LeuNH2*HBr | 108039-98-1

• 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: LeuNH2*HBr
• 英文别名: (S)-2-amino-4-methylpentanamide hydrobromide；HBr*H-(L)Leu-NH2；L-leucine amide; hydrobromide；L-Leucin-amid; Hydrobromid；Leucinamide hydrobromide；(2S)-2-amino-4-methylpentanamide;hydrobromide
• CAS: 108039-98-1
• 化学式: BrH*C₆H₁₄N₂O
• 分子量: 211.102
• InChiKey: PMMQRTXUHAUPDL-JEDNCBNOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.42
• 重原子数：
  10
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  69.1
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  LeuNH2*HBr 、 N-Moc-S-phenylalanine-α-methoxyglycine 在 三乙胺 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以53%的产率得到N-Moc-S-phenylalanine-α-methoxyglycyl-S-leucineamide
  参考文献：
  名称：

  芳香族化合物的分子内酰胺烷基化反应。构象受限的Phe-Gly桥联肽类似物的合成

  摘要：

  制备了Phe-α-甲氧基甘氨酸的衍生物（4），发现其进行了立体有择的分子内酰胺烷基化反应，得到了4-氨基-2-苯并ze庚因-3-一-1-羧酸5（ABZC）的衍生物。环状化合物5a-g是含有桥连的Phe-Gly部分的构象受限的肽。

  DOI：

  10.1016/s0040-4020(01)89269-3
• 作为产物：
  描述：

  苄氧羰基-亮氨酰胺 在 氢溴酸 作用下， 以 溶剂黄146 为溶剂， 反应 2.0h， 以84%的产率得到LeuNH2*HBr
  参考文献：
  名称：

  Optimization and Structure–Activity Relationships of Phosphinic Pseudotripeptide Inhibitors of Aminopeptidases That Generate Antigenic Peptides

  摘要：

  The oxytocinase subfamily of M1 aminopeptidases, Consisting of ER aminopeptidase 1 (ERAP1), ER aminopeptidase 2 (ERAP2), and insulin-regulated aminopeptidase (IRAP), plays critical roles in the generation of antigenic peptides and indirectly regulates human adaptive immune responses. We have previously,demonstrated that phosphinic pseudotripeptides can constitute potent inhibitors of this group of enzymes. In this study, we used synthetic methodologies able to furnish a series of stereochemically defined phosphinic pseudotripeptides and demonstrate that side chains at P-1' and P-2' positions are Critical determinants in driving potency and selectivity. We identified low nanomolar inhibitors of ERAP2 and IRAP that display selectivity of more than 2 and 3 orders of magnitude, respectively. Cellular analysis demonstrated that one of the compounds that is a selective IRAP inhibitor can reduce IRAP-dependent but not, ERAP1-dependent cross-presentation by dendritic cells with nanomolar efficacy. Our results encourage further preclinical development of phosphinic pseudotripeptides as regulators of adaptive immune responses.

  DOI：

  10.1021/acs.jmedchem.6b01031

文献信息

• AN ENZYME-CATALYZED PROCESS FOR PREPARING N-ACYL AMINO ACIDS AND N-ACYL AMINO ACID AMIDES
  申请人：NOVO NORDISK A/S

  公开号：EP0473700A1

  公开（公告）日：1992-03-11
• US6046016A
  申请人：——

  公开号：US6046016A

  公开（公告）日：2000-04-04
• [EN] AN ENZYME-CATALYZED PROCESS FOR PREPARING N-ACYL AMINO ACIDS AND N-ACYL AMINO ACID AMIDES
  申请人：NOVO NORDISK A/S

