N2-[(丁氧基)羰基]-N4,N4-二甲基天冬酰胺 | 70232-19-8

• 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: N2-[(丁氧基)羰基]-N4,N4-二甲基天冬酰胺
• 中文别名: (S)-2-((叔丁氧基羰基)氨基)-4-(二甲基氨基)-4-氧代丁酸
• 英文名称: Boc-Asn(Me)2-OH
• 英文别名: Boc-Asn(Me2)-OH；(S)-2-((tert-Butoxycarbonyl)amino)-4-(dimethylamino)-4-oxobutanoic acid；(2S)-4-(dimethylamino)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxobutanoic acid
• CAS: 70232-19-8
• 化学式: C₁₁H₂₀N₂O₅
• 分子量: 260.29
• InChiKey: WNVCRAUZUATQRQ-ZETCQYMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  95.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N2-[(丁氧基)羰基]-N4,N4-二甲基天冬酰胺 在 palladium on activated charcoal 盐酸 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 51.0h， 生成 3-{(S)-2-[(S)-2-(3,3-Dimethyl-butyrylamino)-3,3-dimethyl-butyrylamino]-3-dimethylcarbamoyl-propionylamino}-2-hydroxy-butyric acid
  参考文献：
  名称：

  Peptidomimetic Inhibitors of the Human Cytomegalovirus Protease

  摘要：

  The development of peptidomimetic inhibitors of the human cytomegalovirus (HCMV) :protease showing sub-micromolar potency in an enzymatic assay is described. Selective substitution of the amino acid residues of these inhibitors led to the identification of tripeptide inhibitors showing improvements in inhibitor potency cf 27-fold relative to inhibitor 39 based upon the natural tetrapeptide sequence. Small side chains at P-1 were well tolerated by this enzyme, a fact consistent with previous observations. The S-2 binding pocket of HCMV protease was very permissive, tolerating lipophilic and basic residues. The substitutions tried at P-3 indicated that a small increase in inhibitor potency could be realized by the substitution of a tert-leucine residue for valine. Substitutions of the N-terminal capping group did not significantly affect inhibitor potency. Pentafluoroethyl ketones, alpha,alpha-difluoro-beta-keto amides, phosphonates and a-keto amides were all effective substitutions for the activated carbonyl component and gave inhibitors which were selective for HCMV protease. A slight increase in potency was observed by lengthening the P-1' residue of the alpha-keto amide series of inhibitors. This position also tolerated a variety of groups making this a potential site for future modifications which could modulate the physicochemical properties of these molecules.

  DOI：

  10.1021/jm970104t
• 作为产物：
  描述：

  Boc-L-天冬氨酸 1-苄酯 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 异丙醇 为溶剂， 生成 N2-[(丁氧基)羰基]-N4,N4-二甲基天冬酰胺
  参考文献：
  名称：

  Short synthesis of protease inhibitors via modified Passerini condensation of N-Boc-α-aminoaldehydes

  摘要：

  Extension of the previously reported modification of Passerini multicomponent reaction (involving condensation with N-Boc-alpha-aminoaldehydes followed by a deprotection-transacylation step) to alpha-aminoacid derived carboxylic or isocyanide components, allowed the highly convergent and short synthesis of complex peptidomimetic structures, including known potent inhibitors of serine proteases. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(02)00728-1

文献信息

• Diamide amino-imidazoles: A novel series of γ-secretase inhibitors for the treatment of Alzheimer’s disease
  作者：Michael A. Brodney、David D. Auperin、Stacey L. Becker、Brian S. Bronk、Tracy M. Brown、Karen J. Coffman、James E. Finley、Carol D. Hicks、Michael J. Karmilowicz、Thomas A. Lanz、Dane Liston、Xingrong Liu、Barbara-Anne Martin、Robert B. Nelson、Charles E. Nolan、Christine E. Oborski、Christine P. Parker、Karl E.G. Richter、Nikolay Pozdnyakov、Barbara G. Sahagan、Joel B. Schachter、Sharon A. Sokolowski、Barbara Tate、Jeffrey W. Van Deusen、Douglas E. Wood、Kathleen M. Wood

  DOI：10.1016/j.bmcl.2010.12.117

  日期：2011.5

  structure–activity relationship (SAR) of a novel series of di-substituted imidazoles, derived from modification of DAPT, are described. Subsequent optimization led to identification of a highly potent series of inhibitors that contain a β-amine in the imidazole side-chain resulting in a robust in vivo reduction of plasma and brain Aβ in guinea pigs. The therapeutic index between Aβ reductions and changes in B-cell

