9-trityloxynonanoic acid | 181703-84-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 9-trityloxynonanoic acid
• 英文别名: 9-Trityloxy-nonanoic acid
• CAS: 181703-84-4
• 化学式: C₂₈H₃₂O₃
• 分子量: 416.56
• InChiKey: GILCBWSINFBUNW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  31
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  9-trityloxynonanoic acid 在 吗啉 、 甲醇 、 四(三苯基膦)钯 、 对甲苯磺酸 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 13.0h， 生成
  参考文献：
  名称：

  New Antibacterial Agents Derived from the DNA Gyrase Inhibitor Cyclothialidine

  摘要：

  Cyclothialidine (1, Ro 09-1437) is a potent DNA gyrase inhibitor that was isolated from Streptomyces filipinensis NR0484 and is a member of a new family of natural products. It acts by competitively inhibiting the ATPase activity exerted by the B subunit of DNA gyrase but barely exhibits any growth inhibitory activity against intact bacterial cells, presumably due to insufficient permeation of the cytoplasmic membrane. To explore the antibacterial potential of 1, we developed a flexible synthetic route allowing for the systematic modification of its structure. From a first set of analogues, structure-activity relationships (SAR) were established for different substitution patterns, and the 14-hydroxylated, bicyclic core (X) of 1 seemed to be the structural prerequisite for DNA gyrase inhibitory activity. The variation of the lactone ring size, however, revealed that activity can be found among 11- to 16-membered lactones, and even seco-analogues were shown to maintain some enzyme inhibitory properties, thereby reducing the minimal structural requirements to a rather simple, hydroxylated benzyl sulfide (XI). On the basis of these "minimal structures" a modification program afforded a number of inhibitors that showed in vitro activity against Gram-positive bacteria. The best activities were displayed by 14-membered lactones, and representatives of this subclass exhibit excellent and broad in vitro antibacterial activity against Gram-positive pathogens, including Staphylococcus aureus, Streptococcus pyogenes, and Enterococcus faecalis, and overcome resistance against clinically used drugs. By improving the pharmacokinetic properties of the most active compounds (94, 97), in particular by lowering their lipophilic properties, we were able to identify congeners of cyclothialidine (1) that showed efficacy in vivo.

  DOI：

  10.1021/jm0310232
• 作为产物：
  描述：

  1,9-壬二醇 在 吡啶 、 potassium permanganate 、 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 19.83h， 生成 9-trityloxynonanoic acid
  参考文献：
  名称：

  New Antibacterial Agents Derived from the DNA Gyrase Inhibitor Cyclothialidine

  摘要：

  Cyclothialidine (1, Ro 09-1437) is a potent DNA gyrase inhibitor that was isolated from Streptomyces filipinensis NR0484 and is a member of a new family of natural products. It acts by competitively inhibiting the ATPase activity exerted by the B subunit of DNA gyrase but barely exhibits any growth inhibitory activity against intact bacterial cells, presumably due to insufficient permeation of the cytoplasmic membrane. To explore the antibacterial potential of 1, we developed a flexible synthetic route allowing for the systematic modification of its structure. From a first set of analogues, structure-activity relationships (SAR) were established for different substitution patterns, and the 14-hydroxylated, bicyclic core (X) of 1 seemed to be the structural prerequisite for DNA gyrase inhibitory activity. The variation of the lactone ring size, however, revealed that activity can be found among 11- to 16-membered lactones, and even seco-analogues were shown to maintain some enzyme inhibitory properties, thereby reducing the minimal structural requirements to a rather simple, hydroxylated benzyl sulfide (XI). On the basis of these "minimal structures" a modification program afforded a number of inhibitors that showed in vitro activity against Gram-positive bacteria. The best activities were displayed by 14-membered lactones, and representatives of this subclass exhibit excellent and broad in vitro antibacterial activity against Gram-positive pathogens, including Staphylococcus aureus, Streptococcus pyogenes, and Enterococcus faecalis, and overcome resistance against clinically used drugs. By improving the pharmacokinetic properties of the most active compounds (94, 97), in particular by lowering their lipophilic properties, we were able to identify congeners of cyclothialidine (1) that showed efficacy in vivo.

