(S)-2-Amino-4-bromo-butyric acid tert-butyl ester | 438542-12-2

• 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: (S)-2-Amino-4-bromo-butyric acid tert-butyl ester
• 英文别名: tert-butyl (2S)-2-amino-4-bromobutanoate
• CAS: 438542-12-2
• 化学式: C₈H₁₆BrNO₂
• 分子量: 238.125
• InChiKey: JQZFTTNXRQSVDT-LURJTMIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  12
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-2-Amino-4-bromo-butyric acid tert-butyl ester 在 sodium tetrahydroborate 、 碳酸氢钠 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 0.5h， 生成 tert-butyl (2S)-2-(N-benzyloxycarbonyl)amino-4-(phenylselenyl)butyrate
  参考文献：
  名称：

  Prodrug Forms of N-[(4-Deoxy-4-amino-10-methyl)pteroyl]glutamate-γ-[ψP(O)(OH)]-glutarate, a Potent Inhibitor of Folylpoly-γ-glutamate Synthetase: Synthesis and Hydrolytic Stability

  摘要：

  Ester prodrugs of the phosphinate pseudopeptide N-[(4-deoxy-4-amino-10-methyl)pteroyl]glutamate-gamma-[psi P(0)(OH)]-glutarate (1a) were synthesized. H-phosphinic acids derived from N-Cbz vinyl glycine esters were converted to the desired pseudopeptides by Michael addition to alpha-methyleneglutarate esters. Pivaloyloxymethyl (POM) ester moieties were incorporated in both the N-terminal and C-terminal fragments prior to formation of either C-P bond. N-Alkylation of the corresponding amides derived from p-(N-methyl)aminobenzoic acid with 2,4-diamino-6-(bromomethyl)pteridine gave the target compounds. POM esters of methotrexate and the corresponding gamma-glutamyl conjugate were also synthesized using the same strategy. All prodrugs were evaluated in Chinese hamster ovary cells. Although the pseudopeptide prodrugs were ineffective, prodrugs of methotrexate and the corresponding gamma-glutamyl conjugate were equipotent with the parent compounds. Stability of the prodrugs was investigated in both phosphate buffer and cell line medium to provide a rationale for the observed biological data.

  DOI：

  10.1021/jm050871p
• 作为产物：
  描述：

  (2S)-2-amino-4-bromobutanoic acid 、 异丁烯 在 硫酸 作用下， 以 二氯甲烷 为溶剂， 反应 96.0h， 生成 (S)-2-Amino-4-bromo-butyric acid tert-butyl ester
  参考文献：
  名称：

  Prodrug Forms of N-[(4-Deoxy-4-amino-10-methyl)pteroyl]glutamate-γ-[ψP(O)(OH)]-glutarate, a Potent Inhibitor of Folylpoly-γ-glutamate Synthetase: Synthesis and Hydrolytic Stability

  摘要：

  Ester prodrugs of the phosphinate pseudopeptide N-[(4-deoxy-4-amino-10-methyl)pteroyl]glutamate-gamma-[psi P(0)(OH)]-glutarate (1a) were synthesized. H-phosphinic acids derived from N-Cbz vinyl glycine esters were converted to the desired pseudopeptides by Michael addition to alpha-methyleneglutarate esters. Pivaloyloxymethyl (POM) ester moieties were incorporated in both the N-terminal and C-terminal fragments prior to formation of either C-P bond. N-Alkylation of the corresponding amides derived from p-(N-methyl)aminobenzoic acid with 2,4-diamino-6-(bromomethyl)pteridine gave the target compounds. POM esters of methotrexate and the corresponding gamma-glutamyl conjugate were also synthesized using the same strategy. All prodrugs were evaluated in Chinese hamster ovary cells. Although the pseudopeptide prodrugs were ineffective, prodrugs of methotrexate and the corresponding gamma-glutamyl conjugate were equipotent with the parent compounds. Stability of the prodrugs was investigated in both phosphate buffer and cell line medium to provide a rationale for the observed biological data.

  DOI：

  10.1021/jm050871p

文献信息

• ALPHA AMINOACID ESTER-DRUG CONJUGATES HYDROLYSABLE BY CARBOXYLESTERASE
  申请人：GlaxoSmithKline Intellectual Property Development Limited

  公开号：EP3530290A1

  公开（公告）日：2019-08-28

  Covalent conjugation of an alpha amino acid ester to a modulator of the activity of a target intracellular enzyme or receptor, wherein the ester group of the conjugate is hydrolysable by intracellular carboxylesterase enzyme hCE1 and not by hCE2 or hCE3 to the corresponding acid, leads to selective accumulation of the carboxylic acid hydrolysis product in monocyte/macrophage cell and enables improved or more prolonged enzyme or receptor modulation in those cells relative to the unconjugated modulator.

  将α-氨基酸酯与细胞内目标酶或受体活性调节剂共价共轭，其中共轭物的酯基可被细胞内羧基酯酶hCE1水解为相应的酸，而不能被hCE2或hCE3水解为相应的酸、导致羧酸水解产物在单核细胞/巨噬细胞中选择性积累，与未共轭的调节剂相比，可改善或延长对这些细胞中酶或受体的调节。
• ENZYME AND RECEPTOR MODULATION
  申请人：GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED

  公开号：US20190231887A1

  公开（公告）日：2019-08-01

  Covalent conjugation of an alpha amino acid ester to a modulator of the activity of a target intracellular enzyme or receptor, wherein the ester group of the conjugate is hydrolysable by one or more intracellular carboxylesterase enzymes to the corresponding acid, leads to accumulation of the carboxylic acid hydrolysis product in the cell and enables improved or more prolonged enzyme or receptor modulation relative to the unconjugated modulator.
• US7317040B2
  申请人：——

  公开号：US7317040B2

  公开（公告）日：2008-01-08
• Prodrug Forms of <i>N</i>-[(4-Deoxy-4-amino-10-methyl)pteroyl]glutamate-γ-[ψP(O)(OH)]-glutarate, a Potent Inhibitor of Folylpoly-γ-glutamate Synthetase: Synthesis and Hydrolytic Stability
  作者：Yan Feng、James K. Coward

  DOI：10.1021/jm050871p

  日期：2006.1.1

  Ester prodrugs of the phosphinate pseudopeptide N-[(4-deoxy-4-amino-10-methyl)pteroyl]glutamate-gamma-[psi P(0)(OH)]-glutarate (1a) were synthesized. H-phosphinic acids derived from N-Cbz vinyl glycine esters were converted to the desired pseudopeptides by Michael addition to alpha-methyleneglutarate esters. Pivaloyloxymethyl (POM) ester moieties were incorporated in both the N-terminal and C-terminal fragments prior to formation of either C-P bond. N-Alkylation of the corresponding amides derived from p-(N-methyl)aminobenzoic acid with 2,4-diamino-6-(bromomethyl)pteridine gave the target compounds. POM esters of methotrexate and the corresponding gamma-glutamyl conjugate were also synthesized using the same strategy. All prodrugs were evaluated in Chinese hamster ovary cells. Although the pseudopeptide prodrugs were ineffective, prodrugs of methotrexate and the corresponding gamma-glutamyl conjugate were equipotent with the parent compounds. Stability of the prodrugs was investigated in both phosphate buffer and cell line medium to provide a rationale for the observed biological data.