methyl 2-(4-(but-2-yn-1-yloxy)benzamido)-3-((tert-butoxycarbonyl)amino)-3-methylbutanoate | 1219366-51-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 2-(4-(but-2-yn-1-yloxy)benzamido)-3-((tert-butoxycarbonyl)amino)-3-methylbutanoate
• 英文别名: Methyl 2-[(4-but-2-ynoxybenzoyl)amino]-3-methyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]butanoate
• CAS: 1219366-51-4
• 化学式: C₂₂H₃₀N₂O₆
• 分子量: 418.49
• InChiKey: PGKRQEVACFEJFX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 2-(4-(but-2-yn-1-yloxy)benzamido)-3-((tert-butoxycarbonyl)amino)-3-methylbutanoate 在 羟胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 0.5h， 生成 (R)-N-(3-amino-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl)-4-(but-2-yn-1-yloxy)benzamide
  参考文献：
  名称：

  Design, Synthesis, and Properties of a Potent Inhibitor of Pseudomonas aeruginosa Deacetylase LpxC

  摘要：

  Over the past several decades, the frequency of antibacterial resistance in hospitals, including multidrug resistance (MDR) and its association with serious infectious diseases, has increased at alarming rates. Pseudomonas aeruginosa is a leading cause of nosocomial infections, and resistance to virtually all approved antibacterial agents is emerging in this pathogen. To address the need for new agents to treat MDR P. aeruginosa, we focused on inhibiting the first committed step in the biosynthesis of lipid A, the deacetylation of uridyldiphospho-3-O-(R-hydroxydecanoyl)-N-acetylglucosamine by the enzyme LpxC. We approached this through the design, synthesis, and biological evaluation of novel hydroxamic acid LpxC inhibitors, exemplified by 1, where cytotoxicity against mammalian cell lines was reduced, solubility and plasma-protein binding were improved while retaining potent anti-pseudomonal activity in vitro and in vivo.

  DOI：

  10.1021/acs.jmedchem.7b00377
• 作为产物：
  描述：

  β-Nitrovaline 在 氯化亚砜 、 碳酸氢钠 、 溶剂黄146 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 锌 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 223.67h， 生成 methyl 2-(4-(but-2-yn-1-yloxy)benzamido)-3-((tert-butoxycarbonyl)amino)-3-methylbutanoate
  参考文献：
  名称：

  Design, Synthesis, and Properties of a Potent Inhibitor of Pseudomonas aeruginosa Deacetylase LpxC

  摘要：

  Over the past several decades, the frequency of antibacterial resistance in hospitals, including multidrug resistance (MDR) and its association with serious infectious diseases, has increased at alarming rates. Pseudomonas aeruginosa is a leading cause of nosocomial infections, and resistance to virtually all approved antibacterial agents is emerging in this pathogen. To address the need for new agents to treat MDR P. aeruginosa, we focused on inhibiting the first committed step in the biosynthesis of lipid A, the deacetylation of uridyldiphospho-3-O-(R-hydroxydecanoyl)-N-acetylglucosamine by the enzyme LpxC. We approached this through the design, synthesis, and biological evaluation of novel hydroxamic acid LpxC inhibitors, exemplified by 1, where cytotoxicity against mammalian cell lines was reduced, solubility and plasma-protein binding were improved while retaining potent anti-pseudomonal activity in vitro and in vivo.

  DOI：

  10.1021/acs.jmedchem.7b00377

文献信息

• [EN] ORGANIC COMPOUNDS FOR APPLICATIONS IN BACTERIAL INFECTIONS TREATMENT<br/>[FR] COMPOSÉS ORGANIQUES DESTINÉS À ÊTRE APPLIQUÉS DANS LE TRAITEMENT D'INFECTIONS BACTÉRIENNES
  申请人：NOVARTIS AG

  公开号：WO2010031750A1

  公开（公告）日：2010-03-25

  The present application describes organic compounds that are useful for the treatment, prevention and/or amelioration of human diseases.

  本申请描述了对治疗、预防及/or改善人类疾病的有机化合物。
• ORGANIC COMPOUNDS AND THEIR USES
  申请人：Dobler Markus Rolf

  公开号：US20100120872A1

  公开（公告）日：2010-05-13

  The present application describes organic compounds that are useful for the treatment, prevention and/or amelioration of human diseases.
• US8372885B2
  申请人：——

  公开号：US8372885B2

  公开（公告）日：2013-02-12
• Design, Synthesis, and Properties of a Potent Inhibitor of <i>Pseudomonas aeruginosa</i> Deacetylase LpxC
  作者：Grazia Piizzi、David T. Parker、Yunshan Peng、Markus Dobler、Anup Patnaik、Som Wattanasin、Eugene Liu、Francois Lenoir、Jill Nunez、John Kerrigan、David McKenney、Colin Osborne、Donghui Yu、Leanne Lanieri、Jade Bojkovic、JoAnn Dzink-Fox、Maria-Dawn Lilly、Elizabeth R. Sprague、Yipin Lu、Hongming Wang、Srijan Ranjitkar、Lili Xie、Bing Wang、Meir Glick、Lawrence G. Hamann、Ruben Tommasi、Xia Yang、Charles R. Dean

  DOI：10.1021/acs.jmedchem.7b00377

  日期：2017.6.22

  Over the past several decades, the frequency of antibacterial resistance in hospitals, including multidrug resistance (MDR) and its association with serious infectious diseases, has increased at alarming rates. Pseudomonas aeruginosa is a leading cause of nosocomial infections, and resistance to virtually all approved antibacterial agents is emerging in this pathogen. To address the need for new agents to treat MDR P. aeruginosa, we focused on inhibiting the first committed step in the biosynthesis of lipid A, the deacetylation of uridyldiphospho-3-O-(R-hydroxydecanoyl)-N-acetylglucosamine by the enzyme LpxC. We approached this through the design, synthesis, and biological evaluation of novel hydroxamic acid LpxC inhibitors, exemplified by 1, where cytotoxicity against mammalian cell lines was reduced, solubility and plasma-protein binding were improved while retaining potent anti-pseudomonal activity in vitro and in vivo.