4(S)-4-tert-butoxycarbonylamino-5-oxo-pentanoic acid tert-butyl ester | 211185-89-6

• 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: 4(S)-4-tert-butoxycarbonylamino-5-oxo-pentanoic acid tert-butyl ester
• 英文别名: (4S)-4-(tert-Butyloxycarbonylamino)-5-oxopentanoic acid tert-butyl ester；tert-butyl (4S)-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxopentanoate
• CAS: 211185-89-6
• 化学式: C₁₄H₂₅NO₅
• 分子量: 287.356
• InChiKey: LDUGHSSAMOWUMF-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  20
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  磷酰基乙酸三乙酯 、 4(S)-4-tert-butoxycarbonylamino-5-oxo-pentanoic acid tert-butyl ester 在 sodium hexamethyldisilazane 作用下， 生成 (E)-(S)-4-tert-Butoxycarbonylamino-hept-2-enedioic acid 7-tert-butyl ester 1-ethyl ester
  参考文献：
  名称：

  Structure-Based Design, Synthesis, and Biological Evaluation of Irreversible Human Rhinovirus 3C Protease Inhibitors. 2. Peptide Structure−Activity Studies

  摘要：

  The structure-based design, chemical synthesis, and biological evaluation of various peptide-derived human rhinovirus (HRV) 3C protease (3CP) inhibitors are described. These compounds are comprised of an ethyl propenoate Michael acceptor moiety and a tripeptidyl binding determinant. The systematic modification of each amino acid residue present in the binding determinant as well as the N-terminal functionality is described. Such modifications are shown to provide irreversible HRV-14 3CP inhibitors with anti-3CP activities (k(obs)/[I]) ranging from 60 to 280 000 M-1 s(-1) and antiviral EC50's which approach 0.15 mu M. An optimized inhibitor which incorporates several improvements identified by the structure-activity studies is also described. This molecule displays very rapid irreversible inhibition of HRV-14 3CP (k(obs)/[I] = 800 000 M-1 s(-1)) and potent antiviral activity against HRV-14 in cell culture (EC50 = 0.056 mu M). A 1.9 Angstrom crystal structure of an S-alkylthiocarbamate-containing inhibitor complexed with HRV-8 3CP is also detailed.

  DOI：

  10.1021/jm9800696
• 作为产物：
  描述：

  4(S)-butoxycarbonylamino-4-(methoxymethylcarbamoyl)butyric acid tert-butyl ester 在 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 反应 2.67h， 以93%的产率得到4(S)-4-tert-butoxycarbonylamino-5-oxo-pentanoic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis of Tetrahydro-β-carbolines and Studies of the Pictet–Spengler Reaction

  摘要：

  Tetrahydro-beta-carbolines have been prepared in a diastereomerically pure form by a short, efficient synthetic sequence consisting of reaction of cl-aminoaldehydes with tryptamine. A study was made of the major factors affecting the stereoselectivity of the Pictet-Spengler reaction. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(00)00165-4

文献信息

• Selenoglutathione Diselenide: Unique Redox Reactions in the GPx-Like Catalytic Cycle and Repairing of Disulfide Bonds in Scrambled Protein
  作者：Shingo Shimodaira、Yuki Asano、Kenta Arai、Michio Iwaoka

  DOI：10.1021/acs.biochem.7b00751

  日期：2017.10.24

  Selenoglutathione (GSeH) is a selenium analogue of naturally abundant glutathione (GSH). In this study, this water-soluble small tripeptide was synthesized in a high yield (up to 98%) as an oxidized diselenide form, i.e., GSeSeG (1), by liquid-phase peptide synthesis (LPPS). Obtained 1 was applied to the investigation of the glutathione peroxidase (GPx)-like catalytic cycle. The important intermediates

  硒谷胱甘肽（GSeH）是天然丰富的谷胱甘肽（GSH）的硒类似物。在这项研究中，这种水溶性小三肽是通过液相肽合成（LPPS）以高产率（高达98％）以氧化二硒化物形式（即GSeSeG（1））合成的。将获得的1用于研究谷胱甘肽过氧化物酶（GPx）样的催化循环。除了GSeO 2 H以外，还通过77 Se NMR光谱对重要的中间体GSe –和GSeSG进行了表征。GSeSG的各种硫醇，如半胱氨酸和二硫苏糖醇硫醇交换，结果发现，以促进转换为GSE -显著。此外，GSeSR与1的比例不成比例观察到RSSR，这是由Se-S键的杂合裂解引发的，并被生成的硒酸酯催化。根据这些氧化还原行为，有人提出，硒原子与GPx活性位点上存在的氨基或芳香基团之间的相互作用可以促进Se-S键的杂化裂解。另一方面，当在NADPH和谷胱甘肽还原酶的存在下，催化量1与加扰的RNase A的4S物种反应时，天然蛋白质得到了有效的再生，
• Selective Cysteine Protease Inhibitors and Uses Thereof
  申请人：Ahlfors Jan-Eric

