(2S)-3-(4-fluorophenyl)-2-[[(2S)-3-methyl-2-[(5-methyl-1,2-oxazole-3-carbonyl)amino]butanoyl]amino]propanoic acid | 941582-89-4

• 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
• 英文名称: (2S)-3-(4-fluorophenyl)-2-[[(2S)-3-methyl-2-[(5-methyl-1,2-oxazole-3-carbonyl)amino]butanoyl]amino]propanoic acid
• CAS: 941582-89-4
• 化学式: C₁₉H₂₂FN₃O₅
• 分子量: 391.399
• InChiKey: SNIIQQXQYUYPCS-HOTGVXAUSA-N

物化性质

• 沸点：
  671.0±55.0 °C(Predicted)
• 密度：
  1.286±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  122
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S)-3-(4-fluorophenyl)-2-[[(2S)-3-methyl-2-[(5-methyl-1,2-oxazole-3-carbonyl)amino]butanoyl]amino]propanoic acid 在 hydrazine hydrate 作用下， 以 甲醇 、 乙醚 、 乙醇 为溶剂， 反应 1.0h， 生成 N-((S)-1-(((S)-3-(4-fluorophenyl)-1-oxo-1-(2-((E)-2,3,4-trihydroxybenzylidene)hydrazinyl)propan-2-yl)amino)-3-methyl-1-oxobutan-2-yl)-5-methylisoxazole-3-carboxamide
  参考文献：
  名称：

  Kim, Bo-Kyoung; Ko, Hyojin; Jeon, Eun-Seok, European Journal of Medicinal Chemistry, 2016, vol. 120, p. 202 - 216

  摘要：

  DOI：
• 作为产物：
  描述：

  5-甲基异恶唑-3-甲酸 、 Fmoc-L-缬氨酸 、 FMOC-L-4-氟苯丙氨酸 在 N,N-二异丙基乙胺 、 哌啶 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 16.0h， 生成 (2S)-3-(4-fluorophenyl)-2-[[(2S)-3-methyl-2-[(5-methyl-1,2-oxazole-3-carbonyl)amino]butanoyl]amino]propanoic acid
  参考文献：
  名称：

  Development of anti-coxsackievirus agents targeting 3C protease

  摘要：

  Peptidomimetic anti-viral agents against Coxsackievirus B3 (CVB3) were developed using a strategy involving the inhibition of 3C protease (CVB3 3C(pro)), a target for CVB3-mediated myocarditis or pericarditis. In an attempt to improve the inhibitory activity against CVB3, a variety of hetero-aromatic groups were incorporated into the alpha,beta-unsaturated ester as Michael acceptor moiety, which is the position of interaction with the cysteine moiety in the P1' active site of CVB3 3C(pro). Among these hetero-aromatic groups, the quinoline analogs 9c and 9e, with IC50 values of 250 and 130 nM as determined from an enzyme assay, significantly inhibited the CVB3-mediated cell cytotoxicity, indicating parallel anti-viral activities. A comparison of the binding modes of the potent inhibitor 9e and the relatively weak inhibitor 9n was explored in a molecular docking study, which revealed that compound 9n lacked hydrogen bonds in its interactions with Gly129, 128, and 145. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.120

文献信息

• Development of anti-coxsackievirus agents targeting 3C protease
  作者：Bo-Kyoung Kim、Jeong-Hyun Kim、Na-Ri Kim、Won-Gil Lee、So-Deok Lee、Soo-Hyeon Yun、Eun-Seok Jeon、Yong-Chul Kim

  DOI：10.1016/j.bmcl.2012.08.120

  日期：2012.11

  Peptidomimetic anti-viral agents against Coxsackievirus B3 (CVB3) were developed using a strategy involving the inhibition of 3C protease (CVB3 3C(pro)), a target for CVB3-mediated myocarditis or pericarditis. In an attempt to improve the inhibitory activity against CVB3, a variety of hetero-aromatic groups were incorporated into the alpha,beta-unsaturated ester as Michael acceptor moiety, which is the position of interaction with the cysteine moiety in the P1' active site of CVB3 3C(pro). Among these hetero-aromatic groups, the quinoline analogs 9c and 9e, with IC50 values of 250 and 130 nM as determined from an enzyme assay, significantly inhibited the CVB3-mediated cell cytotoxicity, indicating parallel anti-viral activities. A comparison of the binding modes of the potent inhibitor 9e and the relatively weak inhibitor 9n was explored in a molecular docking study, which revealed that compound 9n lacked hydrogen bonds in its interactions with Gly129, 128, and 145. (C) 2012 Elsevier Ltd. All rights reserved.
• Kim, Bo-Kyoung; Ko, Hyojin; Jeon, Eun-Seok, European Journal of Medicinal Chemistry, 2016, vol. 120, p. 202 - 216
  作者：Kim, Bo-Kyoung、Ko, Hyojin、Jeon, Eun-Seok、Ju, Eun-Seon、Jeong, Lak Shin、Kim, Yong-Chul

  DOI：——

  日期：——
• Peptidomimetic ethyl propenoate covalent inhibitors of the enterovirus 71 3C protease: a P2–P4 study
  作者：Melgious J. Y. Ang、Qiu Ying Lau、Fui Mee Ng、Siew Wen Then、Anders Poulsen、Yuen Kuen Cheong、Zi Xian Ngoh、Yong Wah Tan、Jianhe Peng、Thomas H. Keller、Jeffrey Hill、Justin J. H. Chu、C. S. Brian Chia

  DOI：10.3109/14756366.2015.1018245

  日期：2016.3.3

  Enterovirus 71 (EV71) is a highly infectious pathogen primarily responsible for Hand, Foot, and Mouth Disease, particularly among children. Currently, no approved antiviral drug has been developed against this disease. The EV71 3C protease is deemed an attractive drug target due to its crucial role in viral polyprotein processing. Rupintrivir, a peptide-based inhibitor originally developed to target the human rhinovirus 3C protease, was found to inhibit the EV71 3C protease. In this communication, we report the inhibitory activities of 30 Rupintrivir analogs against the EV71 3C protease. The most potent inhibitor, containing a P2 ring-constrained phenylalanine analog (compound 9), was found to be two-fold more potent than Rupintrivir (IC50 value 3.4 +/- 0.4 versus 7.3 +/- 0.8 mu M). Our findings suggest that employing geometrically constrained residues in peptide-based protease inhibitors can potentially enhance their inhibitory activities.