dibenzyl (3-indolylethylidene)acetamidomalonate | 19955-84-1

• 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: dibenzyl (3-indolylethylidene)acetamidomalonate
• 英文别名: acetylamino-(1-indol-3-yl-ethyl)-malonic acid dibenzyl ester；Acetylamino-(1-indol-3-yl-aethyl)-malonsaeure-dibenzylester；dibenzyl 2-acetamido-2-[1-(1H-indol-3-yl)ethyl]propanedioate
• CAS: 19955-84-1
• 化学式: C₂₉H₂₈N₂O₅
• 分子量: 484.552
• InChiKey: ZFDLPLQZTAOQFQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  36
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  97.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  dibenzyl (3-indolylethylidene)acetamidomalonate 在 钯 吡啶 、 氯化亚砜 、 氘氧化钠 、 硫酸 、 氢气 、 乙酸酐 、 α-chymotrypsin 作用下， 反应 25.5h， 生成 (2S,3R)-3-methyl-<2-2H>tryptophan
  参考文献：
  名称：

  Spoendlin, Christoph; Tamm, Christoph, Heterocycles, 1989, vol. 28, # 1, p. 453 - 465

  摘要：

  DOI：
• 作为产物：
  描述：

  乙酰氨基丙二酸二乙酯 在 sodium methylate 、 甲苯 作用下， 生成 dibenzyl (3-indolylethylidene)acetamidomalonate
  参考文献：
  名称：

  The Synthesis of the 2-Amino-3-(3-indolyl)-butyric Acids (β-Methyltryptophans)

  摘要：

  DOI：

  10.1021/ja01566a050

文献信息

• Novel sst₄-Selective Somatostatin (SRIF) Agonists. 3. Analogues Amenable to Radiolabeling
  作者：Judit Erchegyi、Beatrice Waser、Jean-Claude Schaer、Renzo Cescato、Jean François Brazeau、Jean Rivier、Jean Claude Reubi

  DOI：10.1021/jm030245x

  日期：2003.12.1

  After our discovery that H-c [Cys-Phe-Phe-DNal-Lys-Thr-Phe-Cys]-OH (ODN-8) had high affinity and marginal selectivity for human sst(3) (part 2 of this series: Erchegyi et al. J. Med. Chem., preceding paper in this issue)(11) and that H-c[Cys-Phe-Phe-DTrp-Lys-Thr-Phe-Cys]-OH (ODT-8, 3) had high affinity and marginal selectivity for human sst(4), that H-c[Cys-Phe-Tyr-D-threo-beta-Me2Nal-Lys-Thr-Phe-Cys]-OH had high affinity for all sst's except for sst(1), and that H-c[Cys-Phe-Tyr-L-threo-beta-Me2Nal-Lys-Thr-Phe-Cys]-OH had high affinity for sst(4) (IC50 = 2.1 nM), with more than 50-fold selectivity toward the other receptors (parts 1 and 2 of this series: Rivier et al. and Erchegyi et al. J Med. Chem., preceding papers in this issue), we found H-c[Cys-Phe-Phe-Trp-Lys-Thr-Phe-Cys]-OH (OLT-8,2), H-c[Cys-Phe-Phe-L-threo-beta-MeTrp-Lys-Thr-Phe-Cys]-OH (4) and H-c[Cys-Phe-Phe-D-threo-beta-MeTrp-Lys-Thr-Phe-Cys]-OH (5) to have very high affinity for sst(4) (IC50 = 0.7, 1.8, and 4.0 nM, respectively) and 5- to 10-fold selectivity versus the other sst's. From earlier work, we concluded that an L-amino acid at position 8 and a tyrosine or 4-aminophenylalanine substitution at position 7 may lead to high sst(4) selectivity. In fact, [Tyr(7)]-2 (6) and [Tyr(7)]-3 (7) show ca. 5-fold selectivity for sst(4), and [Aph(7)]-2 (8) and [Aph(7)]-3 (9) have high sst(4) affinity (IC50 = 1.2 and 0.88 nM, respectively) and selectivity, suggesting that indeed an L-residue at position 8 will direct selectivity toward sst(4) Unexpectedly, [Ala(7)]-2 (10) and [Ala(7)]-3 (11) have very high sst(4) affinity (IC50 = 0.84 and 0.98 nM, respectively) and selectivity (>600- and 200-fold, respectively). The combination of Tyr(2) and DTrp(8) in analogues 14 and 22 did not affect the affinity of the analogues for sst(4) (IC50 = 1.2 and 1.1 nM, respectively) but resulted in loss of selectivity, whereas the combination of Tyr(2) and LTrp(8) in H-Tyr-c[Cys-Phe-Aph-Trp-Lys-Thr-Phe-Cys]-OH (13) and H-Tyr-c[Cys-Phe-Ala-Trp-Lys-Thr-Phe-Cys]-OH-(19) retained high affinity (IC50 = 1.9 and 1.98 nM, respectively) and sst(4) selectivity (>50 and >250, respectively). Interestingly, the same substitutions at positions 2 and 7, with L-threo-beta-MeTrp at position 8, yielded a much less selective analogue (20). Carbamoylation of the N-terminus of most of these analogues resulted in slightly improved affinity, selectivity, or both. Other amino acid substitutions in this series, such as those with Amp (25, 26), Orn (27), or LAmp (29) at position 7, were also tolerated but with a 2- to Mold loss of affinity and concomitant loss of selectivity. Analogous peptides with a tyrosine at position 11 (31-36) were less selective than the corresponding peptides with a tyrosine at position 2. Several analogues in this series compared favorably with the non-peptide L-803,087 (37) in terms of affinity and selectivity. Analogues 8, 10, and 21 potently inhibited the forskolin-stimulated cAMP production in sst(4)-transfected cells, therefore acting as full agonists. Cold monoiodination of 19 yielded 21, with retention of high sst(4) selectivity and affinity (IC50 = 3.5 nM). (125)Iodinated 19 selectively binds to sst(4)-transfected cells but not to sst(1-3)- or sst(5)-transfected cells.Binding in sst(4)-transfected cells was completely displaced by SRIF-28 or the sst(4)-selective L-803,087.
• Spoendlin, Christoph; Tamm, Christoph, Heterocycles, 1989, vol. 28, # 1, p. 453 - 465
  作者：Spoendlin, Christoph、Tamm, Christoph

  DOI：——

  日期：——
• The Synthesis of the 2-Amino-3-(3-indolyl)-butyric Acids (β-Methyltryptophans)
  作者：H. R. Snyder、Donald S. Matteson

  DOI：10.1021/ja01566a050

  日期：1957.5