N^α-Boc-ε-benzyl-D-glutamic acid dipropylamide | 117997-80-5

• 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: N^α-Boc-ε-benzyl-D-glutamic acid dipropylamide
• 英文别名: benzyl (4R)-5-(dipropylamino)-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxopentanoate
• CAS: 117997-80-5
• 化学式: C₂₃H₃₆N₂O₅
• 分子量: 420.549
• InChiKey: UFDPPKGPDXLEDQ-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  30
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  84.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N^α-Boc-ε-benzyl-D-glutamic acid dipropylamide 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 反应 0.33h， 以89%的产率得到ε-benzyl-D-glutamic acid dipropylamide hydrochloride
  参考文献：
  名称：

  Novel glutamic acid-derived cholecystokinin receptor ligands

  摘要：

  Novel aryl amide analogues of glutamic acid dialkylamide have been synthesized to test for a possible structural analogy between glutamic acid and benzodiazepine CCK antagonists such as compounds 2 and 24 (lorglumide and MK-329, respectively). In support of the structural model, certain of these hybrid compounds are more potent in pancreas CCK radioligand binding assays than corresponding lorglumide-type reference compounds. Modifications previously found in the benzodiazepine antagonists to result in brain CCK/gastrin receptor selectivity were also incorporated to produce an aryl urea series of glutamic acid analogues. None of these compounds were brain CCK/gastrin selective; however, one was potent and selective in the pancreas binding assay. The model appears to be most useful in the design of selective ligands for the pancreas type CCK receptor.

  DOI：

  10.1021/jm00164a020
• 作为产物：
  描述：

  D-谷氨酸 在 TEA 、 氢碘酸 、 双(2-氧代-3-恶唑烷基)次磷酰氯 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 N^α-Boc-ε-benzyl-D-glutamic acid dipropylamide
  参考文献：
  名称：

  Synthesis of a radiolabeled type A cholecystokinin receptor antagonist, (R)-N-pentyl-N-(4,5-di[3H]pentyl) N?-(3-quinolinoyl)glutamic acid amide

  摘要：

  A method for the preparation of a radiolabeled CCKA-specific antagonist, (R)-N-pentyl-N-(4, 5-di[H-3]pentyl) N-alpha-(3-quinolinoyl)glutamic acid amide, [H-3]-A-65186, is described. (R)-gamma-Benzyl-N-BOC-glutamic acid was coupled with N-(4-pentenyl)-N-pentylamine using BOPCl and TEA in dichloromethane to provide the corresponding amide. Deprotection of the alpha-amino moiety followed by coupling with 3-quinolinecarboxylic acid in the presence of EDCI, TEA, and HOBt in dichloromethane resulted in (R)-N-(4-pentenyl)-N-pentyl gamma-benzyl-N-alpha-(3-quinolinoyl)glutamic acid amide. Tritiation with concomitant hydrogenolysis of the benzyl ester proceeds smoothly to provide [H-3]-A-65186.

  DOI：

  10.1002/(sici)1099-1344(200001)43:1<77::aid-jlcr292>3.0.co;2-v

文献信息

• Synthesis of N-acyl-.GAMMA.-D-glutamyl peptide derivatives containing a C-terminal small fragment of cholecystokinin and their effects on gastric secretion.
  作者：KOJI IUCHI、KEIZO ITO、GORO TSUKAMOTO

  DOI：10.1248/cpb.36.3433

  日期：——

  N-Acyl-γ-D-glutamyl peptide derivatives containing a C-terminal small fragment of cholecystokinin were prepared and their effects on gastric secretion were investigated. PhCO-D-Glu(Phe-NH2)-NPr2 and PhCO-D-Glu(Asp-Phe-NH2)-NPr2 inhibited gastric secretion, while PhCO-D-Glu(Met-Asp-Phe-NH2)-NPr2 and PhCO-D-Glu(Trp-Met-Asp-Phe-NH2)-NPr2 stimulated gastric secretion. The substitution of the acyl function at the N-terminal of PhCO-D-Glu(Phe-NH2)-NPr2 affected the activity. Z-D-Glu(Phe-NH2)-NPr2, 4-chlorobenzoyl-D-Glu-(Phe-NH2)-NPr2 and isonicotinoyl-D-Glu(Phe-NH2)-NPr2 were found to have more potent inhibitory activity against gastric secretion than proglumide (PhCO-DL-Glu-NPr2).

