Z-Trp-NHCH2Ph | 158951-60-1

• 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: Z-Trp-NHCH2Ph
• 英文别名: Cbz-Trp-NHBn；benzyl N-[(2S)-1-(benzylamino)-3-(1H-indol-3-yl)-1-oxopropan-2-yl]carbamate
• CAS: 158951-60-1
• 化学式: C₂₆H₂₅N₃O₃
• 分子量: 427.503
• InChiKey: OVIFCTPLVXTQKR-DEOSSOPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 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：

  Z-Trp-NHCH2Ph 在 palladium on activated charcoal 盐酸 、 氢气 、 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 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 Tyr(Bn)-Lys-Trp-NHCH2Ph*3HCl
  参考文献：
  名称：

  Linear TMC-95-Based Proteasome Inhibitors

  摘要：

  We have designed and evaluated 45 linear analogues of the natural constrained cyclopeptide TMC-95A. These synthetically less demanding molecules are based on the tripeptide sequence Y-N-W of TMC-95A. Structural variations in the amino acid side chains and termini greatly influenced both the efficiency and selectivity of action on a given type of active site. Inhibition constants were submicromolar (K-i approximate to 300 nM) despite the absence of the entropically favorable constrained conformation that is characteristic of TMC-95A and its cyclic analogues. These linear compounds were readily prepared and reasonably stable in culture medium and could be optimized to inhibit one, two, or all three proteasome catalytic sites. Cytotoxicity assays performed on a series of human tumor cell lines identified the most potent inhibitors in cells.

  DOI：

  10.1021/jm0701324
• 作为产物：
  描述：

  N-苄氧羰基-L-色氨酸 以 四氢呋喃 为溶剂， 反应 11.0h， 生成 Z-Trp-NHCH2Ph
  参考文献：
  名称：

  衍生自α-氨基酰胺的C 2对称镍络合物，作为将二烷基锌试剂对醛对映选择性加成的有效催化剂

  摘要：

  研究了由α-氨基酰胺衍生的一系列C 2对称的1：2 Ni：L络合物，用于将二烷基锌试剂对映异构地加成到醛中。配体上的不同结构元素似乎在确定观察到的对映选择性中起重要作用。通过的结构和反应条件的优化，最佳配位体以优良产率（高达98％）和高达99％ee的对（对映选择性的提供仲醇ř）-对映体。已经提出了一种过渡状态模型，用于基于DFT级别的计算结果解释所观察到的对映选择性。非常有趣的是，计算表明通过羰基氧的孤对与氨基氢原子的缔合，醛与金属络合物的配位模型。

  DOI：

  10.1016/j.tet.2012.11.025

文献信息

• Mechanistic implications of the enantioselective addition of alkylzinc reagents to aldehydes catalyzed by nickel complexes with α-amino amide ligands
  作者：Jorge Escorihuela、M. Isabel Burguete、Gregori Ujaque、Agustí Lledós、Santiago V. Luis

  DOI：10.1039/c6ob01878e

  日期：——

  The enantioselective alkylation of aldehydes catalysed by nickel(II)-complexes derived from α-amino amides was studied by means of density functional theory (DFT) and ONIOM (B3LYP:UFF) calculations. A mechanism was proposed in order to investigate the origin of enantioselectivity. The chirality-determining step for the alkylation was the formation of the intermediate complexes with the involvement

  通过密度泛函理论（DFT）和ONIOM（B3LYP：UFF）计算研究了由α-氨基酰胺衍生的镍（II）配合物催化的醛的对映选择性烷基化。为了研究对映选择性的起源，提出了一种机制。烷基化的手性确定步骤是中间体配合物的形成，其中涉及5/4 / 4-稠合的三环过渡态。理论上预测的主要产物为（S）-构型，与实验观察结果非常吻合。检查了反应范围，观察到对映选择性添加Et 2 Zn和Me 2的高产率和对映选择性锌为芳香族和脂肪族醛。
• Mercaptosulfide metalloproteinase inhibitors
  申请人：Florida State University

