N1-异戊烷-L-亮氨酰胺 | 84851-37-6

• 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
• 中文名称: N1-异戊烷-L-亮氨酰胺
• 英文名称: L-leucine isoamylamide
• 英文别名: (2S)-2-Amino-4-methyl-N-(3-methylbutyl)pentanamide
• CAS: 84851-37-6
• 化学式: C₁₁H₂₄N₂O
• 分子量: 200.324
• InChiKey: HCDLAJHOIWLVLK-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  14
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N1-异戊烷-L-亮氨酰胺 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 potassium hydroxide 作用下， 以 乙酸乙酯 为溶剂， 反应 20.0h， 生成 阿洛司他丁酸
  参考文献：
  名称：

  Design, synthesis, and screen of cathepsin K inhibitors

  摘要：

  We synthesized a series of epoxysuccinic acid derivatives and evaluated their in vitro cathepsin K inhibitory activity The screening results show that the potency of compounds 9e, 9d, 9p, 9j and 9k (IC50 <= 0.005 mu mol/L) were equal to or greater than that of the lead compound 9a. Less hydrophobic compounds showed weaker potency, which can be explained by the hydrophobic nature of the cathepsin K binding pockets. (C) 2013 Jun-Hai Xiao and Xiao-Hong Yang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

  DOI：

  10.1016/j.cclet.2013.05.002
• 作为产物：
  描述：

  N-苄氧羰基-L-亮氨酸 在 palladium on activated charcoal N-甲基吗啉 、 氢气 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 19.5h， 生成 N1-异戊烷-L-亮氨酰胺
  参考文献：
  名称：

  N-Haloacetyl-amino-acid amides as active-site-directed inhibitors of papain and cathepsin B

  摘要：

  A series of N-haloacetyl-amino-acid amides were synthesized and tested as models of cysteine-protease inhibitors. They irreversibly inactivated papain and cathepsin B via a reversible enzyme--inhibitor intermediate. Apparent second-order rate constants of inactivation ranging from 65 to 16 700 M-1 s-1 were observed. Reactivity against papain, as compared to glutathione, was increased 16 400-fold for N-bromoacetyl-leucine isopentylamide and 25 700-fold for the corresponding iodoacetyl derivative; these increases are probably due to proximity effects. No inhibition of trypsin, chymotrypsin and porcine pancreatic elastase was observed. Haloacetamides represent an interesting class of easily synthesized, efficient. irreversible inhibitors of cysteine proteases, which have low non-specific alkylating properties.

  DOI：

  10.1016/0223-5234(92)90018-v

文献信息

• 1,2,4-Thiadiazole: A novel Cathepsin B inhibitor
  作者：Regis Leung-Toung、Jolanta Wodzinska、Wanren Li、Jayme Lowrie、Rahul Kukreja、Denis Desilets、Khashayar Karimian、Tim Fat Tam

  DOI：10.1016/j.bmc.2003.09.040

  日期：2003.12

  inhibitor in this series. The enhanced inhibitory potency of 3a is a consequence of its increased enzyme binding affinity (lower K(i)) rather than its increased intrinsic reactivity (higher k(i)). In addition, 3a is inactive against Cathepsin S, is a poor inhibitor of Cathepsin H and is >100-fold more selective for Cat B over papain.

  已经开发出具有1,2,4-噻二唑杂环作为硫醇捕获药效团的新型组织蛋白酶B抑制剂。在C5位置具有不同二肽识别序列（即P1'-P2'= Leu-Pro-OH或P2-P1 = Cbz-Phe-Ala）且具有不同取代基（即OMe，Ph或COOH）的几种化合物已经合成了1,2,4-噻二唑环的C3位上的化合物，并测试了它们的抑制活性。取代的噻二唑3a-h以时间依赖性，不可逆的方式抑制CatB。提出了基于在活性位点半胱氨酸硫醇和杂环的硫原子之间形成二硫键而使酶的活性位点定向失活的机理。具有C3甲氧基部分和Leu-Pro-OH二肽识别序列的化合物3a（K（i）= 2.6 microM，k（i）K（i）= 5630 M（-1）s（-1）），被发现是该系列中最有效的抑制剂。3a抑制力的增强是其酶结合亲和力提高（K（i）较低）而不是固有反应性提高（k（i）较高）的结果。此外，3a对组织蛋白酶S无活性，对组织蛋白酶H的抑制作用较弱，对Cat
• Methods and compositions for controlled polypeptide synthesis
  申请人：——

