<4S-(4α,12aα)>-4-(dimethylamino)-9-nitro-1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-2-naphthacenecarboxamide | 120793-45-5

• 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: <4S-(4α,12aα)>-4-(dimethylamino)-9-nitro-1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-2-naphthacenecarboxamide
• 英文别名: 9-nitrodoxycycline
• CAS: 120793-45-5
• 化学式: C₂₂H₂₃N₃O₁₀
• 分子量: 489.439
• InChiKey: YYQFXYBHMJRYIX-PLYBKPSTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.44
• 重原子数：
  35.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  224.76
• 氢给体数：
  6.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  <4S-(4α,12aα)>-4-(dimethylamino)-9-nitro-1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-2-naphthacenecarboxamide 在 palladium on activated charcoal 亚硝酸丁酯 、 氢气 作用下， 以 盐酸 、 甲醇 为溶剂， 生成 9-azidodoxycycline
  参考文献：
  名称：

  8位取代的四环素衍生物的合成，第一个8位碳-碳键

  摘要：

  描述了使用Stille偶联法合成C8-官能化的四环素。这些衍生物是第一个在四环素的8位上带有碳-碳键的报告，其与8位取代的四环素的总合成路线却相反。

  DOI：

  10.1016/s0040-4039(00)00768-1
• 作为产物：
  描述：

  强力霉素 在 硫酸 、 potassium nitrate 作用下， 生成 <4S-(4α,12aα)>-4-(dimethylamino)-9-nitro-1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-2-naphthacenecarboxamide
  参考文献：
  名称：

  8位取代的四环素衍生物的合成，第一个8位碳-碳键

  摘要：

  描述了使用Stille偶联法合成C8-官能化的四环素。这些衍生物是第一个在四环素的8位上带有碳-碳键的报告，其与8位取代的四环素的总合成路线却相反。

  DOI：

  10.1016/s0040-4039(00)00768-1

文献信息

• [EN] POLYMER DRUG CONJUGATES FOR THE TREATMENT OF AMYLOIDOSIS<br/>[FR] CONJUGUES DE MEDICAMENTS POLYMERES POUR LE TRAITEMENT DE L'AMYLOSE
  申请人：FUNDACIÓN COMUNIDAD VALENCIADA CT DE INVESTIGACIÓN PRÍNCIPE FELIPE

  公开号：WO2014187654A1

  公开（公告）日：2014-11-27

  The present invention is referred to novel polymeric conjugates to which at least it is linked a fibril disruptor agent and/or a aggregates blocking agent, and additionally a targeting moiety and/or a probe for therapy and diagnosis. In the polymer-drug conjugate, the polymeric platform transports at least one bioactive agent, selected from the group of anthracyclines antibiotics which includes tetracycline, rolitethracycline, minocycline and/or doxycycline and their derivatives, etc..., able to disaggregate or break the amyloid fibrils and/or block the aggregates. This conjugate could contain in its structure one or several targeting moieties, which will provide an effective targeting of the polymer-drug conjugate to the selected diseased area for drug activity, increasing the therapeutic efficacy in the treatment of amyloidosis related diseases, including amyloidosis related to polyneuropathic disorders and neurodegenerative diseases like FAP and AD.

  本发明涉及新型聚合物共轭物，其中至少连接有纤维破坏剂和/或聚集体阻断剂，以及附加的靶向基团和/或治疗和诊断探针。在聚合物药物共轭物中，聚合物平台运输至少一种生物活性物质，选自包括四环素、罗利四环素、米诺环素和/或多西环素及其衍生物等蒽环素类抗生素，能够分散或破坏淀粉样纤维和/或阻断聚集体。该共轭物可以在其结构中包含一个或多个靶向基团，这将为药物活性提供有效的靶向，增加治疗淀粉样变性相关疾病的治疗效果，包括与多发性神经病变和神经退行性疾病相关的淀粉样变性。
• Synthesis and biological evaluation of 9-substituted tetracycline derivatives
  作者：Darrell J Koza、Yaw A Nsiah

  DOI：10.1016/s0960-894x(02)00369-4

  日期：2002.8

  The synthesis of 9-substituted tetracycline derivatives has been accomplished by the reaction of C9 diazonium tetrafluoroborate tetracycline salts with organotin reagents under modified Stille coupling conditions. Several of these unreported derivatives show promising in vitro biological activity against tetracycline resistant and antibiotic resistant bacteria.

  9-取代的四环素衍生物的合成已通过在改良的Stille偶联条件下使C9重氮四氟硼酸盐四环素盐与有机锡试剂反应来完成。这些未报道的衍生物中的几种显示出对四环素抗性和抗生素抗性细菌有希望的体外生物学活性。
• Synthesis and Characterization of Photoactivatable Doxycycline Analogues Bearing Two-Photon-Sensitive Photoremovable Groups Suitable for Light-Induced Gene Expression
  作者：Bastien Goegan、Firat Terzi、Frédéric Bolze、Sidney Cambridge、Alexandre Specht

  DOI：10.1002/cbic.201700628

  日期：2018.6.18

  Photolabile caged versions of 9‐aminodoxycycline that photolyse after visible light irradiation or 740 nm two‐photon excitation are reported. 9‐Aminodoxycycline is a tetracycline analogue that can be efficiently coupled to photoremovable protecting groups by carbamoylation, leading to new caged doxycycline derivatives that can be used in combination with the TetOn system for photoactivated gene expression

  据报道，在可见光辐照或740 nm双光子激发后，光解笼罩的9-氨基多西环素会发生光解。9‐Aminodoxycycline是一种四环素类似物，可通过氨基甲酰化作用与光可去除保护基团有效偶联，从而产生可与TetOn系统结合使用的新笼状强力霉素衍生物，以进行光激活基因表达。
• "Glycylcyclines". 3. 9-Aminodoxycyclinecarboxamides
  作者：Timothy C. Barden、Brian L. Buckwalter、Raymond T. Testa、Peter J. Petersen、Ving J. Lee

  DOI：10.1021/jm00046a003

  日期：1994.9

  A series of 9-(acylamino)doxycycline derivatives has been prepared. These analogs exhibit good activity against both tetracycline sensitive and tetracycline resistant Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria that are encoded with the efflux and ribosomal resistance gene factors. N,N-Dialkylglycylamido derivatives possessed the highest activity. Replacement of glycine moiety with other amino acids did not further enhance the activity.
• Synthesis and Antibacterial Activity of Doxycycline Neoglycosides
  作者：Jianjun Zhang、Larissa V. Ponomareva、Karen Marchillo、Maoquan Zhou、David R. Andes、Jon S. Thorson

  DOI：10.1021/np4003096

  日期：2013.9.27

  A set of 37 doxycycline neoglycosides were prepared, mediated via a C-9 alkoxyamino-glycyl-based spacer reminiscent of that of tigecycline. Subsequent in vitro antibacterial assays against representative drug-resistant Gram negative and Gram positive strains revealed a sugar-dependent activity profile and one doxycycline neoglycoside, the 2'-amino-alpha-D-glucoside conjugate, to rival that of the parent pharmacophore. In contrast, the representative tetracycline-susceptible strain E. coli 25922 was found to be relatively responsive to a range of doxycycline neoglycosides. This study also extends the use of aminosugars in the context of neoglycosylation via a simple two-step strategy anticipated to be broadly applicable for neoglycorandomization.