  公开号：US05455262A1

  公开（公告）日：1995-10-03

  Novel mercaptosulfide matrix metalloproteinase inhibitors of the Formula I, ##STR1## wherein: n is 0 or 1; R.sup.1 is selected from the group consisting of hydrogen, lower alkyl, amino lower alkyl, carbamoyl lower alkyl, PhtN(lower alkyl), TsNH(lower alkyl); and R.sup.2 is selected from the group consisting of hydrogen, lower alkyl, amino lower alkyl, carbamoyl lower alkyl, PhtN(lower alkyl), TsNH (lower alkyl); or R.sup.1 and R.sup.2 together are --CH.sub.2 --CH.sub.2 --CH.sub.2 --; R.sup.3 is selected from the group consisting of hydrogen, lower alkyl, aralkyl and heteroaralkyl; and R.sup.4 is selected from the group consisting of hydrogen, lower alkyl, amino lower-alkyl, guanyl lower-alkyl, imidazoylalkyl, aralkyl and 2-indolylmethyl; and R.sup.5 is selected from the group consisting of lower alkyl, aralkyl and --CH(R.sup.6)--C(O)NH.sub.2, wherein R.sup.6 is selected from the group consisting of hydrogen, lower-alkyl, amino lower-alkyl, guanyl lower-alkyl, imidazoylalkyl, hydroxymethyl, 1-hydroxyethyl, mercapto lower-alkyl, and methylthio lower-alkyl; or a pharmaceutically acceptable ester, ether or salt thereof, useful for treating diseases and disease conditions associated with matrix metalloproteinase modulation.

  化合物I的新型巯基硫酸酯基基质金属蛋白酶抑制剂，其中：n为0或1；R.sup.1选自氢、较低烷基、氨基较低烷基、氨基甲酰较低烷基、PhtN（较低烷基）、TsNH（较低烷基）组成的群；R.sup.2选自氢、较低烷基、氨基较低烷基、氨基甲酰较低烷基、PhtN（较低烷基）、TsNH（较低烷基）组成的群；或R.sup.1和R.sup.2一起是--CH.sub.2--CH.sub.2--CH.sub.2--；R.sup.3选自氢、较低烷基、芳基烷基和杂芳基烷基组成的群；R.sup.4选自氢、较低烷基、氨基较低烷基、鸟氨酸较低烷基、咪唑烷基、芳基烷基和2-吲哚甲基；R.sup.5选自较低烷基、芳基烷基和--CH（R.sup.6）--C（O）NH.sub.2，其中R.sup.6选自氢、较低烷基、氨基较低烷基、鸟氨酸较低烷基、咪唑烷基、羟甲基、1-羟乙基、巯基较低烷基和甲硫基较低烷基组成的群；或其药学上可接受的酯、醚或盐，用于治疗与基质金属蛋白酶调节相关的疾病和疾病状况。
• Sulfoximine and suldodiimine matrix metalloproteinase inhibitors
  申请人：Florida State University

  公开号：US05470834A1

  公开（公告）日：1995-11-28

  Novel sulfoximine and sulfodiimine matrix metalloproteinase inhibitors of the formula, ##STR1## wherein: R.sup.1 is selected from the group consisting of lower-alkyl, hydroxy lower-alkyl, amino lower-alkyl, carbamoyl lower-alkyl, lower-alkyl carbonyl, lower-alkyoxyalkyl, aralkyl and heteroaralkyl; X is NH or O; R.sup.2 is selected from the group consisting of hydrogen, lower-alkyl and aralkyl; R.sup.3 is selected from the group consisting of hydrogen, lower-alkyl, amino lower-alkyl, guanyl lower-alkyl, aralkyl and heteroaralkyl; and R.sup.4 is selected from the group consisting of lower alkyl, aralkyl and --CH(R.sup.5)--C(O)NH.sub.2, wherein R.sup.5 is selected from the group consisting of hydrogen, lower-alkyl, amino lower-alkyl, guanyl lower-alkyl, imidazoylalkyl, hydroxymethyl, 1-hydroxyethyl, mercapto lower-alkyl, and methylthio lower-alkyl; useful for modulating physiological functions or treating diseases and disease conditions associated with matrix metalloproteinase modulation.

