BOC-D-色氨酸(Nin-甲酰) | 64905-10-8

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 色氨酸类衍生物
• 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
• 中文名称: BOC-D-色氨酸(Nin-甲酰)
• 中文别名: BOC-D-色氨酸(NIN-甲酰)
• 英文名称: Boc-D-Trp(For)-OH
• 英文别名: (2R)-3-(1-formylindol-3-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid
• CAS: 64905-10-8
• 化学式: C₁₇H₂₀N₂O₅
• mdl: MFCD00038004
• 分子量: 332.356
• InChiKey: IHXHBYFWSOYYTR-CYBMUJFWSA-N

物化性质

• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.352
• 拓扑面积：
  97.6
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  BOC-D-色氨酸(Nin-甲酰) 在 盐酸 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.17h， 生成 FR 113680
  参考文献：
  名称：

  神经激肽拮抗剂的研究。2.新型三肽物质P拮抗剂Nα-[Nα-（Nα-乙酰基-L-苏氨酸）-N1-甲酰基-D-色氨酸] -N-甲基-N-（苯甲基）的设计与构效关系）-L-苯丙氨酰胺及其相关化合物。

  摘要：

  继续研究先前报道的新型三肽SP拮抗剂Nα-[Nα-[Nα-（叔丁氧基羰基）谷氨酰胺基] -N1-甲酰基-D-色氨酸]苯丙氨酸苄酯[Boc-Gln- D-Trp-（CHO）-Phe-OBzl（1）]在本文中描述。我们最初研究了豚鼠血浆和肝脏匀浆中1的稳定性，以阐明结构中最不稳定的部分。结果表明，苄基酯部分易于水解以产生惰性酸类似物。因此，我们搜索了对水解酶更具抗性的苄基酯替代物。该方法发现了等价酰胺结构，N-甲基-N-（苯甲基）酰胺，其效力和稳定性均合适。随后将氨基末端修饰成Nα-乙酰基-L-苏氨酸导致了最有效的化合物Nα-[Nα-（Nα-乙酰基-L-苏氨酸）-N1-甲酰基-D-色氨酸] -N -甲基-N-（苯甲基）-L-苯丙氨酰胺[Ac-Thr-D-Trp（CHO）-Phe-NMeBzl（5a，FR113680）]。该化合物5a有效阻断3H-SP与豚鼠肺膜的结合，IC50为（5.8 +/-

  DOI：

  10.1021/jm00095a013

文献信息

• Kasumigamide, an Antialgal Peptide from the Cyanobacterium <i>Microcystis aeruginosa</i>
  作者：Keishi Ishida、Masahiro Murakami

  DOI：10.1021/jo991918f

  日期：2000.9.1

  Kasumigamide (1), a novel antialgal tetrapeptide containing an N-terminal alpha-hydroxy acid, was isolated from the freshwater cyanobacterium Microcystis aeruginosa (NIES-87). Its structure was elucidated by two-dimensional (1)H-(1)H and (1)H-(13)C NMR correlation experiments and confirmed by mass spectral and amino acid analyses. The absolute stereochemistry of 1 was determined by chemical studies

  从淡水蓝藻铜绿微囊藻（NIES-87）中分离出了一种Kasumigamide（1），它是一种含有N末端α-羟基酸的新型抗藻四肽。通过二维（1）H-（1）H和（1）H-（13）C NMR相关实验阐明了其结构，并通过质谱和氨基酸分析证实了该结构。1的绝对立体化学是通过化学研究确定的。该肽对绿藻衣藻（NIES-439）显示出抗藻活性。
• Acyclic structural variants of growth hormone secretagogue L-692,429
  作者：Peter Lin、Judith M. Pisano、William R. Schoen、Kang Cheng、Wanda W.-S. Chan、Bridget S. Butler、Roy G. Smith、Michael H. Fisher、Matthew J. Wyvratt

  DOI：10.1016/s0960-894x(99)00568-5

  日期：1999.11

  Systematic investigation of acyclic analogs of L-692,429, the prototype benzolactam growth hormone secretagogue, has helped to further define the structural requirements for the release of growth hormone from rat pituitary cells for this class of secretagogues.

  对L-692,429（原型苯并内酰胺生长激素促分泌素）的无环类似物的系统研究有助于进一步确定此类促泌素从大鼠垂体细胞释放生长激素的结构要求。
• Peptide compounds, processes for preparation thereof and pharmaceutical
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US05187156A1

  公开（公告）日：1993-02-16

  The present invention relates to DTrp-Phe containing tripeptides and pharmaceuticals, which possess tachykinin antagonism activity as well as processes of making such peptides.

