tert-butyl N⁵-benzyl-N²-((benzyloxy)carbonyl)-L-glutaminate | 95063-81-3

• 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: tert-butyl N⁵-benzyl-N²-((benzyloxy)carbonyl)-L-glutaminate
• 英文别名: N-Cbz-L-Gln(Bn)-OtBu；(S)-4-Benzylcarbamoyl-2-benzyloxycarbonylamino-butyric acid tert-butyl ester；tert-butyl (2S)-5-(benzylamino)-5-oxo-2-(phenylmethoxycarbonylamino)pentanoate
• CAS: 95063-81-3
• 化学式: C₂₄H₃₀N₂O₅
• 分子量: 426.513
• InChiKey: RUZXZJNGKXNABR-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.72
• 重原子数：
  31.0
• 可旋转键数：
  9.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  93.73
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  tert-butyl N⁵-benzyl-N²-((benzyloxy)carbonyl)-L-glutaminate 在 palladium on activated charcoal diethyl cyanophosphoridate 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 6.0h， 生成 (S)-4-Benzylcarbamoyl-2-{4-[(2-methyl-4-oxo-3,4-dihydro-quinazolin-6-ylmethyl)-prop-2-ynyl-amino]-benzoylamino}-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
• 作为产物：
  描述：

  N-苄氧羰基-L-谷氨酸 在 高氯酸 、 三乙胺 、 氯甲酸异丁酯 作用下， 反应 2.0h， 生成 tert-butyl N⁵-benzyl-N²-((benzyloxy)carbonyl)-L-glutaminate
  参考文献：
  名称：

  Antonjuk, David J.; Boadle, Deborah K.; Cheung, H.T.Andrew, Journal of the Chemical Society. Perkin transactions I, 1984, p. 1989 - 2004

  摘要：

  DOI：

文献信息

• DUAL MODE RADIOTRACER AND -THERAPEUTICS
  申请人：Technische Universität München

  公开号：EP4023250A1

  公开（公告）日：2022-07-06

  The present disclosure relates to compounds of Formula (1a), (1b), (1c) or (1d): and pharmaceutically acceptable salts thereof, wherein X, Z, L, CM and R1 are defined herein, and their use as cancer diagnostic or imaging agents.

  本公开涉及以下式子的化合物（1a）、（1b）、（1c）或（1d）：以及其药学上可接受的盐，其中X、Z、L、CM和R1在此定义，并且它们作为癌症诊断或成像剂的用途。