  新型的磺酰亚胺和磺二亚胺基基质金属蛋白酶抑制剂的化学式为：##STR1## 其中：R1选自以下组成的群体：低碳基、羟基低碳基、氨基低碳基、氨基甲酰低碳基、低碳基酰基、低碳氧基烷基、芳基烷基和杂芳基烷基；X为NH或O；R2选自以下组成的群体：氢、低碳基和芳基烷基；R3选自以下组成的群体：氢、低碳基、氨基低碳基、鸟氨酸基低碳基、芳基烷基和杂芳基烷基；R4选自以下组成的群体：低碳基、芳基烷基和--CH(R5)--C(O)NH2，其中R5选自以下组成的群体：氢、低碳基、氨基低碳基、鸟氨酸基低碳基、咪唑基烷基、羟甲基、1-羟基乙基、巯基低碳基和甲硫基低碳基；用于调节生理功能或治疗与基质金属蛋白酶调节相关的疾病和疾病状况。
• Compounds Useful as Modulators of the Proteasome Activity
  申请人：Reboud-Ravaux Michele Claude Yvonne

  公开号：US20090069222A1

  公开（公告）日：2009-03-12

  The present invention relates to the use of compounds of the following general formula (I): wherein n o is 0 or 1, and when n o is 1, X=CH 2 or X=NCH 2 C 6 H 5 ; R 1 is OH, or a OR 10 group, or a group of formula NH—(CH 2 ) n1 —R 11 ; R 2 is H, or an alkyl group, or a group of formula (CH 2 ) n2 —(CO) n3 —NR 13 R 14 ; R 3 is H, or an alkyl group; R 4 is H, or Boc, or Z; R 5 is H, or Boc, or Z; R 6 is a OR 16 group; R 7 and R 8 are H, or a halogen atom, as modulators of the proteasome activity, in the frame of the preparation of a medicament useful for the prevention or treatment of diseases wherein the proteasome is involved, or the preparation of cosmetic compositions, or of phytosanitary compositions

  本发明涉及使用以下通式（I）的化合物：其中nois为0或1，当nois为1时，X=CH2或X=N C6H5; R1为OH，或OR10基团，或公式NH—（ ）n1—R11的基团; R2为H，或烷基，或公式（ ）n2—（CO）n3—NR13R14的基团; R3为H，或烷基; R4为H，或Boc，或Z; R5为H，或Boc，或Z; R6为OR16基团; R7和R8为H，或卤原子，作为蛋白酶体活性调节剂，用于制备用于预防或治疗蛋白酶体参与的疾病的药物，或制备化妆品组合物或植物保护组合物。
• Compounds useful as modulators of the proteasome activity
  申请人：Centre National de la Recherche Scientifique (C.N.R.S.)

  公开号：US07919468B2

  公开（公告）日：2011-04-05

  Compounds of the following general formula (I): are provided. The compounds can be used as modulators of the proteasome activity, in the preparation of a medicament useful for the prevention or treatment of diseases wherein the proteasome is involved, such as diseases of inflammatory processes, various hematological and solid tumor cancers, immunological and autoimmune diseases, cardiac pathologies, myopathies, AIDS, cystic fibrosis, Alzheimer's and Parkinson's disease, or in the preparation of cosmetic compositions or phytosanitary compositions.

  提供了以下一般式（I）的化合物。这些化合物可用作蛋白酶体活性的调节剂，用于制备有用于预防或治疗蛋白酶体参与的疾病的药物，如炎症过程疾病、各种血液和实体肿瘤癌症、免疫和自身免疫性疾病、心脏病理学、肌病、艾滋病、囊性纤维化、阿尔茨海默病和帕金森病，或用于制备化妆品组合物或植物保护组合物。