  公开号：US20140038903A1

  公开（公告）日：2014-02-06

  The present invention relates to compounds of Formula I, II, IA-VA, IVA1-IVA5, IIIA1-IIIA5 and their pharmaceutical uses. Particular aspects of the invention relate to the use of those compounds for the selective inhibition of one or more cysteine proteases. Also described are methods where the compounds of Formula I, II, IA-VA, IVA1-IVA5, IIIA1-IIIA5 are used in the prevention and/or treatment of various diseases and conditions in subjects, including cysteine protease-mediated diseases and/or caspase-mediated diseases such as sepsis, myocardial infarction, cancer, tissue atrophy, ischemia, ischemic stroke, spinal cord injury (SCI), traumatic brain injury (TBI) and neurodegenerative diseases such as multiple sclerosis (MS), ALS, Alzheimer's disease, Parkinson's disease, and Huntington's disease).

  本发明涉及公式I、II、IA-VA、IVA1-IVA5、IIIA1-IIIA5化合物及其药物用途。本发明的特定方面涉及使用这些化合物选择性地抑制一个或多个半胱氨酸蛋白酶的用途。还描述了使用公式I、II、IA-VA、IVA1-IVA5、IIIA1-IIIA5化合物在预防和/或治疗受体中的各种疾病和病况，包括半胱氨酸蛋白酶介导的疾病和/或半胱氨酸蛋白酶介导的疾病，如败血症、心肌梗塞、癌症、组织萎缩、缺血、缺血性中风、脊髓损伤（SCI）、创伤性脑损伤（TBI）和神经退行性疾病，如多发性硬化症（MS）、ALS、阿尔茨海默病、帕金森病和亨廷顿病等。
• Selective cysteine protease inhibitors and uses thereof
  申请人：Genesis Technologies Limited

  公开号：US10975119B2

  公开（公告）日：2021-04-13

  The present invention relates to compounds of Formula I, II, IA-VA, IVA1-IVA5, IIIA1-IIIA5 and their pharmaceutical uses. Particular aspects of the invention relate to the use of those compounds for the selective inhibition of one or more cysteine proteases. Also described are methods where the compounds of Formula I, II, IA-VA, IVA1-IVA5, IIIA1-IIIA5 are used in the prevention and/or treatment of various diseases and conditions in subjects, including cysteine protease-mediated diseases and/or caspase-mediated diseases such as sepsis, myocardial infarction, cancer, tissue atrophy, ischemia, ischemic stroke, spinal cord injury (SCI), traumatic brain injury (TBI) and neurodegenerative diseases such as multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Parkinson's disease, and Huntington's disease.

  本发明涉及式 I、II、IA-VA、IVA1-IVA5、IIIA1-IIIA5 的化合物及其药物用途。本发明的特定方面涉及这些化合物在选择性抑制一种或多种半胱氨酸蛋白酶方面的用途。还描述了式 I、II、IA-VA、IVA1-IVA5、IIIA1-IIIA5 的化合物用于预防和/或治疗受试者的各种疾病和病症的方法，包括半胱氨酸蛋白酶介导的疾病和/或 Caspase 介导的疾病，如败血症、心肌梗塞、癌症、组织萎缩、缺血、缺血性中风、脊髓损伤 (SCI)、创伤性脑损伤 (TBI) 和神经退行性疾病，如多发性硬化症 (MS)、肌萎缩性脊髓侧索硬化症 (ALS)、阿尔茨海默氏病、帕金森氏病和亨廷顿氏病。
• SELECTIVE CYSTEINE PROTEASE INHIBITORS AND USES THEREOF
  申请人：Genesis Technologies Limited

  公开号：EP2697246B1

  公开（公告）日：2018-03-07
• US9944674B2
  申请人：——

  公开号：US9944674B2

  公开（公告）日：2018-04-17