N^ε-[(benzyloxy)carbonyl]-L-lysine N-methylamide | 57499-17-9

• 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^ε-[(benzyloxy)carbonyl]-L-lysine N-methylamide
• 英文别名: H-Lys(Cbz)-NHMe；benzyl N-[(5S)-5-amino-6-(methylamino)-6-oxohexyl]carbamate
• CAS: 57499-17-9
• 化学式: C₁₅H₂₃N₃O₃
• 分子量: 293.366
• InChiKey: YTEKWQVLMATSCN-ZDUSSCGKSA-N

物化性质

• 沸点：
  539.2±50.0 °C(Predicted)
• 密度：
  1.127±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  21
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  93.4
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N^ε-[(benzyloxy)carbonyl]-L-lysine N-methylamide 在 盐酸 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 28.5h， 生成 (2S,5S)-1-benzoyl-5-(4'-<(benzyloxycarbonyl)amino>butyl)-2-(tert-butyl)-3-methyl-4-imidazolidinon
  参考文献：
  名称：

  Herstellung对映体reiner，α-烷基赖氨酸，Ornithin和色氨酸衍生物

  摘要：

  对映体纯的α-烷基赖氨酸，鸟氨酸和色氨酸衍生物的合成

  DOI：

  10.1002/hlca.19880710124
• 作为产物：
  描述：

  N-Boc-L-Lys(Cbz)-NMe 在 三氟乙酸 作用下， 反应 0.25h， 生成 N^ε-[(benzyloxy)carbonyl]-L-lysine N-methylamide
  参考文献：
  名称：

  表面的横向自分类：双通道光系统的实用方法

  摘要：

  我们报告说，自组织表面引发共聚（co-SOSIP）过程中的自分类提供了对定向多组分体系结构的轻松访问。发现交替横向和均匀轴向自分类到正式的超分子 n/p-异质结光系统中，产生高达 40 倍的光电流。或多或少的拓扑匹配分别导致交替轴向自分选到非活性电荷转移复合物或均匀横向分选到不太活跃的宏域中。报告了在 co-SOSIP 期间对自我修复的实验支持。表面上的引发剂被证明可以作为自分类到具有自由可变成分的多通道架构的模板。

  DOI：

  10.1021/ja204020p

文献信息

• Self-Organizing Surface-Initiated Polymerization: Facile Access to Complex Functional Systems
  作者：Naomi Sakai、Marco Lista、Oksana Kel、Shin-ichiro Sakurai、Daniel Emery、Jiri Mareda、Eric Vauthey、Stefan Matile

  DOI：10.1021/ja203792n

  日期：2011.10.5

  materials of the future. Herein, we report self-organizing surface-initiated polymerization (SOSIP) as a user-friendly method to create ordered as well as oriented functional systems on transparent oxide surfaces. In SOSIP, self-organization of monomers and ring-opening disulfide exchange polymerization are combined to ensure the controlled growth of the polymer from the surface. This approach provides

  轻松访问复杂系统对于生成未来的功能材料至关重要。在此，我们报告了自组织表面引发聚合（SOSIP）作为一种用户友好的方法，可以在透明氧化物表面上创建有序和定向的功能系统。在 SOSIP 中，单体的自组织和开环二硫化物交换聚合相结合，以确保聚合物从表面受控生长。这种方法可以快速获得具有光滑、可再活化表面和长程有序、缺陷少且精度高的厚膜，包括具有定向四组分氧化还原梯度的全色光系统。SOSIP 架构的活动性明显优于无序控制。
• Phosphinic acid derivatives
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0276436A1

  公开（公告）日：1988-08-03

  The invention provides compounds of the formula wherein R¹-R⁵ and X have the significance given in the description, and their pharmaceutically acceptable salts. They inhibit the enzyme collagenase and can be used in the form of medicaments for the control or prevention of degenerative joint diseases such as rheumatoid arthritis and osteoarthritis. The compounds of formula I and their pharmaceutically acceptable salts can be manufactured according to generally known methods.

  本发明提供了式中 R¹-R⁵ 和 X 的化合物及其药学上可接受的盐，它们能抑制胶原酶，并能以药物的形式用于控制或预防退行性关节疾病，如类风湿性关节炎和骨关节炎。 式 I 的化合物及其药学上可接受的盐可以按照一般已知的方法制造。
• Synthesis of novel N-phosphonoalkyl dipeptide inhibitors of human collagenase
  作者：John Bird、Rachel C. De Mello、Gregory P. Harper、David J. Hunter、Eric H. Karran、Roger E. Markwell、Anette J. Miles-Williams、Shahzad S. Rahman、Robert W. Ward

  DOI：10.1021/jm00027a020

  日期：1994.1

  The synthesis of a series of N-phosphonoalkyl dipeptides 6 is described. Syntheses were devised that allowed the preparation of single diastereoisomers and the assignment of stereochemistry. The compounds were evaluated in vitro for their ability to inhibit the degradation of radiolabeled collagen by purified human lung fibroblast collagenase. Several of the compounds were potent collagenase inhibitors and were at least l0-fold more potent than their corresponding N-carboxyalkyl analogues. Activity was lost when the phosphonic acid group P(O)(OH)(2) was replaced by the phosphinic acid groups P(O)(H)(OH) and P(O)(Me)(OH). At the P-1 position, (R)- or (S)-allkyl groups, especially ethyl and methyl (e.g., 12a,b, 52a,b, and 53a,b), or an (R)-phenethyl moiety (55a) conferred high potency (IC50 values in the range 0.23-0.47 mu M). (S)-Stereochemistry was preferred for the P-1(') isobutyl side chain. Structure-activity relationships were also investigated at the P-2(') site, and interestingly, compounds with basic side chains such as the guanidine 57a, were equipotent with more lipophilic compounds, such as 52a. As with other series of collagenase inhibitors, potency was enhanced by introducing bicyclic aromatic P-2(') substituents. The most potent phosphonic acid of the series was the bicyclic aromatic P-2(') tryptophan analogue 59a (IC50 0.05 mu M).
• 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.
• Design and Synthesis of Cyclic Inhibitors of Matrix Metalloproteinases and TNF-α Production
  作者：Chu-Biao Xue、Xiaohua He、John Roderick、William F. DeGrado、Robert J. Cherney、Karl D. Hardman、David J. Nelson、Robert A. Copeland、Bruce D. Jaffee、Carl P. Decicco

  DOI：10.1021/jm970849z

  日期：1998.5.1