N-甲基-Nalpha-{[(2-甲基-2-丙基)氧基]羰基}-L-色氨酰胺 | 122900-21-4

• 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: N-甲基-Nalpha-{[(2-甲基-2-丙基)氧基]羰基}-L-色氨酰胺
• 英文名称: N^α-Boc-L-tryptophan N-methylamide
• 英文别名: (S)-tert-butyl (3-(1H-indol-3-yl)-1-methylamino-1-oxopropan-2-yl)carbamate；Boc-Trp-NHME；tert-butyl N-[(2S)-3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]carbamate
• CAS: 122900-21-4
• 化学式: C₁₇H₂₃N₃O₃
• 分子量: 317.388
• InChiKey: ZRYIVAXOMUWFLO-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 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：

  N-甲基-Nalpha-{[(2-甲基-2-丙基)氧基]羰基}-L-色氨酰胺 在 盐酸 、 氢氧化钾 、 盐酸羟胺 、 potassium carbonate 、 三乙胺 、 N,N'-羰基二咪唑 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 30.0h， 生成 (2R)-N-[(2S)-3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]-2-(2-methylpropyl)-N'-phenylmethoxybutanediamide
  参考文献：
  名称：

  Matrix Metalloproteinase Inhibitors:  A Structure−Activity Study

  摘要：

  Modifications around the dipeptide-mimetic core of a hydroxamic acid based matrix metalloproteinase inhibitor were studied. These variations incorporated a variety of natural, unnatural, and synthetic amino acids in addition to modifications of the P1' and P3' substituents. The results of this study indicate the following structural requirements: (1) Two key hydrogen bonds must be present between the enzyme and potent substrates. (2) Potent inhibitors must possess strong zinc-binding functionalities. (3) The potential importance of the hydrophobic group at position R3 as illustrated by its ability to impart greater relative potency against stromelysin when larger hydrophobic groups are used. (4) Requirements surrounding the nature of the amino acid appear to be more restrictive for stromelysin than for neutrophil collagenase, 72 kDa gelatinase, and 92 kDa gelatinase. These requirements may involve planar fused-ring aryl systems and possibly hydrogen-bonding capabilities.

  DOI：

  10.1021/jm970494j
• 作为产物：
  描述：

  盐酸甲胺 、 N-叔丁氧羰基-L-色氨酸 在 N,N-Diisopropylethylamine p-toluenesulfonate salt 、 1-丙基磷酸酐 作用下， 以 二氯甲烷 为溶剂， 生成 N-甲基-Nalpha-{[(2-甲基-2-丙基)氧基]羰基}-L-色氨酰胺
  参考文献：
  名称：

  一种萘啶酰胺类化合物及其制备方法与应用

  摘要：

  本发明公开了一种萘啶酰胺类化合物及其制备方法与应用，该萘啶酰胺类化合物具有式(A)的结构或其农药学上可接受的盐或其光学异构体； 本发明萘啶酰胺类化合物作为促分裂原活化蛋白激酶Mps1抑制剂，表现出优良的抑制稻瘟菌等真菌致病能力，可以有效防治水稻稻瘟病等真菌病害。

  公开号：

  CN115043834A

文献信息

• Phosphoramidate peptide inhibitors of human skin fibroblast collagenase
  作者：Zbigniew P. Kortylewicz、Richard E. Galardy