  描述了衍生自DAPT修饰的一系列新型二取代咪唑的合成及其构效关系（SAR）。随后的优化导致鉴定出一系列高效抑制剂，这些抑制剂在咪唑侧链中包含β-胺，可导致豚鼠体内血浆和大脑Aβ大量降低。研究了化合物10h的Aβ减少与B细胞群变化之间的治疗指数。
• A New Amino Acid for Improving Permeability and Solubility in Macrocyclic Peptides through Side Chain-to-Backbone Hydrogen Bonding
  作者：Jaru Taechalertpaisarn、Satoshi Ono、Okimasa Okada、Timothy C. Johnstone、R. Scott Lokey

  DOI：10.1021/acs.jmedchem.2c00010

  日期：2022.3.24

  poor membrane permeability of peptides, many cyclic peptide natural products show high passive membrane permeability and potently inhibit a variety of “undruggable” intracellular targets. A major impediment to the design of cyclic peptides with good permeability is the high desolvation energy associated with the peptide backbone amide NH groups. While several strategies have been proposed to mitigate

  尽管肽的膜通透性较差，但许多环肽天然产物表现出较高的被动膜通透性，并有效抑制各种“不可成药”的细胞内靶标。设计具有良好渗透性的环肽的一个主要障碍是与肽主链酰胺NH基团相关的高去溶剂化能。虽然已经提出了几种策略来减轻这种有害影响，但只有少数研究使用极性侧链来隔离主链 NH 基团。我们研究了N , N-吡咯烷基谷氨酰胺 (Pye)的能力，其侧链包含强大的氢键接受 C=O 酰胺基团，但没有氢键供体，在一系列环状六肽非对映体中螯合暴露的主链 NH 基团。分析表明，特定的 Leu 至 Pye 取代以支架和位置依赖性方式显着改善了水溶性和渗透性。因此，该方法为改善环肽的膜渗透性和溶解度提供了补充工具。
• Iterative Approach to the Discovery of Novel Degarelix Analogues:  Substitutions at Positions 3, 7, and 8. Part II
  作者：Manoj P. Samant、Jozsef Gulyas、Doley J. Hong、Glenn Croston、Catherine Rivier、Jean Rivier

  DOI：10.1021/jm050134t

  日期：2005.7.1

  extent (efficacy and duration of action) of inhibition of luteinizing hormone (LH) release. Structurally, this series of analogues has novel substitutions at positions 3, 7, and 8 and N(alpha)-methylation at positions 6, 7, and 8 in the structure of degarelix. These substitutions were designed to probe the spatial limitations of the receptor's cavity and to map the steric and ionic boundaries. Some

  Degarelix（FE200486，Ac-d-2Nal（1）-d-4Cpa（2）-d-3Pal（3）-Ser（4）-4Aph（1-Hor）（5）-d-4Aph（Cbm）（6 ）-Leu（7）-ILys（8）-Pro（9）-d-Ala（10）-NH（2））是哺乳动物皮下给药后促性腺激素释放激素（GnRH）的强效且长效拮抗剂包括人类。在表达人GnRH受体的HEK-293细胞中，通过报告基因分析法合成，表征并表征了地加瑞克的类似物，并筛选了GnRH诱导的应答的拮抗作用。在去势雄性大鼠试验中还测定了作用的持续时间，以测量抑制黄体生成素（LH）释放的程度（作用和作用的持续时间）。从结构上讲，这一系列类似物在地加瑞克的结构中的3、7和8位具有新的取代基，并在6、7和8位具有Nα-甲基化。设计这些替代物以探测受体腔的空间限制并绘制空间和离子边界。引入了一些官能团，这些官能团被认为会影响类似物的药动学性
• Chemical Tailoring of Teicoplanin with Site-Selective Reactions
  作者：Tejas P. Pathak、Scott J. Miller

  DOI：10.1021/ja4038998

  日期：2013.6.5

  selectivity often undermines efficiency. The complex antibiotic teicoplanin eradicates bacterial infections. However, as resistance emerges, the demand for improved analogues grows. We have discovered chemical reactions that achieve site-selective alteration of teicoplanin. Utilizing peptide-based additives that alter reaction selectivities, certain bromo-teicoplanins are accessible. These new compounds

  天然产物衍生物的半合成将发酵的力量与正交化学反应相结合。然而，复杂结构的化学修饰是一个尚未解决的挑战，因为选择性差通常会降低效率。复合抗生素替考拉宁可根除细菌感染。然而，随着耐药性的出现，对改良类似物的需求也在增长。我们发现了实现替考拉宁位点选择性改变的化学反应。利用改变反应选择性的基于肽的添加剂，可以使用某些溴代替考拉宁。这些新化合物也是选择性交叉偶联反应的支架，可进一步实现分子多样化。这些研究能够两步获得糖肽类似物，这些糖肽类似物不能单独通过生物合成或快速全化学合成获得。
• Theodoropoulos; Pinas; Poulos, European Journal of Medicinal Chemistry, 1982, vol. 17, # 6, p. 527 - 530
  作者：Theodoropoulos、Pinas、Poulos、et al.

  DOI：——

  日期：——