  制备了含有胆囊收缩素 C 端小片段的 N-酰基-γ-D-谷氨酰肽衍生物，并研究了它们对胃液分泌的影响。PhCO-D-Glu(Phe-NH2)-NPr2和PhCO-D-Glu(Asp-Phe-NH2)-NPr2抑制胃液分泌，而PhCO-D-Glu(Met-Asp-Phe-NH2)-NPr2和PhCO-D-Glu(Trp-Met-Asp-Phe-NH2)-NPr2刺激胃液分泌。PhCO-D-Glu(Phe-NH2)-NPr2 N 端酰基功能的替代影响了其活性。研究发现，Z-D-Glu(Phe-NH2)-NPr2、4-氯苯甲酰基-D-Glu-(Phe-NH2)-NPr2 和异烟酰基-D-Glu(Phe-NH2)-NPr2 对胃液分泌的抑制活性比丙谷胺（PhCO-DL-Glu-NPr2）更强。
• IUCHI, KOJI;ITO, KEIZO;TSUKAMOTO, GORO, CHEM. AND PHARM. BULL., 36,(1988) N 9, C. 3433-3438
  作者：IUCHI, KOJI、ITO, KEIZO、TSUKAMOTO, GORO

  DOI：——

  日期：——
• Novel glutamic acid-derived cholecystokinin receptor ligands
  作者：R. M. Freidinger、W. L. Whitter、N. P. Gould、M. K. Holloway、R. S. L. Chang、V. J. Lotti

  DOI：10.1021/jm00164a020

  日期：1990.2

  Novel aryl amide analogues of glutamic acid dialkylamide have been synthesized to test for a possible structural analogy between glutamic acid and benzodiazepine CCK antagonists such as compounds 2 and 24 (lorglumide and MK-329, respectively). In support of the structural model, certain of these hybrid compounds are more potent in pancreas CCK radioligand binding assays than corresponding lorglumide-type reference compounds. Modifications previously found in the benzodiazepine antagonists to result in brain CCK/gastrin receptor selectivity were also incorporated to produce an aryl urea series of glutamic acid analogues. None of these compounds were brain CCK/gastrin selective; however, one was potent and selective in the pancreas binding assay. The model appears to be most useful in the design of selective ligands for the pancreas type CCK receptor.
• Synthesis of a radiolabeled type A cholecystokinin receptor antagonist, (R)-N-pentyl-N-(4,5-di[3H]pentyl) N?-(3-quinolinoyl)glutamic acid amide
  作者：Justin A. Malone、Roger D. Reidelberger、Martin Hulce

  DOI：10.1002/(sici)1099-1344(200001)43:1<77::aid-jlcr292>3.0.co;2-v

  日期：2000.1

  A method for the preparation of a radiolabeled CCKA-specific antagonist, (R)-N-pentyl-N-(4, 5-di[H-3]pentyl) N-alpha-(3-quinolinoyl)glutamic acid amide, [H-3]-A-65186, is described. (R)-gamma-Benzyl-N-BOC-glutamic acid was coupled with N-(4-pentenyl)-N-pentylamine using BOPCl and TEA in dichloromethane to provide the corresponding amide. Deprotection of the alpha-amino moiety followed by coupling with 3-quinolinecarboxylic acid in the presence of EDCI, TEA, and HOBt in dichloromethane resulted in (R)-N-(4-pentenyl)-N-pentyl gamma-benzyl-N-alpha-(3-quinolinoyl)glutamic acid amide. Tritiation with concomitant hydrogenolysis of the benzyl ester proceeds smoothly to provide [H-3]-A-65186.