13-(benzylthio)-5-hydroxy-6-α-deoxytetracycline | 146253-75-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 四环素类
• 英文名称: 13-(benzylthio)-5-hydroxy-6-α-deoxytetracycline
• CAS: 146253-75-0
• 化学式: C₂₉H₃₀N₂O₈S
• 分子量: 566.632
• InChiKey: NEHMDTSJHHPKTB-SWHKYAELSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.57
• 重原子数：
  40.0
• 可旋转键数：
  6.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  181.62
• 氢给体数：
  6.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  13-(benzylthio)-5-hydroxy-6-α-deoxytetracycline 在 Oxone 作用下， 以 乙醇 为溶剂， 反应 0.42h， 以35%的产率得到13-(benzylsulfinyl)-5-hydroxy-6-α-deoxytetracycline
  参考文献：
  名称：

  Inhibition of the tetracycline efflux antiport protein by 13-thio-substituted 5-hydroxy-6-deoxytetracyclines

  摘要：

  A series of 13-(alkylthio) and 13-(arylthio) derivatives of 5-hydroxy-6-deoxytetracycline (tetracycline, Tc) were synthesized and compared to the clinically used antibiotics tetracycline, methacycline, and minocycline for their ability to inhibit tetracycline efflux in an everted membrane vesicle assay of bacterial resistance to tetracyclines. The assay screened for the ability of tetracycline analogues to inhibit [H-3] tetracycline uptake into everted membrane vesicles, thereby evaluating the molecular prerequisites for inhibition of an efflux-dependent resistant bacterial system. Thiol adducts attached at the exocyclic C13 carbon of methacycline led to an increase in inhibitor potency as compared to the reference antibiotics. The most potent inhibitors of [H-3] tetracycline uptake into everted vesicles among these analogues, particularly members of the alkyl series, revealed important structure-activity relationships between inhibitor potency, steric parameters, and lipophilicity at the C13 sulfur position.

  DOI：

  10.1021/jm00055a008
• 作为产物：
  描述：

  盐酸甲烯土霉素 、 苄硫醇 在 偶氮二异丁腈 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以26%的产率得到13-(benzylthio)-5-hydroxy-6-α-deoxytetracycline
  参考文献：
  名称：

  Inhibition of the tetracycline efflux antiport protein by 13-thio-substituted 5-hydroxy-6-deoxytetracyclines

  摘要：

  A series of 13-(alkylthio) and 13-(arylthio) derivatives of 5-hydroxy-6-deoxytetracycline (tetracycline, Tc) were synthesized and compared to the clinically used antibiotics tetracycline, methacycline, and minocycline for their ability to inhibit tetracycline efflux in an everted membrane vesicle assay of bacterial resistance to tetracyclines. The assay screened for the ability of tetracycline analogues to inhibit [H-3] tetracycline uptake into everted membrane vesicles, thereby evaluating the molecular prerequisites for inhibition of an efflux-dependent resistant bacterial system. Thiol adducts attached at the exocyclic C13 carbon of methacycline led to an increase in inhibitor potency as compared to the reference antibiotics. The most potent inhibitors of [H-3] tetracycline uptake into everted vesicles among these analogues, particularly members of the alkyl series, revealed important structure-activity relationships between inhibitor potency, steric parameters, and lipophilicity at the C13 sulfur position.

  DOI：

  10.1021/jm00055a008

文献信息

• TETRACYCLINE COMPOUNDS HAVING TARGET THERAPEUTIC ACTIVITIES
  申请人：Paratek Pharmaceuticals, Inc.

  公开号：US20180016225A1

  公开（公告）日：2018-01-18

  Methods and compounds for treating diseases with tetracycline compounds having a target therapeutic activity are described.

  使用具有目标治疗活性的四环素化合物治疗疾病的方法和化合物被描述。
• Methods of Using Substituted Tetracycline Compounds to Modulate RNA
  申请人：Levy Stuart B.

  公开号：US20120245130A1

  公开（公告）日：2012-09-27

  A method for modulating RNA with tetracycline compounds is described.

  本文描述了一种使用四环素化合物调节RNA的方法。
• SubstitutedTetracycline Compounds for the Treatment of Malaria
  申请人：DRAPER Michael

  公开号：US20120101071A1

  公开（公告）日：2012-04-26

  This invention provides a method for treating or preventing malaria in a subject. The method includes administering to the subject an effective amount of a substituted tetracycline compound, such that malaria is treated or prevented. In one aspect, the invention relates to pharmaceutical compositions which include an effective amount of a tetracycline compound to treat malaria in a subject and a pharmaceutically acceptable carrier. The substituted tetracycline compounds of the invention can be used to in combination with one or more anti-malarial compounds or can be used to treat or prevent malaria which is resistant to one or more other anti-malarial compounds.

  本发明提供了一种治疗或预防疟疾的方法。该方法包括向受试者施用足够量的取代四环素化合物，以治疗或预防疟疾。在一方面，本发明涉及制药组合物，其包括足够量的四环素化合物以治疗受试者的疟疾和药学上可接受的载体。本发明的取代四环素化合物可以与一种或多种抗疟疾化合物结合使用，或者可以用于治疗或预防对一种或多种其他抗疟疾化合物产生耐药性的疟疾。
• Substituted tetracycline compounds for the treatment of malaria
  申请人：Paratek Pharmaceuticals, Inc.

  公开号：EP2277504A1

  公开（公告）日：2011-01-26

  This invention provides a method for treating or preventing malaria in a subject. The method includes administering to the subject an effective amount of a substituted tetracycline compound, such that malaria is treated or prevented. In one aspect, the invention relates to pharmaceutical compositions which include an effective amount of a tetracycline compound to treat malaria in a subject and a pharmaceutically acceptable carrier. The substituted tetracycline compounds of the invention can be used to in combination with one or more anti-malarial compounds or can be used to treat or prevent malaria which is resistant to one or more other anti-malarial compounds.

  本发明提供了一种治疗或预防受试者疟疾的方法。该方法包括向受试者施用有效量的取代四环素化合物，从而治疗或预防疟疾。在一个方面，本发明涉及药物组合物，其中包括治疗受试者疟疾的有效量的四环素化合物和药学上可接受的载体。本发明的取代四环素化合物可与一种或多种抗疟疾化合物联合使用，也可用于治疗或预防对一种或多种其他抗疟疾化合物有抗药性的疟疾。
• US7960366B2
  申请人：——

  公开号：US7960366B2

  公开（公告）日：2011-06-14