(benzoyl-L-phenylalanyl)-L-alanine | 65049-90-3

• 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: (benzoyl-L-phenylalanyl)-L-alanine
• 英文别名: Bz-Phe-Ala-OH；(2S)-2-[[(2S)-2-benzamido-3-phenylpropanoyl]amino]propanoic acid
• CAS: 65049-90-3
• 化学式: C₁₉H₂₀N₂O₄
• 分子量: 340.379
• InChiKey: RTSMBLLZBBYZQP-BBRMVZONSA-N

物化性质

• 沸点：
  692.1±55.0 °C(Predicted)
• 密度：
  1.240±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  95.5
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (benzoyl-L-phenylalanyl)-L-alanine 在 锂硼氢 、 碘苯二乙酸 、 碘 作用下， 以 丙醇 、 二氯甲烷 为溶剂， 反应 7.67h， 生成 N-(N-benzoyl-L-phenylalanyl)-α,α-dimethyl-L-β-homoalaninol
  参考文献：
  名称：

  Preparation of modified peptides: direct conversion of α-amino acids into β-amino aldehydes

  摘要：

  开发了一种将α-氨基酸转化为β-氨基醛的直接方法，并应用于肽的C末端残基的修饰。该方法在温和条件下进行，产率良好。同时还描述了该方法在制备含有γ-氨基醇单元的小肽方面的应用，这些单元是肽类抗生素类似物的前体。

  DOI：

  10.1039/c2ob25433f
• 作为产物：
  描述：

  ethyl N-benzoyl-L-phenylalanyl-L-alaninate 在 lithium hydroxide monohydrate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.0h， 以48%的产率得到(benzoyl-L-phenylalanyl)-L-alanine
  参考文献：
  名称：

  The Discovery of Potent, Selective, and Reversible Inhibitors of the House Dust Mite Peptidase Allergen Der p 1: An Innovative Approach to the Treatment of Allergic Asthma

  摘要：

  Blocking the bioactivity of allergens is conceptually attractive as a small-molecule therapy for allergic diseases but has not been attempted previously. Group 1 allergens of house dust mites (HDM) are meaningful targets in this quest because they are globally prevalent and clinically important triggers of allergic asthma. Group 1 HDM allergens are cysteine peptidases whose proteolytic activity triggers essential steps in the allergy cascade. Using the HDM allergen Der p 1 as an archetype for structure-based drug discovery, we have identified a series of novel, reversible inhibitors. Potency and selectivity were manipulated by optimizing drug interactions with enzyme binding pockets, while variation of terminal groups conferred the physicochemical and pharmacokinetic attributes required for inhaled delivery. Studies in animals challenged with the gamut of HDM allergens showed an attenuation of allergic responses by targeting just a single component, namely, Der p 1. Our findings suggest that these inhibitors may be used as novel therapies for allergic asthma.

  DOI：

  10.1021/jm501102h

文献信息

• Catalytic, One-Pot Synthesis of β-Amino Acids from α-Amino Acids. Preparation of α,β-Peptide Derivatives
  作者：Carlos Saavedra、Rosendo Hernández、Alicia Boto、Eleuterio Álvarez

  DOI：10.1021/jo9004487

  日期：2009.7.3

  The one-pot conversion of readily available α-amino acid into β-amino acid derivatives was carried out in good yields. The method is a sequential process initiated by a tandem radical decarboxylation−oxidation reaction; the resulting acyliminium ion was trapped by silyl ketenes. Stoichiometric and catalytic versions of this reaction were developed and then applied to prepare modified di- and tripeptides

  容易获得的α-氨基酸一锅转化为β-氨基酸衍生物的收率很高。该方法是由串联自由基脱羧氧化反应引发的顺序过程。所得的丙烯酰亚胺离子被甲硅烷基烯酮捕获。开发了该反应的化学计量和催化形式，然后用于制备修饰的二肽和三肽。有趣的是，一些三肽在固态下形成了扩展的β-转角。
• Metal-free, direct conversion of α-amino acids into α-keto γ-amino esters for the synthesis of α,γ-peptides
  作者：D. Hernández、A. Boto、D. Guzmán、E. Alvarez

  DOI：10.1039/c7ob02033c

  日期：——

  An efficient, metal-free synthesis of unusual α-keto γ-amino esters from α-amino acids is achieved by a radical scission–oxidation–addition of silyloxy acrylates procedure, where no purification of the reaction intermediates is needed. This protocol can be applied to the selective modification of the C-terminal position in peptides to give α,γ-hybrids.

  通过自由基裂解-氧化-添加甲硅烷氧基丙烯酸酯的方法可以有效地，无金属地从α-氨基酸合成不寻常的α-酮γ-氨基酯，而无需纯化反应中间体。该方案可应用于肽中C端位置的选择性修饰以产生α，γ杂化物。
• Development of a novel oxidatively removable and recyclable linker for combinatorial solid phase synthesis
  作者：Wen-Ren Li、Nai-Mu Hsu、Hsueh-Hsuan Chou、Sung Tsai Lin and、Yu-Sheng Lin

  DOI：10.1039/a909236f

  日期：——

  An appropriately derivatized phenanthridine is shown to behave as a novel, reusable linker which is based on a disubstituted amide anchorage and forms an acid group on oxidative cleavage, but tolerates exposure to acidic, basic and reductive reaction conditions.

