L-亮氨酰-N,3-二甲基-L-缬氨酰胺 | 178933-95-4

• 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: L-亮氨酰-N,3-二甲基-L-缬氨酰胺
• 英文名称: L-leucyl-L-tert-leucine methyl amide
• 英文别名: L-leucyl-L-tert-leucine methylamide；H-Leu-Tle-NHMe；L-leucyl-L-tert-leucine N-methylamide；L-Leucyl-tert-leucine N-methylamide；L-Valinamide,L-leucyl-N,3-dimethyl；(2S)-2-amino-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-4-methylpentanamide
• CAS: 178933-95-4
• 化学式: C₁₃H₂₇N₃O₂
• 分子量: 257.376
• InChiKey: SUFUXERBHBKUOK-VHSXEESVSA-N

物化性质

• 沸点：
  461.6±30.0 °C(Predicted)
• 密度：
  0.990±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  84.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  L-亮氨酰-N,3-二甲基-L-缬氨酰胺 在 劳森试剂 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 (2S)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-2-[[2-[hydroxy(methyl)amino]-4-oxo-3-sulfanylidenecyclobuten-1-yl]amino]-4-methylpentanamide
  参考文献：
  名称：

  Squaric Acid-Based Peptidic Inhibitors of Matrix Metalloprotease-1

  摘要：

  A series of squaric acid-peptide conjugates were synthesized and evaluated as inhibitors of MMP-1. The cyclobut-3-enedione core was substituted at the 3-position with several functional groups, such as -N(alkyl)OH, -NHOH, and -OH, that are designed to bind to the zinc atom in the active site of the metalloprotease. The 4-position of the cyclobut-3-enedione was derivatized with mono- or dipeptides that are designed to bind in the S1' and S2' subsites of the enzyme, and position the metal chelating group appropriately in the active site for binding to zinc. Positional scanning revealed that -N(Me)OH provided the highest level of inhibition among the chelating groups that were tested, and Leu-Tle-NHMe was the preferred amino acid sequence. A combination of these groups yielded an inhibitor with an IC50 value of 95 mu M. For one inhibitor, conversion of one of the carbonyl groups on the cyclobut-3-enedione core to a thiocarbonyl group resulted in a 18-fold increase in potency, and yielded a compound with an IC50 value of 15 mu M.

  DOI：

  10.1021/jo0517848
• 作为产物：
  描述：

  N-Boc-L-叔亮氨酸 在 N-羟基丁二酰亚胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.34h， 生成 L-亮氨酰-N,3-二甲基-L-缬氨酰胺
  参考文献：
  名称：

  Squaric Acid-Based Peptidic Inhibitors of Matrix Metalloprotease-1

  摘要：

  A series of squaric acid-peptide conjugates were synthesized and evaluated as inhibitors of MMP-1. The cyclobut-3-enedione core was substituted at the 3-position with several functional groups, such as -N(alkyl)OH, -NHOH, and -OH, that are designed to bind to the zinc atom in the active site of the metalloprotease. The 4-position of the cyclobut-3-enedione was derivatized with mono- or dipeptides that are designed to bind in the S1' and S2' subsites of the enzyme, and position the metal chelating group appropriately in the active site for binding to zinc. Positional scanning revealed that -N(Me)OH provided the highest level of inhibition among the chelating groups that were tested, and Leu-Tle-NHMe was the preferred amino acid sequence. A combination of these groups yielded an inhibitor with an IC50 value of 95 mu M. For one inhibitor, conversion of one of the carbonyl groups on the cyclobut-3-enedione core to a thiocarbonyl group resulted in a 18-fold increase in potency, and yielded a compound with an IC50 value of 15 mu M.

