(S)-2-((叔丁氧基羰基)氨基)-5-(二甲基氨基)-5-氧代戊酸 | 72449-42-4

• 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: (S)-2-((叔丁氧基羰基)氨基)-5-(二甲基氨基)-5-氧代戊酸
• 英文名称: Boc-Gln(Me2)-OH
• 英文别名: (S)-2-((tert-Butoxycarbonyl)amino)-5-(dimethylamino)-5-oxopentanoic acid；(2S)-5-(dimethylamino)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxopentanoic acid
• CAS: 72449-42-4
• 化学式: C₁₂H₂₂N₂O₅
• 分子量: 274.317
• InChiKey: MZRAADPAONILMH-QMMMGPOBSA-N

物化性质

• 沸点：
  460.4±40.0 °C(Predicted)
• 密度：
  1.150±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  95.9
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P305+P351+P338,P330,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  (S)-2-((叔丁氧基羰基)氨基)-5-(二甲基氨基)-5-氧代戊酸 在 10percent Pd/C 三乙基硅烷 、 溶剂黄146 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.25h， 生成 (4S,5RS)-N,N-dimethyl-4-(tert-butyloxycarbonylamino)-5-cyano-5-hydroxypentanamide
  参考文献：
  名称：

  Synthesis and Evaluation of Keto-Glutamine Analogues as Inhibitors of Hepatitis A Virus 3C Proteinase

  摘要：

  Hepatitis A virus (HAV) 3C enzyme is a picornaviral cysteine proteinase involved in the processing of the initially synthesized viral polyprotein and is therefore important for viral maturation and infectivity, Although it is a cysteine proteinase, this enzyme has a topology similar to those of the chymotrypsin-like serine proteinases. Since the enzyme recognizes peptide substrates with a glutamine residue at the P, site, a number of ketone-containing glutamine compounds analogous to nanomolar inhibitors of cathepsin K were synthesized and tested for inhibition against HAV 3C proteinase. In addition, a 3-azetidinone scaffold was incorporated into the glutamine fragment but gave only modest inhibition. However, introduction of a phthalhydrazido group a to the ketone moiety gave significantly better inhibitors with IC50 values ranging from 13 to 164 muM, presumably due to the effect of intramolecular hydrogen bonding to the ketone. In addition, the tetrapeptide phthalhydrazide 24 was found to be a competitive reversible inhibitor (K-i = 9 x 10(-6) M) and also showed no loss of inhibitory potency in the presence of dithiothreitol.

  DOI：

  10.1021/jo0157831
• 作为产物：
  描述：

  N²-(tert-butyloxycarbonyl)-N⁵,N⁵-dimethylglutamine benzyl ester 在 10percent Pd/C 氢气 作用下， 以 甲醇 为溶剂， 反应 6.0h， 以90%的产率得到(S)-2-((叔丁氧基羰基)氨基)-5-(二甲基氨基)-5-氧代戊酸
  参考文献：
  名称：

  Synthesis and Evaluation of Keto-Glutamine Analogues as Inhibitors of Hepatitis A Virus 3C Proteinase

  摘要：

  Hepatitis A virus (HAV) 3C enzyme is a picornaviral cysteine proteinase involved in the processing of the initially synthesized viral polyprotein and is therefore important for viral maturation and infectivity, Although it is a cysteine proteinase, this enzyme has a topology similar to those of the chymotrypsin-like serine proteinases. Since the enzyme recognizes peptide substrates with a glutamine residue at the P, site, a number of ketone-containing glutamine compounds analogous to nanomolar inhibitors of cathepsin K were synthesized and tested for inhibition against HAV 3C proteinase. In addition, a 3-azetidinone scaffold was incorporated into the glutamine fragment but gave only modest inhibition. However, introduction of a phthalhydrazido group a to the ketone moiety gave significantly better inhibitors with IC50 values ranging from 13 to 164 muM, presumably due to the effect of intramolecular hydrogen bonding to the ketone. In addition, the tetrapeptide phthalhydrazide 24 was found to be a competitive reversible inhibitor (K-i = 9 x 10(-6) M) and also showed no loss of inhibitory potency in the presence of dithiothreitol.

