(S)-2-Amino-4-ethylcarbamoyl-butyric acid tert-butyl ester | 255915-26-5

• 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-ethylcarbamoyl-butyric acid tert-butyl ester
• 英文别名: tert-butyl (2S)-2-amino-4-(ethylcarbamoyl)butanoate；tert-butyl (2S)-2-amino-5-(ethylamino)-5-oxopentanoate
• CAS: 255915-26-5
• 化学式: C₁₁H₂₂N₂O₃
• 分子量: 230.307
• InChiKey: JKOAROORAZPPCP-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.57
• 重原子数：
  16.0
• 可旋转键数：
  5.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  81.42
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (S)-2-Amino-4-ethylcarbamoyl-butyric acid tert-butyl ester 在 diethyl cyanophosphoridate 、 三乙胺 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 (S)-4-Ethylcarbamoyl-2-{4-[(2-methyl-4-oxo-3,4-dihydro-quinazolin-6-ylmethyl)-prop-2-ynyl-amino]-benzoylamino}-butyric acid
  参考文献：
  名称：

  The Synthesis and Thymidylate Synthase Inhibitory Activity of L-.gamma.-L-Linked Dipeptide and L-.gamma.-Amide Analogs of 2-Desamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI 198583)

  摘要：

  Sixteen gamma-linked dipeptide and four L-Glu-gamma-amide analogues of 2-desamino-2-methyl-N-10-propargyl-5,8-dideazafolic acid (ICI 198583) have been synthesized and evaluated as inhibitors of thymidylate synthase (TS). Z-blocked L-Glu-gamma-L-linked dipeptides and L-Glu-gamma-amides were prepared by condensing alpha-tert-butyl-N-(benzyloxycarbonyl)-L-glutamic acid with the appropriate tert-butyl-protected L-amino acid or amine. The Z group was removed by catalytic hydrogenolysis, and the resulting dipeptides or L-Glu-gamma-amides were condensed with the appropriate pteroic acid analogue trifluoroacetate salt using diethyl cyanophosphoridate as coupling reagent. Deprotection with trifluoroacetic acid in the final step gave the desired quinazoline gamma-linked dipeptides and L-Glu-gamma-amides as their trifluoroacetate salts. Nearly all the dipeptide analogues were potent inhibitors of TS, the best being ICI 198583-gamma-L-2-aminoadipate (IC50 = 2 nM). Several of these dipeptides were found to be susceptible to enzymatic hydrolysis in mice. The quinazoline monocarboxylate L-Glu-gamma-amides, lacking an alpha'-carboxyl group, are less active against TS and L1210 cell growth but are also not susceptible to enzymatic hydrolysis in mice.

  DOI：

  10.1021/jm00046a014
• 作为产物：
  描述：

  Z-谷安酸叔丁基酯 在 palladium on activated charcoal N-甲基吗啉 、 氢气 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 为溶剂， -20.0 ℃ 、101.33 kPa 条件下， 反应 4.33h， 生成 (S)-2-Amino-4-ethylcarbamoyl-butyric acid tert-butyl ester
  参考文献：
  名称：

  The Synthesis and Thymidylate Synthase Inhibitory Activity of L-.gamma.-L-Linked Dipeptide and L-.gamma.-Amide Analogs of 2-Desamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI 198583)

  摘要：

  Sixteen gamma-linked dipeptide and four L-Glu-gamma-amide analogues of 2-desamino-2-methyl-N-10-propargyl-5,8-dideazafolic acid (ICI 198583) have been synthesized and evaluated as inhibitors of thymidylate synthase (TS). Z-blocked L-Glu-gamma-L-linked dipeptides and L-Glu-gamma-amides were prepared by condensing alpha-tert-butyl-N-(benzyloxycarbonyl)-L-glutamic acid with the appropriate tert-butyl-protected L-amino acid or amine. The Z group was removed by catalytic hydrogenolysis, and the resulting dipeptides or L-Glu-gamma-amides were condensed with the appropriate pteroic acid analogue trifluoroacetate salt using diethyl cyanophosphoridate as coupling reagent. Deprotection with trifluoroacetic acid in the final step gave the desired quinazoline gamma-linked dipeptides and L-Glu-gamma-amides as their trifluoroacetate salts. Nearly all the dipeptide analogues were potent inhibitors of TS, the best being ICI 198583-gamma-L-2-aminoadipate (IC50 = 2 nM). Several of these dipeptides were found to be susceptible to enzymatic hydrolysis in mice. The quinazoline monocarboxylate L-Glu-gamma-amides, lacking an alpha'-carboxyl group, are less active against TS and L1210 cell growth but are also not susceptible to enzymatic hydrolysis in mice.

  DOI：

  10.1021/jm00046a014

文献信息

• The Synthesis and Thymidylate Synthase Inhibitory Activity of L-.gamma.-L-Linked Dipeptide and L-.gamma.-Amide Analogs of 2-Desamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI 198583)
  作者：Graham M. F. Bisset、Vassilios Bavetsias、Timothy J. Thornton、Krzysztof Pawelczak、A. Hilary Calvert、Leslie R. Hughes、Ann L. Jackman

  DOI：10.1021/jm00046a014

  日期：1994.9

  Sixteen gamma-linked dipeptide and four L-Glu-gamma-amide analogues of 2-desamino-2-methyl-N-10-propargyl-5,8-dideazafolic acid (ICI 198583) have been synthesized and evaluated as inhibitors of thymidylate synthase (TS). Z-blocked L-Glu-gamma-L-linked dipeptides and L-Glu-gamma-amides were prepared by condensing alpha-tert-butyl-N-(benzyloxycarbonyl)-L-glutamic acid with the appropriate tert-butyl-protected L-amino acid or amine. The Z group was removed by catalytic hydrogenolysis, and the resulting dipeptides or L-Glu-gamma-amides were condensed with the appropriate pteroic acid analogue trifluoroacetate salt using diethyl cyanophosphoridate as coupling reagent. Deprotection with trifluoroacetic acid in the final step gave the desired quinazoline gamma-linked dipeptides and L-Glu-gamma-amides as their trifluoroacetate salts. Nearly all the dipeptide analogues were potent inhibitors of TS, the best being ICI 198583-gamma-L-2-aminoadipate (IC50 = 2 nM). Several of these dipeptides were found to be susceptible to enzymatic hydrolysis in mice. The quinazoline monocarboxylate L-Glu-gamma-amides, lacking an alpha'-carboxyl group, are less active against TS and L1210 cell growth but are also not susceptible to enzymatic hydrolysis in mice.