  DOI：

  10.1021/jo0517848
• 作为试剂：
  描述：

  2-Acetylsulfanyl-4-(3,4,4-trimethyl-2,5-dioxoimidazolidin-1-yl)butanoic acid 、 L-亮氨酰-N,3-二甲基-L-缬氨酰胺 在 L-亮氨酰-N,3-二甲基-L-缬氨酰胺 作用下， 以65的产率得到N-[2-(Acetylthio)-4-(1,5,5-trimethylhydantoinyl)butanoyl]-L-Leucyl-L-tert-leucine N-methylamide
  参考文献：
  名称：

  [EN] THIO-SUBSTITUTED PEPTIDES AS INHIBITORS FOR METALLOPROTEINASES AND TNF LIBERATION
  [FR] PEPTIDES THIO-SUBSTITUES UTILES COMME INHIBITEURS DE METALLOPROTEASES ET DE LA LIBERATION DU TNF

  摘要：

  这是一种公式为(I)的肽化合物。这些肽是(基质)金属蛋白酶如胶原酶和基质金属蛋白酶的抑制剂。此外，它们还抑制肿瘤坏死因子$g(a)(TNF$g(a))的释放。

  公开号：

  WO1997012902A1

文献信息

• [EN] PROCESS FOR THE PREPARATION OF AN alpha-AMINO CARBONYL COMPOUND<br/>[FR] PROCEDE DE PREPARATION D'UN COMPOSE DOLLAR G(A)-AMINO CARBONYLE
  申请人：DSM IP ASSETS BV

  公开号：WO2004078702A1

  公开（公告）日：2004-09-16

  The invention relates to a process for the preparation of an α-amino carbonyl compound by reacting an imine starting material with a suitable electrophile in the presence of a base. This process has the advantage that the imine starting materials can be prepared from glyoxylic acid esters or glyoxylic acid ester derivatives and α-hydrogen containing primary amines, which are usually cheap and readily available. These imine starting materials can usually be prepared with a high yield and/or almost without the formation of any side products.

  该发明涉及一种通过在碱存在下，将亚胺起始物与适当的亲电试剂反应制备α-氨基羰基化合物的方法。这种方法的优点在于，亚胺起始物可以由乙酰乙酸酯或乙酰乙酸酯衍生物和α-氢含量的一级胺反应制备，这些原料通常便宜且易得。这些亚胺起始物通常可以高产率地制备，或几乎不形成任何副产物。
• Dynamic resolution of isomers and resolved isomers
  申请人：——

  公开号：US20020111512A1

  公开（公告）日：2002-08-15

  Provided is a dynamic resolution method of enriching a desired isomer of an alpha-substituted carboxylic acid relative to an undesired isomer, the method comprising: (a) in a solvent, contacting the alpha-substituted carboxylic acid, wherein the alpha substitution is with a leaving group and wherein the alpha carbon is chiral, with a homochiral amine to form a salt that is partially insoluble under selected reaction conditions, wherein the homochiral amine is selected so that the solubility of the amine salt of the undesired alpha-substituted carboxylic acid is greater than that of the amine salt of the desired alpha-substituted carboxylic acid under the selected reaction conditions; (b) reacting under the selected reaction conditions the salt with a nucleophile, wherein the reacting is effective in producing a net increase in the less soluble amine salt of the alpha-substituted carboxylic acid, and wherein the selected conditions are selected to (i) promote nucleophilic substitution of the nucleophile and the leaving group or (ii) to produce the increase in the less soluble amine salt in the absence of a strong base; and (c) maintaining the reaction for a period of time effective to increase the amount of the desired alpha-substituted carboxylic acid isomer.

