摩尔摩尔对人GCPII的新型基于异羟肟酸的抑制剂的生物活性。GCPII /异羟肟酸酯复合物的晶体结构揭示了前所未有的结合模式，其中推定的P1'谷氨酸占据了宽敞的入口漏斗，而不是保守的结合谷氨酸的S1'口袋。这种独特的结合模式为结构-活性关系数据提供了机械解释，最值得注意的是缺乏对映体特异性以及对作为规范谷氨酸部分的取代基的大体积/疏水功能的耐受性。

  DOI：

  10.1021/acs.jmedchem.5b01806

文献信息

• [EN] PRODRUGS OF HYDROXAMATE-BASED GCPII INHIBITORS<br/>[FR] PROMÉDICAMENTS D'INHIBITEURS DE GCPII À BASE D'HYDROXAMATE
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2018094334A1

  公开（公告）日：2018-05-24

  Prodrugs of hydroxamate-based GCPII inhibitors and methods of their use for treating a disease or condition are disclosed.

  本发明揭示了羟肟基GCPII抑制剂的前药及其用于治疗疾病或病况的方法。
• Hydroxamic acids and acyl hydroxamines as NAALADase inhibitors
  申请人：Tsukamoto Takashi

  公开号：US20060009525A1

  公开（公告）日：2006-01-12

  This invention relates to new compounds, pharmaceutical compositions and diagnostic kits comprising such compounds, and methods of using such compounds for inhibiting NAALADase enzyme activity, detecting diseases where NAALADase levels are altered, effecting neuronal activity, effecting TGF-β activity, inhibiting angiogenesis, and treating glutamate abnormalities, neuropathy, pain, compulsive disorders, prostate diseases, cancers and glaucoma.

  本发明涉及新化合物、制药组合物和诊断试剂盒，包括这些化合物，并使用这些化合物抑制NAALADase酶活性、检测NAALADase水平改变的疾病、影响神经元活动、影响TGF-β活性、抑制血管生成，并治疗谷氨酸异常、神经病、疼痛、强迫症、前列腺疾病、癌症和青光眼。
• Naaladase inhibitors for treating opioid tolerance
  申请人：Guilford Pharmaceuticals Inc.

  公开号：US20040186081A1

  公开（公告）日：2004-09-23

  The present invention relates to pharmaceutical compositions and methods for treating opioid tolerance using NAALADase inhibitors.

  本发明涉及制药组合物和使用NAALADase抑制剂治疗阿片类药物耐受性的方法。
• Prodrug compositions and utility of hydroxamate-based GCPII inhibitors
  申请人：The Johns Hopkins University

  公开号：US11059775B2

  公开（公告）日：2021-07-13

  Prodrugs of hydroxamate-based GCPII inhibitors and methods of their use for treating a disease or condition are disclosed.

  本发明公开了羟基氨基甲酸酯类 GCPII 抑制剂的原药及其用于治疗疾病或病症的方法。
• Compounds which bind PSMA and uses thereof
  申请人：Heston Warren D.W.

  公开号：US20080311037A1

  公开（公告）日：2008-12-18

  A compound is represented by Structural Formula A1: C—B-L-A  A1 or a pharmaceutically acceptable salt or solvate thereof. A is a prostate specific membrane antigen (PSMA) ligand; L is an optionally substituted aliphatic or heteroaliphatic linking group; B includes at least one optionally substituted moiety selected from the group consisting of a sugar, a charged group, an aryl ring, and a heteroaryl ring, wherein B optionally includes a drug or a labeling agent; and C is H, a drug, or a labeling agent, wherein CB together comprises the drug or the labeling agent. The compounds are useful as PSMA agents and in pharmaceutical compositions, methods for treating and detecting diseases such as cancer in a subject, methods for identifying cancer cells in a sample, methods for inhibiting tumor neovascularization, methods for identifying drugs that can treat cancer, and the like.