  DOI：

  10.1021/jo0157831

文献信息

• Studies on neurokinin antagonists. 2. Design and structure-activity relationships of novel tripeptide substance P antagonists, N.alpha.-[N.alpha.-(N.alpha.-acetyl-L-threonyl)-N1-formyl-D-tryptophyl]-N-methyl-N-(phenylmethyl)-L-phenylalaninamide and its related compounds
  作者：Daijiro Hagiwara、Hiroshi Miyake、Hiroshi Morimoto、Masako Murai、Takashi Fujii、Masaaki Matsuo

  DOI：10.1021/jm00095a013

  日期：1992.8

  terms of potency and stability. Subsequent modification of the amino terminal into N alpha-acetyl-L-threonine led to the most potent compound, N alpha-[N alpha-(N alpha-acetyl-L-threonyl)-N1-formyl-D-tryptophyl]-N- methyl-N-(phenylmethyl)-L-phenylalaninamide [Ac-Thr-D-Trp(CHO)-Phe-NMeBzl (5a, FR113680)]. This compound 5a potently blocked 3H-SP binding to guinea pig lung membranes with IC50 of (5.8 +/-

  继续研究先前报道的新型三肽SP拮抗剂Nα-[Nα-[Nα-（叔丁氧基羰基）谷氨酰胺基] -N1-甲酰基-D-色氨酸]苯丙氨酸苄酯[Boc-Gln- D-Trp-（CHO）-Phe-OBzl（1）]在本文中描述。我们最初研究了豚鼠血浆和肝脏匀浆中1的稳定性，以阐明结构中最不稳定的部分。结果表明，苄基酯部分易于水解以产生惰性酸类似物。因此，我们搜索了对水解酶更具抗性的苄基酯替代物。该方法发现了等价酰胺结构，N-甲基-N-（苯甲基）酰胺，其效力和稳定性均合适。随后将氨基末端修饰成Nα-乙酰基-L-苏氨酸导致了最有效的化合物Nα-[Nα-（Nα-乙酰基-L-苏氨酸）-N1-甲酰基-D-色氨酸] -N -甲基-N-（苯甲基）-L-苯丙氨酰胺[Ac-Thr-D-Trp（CHO）-Phe-NMeBzl（5a，FR113680）]。该化合物5a有效阻断3H-SP与豚鼠肺膜的结合，IC50为（5.8 +/-
• 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。
• PROTEASE INHIBITORS FOR CORONAVIRUSES AND SARS-COV AND THE USE THEREOF
  申请人：Cai Sui Xiong

  公开号：US20080300191A1

  公开（公告）日：2008-12-04

  Disclosed are protease inhibitors for coronaviruses and SARS-CoV, or picornaviruses, and the use of these protease inhibitors for preventing, reducing, ameliorating and treating a disease or condition caused by coronaviruses and SARS-CoV, or picornaviruses. Also disclosed are methods of reducing or preventing the spread of coronavirus, or picornaviruses, and preventing or reducing the replication of coronavirus, or picornaviruses, with the compounds of the present invention

  本申请公开了用于冠状病毒和SARS-CoV，或小RNA病毒的蛋白酶抑制剂，以及利用这些蛋白酶抑制剂预防、减少、改善和治疗由冠状病毒和SARS-CoV，或小RNA病毒引起的疾病或症状的用途。还公开了使用本发明的化合物减少或预防冠状病毒，或小RNA病毒的传播，并预防或减少冠状病毒，或小RNA病毒的复制的方法。
• In vitro and ex vivo inhibition of hepatitis A virus 3C proteinase by a peptidyl monofluoromethyl ketone
  作者：Tina S Morris、Sven Frormann、Shirley Shechosky、Christopher Lowe、Manjinder S Lall、Verena Gauss-Müller、Robert H Purcell、Suzanne U Emerson、John C Vederas、Bruce A Malcolm

  DOI：10.1016/s0968-0896(97)88649-x

  日期：1997.5

  configuration like those of the mammalian serine proteinases (Malcolm, B. A. Protein Science 1995, 4, 1439). A peptidyl monofluoromethyl ketone (peptidyl-FMK) based on the preferred peptide substrates for HAV 3C proteinase was generated by first coupling the precursor, N,N-dimethylglutamine fluoromethylalcohol, to the tripeptide, Ac-Leu-Ala-Ala-OH, and then oxidizing the product to the corresponding peptidyl-FMK

  甲型肝炎病毒（HAV）3C蛋白酶是负责处理病毒多蛋白的酶。尽管是半胱氨酸蛋白酶，但它表现出类似于哺乳动物丝氨酸蛋白酶的活性位点构型（Malcolm，BA Protein Science 1995，4，1439）。通过首先将前体N，N-二甲基谷氨酰胺氟甲基醇与三肽Ac-Leu-ALA-ALA-OH偶联，然后生成基于HAV 3C蛋白酶优选肽底物的肽基单氟甲基酮（peptidyl-FMK）。将产物氧化为相应的肽基-FMK（Ac-LAAQ'-FMK）。发现该分子是HAV 3C的不可逆灭活剂，其二级速率常数为3.3 x 10（2）M-1 s-1。19 F NMR光谱表明在氟甲基酮使酶失活时氟化物的置换。13C标记的抑制剂和HAV 3C蛋白酶之间的复合物的NMR光谱表明形成了（烷硫基）甲基酮。使用体外转录/翻译产生的各种底物进行的多蛋白加工研究表明，即使是最快速的蛋白水解事件，如2A-2B和2C-3A
• 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：——