  提供一种动态分辨方法，用于富集所需的α-取代羧酸同分异构体相对于不需要的同分异构体，该方法包括：（a）在溶剂中，将α-取代羧酸与手性同构胺接触，其中α取代基带有离去基团，α碳是手性的，形成部分不溶于所选反应条件下的盐，其中所选的手性同构胺被选择为在所选反应条件下，不需要的α-取代羧酸胺盐的溶解度大于所需的α-取代羧酸胺盐的溶解度；（b）在所选的反应条件下，用亲核试剂反应所述盐，反应有效地产生较不溶的α-取代羧酸胺盐的净增加，所选条件被选择为（i）促进亲核试剂和离去基团的亲核取代或（ii）在没有强碱的情况下产生较不溶的胺盐的增加；（c）维持反应一段有效时间，以增加所需的α-取代羧酸同分异构体的数量。
• [EN] SELECTIVE MMP INHIBITORS HAVING REDUCED SIDE-EFFECTS<br/>[FR] INHIBITEURS SELECTIFS DE LA METALLOPROTEASE MATRICIELLE PRESENTANT DES EFFETS SECONDAIRES REDUITS
  申请人：DARWIN DISCOVERY LIMITED

  公开号：WO1998039024A1

  公开（公告）日：1998-09-11

  (EN) A matrix metalloproteinase (MMP) inhibitor that exhibits an IC50 of below 10-4M against MMP and has substantially no activity against non-MMP metalloproteinase-related events has reduced side-effects, especially with respect to joint pain.(FR) L'invention concerne un inhibiteur de la métalloprotéase matricielle qui présente une concentration inhibitrice 50 de moins de 10-4M contre la métalloprotéase matricielle, et n'exerce sensiblement aucune activité contre les évènements non liés à la métalloprotéase matricielle. Cet inhibiteur présente des effets secondaires réduits, en particulier, dans le domaine des douleurs articulaires.

  一种基质金属蛋白酶（MMP）抑制剂，对MMP的IC50低于10-4M，并且几乎没有对非MMP金属蛋白酶相关事件的活性，具有减少副作用的作用，尤其是对关节疼痛方面的作用。
• Enzyme-mediated synthesis of peptidomimetics
  申请人：Darwin Discovery, Ltd.

  公开号：US06436697B1

  公开（公告）日：2002-08-20

  A process for the preparation of a compound of formula (1) comprises reacting compounds of formulae (2) and (3) in the presence of an enzyme, wherein A is a thiol-protecting group, B, C and D are each the same or different organic groups of up to 30 C atoms, optionally functionalized at any position, provided that neither a primary amine nor a primary amide is present, and X is a group that can be displaced by NH2.

  一种制备公式(1)化合物的过程，包括在酶的存在下，反应公式(2)和(3)化合物，其中A是硫醇保护基，B、C和D是相同或不同的有机基团，可在任何位置上进行官能化，并且不含一级胺或一级酰胺，X是可以被NH2取代的基团。
• Method of producing n-[(2S)-sulfanyl-4-(1,5,5-trimethylhydantoinyl)butanoyl]-L-leucyl-L-tert-leucine N-methylamide and intermediate thereof
  申请人：——

  公开号：US20030166506A1

  公开（公告）日：2003-09-04

  Process for producing N-[(2S)-sulfanyl-4-(1,5,5-trimethylhydantoinyl) butanoyl]-L-leucyl-L-tert-leucine N-methylamide by forming an intermediate compound N-[(2S)-thiobenzoyl-4-(1,5,5-trimethylhydantoinyl)butanoyl]-L-leucyl-L-tert-leucine N-methylamide by an improved process that substantially reduces the presence of contaminants in the reaction mixture.

  通过形成中间化合物 N-[(2S)-硫苯甲酰基-4-(1,5,5-三甲基海因基)丁酰基]-L-亮氨酰-L-叔亮氨酸 N-甲酰胺生产 N-[(2S)-硫苯甲酰基-4-(1,5,5-三甲基海因基)丁酰基]-L-亮氨酰-L-叔亮氨酸 N-甲酰胺的工艺(2S)-硫代苯甲酰基-4-(1,5,5-三甲基海因)丁酰基]-L-亮氨酰-L-叔亮氨酸 N-甲酰胺的改进工艺，该工艺大大减少了反应混合物中污染物的存在。