  DOI：

  10.1021/jm0310232
• 作为试剂：
  描述：

  、 methyl 6-trityloxyhexanoate 、 methyl 9-trityloxynonanoate 、 methyl 12-trityloxydodecanoate 在 6-(trityloxy)hexanoic acid 、 9-trityloxynonanoic acid 作用下， 以12-trityloxydodecanoic acid 16c were isolated的产率得到12-triphenylmethyloxydodecanoic acid
  参考文献：
  名称：

  NOVEL GHRELIN ANALOGUES

  摘要：

  本发明提供了具有高亲和力的 ghrelin 类似物，用于疾病细胞中的靶受体，以及利用这些类似物进行诊断和治疗的方法。

  公开号：

  US20110110855A1

文献信息

• Fluorine and Rhenium Substituted Ghrelin Analogues as Potential Imaging Probes for the Growth Hormone Secretagogue Receptor
  作者：Dina Rosita、Matthew A. DeWit、Leonard G. Luyt

  DOI：10.1021/jm8014519

  日期：2009.4.23

  prepared containing rhenium, as a surrogate metal for technetium-99m, with a cyclopentadienylrhenium tricarbonyl being situated at the terminus of the residue-3 side chain, yielding compounds the best of which had a 35 nM IC50. This represents a rare case of incorporating rhenium into a peptide structure where the metal complex is required for biological activity. These fluorine and rhenium derivatives demonstrate

  在努力创建针对生长激素促分泌素受体（GHSR）的成像探针的过程中，我们现在报告了通过修饰正辛酰基Ser-3侧链设计和合成含氟和rh的生长素释放肽类似物的过程。使用二氨基丙酸（Dpr）作为残基-3，设计了氟类似物，使氟原子位于脂族链的末端。制备了截短的ghrelin（1-5）和ghrelin（1-14）含氟类似物，其中最好的类似物具有用于GHSR的28 nM IC 50。还制备了Ghrelin（1-14）类似物，其中含有rh，作为m 99m的替代金属，三羰基环戊二烯基r位于残基3侧链的末端，产生的化合物中最好的是35 nM IC50。这代表了将rh掺入肽结构的罕见情况，其中金属配合物是生物活性所必需的。这些氟和rh衍生物表现出修饰ghrelin的Ser-3侧链的能力，以便为GHSR创建成像探针。
• Ghrelin analogues
  申请人：Luyt Leonard G.

  公开号：US08623326B2

  公开（公告）日：2014-01-07

  Ghrelin analogues having high affinity for a target receptor in diseased cells are provided, as well as methods of diagnosis and treatment utilizing such analogues.

  提供了对疾病细胞中靶受体具有高亲和力的胃饥饿素类似物，以及利用这些类似物进行诊断和治疗的方法。
• US8623326B2
  申请人：——

  公开号：US8623326B2

  公开（公告）日：2014-01-07
• [EN] NOVEL GHRELIN ANALOGUES<br/>[FR] NOUVEAUX ANALOGUES DE GHRÉLINE
  申请人：UNIV WESTERN ONTARIO

  公开号：WO2009140763A1

  公开（公告）日：2009-11-26

  Ghrelin analogues having high affinity for a target receptor in diseased cells are provided, as well as methods of diagnosis and treatment utilizing such analogues.
• NOVEL GHRELIN ANALOGUES
  申请人：Luyt Leonard G.

  公开号：US20110110855A1

  公开（公告）日：2011-05-12

  Ghrelin analogues having high affinity for a target receptor in diseased cells are provided, as well as methods of diagnosis and treatment utilizing such analogues.

  提供具有高亲和力的ghrelin类似物，用于疾病细胞中的靶受体，以及利用这些类似物进行诊断和治疗的方法。