benzyl 3-((1,3-dioxoisoindolin-2-yl)oxy)-2,2-dimethylpropanoate | 464189-15-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: benzyl 3-((1,3-dioxoisoindolin-2-yl)oxy)-2,2-dimethylpropanoate
• 英文别名: Benzyl 3-(1,3-dioxoisoindol-2-yl)oxy-2,2-dimethylpropanoate
• CAS: 464189-15-9
• 化学式: C₂₀H₁₉NO₅
• 分子量: 353.375
• InChiKey: UGUDQFQXMYFKBJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  benzyl 3-((1,3-dioxoisoindolin-2-yl)oxy)-2,2-dimethylpropanoate 在 palladium on activated charcoal N-羟基-7-氮杂苯并三氮唑 、 氢气 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 、 氯仿 为溶剂， 反应 1.5h， 生成
  参考文献：
  名称：

  β^2,2-Aminoxy Acids:  A New Building Block for Turns and Helices

  摘要：

  The conformational properties of peptides 1-4 built from 3-aminoxy-2,2-dimethyl-propionic acid, a beta2,2-aminoxy acid, were investigated by NMR spectroscopy and X-ray crystallography. A novel beta N-O turn involving a nine-membered-ring intramolecular hydrogen bond between NHi+2 and COi was formed in diamides 1 and 2, which was further stabilized by another six-membered-ring intramolecular hydrogen bond between NHi+2 and NOi+1. Triamides 3 and 4 displayed a well-defined helical structure featuring two consecutive beta N-O turns. The X-ray structure of 4 revealed that the amide carbonyl group at position i+2 was twisted +65.9 degrees from that at i position, suggesting a novel 1.79 helix. Therefore, beta2,2-aminoxy acid can be used as a new building block for turns and helices.

  DOI：

  10.1021/ja026966n
• 作为产物：
  描述：

  2,2-二甲基-3-羟基丙酸 在 偶氮二甲酸二异丙酯 、 caesium carbonate 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 7.0h， 生成 benzyl 3-((1,3-dioxoisoindolin-2-yl)oxy)-2,2-dimethylpropanoate
  参考文献：
  名称：

  β^2,2-Aminoxy Acids:  A New Building Block for Turns and Helices

  摘要：

  The conformational properties of peptides 1-4 built from 3-aminoxy-2,2-dimethyl-propionic acid, a beta2,2-aminoxy acid, were investigated by NMR spectroscopy and X-ray crystallography. A novel beta N-O turn involving a nine-membered-ring intramolecular hydrogen bond between NHi+2 and COi was formed in diamides 1 and 2, which was further stabilized by another six-membered-ring intramolecular hydrogen bond between NHi+2 and NOi+1. Triamides 3 and 4 displayed a well-defined helical structure featuring two consecutive beta N-O turns. The X-ray structure of 4 revealed that the amide carbonyl group at position i+2 was twisted +65.9 degrees from that at i position, suggesting a novel 1.79 helix. Therefore, beta2,2-aminoxy acid can be used as a new building block for turns and helices.

  DOI：

  10.1021/ja026966n

文献信息

• [EN] NEW PEPTIDE-LINKED ESTER PRODRUGS ACTIVATED BY PROSTATE-SPECIFIC ANTIGEN<br/>[FR] NOUVEAUX PROMÉDICAMENTS D'ESTER À LIAISON PEPTIDIQUE ACTIVÉS PAR UN ANTIGÈNE SPÉCIFIQUE DE LA PROSTATE
  申请人：UNIV RUTGERS

  公开号：WO2018144880A1

  公开（公告）日：2018-08-09

  The present disclosure is directed to a series of target-selective chemotherapeutic ester prodrugs comprising PSA-cleavable peptides that promote the delivery of free doxorubicin and other chemotherapeutic agents into the prostate and/or prostate tumors with greater efficiency.

  本公开涉及一系列目标选择性化疗酯前药，包括促进游离阿霉素和其他化疗药物更有效地输送到前列腺和/或前列腺肿瘤的PSA可切割肽。
• Synthesis and evaluation of new peptide-linked doxorubicin conjugates as prodrugs activated by prostate-specific antigen
  作者：Herve Aloysius、Longqin Hu

  DOI：10.1007/s00044-020-02573-w

  日期：2020.7

  and resistance to non-PSA-mediated hydrolysis in plasma, GABA ← mGly-Ala-Ser-Chg-Gln and glutaryl-Ser-Ala-Ser-Chg-Gln were selected as optimal promoieties and coupled to doxorubicin (Dox) as PSA-targeted prodrugs, using Ser-Leu linkers. Following 72-h incubations with Dox prodrugs, there was insignificant cytotoxicity in non-PSA-producing DU145 cells. The Dox prodrugs, glutaryl-Hyp-Ala-Ser-Chg-Gln-Ser-Leu-Dox

  细胞毒性剂的靶向递送到前列腺癌细胞经由先前已经证明了前列腺特异性抗原（PSA）对肽连接的前药的选择性激活。在我们继续设计具有改善的前列腺肿瘤特异性的前药的过程中，我们开发了GABA←mGly-Ala-Ser-Chg-Gln和谷氨酰-Ser-Ala-Ser-Chg-Gln作为从已知底物序列开始具有增强的PSA特异性的促销品。戊二酰-Hyp-Ala-Ser-Chg-Gln。根据它们在血浆中的PSA裂解速率和对非PSA介导的水解的抵抗力，选择GABA←mGly-Ala-Ser-Chg-Gln和谷氨酰-Ser-Ala-Ser-Chg-Gln作为最佳蛋白质，并与阿霉素偶联（Dox）作为使用PSA的前药，使用Ser-Leu接头。与Dox前药孵育72小时后，在不产生PSA的DU145细胞中没有明显的细胞毒性。Dox前药，戊二酰-Hyp-Ala-Ser-Chg-Gln-Ser-Leu-Dox（I），戊二酰
• Peptide-linked ester prodrugs activated by prostate-specific antigen
  申请人：RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY

  公开号：US11129901B2

  公开（公告）日：2021-09-28

  The present disclosure is directed to a series of target-selective chemotherapeutic ester prodrugs comprising PSA-cleavable peptides that promote the delivery of free doxorubicin and other chemotherapeutic agents into the prostate and/or prostate tumors with greater efficiency.

  本公开涉及一系列靶向选择性化疗酯原药，这些原药由可清除 PSA 的肽组成，可促进游离多柔比星和其他化疗药物更有效地进入前列腺和/或前列腺肿瘤。