(S)-2-(tert-butoxycarbonylamino)-N-ethyl-4-methylpentanamide | 126257-77-0

• 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: (S)-2-(tert-butoxycarbonylamino)-N-ethyl-4-methylpentanamide
• 英文别名: N'-ehyl-N-(tert-butoxycarbonyl)-L-leucinamide；Boc-Leu-NH-Et；tert-butyl N-[(2S)-1-(ethylamino)-4-methyl-1-oxopentan-2-yl]carbamate
• CAS: 126257-77-0
• 化学式: C₁₃H₂₆N₂O₃
• mdl: MFCD00438605
• 分子量: 258.361
• InChiKey: DJPLHEAOIPCDQL-JTQLQIEISA-N

物化性质

• 熔点：
  105-106 °C
• 沸点：
  407.1±28.0 °C(Predicted)
• 密度：
  0.985±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-2-(tert-butoxycarbonylamino)-N-ethyl-4-methylpentanamide 在 盐酸 作用下， 以 甲醇 为溶剂， 以98.5%的产率得到N'-ethyl-L-leucinamide hydrochloride
  参考文献：
  名称：

  Water Mediated Ligand Functional Group Cooperativity: The Contribution of a Methyl Group to Binding Affinity is Enhanced by a COO^– Group Through Changes in the Structure and Thermodynamics of the Hydration Waters of Ligand–Thermolysin Complexes

  摘要：

  Ligand functional groups can modulate the contributions of one another to the ligand protein binding thermodynamics, producing either positive or negative cooperativity. Data presented for four thermolysin phosphonamidate inhibitors demonstrate that the differential binding free energy and enthalpy caused by replacement of a H with a Me group, which binds in the well-hydrated S2' pocket, are more favorable in presence of a ligand carboxylate. The differential entropy is however less favorable. Dissection of these differential thermodynamic parameters, X-ray crystallography, and density-functional theory calculations suggest that these cooperativities are caused by variations in the thermodynamics of the complex hydration shell changes accompanying the H -> Me replacement. Specifically, the COO- reduces both the enthalpic penalty and the entropic advantage of displacing water molecules from the S2' pocket and causes a subsequent acquisition of a more enthalpically, less entropically, favorable water network. This study contributes to understanding the important role water plays in ligand-protein binding.

  DOI：

  10.1021/jm300472k
• 作为产物：
  描述：

  BOC-L-亮氨酸 、 3-hydroxy-1,2,3-benzotriazin-4(3H)-one ethylammonium salt 在 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以85%的产率得到(S)-2-(tert-butoxycarbonylamino)-N-ethyl-4-methylpentanamide
  参考文献：
  名称：

  Efficient, Racemization-Free Amidation of Protected Amino Acids

  摘要：

  将 L-亮氨酸、S-苄基-L-半胱氨酸和 Nt-(2,4-二硝基苯基)-L-组氨酸的 N-叔丁氧羰基衍生物与 3-羟基-1,2,3-苯并三嗪-4(3H)-酮和 N-羟基琥珀酰亚胺的结晶铵盐、甲铵盐和乙铵盐进行酰胺化反应，得到相应的氨基酸酰胺，产率高，光学纯度好。

  DOI：

  10.1055/s-1992-26093

文献信息

• Influence of Neighboring Groups on the Thermodynamics of Hydrophobic Binding: An Added Complex Facet to the Hydrophobic Effect
  作者：Nader N. Nasief、David Hangauer

  DOI：10.1021/jm401609a

  日期：2014.3.27

  proentropic in others. A remarkable enthalpy–entropy compensation relationship was also observed, reflecting the fact that the hydrophobic effect is governed by the thermodynamic status of the associated aqueous environment. This study could improve our understanding of the hydrophobic effect and may enhance our ability to design potent ligands that are capable of modulating biological processes.

  使用等温滴定量热法（ITC）对在浅疏水口袋中结合的配体侧链进行系统修饰的热力学后果进行了评估，无论是否存在相邻的配体羧酸酯基团。数据显示，羧酸盐可能会通过改变未结合状态和结合状态下水合水的H键/组织状态来显着改变这些修饰的相对热力学特征。发现该羧酸酯基团在某些情况下是前焓的，对熵的，而在另一些情况下是反焓的，对熵的。还观察到了显着的焓-熵补偿关系，这反映了疏水作用受相关水环境的热力学状态支配的事实。
• Inhibitors of cysteine proteases and methods of use thereof
  申请人：Pardes Biosciences, Inc.

  公开号：US11524940B1

  公开（公告）日：2022-12-13

  The disclosure provides compounds with warheads and their use in treating medical diseases or disorders, such as viral infections. Pharmaceutical compositions and methods of making various compounds with warheads are provided. The compounds are contemplated to inhibit proteases, such as the 3C, CL- or 3CL-like protease.

  本公开提供了带有弹头的化合物及其在治疗医学疾病或失调（如病毒感染）中的用途。提供了药物组合物和制造各种带弹头化合物的方法。这些化合物可用于抑制蛋白酶，如 3C、CL 或 3CL 样蛋白酶。
• Ammonium salts from polymer-bound N-hydroxysuccinimide as solid-supported reagents for EDC-mediated amidations
  作者：Rafael Chinchilla、David J Dodsworth、Carmen Nájera、José M Soriano

  DOI：10.1016/s0040-4039(02)02592-3

  日期：2003.1

  New ammonium and alkylammonium salts derived from a polymeric N-hydroxysuccinimide (P-HOSu) have been prepared and used for the amidation of carboxylic acids and amino acids mediated by 1-ethyl-3-(3'-dimethylamino-propyl)carbodiimide hydrochloride (EDC). These polymer-supported ammonium salts afforded the corresponding amides in good yield, without detectable alpha-racemization and with easy recovery of the P-HOSu after the amidation reaction, being especially suitable for the amidation of Fmoc-protected amino acids. (C) 2002 Published by Elsevier Science Ltd.
• Additivity or cooperativity: Which model can predict the influence of simultaneous incorporation of two or more functionalities in a ligand molecule?
  作者：Nader N. Nasief、David Hangauer

  DOI：10.1016/j.ejmech.2014.11.056

  日期：2015.1

  Predicting how binding affinity responds to ligand structural modifications in structure-activity relationship studies (SAR) is a major challenge in medicinal chemistry. This is particularly true when two or more of these modifications are carried out simultaneously. In this study, we present binding affinity data from several series of thermolysin inhibitors in which simultaneous structural modifications were investigated to determine whether they are cooperative or additive. Data revealed that, while additivity is at work in some cases, cooperativity is more commonly demonstrated. Cooperativity and additivity were then correlated with ligand descriptors, such as the spacing and the topological features of the modified groups, in a manner that may provide guidance as to when each model should be utilized. Cooperativity was particularly associated with contiguous groups and small unbranched hydrophobic side chain. Additivity, on the other hand, was associated with moderately distant hydrophobic group combinations and side chain branching. Such correlations can improve the predictability of SAR studies and can provide a starting point for additional investigations that may lead to further significant enhancements in the current scoring functions. (C) 2014 Elsevier Masson SAS. All rights reserved.
• Solid-phase synthesis of N-methyl- and N-ethylamides of peptides using photolytically detachable [(3-nitro-4-[(alkylamino)methyl]benzamido]methyl]polystyrene resin
  作者：A. Ajayaghosh、V. N. Rajasekharan Pillai

  DOI：10.1021/jo00296a049

  日期：1990.4