  适当衍生的菲啶显示为一种新型的、可重复使用的接头，它基于二取代的酰胺锚定并在氧化裂解时形成酸基，但耐受酸性、碱性和还原反应条件。
• Pyruvamide Compounds as Inhibitors of Dust Mite Group 1 Peptidase Allergen and Their Use
  申请人：Robinson Clive

  公开号：US20120322722A1

  公开（公告）日：2012-12-20

  The present invention pertains generally to the field of therapeutic compounds and more specifically to certain pyruvamide compounds of the formula (X) (for convenience, collectively referred to herein as “PVA compounds”), which, inter alia, inhibit a dust mite Group 1 peptidase allergen (e.g., Der p 1, Der f 1, Eur m 1). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit a dust mite Group 1 peptidase allergen, and in the treatment of diseases and disorders that are mediated by a dust mite Group 1 peptidase allergen; that are ameliorated by the inhibition of a dust mite Group 1 peptidase allergen; asthma; rhinitis; allergic conjunctivitis; atopic dermatitis; an allergic condition which is triggered by dust mites; an allergic condition which is triggered by a dust mite Group 1 peptidase allergen; and canine atopy.

  本发明一般涉及治疗化合物领域，更具体地涉及某些丙酮酰胺化合物的公式（X）（为方便起见，以下统称为“PVA化合物”），该化合物在某些情况下抑制尘螨1组蛋白酶过敏原（例如Der p 1、Der f 1、Eur m 1）。本发明还涉及包含这种化合物的药物组合物，以及在体外和体内使用这种化合物和组合物来抑制尘螨1组蛋白酶过敏原，并用于治疗由尘螨1组蛋白酶过敏原介导的疾病和疾病，通过抑制尘螨1组蛋白酶过敏原而得到缓解的疾病和疾病；哮喘；鼻炎；过敏性结膜炎；特应性皮炎；由尘螨引发的过敏症状；由尘螨1组蛋白酶过敏原引发的过敏症状；以及犬类特应性。
• Allergen Delivery Inhibitors: Characterisation of Potent and Selective Inhibitors of Der p 1 and Their Attenuation of Airway Responses to House Dust Mite Allergens
  作者：Jihui Zhang、Jie Chen、Jie Zuo、Gary Newton、Mark Stewart、Trevor Perrior、David Garrod、Clive Robinson

  DOI：10.3390/ijms19103166

  日期：——

  Group 1 allergens of house dust mites (HDM) are globally significant triggers of allergic disease. They are considered as initiator allergens because their protease activity enables the development of allergy to a spectrum of unrelated allergens from various sources. This initiator-perpetuator function identifies Group 1 HDM allergens as attractive drug design targets for the first small-molecule approach directed towards a non-human, root cause trigger of allergic disease. The purpose of this study was to: (i) identify exemplar inhibitors of these allergens using Der p 1 as a design template, and (ii) characterise the pharmacological profiles of these compounds using in vitro and in vivo models relevant to allergy. Potent inhibitors representing four different chemotypes and differentiated by mechanism of action were investigated. These compounds prevented the ab initio development of allergy to the full spectrum of HDM allergens and in established allergy they inhibited the recruitment of inflammatory cells and blunted acute allergic bronchoconstriction following aerosol challenge with the full HDM allergen repertoire. Collectively, the data obtained in these experiments demonstrate that the selective pharmacological targeting of Der p 1 achieves an attractive range of benefits against exposure to all HDM allergens, consistent with the initiator-perpetuator function of this allergen.

  家居尘螨(Group 1)过敏原是全球重要的过敏疾病诱发因子。它们被认为是引发过敏的过敏原，因为它们的蛋白酶活性可以使人对来自各种来源的不相关过敏原谱系产生过敏反应。这种引发-维持功能将Group 1家居尘螨过敏原确定为针对过敏疾病非人类根本原因触发器的第一种小分子药物设计目标。本研究的目的是：(i)使用Der p 1作为设计模板，识别这些过敏原的样例抑制剂；(ii)使用与过敏相关的体外和体内模型表征这些化合物的药理学特性。研究了代表四种不同化学类型和不同作用机制的强效抑制剂。这些化合物防止了对全谱系家居尘螨过敏原的原始过敏反应，并且在已经发生的过敏反应中，它们抑制了炎症细胞的招募，并且在使用全谱系家居尘螨过敏原进行气溶胶挑战后减轻了急性过敏性支气管痉挛。总的来说，这些实验获得的数据表明，选择性药理靶向Der p 1可以对抗所有家居尘螨过敏原的暴露，与该过敏原的引发-维持功能一致。