(R)-2-[(4-methobenzyloxyformylamino)methyl]hexanoic acid | 1201518-34-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (R)-2-[(4-methobenzyloxyformylamino)methyl]hexanoic acid
• CAS: 1201518-34-4
• 化学式: C₁₆H₂₃NO₅
• 分子量: 309.362
• InChiKey: FGEGJDBWZSQXQP-CQSZACIVSA-N

物化性质

• 沸点：
  463.3±55.0 °C(predicted)
• 密度：
  1.155±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.48
• 重原子数：
  22.0
• 可旋转键数：
  11.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  76.07
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (R)-2-[(4-methobenzyloxyformylamino)methyl]hexanoic acid 在 N-甲基吗啉 、 lithium hydroxide monohydrate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 26.0h， 生成 (S)-1-((R)-2-((N-((4-methoxybenzyl)oxy)formamido)methyl)hexanoyl)-N-(5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl)-2,5-dihydro-1H-pyrrole-2-carboxamide
  参考文献：
  名称：

  Synthesis, antibacterial activity, and biological evaluation of formyl hydroxyamino derivatives as novel potent peptide deformylase inhibitors against drug-resistant bacteria

  摘要：

  Peptide deformylase (PDF) has been identified as a promising target for novel antibacterial agents. In this study, a series of novel formyl hydroxyamino derivatives were designed and synthesized as PDF inhibitors and their antibacterial activities were evaluated. Among the potent PDF inhibitors (1o, 1q, 1o', 1q', and 1x), in vivo studies showed that compound 1q possesses mild toxicity, a good pharmacokinetic profile and protective effects. The good in vivo efficacy and low toxicity suggest that this class of compounds has potential for development and use in future antibacterial drugs. (c) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.07.106
• 作为产物：
  描述：

  在 正丁基锂 、 lithium hydroxide monohydrate 、 双氧水 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 27.0h， 生成 (R)-2-[(4-methobenzyloxyformylamino)methyl]hexanoic acid
  参考文献：
  名称：

  Synthesis, antibacterial activity, and biological evaluation of formyl hydroxyamino derivatives as novel potent peptide deformylase inhibitors against drug-resistant bacteria

  摘要：

  Peptide deformylase (PDF) has been identified as a promising target for novel antibacterial agents. In this study, a series of novel formyl hydroxyamino derivatives were designed and synthesized as PDF inhibitors and their antibacterial activities were evaluated. Among the potent PDF inhibitors (1o, 1q, 1o', 1q', and 1x), in vivo studies showed that compound 1q possesses mild toxicity, a good pharmacokinetic profile and protective effects. The good in vivo efficacy and low toxicity suggest that this class of compounds has potential for development and use in future antibacterial drugs. (c) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.07.106

文献信息

• New peptide deformylase inhibitors design, synthesis and pharmacokinetic assessment
  作者：Fengping Lv、Chen Chen、Yang Tang、Jianhai Wei、Tong Zhu、Wenhao Hu

  DOI：10.1016/j.bmcl.2016.05.077

  日期：2016.8

  the use of azoles as amide bioisosteres had also been investigated. After the completion of chemical synthesis, all the compounds were evaluated through in vitro antibacterial activity assay, some of which were further subject to in vivo rat pharmacokinetic assessment. Those findings in this letter showed that spiro cyclopropyl proline N-formyl hydroxylamines, and especially the bioisosteric azoles

  筛选设计的小分子配体的对接方法导致鉴定了肽去甲酰基酶中螺旋环丙基PDF抑制剂的额外疏水结合的关键精氨酸残基，这为我们寻找更有效的PDF抑制剂以对抗可怕的抗生素耐药性提供了有用的工具。进行了进一步的合成修饰以优化酰胺化合物的效力。为了降低代谢敏感性并进而降低临床上观察到的有害代谢毒性，同时保持所需的抗菌活性，还研究了将唑类用作酰胺类生物等排体。化学合成完成后，通过体外抗菌活性测定法评估所有化合物，其中一些化合物还需进行体内大鼠药代动力学评估。N-甲酰基羟胺，尤其是生物等位唑，可以代表一类有前途的PDF抑制剂。
• 一种酰肼类肽脱甲酰基酶抑制剂及制备方法和应用
  申请人：河南师范大学

  公开号：CN117658886A

  公开（公告）日：2024-03-08

  本发明公开了一种酰肼类肽脱甲酰基酶抑制剂及制备方法和应用，该酰肼类肽脱甲酰基酶抑制剂的结构式为：#imgabs0#本发明还具体公开了该酰肼类肽脱甲酰基酶抑制剂的制备方法及其在制备抑菌制剂中的应用。本发明首次设计合成了一种新型的肽脱甲酰基酶抑制剂，且肽脱甲酰基酶抑制剂具有较好的抑菌活性，该类肽脱甲酰基酶抑制剂以酰肼为基本特征，具有毒性小，活性高，结构新颖的特性。
• 一种1,3,4-噻二唑类肽脱甲酰基酶酶抑制剂及其制备与应用
  申请人：上海大学

  公开号：CN117886808A

  公开（公告）日：2024-04-16

  本发明涉及一种1,3,4‑噻二唑类肽脱甲酰基酶酶抑制剂及其制备与应用。结构式如式(1)所示：#imgabs0#其中，R1为正丁基或环戊甲基；R2为氢、直链烷烃、环状烷烃、芳环、取代联苯或杂环。本发明提供的1,3,4‑噻二唑类肽脱甲酰基酶抑制剂能够有效抑制细菌合成蛋白质，从而达到灭菌的目的。该类化合物对革兰氏阳性耐药菌特别是临床上棘手的耐甲氧西林葡萄球菌(MRSA)展现出优异的抑制活性，特别是部分优选化合物，其抑制活性达到对照品万古霉素、利奈唑胺4‑8倍。本发明提供的1,3,4‑噻二唑类肽脱甲酰基酶抑制剂还展现出对革兰氏阴性耐药菌的抑制活性，特别是对被称为“超级细菌”的耐药鲍曼不动杆菌，其抑菌活性达到0.5μg/mL，远远优于万古霉素、利奈唑胺。
• Design, synthesis and antibacterial activity of 3-methylenepyrrolidine formyl hydroxyamino derivatives as novel peptide deformylase inhibitors
  作者：Wei Shi、Haikun Ma、Yuejiao Duan、Kelly Aubart、Yuhong Fang、Rimma Zonis、Liping Yang、Wenhao Hu

  DOI：10.1016/j.bmcl.2010.11.102

  日期：2011.2

  The synthesis and antibacterial activity of 3-methylenepyrrolidine formyl hydroxyamino derivatives are reported. The antibacterial activities of these derivatives were evaluated to discover SAR at P-1' and P-3' positions, and most of these derivatives exhibit better in vitro antibacterial activity than existing drugs against drug-resistant clinical isolates including MRSA, PRSP, and Haemophilus influenzae. (C) 2010 Elsevier Ltd. All rights reserved.
• SPIRO THREE-MEMBERED RING OR SPIRO FIVE-MEMBERED RING PEPTIDE DEFORMYLASE INHIBITOR AND USE THEREOF AS AN ANTI-TUMOUR AGENT
  申请人：Guangdong Hebo Pharmaceutical Co., Ltd.

  公开号：EP3483155B1

  公开（公告）日：2022-10-26