2-[((S)-3-Amino-3-methoxycarbonyl-propyl)-methoxy-phosphinoylmethyl]-pentanedioic acid dimethyl ester | 875668-11-4

• 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: 2-[((S)-3-Amino-3-methoxycarbonyl-propyl)-methoxy-phosphinoylmethyl]-pentanedioic acid dimethyl ester
• 英文别名: dimethyl 2-[[[(3S)-3-amino-4-methoxy-4-oxobutyl]-methoxyphosphoryl]methyl]pentanedioate
• CAS: 875668-11-4
• 化学式: C₁₄H₂₆NO₈P
• 分子量: 367.336
• InChiKey: ZAJRAMBUOGQGSA-QRPJCFFRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  24
• 可旋转键数：
  14
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  131
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-[((S)-3-Amino-3-methoxycarbonyl-propyl)-methoxy-phosphinoylmethyl]-pentanedioic acid dimethyl ester 在 palladium on activated charcoal 氢气 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 dimethyl 2-[[methoxy-[(3S)-4-methoxy-3-[[4-(methylamino)benzoyl]amino]-4-oxobutyl]phosphoryl]methyl]pentanedioate
  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：

  (S)-2-[(3-benzyloxycarbonylamino-3-methoxycarbonyl-propyl)-methoxy-phosphinoylmethyl]-pentanedioic acid dimethyl ester 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 为溶剂， 以95%的产率得到2-[((S)-3-Amino-3-methoxycarbonyl-propyl)-methoxy-phosphinoylmethyl]-pentanedioic acid dimethyl 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

• 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.