2-[2-(1H-indol-3-yl)ethylazaniumyl]-4-(4-methylphenyl)-4-oxobutanoate

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-[2-(1H-indol-3-yl)ethylazaniumyl]-4-(4-methylphenyl)-4-oxobutanoate
• 化学式: C21H22N2O3
• 分子量: 350.4
• InChiKey: XSSTYCVTZTYEGV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  82.2
• 氢给体数：
  3
• 氢受体数：
  4

文献信息

• A model for glutamate racemase inhibitors and glutamate racemase antibacterial agents
  申请人：Ohio Northern University

  公开号：EP2700631A1

  公开（公告）日：2014-02-26

  The increase in antibacterial resistance has created the demand for new antibiotics. The present invention relates to a more potent antibiotic that targets the enzyme glutamate racemase from known glutamate racemase inhibitors. Glutamate racemase catalyses the interconversion of L-glutamate to D-glutamate, making D-glutamate available, which is required for bacterial peptidoglycan biosynthesis. Knockout mutations have shown glutamate racemase to be necessary for bacterial cell survival and, before the present invention, no antibiotic on the market targeted this enzyme. The present invention relates to new, ligand based glutamate racemase inhibitors, developed using software to extract a pharmacophore model from a group of known glutamate racemase inhibitors. Forty-seven (47) known inhibitors were collected from the literature and several pharmacophore models were extracted therefrom. The functional groups common to all the known inhibitors were included in a pharmacophore model that described the requirements for glutamate racemase inhibition with 82% accuracy. Of these models, one was found to describe the requirements for glutamate racemase inhibition with 82% accuracy. The model was used to search databases of commercially available chemical compounds and 2-(2-(1/i-indol-3-yl)ethylamino)-4-oxo-4-p-tolylbutanoic acid and 2-(2-(1//-indol-3-yl)ethylamino)-4-(4-fluorophenyl)-4-oxobutanoic acid were identified as showing antibacterial activity. These compounds were assayed against S. pneumoniae and were shown to have antibacterial activity against the non- virulent strain R6 and against a multidrug resistant strain.

  抗菌药耐药性的增加导致了对新型抗生素的需求。本发明涉及一种针对谷氨酸消旋酶的更强效抗生素，而不是已知的谷氨酸消旋酶抑制剂。谷氨酸消旋酶催化 L-谷氨酸与 D-谷氨酸的相互转化，使细菌肽聚糖的生物合成需要 D-谷氨酸。基因敲除突变表明，谷氨酸消旋酶是细菌细胞存活所必需的，而在本发明之前，市场上还没有针对这种酶的抗生素。本发明涉及基于配体的新型谷氨酸消旋酶抑制剂，该抑制剂是利用软件从一组已知谷氨酸消旋酶抑制剂中提取药效模型而开发的。我们从文献中收集了四十七（47）种已知抑制剂，并从中提取了若干药效模型。所有已知抑制剂共有的官能团都被纳入了一个药理模型，该模型描述谷氨酸消旋酶抑制要求的准确率为 82%。在这些模型中，发现有一个模型能以 82% 的准确率描述谷氨酸消旋酶抑制的要求。利用该模型搜索了市售化合物数据库，发现 2-(2-(1/i-吲哚-3-基)乙基氨基)-4-氧代-4-对甲苯丁酸和 2-(2-(1/i-吲哚-3-基)乙基氨基)-4-(4-氟苯基)-4-氧代丁酸具有抗菌活性。对这些化合物进行了抗肺炎双球菌试验，结果表明它们对无毒菌株 R6 和耐多药菌株具有抗菌活性。
• A MODEL FOR GLUTAMATE RACEMASE INHIBITORS AND GLUTAMATE RACEMASE ANTIBACTERIAL AGENTS
  申请人：Ohio Northern University

  公开号：EP2359279B1

  公开（公告）日：2014-12-10
• Model for Glutamate Racemase Inhibitors and Glutamate Racemase Antibacterial Agents
  申请人：Mahfouz Tarek M.

  公开号：US20100240727A1

  公开（公告）日：2010-09-23

  The increase in antibacterial resistance has created the demand for new antibiotics. The present invention relates to a more potent antibiotic that targets the enzyme glutamate racemase from known glutamate racemase inhibitors. Glutamate racemase catalyses the interconversion of L-glutamate to D-glutamate, making D-glutamate available, which is required for bacterial peptidoglycan biosynthesis. Knockout mutations have shown glutamate racemase to be necessary for bacterial cell survival and, before the present invention, no antibiotic on the market targeted this enzyme. The present invention relates to new, ligand based glutamate racemase inhibitors, developed using software to extract a pharmacophore model from a group of known glutamate racemase inhibitors. Forty-seven (47) known inhibitors were collected from the literature and several pharmacophore models were extracted therefrom. The functional groups common to all the known inhibitors were included in a pharmacophore model that described the requirements for glutamate racemase inhibition with 82% accuracy. Of these models, one was found to describe the requirements for glutamate racemase inhibition with 82% accuracy. The model was used to search databases of commercially available chemical compounds and 2-(2-(1H-indol-3-yl)ethylamino)-4-oxo-4-p-tolylbutanoic acid and 2-(2-(1H-indol-3-yl)ethylamino)-4-(4-fluorophenyl)-4-oxobutanoic acid were identified as showing antibacterial activity. These compounds were assayed against S. pneumoniae and were shown to have antibacterial activity against the non-virulent strain R6 and against a multidrug resistant strain.
• Model For Glutamate Racemase inhibitors and Glutamate Racemase Antibacterial Agents
  申请人：Mahfouz Tarek M.

  公开号：US20120239365A1

  公开（公告）日：2012-09-20

  Antibiotics that target the enzyme glutamate racemase are disclosed. Ligand based glutamate racemase inhibitors are developed using software to extract a pharmacophore model from a group of known glutamate racemase inhibitors. These compounds are assayed against S. pneumoniae and were shown to have antibacterial activity against the non-virulent strain R6 and against a multidrug resistant strain.
• US8236849B2
  申请人：——

  公开号：US8236849B2

  公开（公告）日：2012-08-07