  DOI：10.1021/jm00163a044

  日期：1990.1

  An extensive series of N-(monoethylphosphoryl)peptides was synthesized and their inhibition of purified human skin fibroblast collagenase examined. At the cleavage site S1 all reported compounds have the (EtO)(OK)P(O) group and the peptide side chain extended toward the C-terminal end (up to P5') of the substrate sequence. These phosphoramidates with a tetrahedrally hybridized phosphorus atom are thought to be transition state analogue inhibitors. They exhibited fair inhibitory potency against this vertebrate collagenase having Ki values in the micromolar range. The most potent of these, (EtO)(OK)P(O)-Ile-TrpNHCH3 (68), inhibits with a Ki value of 1.5 microM and is nearly 100 times stronger than (EtO)(OK)P(O)-Ile-Ala-GlyOK (51) (Ki of 140 microM), which has the sequence matching that of the alpha 1 (I) chain of collagen in P1', P2', P3' after the cleavage site. Several compounds were prepared in an attempt to identify the nature of the S2', S3', and S4' binding sites. Alanine at the P2' position was replaced by leucine, phenylalanine, tryptophan, or tyrosine derivatives, resulting in Ki values in a significantly lower range, 1.0-40 microM, compared to 51. No upper size limitation or specificity has been found at this position, yet similar replacements at the P3' position, which is occupied naturally by a glycine residue, gave weaker inhibitors: (EtO)(OK)P(O)-Ile-Tyr(OBzl)-PheOK (57) had a Ki of 120 microM. Hexapeptide derivatives had weaker activities in the 270 microM-2 mM range. All inhibitors were evaluated by using the synthetic thio peptolide spectrophotometric assay.
• Design, Synthesis, and Structure−Activity Relationships of Macrocyclic Hydroxamic Acids That Inhibit Tumor Necrosis Factor α Release in Vitro and in Vivo
  作者：Chu-Biao Xue、Matthew E. Voss、David J. Nelson、James J.-W. Duan、Robert J. Cherney、Irina C. Jacobson、Xiaohua He、John Roderick、Lihua Chen、Ronald L. Corbett、Li Wang、Dayton T. Meyer、Kenneth Kennedy、William F. DeGrado、Karl D. Hardman、Christopher A. Teleha、Bruce D. Jaffee、Rui-Qin Liu、Robert A. Copeland、Maryanne B. Covington、David D. Christ、James M. Trzaskos、Robert C. Newton、Ronald L. Magolda、Ruth R. Wexler、Carl P. Decicco

  DOI：10.1021/jm010127e

  日期：2001.8.1

  To search for TNF-alpha (tumor necrosis factor alpha) converting enzyme (TACE) inhibitors, we designed a new class of macrocyclic hydroxamic acids by linking the PI and P2 ' residues of acyclic anti-succinate-based hydroxamic acids. A variety of residues including amide, carbamate, alkyl, sulfonamido, Boc-amino, and amino were found to be suitable P1-P2 ' linkers. With an N-methylamide at P3 ', the 13-16-membered macrocycles prepared exhibited low micromolar activities in the inhibition of TNF-alpha release from LPS-stimulated human whole blood. Further elaboration in the P3 ' -P4 ' area using the cyclophane and cyclic carbamate templates led to the identification of a number of potent analogues with IC50 values of less than or equal to 0.2 muM in whole blood assay (WBA). Although the P3 ' area can accommodate a broad array of structurally diversified functional groups including polar residues, hydrophobic residues, and amino and carboxylic acid moieties, in both the cyclophane series and the cyclic carbamate series, a glycine residue at P3 ' was identified as a critical structural component to achieve both good in vitro potency and good oral activity. With a glycine residue at P3 ', an N-methylamide at P4 ' provided the best cyclophane analogue, SL422 (WBA IC50 = 0.22 muM, LPS-mouse ED50 = 15 mg/kg, po), whereas a morpholinylamide at P4 ' afforded the most potent and most orally active cyclic carbamate analogue, SP057 (WBA IC50 = 0.067 muM, LPS-mouse ED50 = 2.3 mg/kg, po). Further profiling for SL422 and SP057 showed that these macrocyclic compounds are potent TACE inhibitors, with K-i values of 12 and 4.2 nM in the porcine TACE assay, and are broad-spectrum MMP inhibitors. Pharmacokinetic studies in beagle dogs revealed that SL422 and SP057 are orally bioavailable, with oral bioavailabilities of 11% and 23%, respectively.
• KORTYLEWICZ, ZBIGNIEW P.;GALARDY, RICHARD E., J. MED. CHEM., 33,(1990) N, C. 263-273
  作者：KORTYLEWICZ, ZBIGNIEW P.、GALARDY, RICHARD E.

  DOI：——

  日期：——