  公开号：WO1990014429A1

  公开（公告）日：1990-11-29

  (EN) Compounds of general formula (I) or (II), wherein R is an optionally substituted alkyl group with 3-23 carbon atoms, and R1 is hydrogen or an optionally substituted branched or straight-chain, saturated or unsaturated, aliphatic or aromatic hydrocarbon group, are prepared by reacting a compound of the general formula (III): RCOOR2, wherein R2 is H or an alkyl group with 1-6 carbon atoms, and R is as defined above, with a compound of general formula (IV), wherein R1 is as defined above, in the presence of an enzyme capable of catalysing the formation of amide bonds, in particular a lipase. The amide group may be removed from the compound (I) by means of a second enzyme capable of selectively cleaving amide bonds, e.g. a carboxypeptidase, resulting in the compound (II).(FR) Des composés de formule générale (I) ou (II), où R est un groupe alcoyle substitué ou non ayant 3-23 atomes de carbone et R1 est l'hydrogène ou un groupe substitué ou non, à chaîne linéaire ou ramifiée d'hydrocarbures aliphatiques ou aromatiques, saturés ou non saturés, sont préparés en faisant réagir un composé de formule générale (II) où R2 est H ou un groupe alcoyle ayant 1-6 atomes de carbone et R correspond à la définition ce-dessus, avec un composé de formule générale (IV) où R est comme défini ci-dessus, en présence d'une enzyme pouvant catalyser la formation de liaisons d'amides, en particulier, une lipase. On peut extraire le groupe amide présent dans le composé (I) à l'aide d'une deuxième enzyme pouvant cliver les liaisons d'amides, par exemple, une carboxypeptidase, ainsi réalisant le composé (II).
• Optimization and Structure–Activity Relationships of Phosphinic Pseudotripeptide Inhibitors of Aminopeptidases That Generate Antigenic Peptides
  作者：Paraskevi Kokkala、Anastasia Mpakali、Francois-Xavier Mauvais、Athanasios Papakyriakou、Ira Daskalaki、Ioanna Petropoulou、Sofia Kavvalou、Mirto Papathanasopoulou、Stefanos Agrotis、Theodora-Markisia Fonsou、Peter van Endert、Efstratios Stratikos、Dimitris Georgiadis

  DOI：10.1021/acs.jmedchem.6b01031

  日期：2016.10.13

  The oxytocinase subfamily of M1 aminopeptidases, Consisting of ER aminopeptidase 1 (ERAP1), ER aminopeptidase 2 (ERAP2), and insulin-regulated aminopeptidase (IRAP), plays critical roles in the generation of antigenic peptides and indirectly regulates human adaptive immune responses. We have previously,demonstrated that phosphinic pseudotripeptides can constitute potent inhibitors of this group of enzymes. In this study, we used synthetic methodologies able to furnish a series of stereochemically defined phosphinic pseudotripeptides and demonstrate that side chains at P-1' and P-2' positions are Critical determinants in driving potency and selectivity. We identified low nanomolar inhibitors of ERAP2 and IRAP that display selectivity of more than 2 and 3 orders of magnitude, respectively. Cellular analysis demonstrated that one of the compounds that is a selective IRAP inhibitor can reduce IRAP-dependent but not, ERAP1-dependent cross-presentation by dendritic cells with nanomolar efficacy. Our results encourage further preclinical development of phosphinic pseudotripeptides as regulators of adaptive immune responses.
• Intramolecular amidoalkylation of aromatics III. Synthesis of conformationally restricted bridged peptide analogues of Phe-Gly
  作者：Amal Rabi-Barakay、Dov Ben-Ishai

  DOI：10.1016/s0040-4020(01)89269-3

  日期：1994.1

  found to undergo stereospecific intramolecular amidoalkylation to give derivatives of 4-amino-2-benzazepin-3-one-1-carboxylic acid 5 (ABZC). The cyclic compounds 5a-g are conformationally restricted peptides containing a bridged Phe-Gly moiety.

  制备了Phe-α-甲氧基甘氨酸的衍生物（4），发现其进行了立体有择的分子内酰胺烷基化反应，得到了4-氨基-2-苯并ze庚因-3-一-1-羧酸5（ABZC）的衍生物。环状化合物5a-g是含有桥连的Phe-Gly部分的构象受限的肽。