噁丙烯并[f]喹啉,1a,2,3,7b-四氢-(9CI) | 107831-79-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 噁丙烯并[f]喹啉,1a,2,3,7b-四氢-(9CI)
• 英文名称: Val-CMK hydrochloride
• 英文别名: Val-CH2Cl*HCl；L-Valine chloromethyl ketone hydrochloride；(3S)-3-amino-1-chloro-4-methylpentan-2-one;hydrochloride
• CAS: 107831-79-8
• 化学式: C₆H₁₂ClNO*ClH
• 分子量: 186.081
• InChiKey: UYCJMRLNPAXBJE-RGMNGODLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  10
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  43.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  噁丙烯并[f]喹啉,1a,2,3,7b-四氢-(9CI) 在 N-甲基吗啉 、 盐酸 、 碳酸氢钠 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 为溶剂， 反应 21.67h， 生成 N-(methoxysuccinyl)-Ala-Ala-Ala-Pro-Val-chloromethyl
  参考文献：
  名称：

  Proteinase K inhibitors, methods and compositions therefor

  摘要：

  描述了一种用烷氧基琥珀酰肽基卤代烷基酮处理样品以准备含有RNA的样品，用于原位分析，以在基本相同温度下灭活蛋白酶K，与裂解步骤相同。

  公开号：

  EP2955233A1
• 作为产物：
  描述：

  (S)-3-(tert-butoxycarbonylamino)-1-diazo-4-methylpentan-2-one 在 盐酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 2.0h， 以5.27 g的产率得到噁丙烯并[f]喹啉,1a,2,3,7b-四氢-(9CI)
  参考文献：
  名称：

  Selectivity profiling of DegP substrates and inhibitors

  摘要：

  Protein quality control factors are involved in many key physiological processes and severe human diseases that are based on misfolding or amyloid formation. Prokaryotic representatives are often virulence factors of pathogenic bacteria. Therefore, protein quality control factors represent a novel class of drug targets. The bacterial serine protease DegP, belonging to the widely conserved family of HtrA proteases, exhibits unusual structural and functional plasticity that could be exploited by small molecule modulators. However, only one weak synthetic peptide substrate and no inhibitors are available to date. We report the identification of a potent heptameric pNA-substrate and chloromethyl ketone based inhibitors of DegP. In addition, specificity profiling resulted in the identification of one strong inhibitor and a potent substrate for subtilisin as well as a number of specific elastase substrates and inhibitors. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.01.073

文献信息

• Synthesis of peptide chloromethyl ketones and examination of their inhibitory effects on human spleen fibrinolytic proteinase(SFP) and human leukocyte elastase(LE).
  作者：YUKO TSUDA、YOSHIO OKADA、YOKO NAGAMATSU、UTAKO OKAMOTO

  DOI：10.1248/cpb.35.3576

  日期：——

  Various substrate-derived chloromethyl ketones were synthesized by a conventional method for the purpose of obtaining specific and potent irreversible inhibitors for human spleen fibrinolytic proteinase (SFP) and human leukocyte elastase (LE) in order to compare the properties of SFP with those of LE. It was found that Boc-Ala-Tyr-Leu-Val-CH2Cl among the peptide chloromethyl ketones exhibited the most effective and specific inhibition of SFP and LE. The two enzymes were inhibited by peptide chloromethyl ketones having a Val residue at the C-terminus in a similar manner, demonstrating a similarity between SFP and LE.

  为了比较人脾纤溶酶（SFP）和人白细胞弹力酶（LE）的性质，通过传统方法合成了多种来自底物的氯甲基酮，旨在获得对这两种酶具有特异性和强效的不可逆抑制剂。在各种肽氯甲基酮中，发现Boc-Ala-Tyr-Leu-Val-CH2Cl对SFP和LE表现出最有效和特异的抑制作用。这两种酶都被C-末端具有Val残基的肽氯甲基酮以类似方式抑制，这表明SFP和LE之间存在相似性。
• Method for preparing specific inhibitors of virus-specified proteases
  申请人：E. I. Du Pont de Nemours and Company

  公开号：US04644055A1

  公开（公告）日：1987-02-17

  A general method for preparing specific inhibitors of virus-specified proteases is disclosed. The inhibitors comprise a halomethyl ketone or methyl ketone moiety covalently linked to a peptide sequence of three, four or five amino acids or amino acid residues, which peptide sequence corresponds to an amino acid sequence found adjacent to and upstream of a cleavage site recognized by a virus-specified protease.

  揭示了一种制备病毒特异性蛋白酶特定抑制剂的通用方法。该抑制剂包括卤代甲基酮或甲基酮部分与三、四或五个氨基酸或氨基酸残基的肽序列共价连接，该肽序列与病毒特异性蛋白酶识别的切割位点相邻并上游的氨基酸序列相对应。
• Inhibition of viral protease activity by peptide halomethyl ketones
  申请人：E. I. Du Pont de Nemours and Company

  公开号：US04636492A1

  公开（公告）日：1987-01-13

  Selected tripeptide and tetrapeptide halomethyl ketones are employed in processes for treating viral infection in mammals. These compounds inhibit picornavirus protease activity.

  选定的三肽和四肽卤代甲基酮可用于治疗哺乳动物病毒感染的过程中。这些化合物抑制小肠病毒蛋白酶活性。
• Synthesis and biological evaluation of modified pentapeptides as potent proteinase K inhibitors
  作者：Anilkumar R. Kore、Muthian Shanmugasundaram、Irudaya Charles、Quoc Hoang

  DOI：10.1016/j.bmcl.2010.03.072

  日期：2010.5

  This communication reports the first demonstration of synthesis and biological validation of modified pentapeptides, such as methoxysuccinyl-Ala-Ala-Ala-Pro-Leu-chloromethyl ketone 6b as a potent proteinase K inhibitor. The efficacy of MeOSuc-AAAPL-CH(2)Cl 6b analog in inhibiting the proteolytic activity of proteinase K was compared with the known MeOSuc-AAPV-CH(2)Cl analog. The examination of inhibitory activity using RT-PCR assay in the presence of proteinase K revealed that the MeOSuc-AAAPL-CH(2)Cl 6b inhibitor at a concentration of 0.05 mM allows a signal to be obtained for an exogenous target ('Xeno RNA') at 30 cycles (i.e., Ct = 30), whereas the control MeOSuc-AAPV-CH(2)Cl requires a fivefold higher concentration (0.25 mM) to produce the same Ct. A plausible explanation for the higher efficiency of MeO-Suc-AAAPL-CH(2)Cl 6b over control is proposed based on the molecular modeling studies. (C) 2010 Elsevier Ltd. All rights reserved.
• TSUDA, YUKO;OKADA, YOSHIO;NAGAMATSU, YOKO;OKAMOTO, UTAKO, CHEM. AND PHARM. BULL., 35,(1987) N 9, 3576-3584
  作者：TSUDA, YUKO、OKADA, YOSHIO、NAGAMATSU, YOKO、OKAMOTO, UTAKO

  DOI：——

  日期：——