4-methylphenylethylidene-1-hydroxy-1,1-bisphosphonic acid | 87600-39-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: 4-methylphenylethylidene-1-hydroxy-1,1-bisphosphonic acid
• 英文别名: 2-(4-tolyl)-1-hydroxyethane-1,1-diphosphonic acid；[1-Hydroxy-2-(4-methylphenyl)-1-phosphonoethyl]phosphonic acid
• CAS: 87600-39-3
• 化学式: C₉H₁₄O₇P₂
• 分子量: 296.153
• InChiKey: BQUYKOLPMHLHRB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.7
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  135
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  对甲苯乙酰氯 在 三(三甲代甲硅烷基)亚磷酸盐 作用下， 反应 1.0h， 以80%的产率得到4-methylphenylethylidene-1-hydroxy-1,1-bisphosphonic acid
  参考文献：
  名称：

  Bisphosphonic acids as effective inhibitors ofMycobacterium tuberculosisglutamine synthetase

  摘要：

  Inhibition of glutamine synthetase (GS) is one of the most promising strategies for the discovery of novel drugs against tuberculosis. Forty-three bisphosphonic and bis-H-phosphinic acids of various scaffolds, bearing aromatic substituents, were screened against recombinant GS from Mycobacterium tuberculosis. Most of the studied compounds exhibited activities in micromolar range, with N-(3,5-dichlorophenyl)-2-aminoethylidenebisphoshonic acid, N-(3,5difluorophenyl)-2-aminoethylidene-bisphoshonic acid and N-(3,4-dichlorophenyl)-1-hydroxy1,1-ethanebisphosphonic acid showing the highest potency with kinetic parameters similar to the reference compound - L-methionine-S-sulfoximine. Moreover, these inhibitors were found to be much more effective against pathogen enzyme than against the human ortholog. Thus, with the bone-targeting properties of the bisphosphonate compounds in mind, this activity/selectivity profile makes these compounds attractive agents for the treatment of bone tuberculosis.

  DOI：

  10.3109/14756366.2015.1070846

文献信息

• Diphosphonsäure-Derivate und diese enthaltende pharmazeutische Präparate
  申请人：SCHERING AKTIENGESELLSCHAFT

  公开号：EP0085321A2

  公开（公告）日：1983-08-10

  Diphosphonsäure-Derivate der allgemeinen Formel I worin n die Ziffern 0, 1 oder 2 bedeuten und worin R, ein Wasserstoffatom oder eine 1 bis 4 Kohlenstoffatome enthaltende Alkylgruppe R2 ein Wasserstoffatom, ein Alkalimetallatom, ein Erdalkalimetallatom oder eine 1 bis 4 Kohlenstoffatome enthaltende Alkylgruppe und Ar einen gegebenenfalls durch Fluoratome, Chloratome, 1 bis 4 Kohlenstoffatome enthaltende Alkylgruppen oder 1 bis 4 Kohlenstoffatome enthaltende Alkoxygruppen substituierten Phenylrest, einen Naphthylrest, einen Biphenylrest oder einen Thienylrest darstellen, sind pharmakologisch wirksame Substanzen.

  通式 I 的二膦酸衍生物 其中 n 是数字 0、1 或 2，其中 R 是氢原子或含有 1 至 4 个碳原子的烷基 R2 代表氢原子、碱金属原子、碱土金属原子或含 1 至 4 个碳原子的烷基，Ar 代表可选被氟原子、氯原子、含 1 至 4 个碳原子的烷基或含 1 至 4 个碳原子的烷氧基、萘基、联苯基或噻吩基取代的苯基。
• US4473560A
  申请人：——

  公开号：US4473560A

  公开（公告）日：1984-09-25
• Bisphosphonic acids as effective inhibitors of<i>Mycobacterium tuberculosis</i>glutamine synthetase
  作者：Paulina Kosikowska、Marta Bochno、Katarzyna Macegoniuk、Giuseppe Forlani、Paweł Kafarski、Łukasz Berlicki

  DOI：10.3109/14756366.2015.1070846

  日期：2016.11.1

  Inhibition of glutamine synthetase (GS) is one of the most promising strategies for the discovery of novel drugs against tuberculosis. Forty-three bisphosphonic and bis-H-phosphinic acids of various scaffolds, bearing aromatic substituents, were screened against recombinant GS from Mycobacterium tuberculosis. Most of the studied compounds exhibited activities in micromolar range, with N-(3,5-dichlorophenyl)-2-aminoethylidenebisphoshonic acid, N-(3,5difluorophenyl)-2-aminoethylidene-bisphoshonic acid and N-(3,4-dichlorophenyl)-1-hydroxy1,1-ethanebisphosphonic acid showing the highest potency with kinetic parameters similar to the reference compound - L-methionine-S-sulfoximine. Moreover, these inhibitors were found to be much more effective against pathogen enzyme than against the human ortholog. Thus, with the bone-targeting properties of the bisphosphonate compounds in mind, this activity/selectivity profile makes these compounds attractive agents for the treatment of bone tuberculosis.