  公开号：US20020032309A1

  公开（公告）日：2002-03-14

  Methods and compositions for the generation of polypeptides having varied material properties are disclosed herein. Methods include means for initiating the polymerization of aminoacid-N-carboxyanhydride (NCA) monomer by combining the monomer with an amido-containing metallacycle, for making self assembling amphiphilic block copolypeptides and related protocols for adding oligo(ethyleneglycol) functionalized aminoacid-N-carboxyanhydrides (NCAs) to polyaminoacid chains. Additional methods include means of adding an end group to the carboxy terminus of a polyaminoacid chain by reacting an alloc-protected amino acid amide with a transition metal-donor ligand complex to forming an amido-amidate metallacycle for use in further polymerization reactions. Novel compositions for use in peptide synthesis and design including five and six membered amido-containing metallacycles and block copolypeptides are also disclosed.

  本文揭示了用于生成具有不同材料特性的多肽的方法和组合物。方法包括通过将氨基酸-N-羧酸酐（NCA）单体与含有酰胺的金属环结合来启动聚合反应，制备自组装的两性块共聚多肽以及相关的添加寡聚（乙二醇基）功能化氨基酸-N-羧酸酐（NCA）到聚氨基酸链的协议。其他方法包括通过将alloc-保护的氨基酸酰胺与过渡金属给体配体复合物反应，形成酰胺-酰胺金属环，从而向聚氨基酸链的羧基末端添加末端基团，用于进一步的聚合反应。此外，还揭示了用于肽合成和设计的新型组合物，包括五元和六元含酰胺的金属环和块共聚多肽。
• Stereoselective Synthesis of the Epoxysuccinyl Peptide E-64c
  作者：Barry Lygo、Stuart Gardiner、Daniel To

  DOI：10.1055/s-2006-948191

  日期：2006.8

  A highly diastereoselective PTC epoxidation is employed in the synthesis of the potent cysteine protease inhibitor E-64c.

  在合成强效半胱天冬酶抑制剂E-64c的过程中，采用了高度非对映选择性的相转移催化环氧化反应。
• Design, synthesis and evaluation of 3-methylene-substituted indolinones as antimalarials
  作者：S. Praveen Kumar、Jiri Gut、Rita C. Guedes、Philip J. Rosenthal、Maria M.M. Santos、Rui Moreira

  DOI：10.1016/j.ejmech.2011.01.008

  日期：2011.3

  The design, synthesis and evaluation of 3-methylene-substituted indolinones as falcipain inhibitors and antiplasmodial agents are described. These compounds react readily with thiols via an addition-elimination mechanism, indicating their potential as cysteine protease inhibitors. Several indolinones containing a Leu-i-amyl recognition moiety were found to be moderate inhibitors of the Plasmodium falciparum

  描述，设计和合成的3-亚甲基取代的吲哚啉酮作为falcipain抑制剂和抗疟原虫剂。这些化合物通过加成消除机制容易与硫醇反应，表明它们作为半胱氨酸蛋白酶抑制剂的潜力。含有具有Leu-几个吲哚满酮我发现戊识别部分是适度抑制剂的恶性疟原虫半胱氨酸蛋白酶falcipain-2，但不相关的蛋白酶falcipain-3，和针对抗氯喹显示抗疟原虫活性恶性疟原虫W2在低微摩尔范围内的应变。将7-氯喹啉部分偶联至3-亚甲基取代的吲哚酮骨架上导致抗血浆活性的显着改善。
• The Bsmoc group as a novel scaffold for the design of irreversible inhibitors of cysteine proteases
  作者：Jim Iley、Rui Moreira、Luísa Martins、Rita C. Guedes、Cláudio M. Soares

  DOI：10.1016/j.bmcl.2006.02.007

  日期：2006.5

  not significantly affected by the nature of the carboxylic or carbamic acid leaving group. These Michael acceptors are irreversible inhibitors of the cysteine proteases papain and human liver cathepsin B, displaying first-order kinetics with respect to inhibitor concentration. In contrast, none of the Bsmoc derivatives inhibited porcine pancreatic elastase, a serine protease.

  1,1-二氧代苯并[b]噻吩-2-基甲氧基羰基（Bsmoc）支架的氨基甲酸酯和酯衍生物可以通过迈克尔加成反应与巯基反应，其反应速率不受羧基或氨基甲酸离去基团性质的明显影响。这些迈克尔受体是半胱氨酸蛋白酶木瓜蛋白酶和人肝组织蛋白酶B的不可逆抑制剂，在抑制剂浓度方面表现出一级动力学。相反，没有Bsmoc衍生物抑制猪胰弹性蛋白酶，一种丝氨酸蛋白酶。