Boc-D-Trp-isoamylamide | 128684-51-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: Boc-D-Trp-isoamylamide
• 英文别名: tert-butyl N-[(2R)-3-(1H-indol-3-yl)-1-(3-methylbutylamino)-1-oxopropan-2-yl]carbamate
• CAS: 128684-51-5
• 化学式: C₂₁H₃₁N₃O₃
• 分子量: 373.495
• InChiKey: KKRHNJJJHIROFE-GOSISDBHSA-N

物化性质

• 熔点：
  124-125 °C
• 沸点：
  610.0±55.0 °C(Predicted)
• 密度：
  1.113±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  83.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Boc-D-Trp-isoamylamide 在 盐酸 、 溶剂黄146 作用下， 反应 0.33h， 以29%的产率得到(2R)-2-amino-3-(1H-indol-3-yl)-N-(3-methylbutyl)propanamide
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of non-peptidic ligands at the Xenopus laevis skin-melanocortin receptor

  摘要：

  Taking the tripeptide D-Trp-Arg-Leu-NH2 as a lead for a Xenopus laevis skin-melanocortin (MC) receptor antagonist, thirteen non-peptidic compounds were synthesized and biologically evaluated at Xenopus laevis melanophores. Six competitive antagonists (shown by Schild analysis) and one partial agonist were identified with moderate activity (IC50: 5-10 muM). Tryptophanamides with aliphatic side chains were inactive whereas basic residues restored activity. Introducing an imidazole residue yielded partial agonist activity (EC50: 32 muM). Interestingly, constraining the inactive S-tryptophan-isoamylamide to a beta-carboline ring yielded an MC receptor antagonist (42). The specificity for MC receptors was tested at various G-protein coupled receptors. In conclusion, the synthesis of non-peptidic MC receptor antagonists is described which may serve as lead compounds for further studies. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved.

  DOI：

  10.1016/s0223-5234(03)00062-x
• 作为产物：
  描述：

  D-色氨酸 在 sodium hydroxide 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 3.0h， 生成 Boc-D-Trp-isoamylamide
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of non-peptidic ligands at the Xenopus laevis skin-melanocortin receptor

  摘要：

  Taking the tripeptide D-Trp-Arg-Leu-NH2 as a lead for a Xenopus laevis skin-melanocortin (MC) receptor antagonist, thirteen non-peptidic compounds were synthesized and biologically evaluated at Xenopus laevis melanophores. Six competitive antagonists (shown by Schild analysis) and one partial agonist were identified with moderate activity (IC50: 5-10 muM). Tryptophanamides with aliphatic side chains were inactive whereas basic residues restored activity. Introducing an imidazole residue yielded partial agonist activity (EC50: 32 muM). Interestingly, constraining the inactive S-tryptophan-isoamylamide to a beta-carboline ring yielded an MC receptor antagonist (42). The specificity for MC receptors was tested at various G-protein coupled receptors. In conclusion, the synthesis of non-peptidic MC receptor antagonists is described which may serve as lead compounds for further studies. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved.

  DOI：

  10.1016/s0223-5234(03)00062-x

文献信息

• Inhibitors of human renin. Cyclic peptide analogs containing a D-Phe-Lys-D-Trp sequence
  作者：Anand S. Dutta、James J. Gormley、Peter F. McLachlan、John S. Major

  DOI：10.1021/jm00171a034

  日期：1990.9

  these compounds. Reducing the ring size gave much less potent compounds. The most potent analogue of the series, CO(CH2)2CHPhCO-D-Phe-Lys-D-Trp-NH(CH2)2CHMe (14, IC50 = 26 nM), was obtained by substituting the methylene group nearer to the D-Phe residue by a -CHPh- group. Compound 14 was 15-fold more potent in inhibiting human renin than porcine renin.

  已经合成了含有D-苯丙氨酸和D-色氨酸残基的环肽，并测试了其作为人肾素的抑制剂。其中大多数是CO（CH2）3CO-D-Phe-Lys-D-Trp-型或CO NH CO-Dhe-Lys-D-Trp-型的三肽衍生物，其中各个侧链亚甲基已被取代-CHMe-，-CMe2-，-CH（Ph）-，-CH（ Ph）-或-CH [ ）2CHMe2）-基团。这三个氨基酸残基和环的大小是这些化合物非常重要的特征。减小环的大小得到的有效化合物少得多。该系列最有效的类似物CO（ ）2CHPhCO-D-Phe-Lys-D-Trp-NH（ ）2CHMe（14，IC50 = 26 nM）通过取代更靠近D-的亚甲基获得-CHPh-基团的Phe残基。化合物14在抑制人肾素方面的效力比猪肾素高15倍。
• DUTTA, ANAND S.;GORMLEY, JAMES J.;MCLACHLAN, PETER F.;MAJOR, JOHN S., J. MED. CHEM., 33,(1990) N, C. 2560-2568
  作者：DUTTA, ANAND S.、GORMLEY, JAMES J.、MCLACHLAN, PETER F.、MAJOR, JOHN S.

  DOI：——

  日期：——