  本发明涉及含有DTrp-Phe的三肽和药物，具有快速激肽拮抗作用，并涉及制备这些肽的方法。
• Peptide compound and its preparation
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US05430022A1

  公开（公告）日：1995-07-04

  Peptide compounds of the formula (I') ##STR1## in which R.sup.1 is acyl, R.sup.2 is lower alkyl, cyclo(lower)alkyl(lower)alkyl or optionally substituted heterocyclic(lower)alkyl, R.sup.3 is optionally substituted heterocyclic(lower)alkyl or optionally substituted ar(lower)alkyl, R.sup.4 is lower alkyl, amino(lower)alkyl, protected amino(lower)alkyl, carboxy(lower)alkyl, protected carboxy(lower)alkyl or optionally substituted heterocyclic(lower)alkyl, R.sup.5 is carboxy, protected carboxy, carboxy(lower)alkyl or protected carboxy(lower)alkyl, R.sup.6 is hydrogen, lower alkyl, C.sub.6-10 ar(lower)alkyl amino(lower)alkyl, protected amino(lower)alkyl, carboxy(lower)alkyl, protected carboxy(lower)alkyl, or heterocyclic(lower)alkyl, R.sup.7 is hydrogen or lower alkyl, and A is --O--, --NH--, lower alkylimino or lower alkylene, or a pharmaceutically acceptable salt thereof are disclosed. The compounds can be used to treat and prevent endothelin mediated diseases such as hypertension. The preparation of such peptides is also disclosed.

  公式（I'）的多肽化合物如下：##STR1## 其中R.sup.1是酰基，R.sup.2是较低的烷基，环（较低）烷基（较低）烷基或可选取代的杂环（较低）烷基，R.sup.3是可选取代的杂环（较低）烷基或可选取代的芳基（较低）烷基，R.sup.4是较低的烷基，氨基（较低）烷基，保护的氨基（较低）烷基，羧基（较低）烷基，保护的羧基（较低）烷基或可选取代的杂环（较低）烷基，R.sup.5是羧基，保护的羧基，羧基（较低）烷基或保护的羧基（较低）烷基，R.sup.6是氢，较低的烷基，C.sub.6-10芳基（较低）烷基氨基（较低）烷基，保护的氨基（较低）烷基，羧基（较低）烷基，保护的羧基（较低）烷基或杂环（较低）烷基，R.sup.7是氢或较低的烷基，A是--O--，--NH--，较低烷基亚胺基或较低烷基烷基，或其药学上可接受的盐。这些化合物可用于治疗和预防内皮素介导的疾病，如高血压。还公开了这些肽的制备方法。
• Biological and Conformational Examination of Stereochemical Modifications Using the Template Melanotropin Peptide, Ac-Nle-c[Asp-His-Phe-Arg-Trp- Ala-Lys]-NH₂, on Human Melanocortin Receptors
  作者：Carrie Haskell-Luevano、Gregory Nikiforovich、Shubh D. Sharma、Ying-Kui Yang、Chris Dickinson、Victor J. Hruby、Ira Gantz

  DOI：10.1021/jm960845e

  日期：1997.5.1

  Examination of conformationally constrained melanotropin peptides (Ac-Nle(4)-c[Asp(5)-His-Phe(7)-Arg-Trp(9)-Ala-Lys]-NH2) on four human melanotropin receptors (hMC1R, hMC3R, hMC4R, and hMC5R) resulted in identifying the importance of ligand stereochemistry at positions 5, 7, and 9 for agonist binding affinity and receptor selectivity. A trend in ligand structure-activity relationships emerged for these peptides, with the hMC1R and hMC4R possessing similar tendencies, as did the hMC3R and hMC5R. alpha-MSH (Ac-Ser-Tyr-Ser-Met(4)-Glu-His-Phe(7)-Arg-Trp-Gly-Lys-Pro-Val-NH2), NDP-MSH (Ac-Ser-Tyr-Ser-Nle(4)-Glu-His-D-Phe(7)-Arg-Pro-Val-NH2), and MTII (Ac-Nle(4)-c[Asp(5),D-Phe(7),Lys(10)]-alpha-MSH(4-10)-NH2) were also examined at each of these melanocortin receptors. Interestingly, the linear NDP-MSH possessed greater binding affinity for the hMC3R and hMC5R than did the cyclic analogue MTII. The peptide Ac-Nle-c[Asp-His-Phe-Arg-D-Trp(9)-Ala-Lys]-NH2 demonstrated the greatest differentiation in binding affinity between the hMC1R and hMC4R (78-fold). Analogue Ac-Nle-c[Asp-His-Phe(7)-Arg-Trp-Ala-Lys]-NH2 resulted in micromolar binding affinity (or greater) at the hMC3R and hMC5R, demonstrating the importance of D-Phe(7) for ligand binding potency at these receptors. Ac-c[Asp-His-Phe-Arg-Trp-Ala-Lys]-NH2 resulted in loss of binding affinity at the hMC5R, implicating the importance of Nle(4) (or a hydrophobic residue in this position) for binding to this receptor. Ac-Nle-c[D-Asp(5)-His-Phe-Arg-Trp-Ala-Lys]-NH2 was unable to competitively displace [I-125]NDP-MSH binding at micromolar concentrations on the hMC3R and hMC5R, suggesting the importance of chirality of Asp(5) either for ligand-receptor interactions or for orientation of the side chain lactam bridge and the structural integrity of the peptide conformation. Energy calculations performed for these peptides resulted in the identification of a low-energy ligand conformer family that is common to all the ligands. The differences in ligand binding affinities observed in this study are postulated to be a result of different ligand-receptor complexed interactions and not solely to the ligand structure.