9alpha,11alpha,15alpha-三羟基-16-苯氧基-17,18,19,20-四去甲前列腺-4,5,13-三烯酸 | 61456-25-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: 9alpha,11alpha,15alpha-三羟基-16-苯氧基-17,18,19,20-四去甲前列腺-4,5,13-三烯酸
• 英文名称: Tptpt
• CAS: 61456-25-5
• 化学式: C₂₂H₂₈O₆
• 分子量: 388.5
• InChiKey: VCNNKFGSVVJGBP-OUKQBFOZSA-N

物化性质

• 沸点：
  614.7±55.0 °C(Predicted)
• 密度：
  1.259±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  28
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  107
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  生成 9alpha,11alpha,15alpha-三羟基-16-苯氧基-17,18,19,20-四去甲前列腺-4,5,13-三烯酸
  参考文献：
  名称：

  JOHNSON, D. M.;TAYLOR, W. F., J. PHARM. SCI., 1984, 73, N 10, 1414-1417

  摘要：

  DOI：

文献信息

• Positively charged water-soluble prodrugs of prostaglandins and related compounds with very high skin penetration rates
  申请人：Techfields Biochem Co. Ltd

  公开号：EP2781505A1

  公开（公告）日：2014-09-24

  The novel positively charged pro-drugs of prostaglandins, prostacyclins and related compounds in the general formula (2) 'Structure 2' were designed and synthesized. The compounds of the general formula (2) 'Structure 2' indicated above can be prepared from protected prostaglandins, prostacyclins, and related compounds, by reaction with suitable alcohols, thiols, or amines and coupling reagents, such as N, N'-Dicyclohexylcarbodiimide, N, N'-Diisopropylcarbodiimide, O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate, O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate, Benzotriazol-1-yl-oxy-tris (dimethylamino)phosphonium hexafluorophosphate, et al. The positively charged amino groups of these pro-drugs not only largely increases the solubility of the drugs in water, but also bonds to the negative charge on the phosphate head group of membranes and pushes the pro-drug into the cytosol. The results suggest that the pro-drugs diffuse through human skin ∼1000 times faster than do prostaglandins, prostacyclins, and related compounds. In plasma, more than 90% of these pro-drugs can change back to the parent drugs in a few minutes. The prodrugs can be used medicinally in treating any prostaglandins, prostacyclins, and related compounds-treatable conditions in humans or animals. The prodrugs can be administered transdermally for any kind of medical treatments and avoid most of the side effects of prostaglandins, prostacyclins, and related compounds. Controlled transdermal administration systems of the prodrug enable prostaglandins, prostacyclins, and related compounds to reach constantly optimal therapeutic blood levels to increase effectiveness and reduce the side effects of prostaglandins, prostacyclins, and related compounds. Another great benefit of transdermal administration of these pro-drugs is that administering medication, especially to children, will be much easier.

  设计并合成了通式（2）'结构 2'中前列腺素、前列环素及相关化合物的新型带正电的原药。上述通式（2）'结构 2'的化合物可以由受保护的前列腺素、前列环素和相关化合物通过与合适的醇、硫醇或胺和偶联试剂（如 N，N'-二环己基碳二亚胺）反应制备、N，N'-二异丙基碳二亚胺、O-(苯并三唑-1-基)-N，N，N'，N'-四甲基脲四氟硼酸盐、O-(苯并三唑-1-基)-N，N，N'，N'-四甲基脲六氟磷酸盐、苯并三唑-1-基氧基-三(二甲基氨基)鏻六氟磷酸盐等。这些原药带正电荷的氨基不仅在很大程度上增加了药物在水中的溶解度，而且还与膜上磷酸头基的负电荷结合，将原药推入细胞质中。结果表明，原药在人体皮肤中的扩散速度比前列腺素、前列环素和相关化合物快 1000 倍。在血浆中，90% 以上的原药可在几分钟内变回母药。这些原药可用于治疗人类或动物的任何前列腺素、前列环素和相关化合物可治疗的疾病。原药可以透皮给药，用于任何类型的医疗，并可避免前列腺素、前列环素和相关化合物的大部分副作用。原药的可控透皮给药系统可使前列腺素、前列环素和相关化合物不断达到最佳治疗血药浓度，从而提高疗效，减少前列腺素、前列环素和相关化合物的副作用。这些原药透皮给药的另一大好处是，用药，尤其是给儿童用药将变得更加容易。
• POSITIVELY CHARGED WATER-SOLUBLE PRODRUGS OF PROSTAGLANDINS AND RELATED COMPOUNDS WITH VERY HIGH SKIN PENETRATION RATES
  申请人：Techfields Biochem Co. Ltd.

  公开号：EP2084124A1

  公开（公告）日：2009-08-05
• [EN] POSITIVELY CHARGED WATER-SOLUBLE PRODRUGS OF PROSTAGLANDINS AND RELATED COMPOUNDS WITH VERY HIGH SKIN PENETRATION RATES<br/>[FR] PROMÉDICAMENTS HYDROSOLUBLES DE PROSTAGLANDINES ET COMPOSÉS ANALOGUES, POSITIVEMENT CHARGÉS, À TAUX DE PÉNÉTRATION CUTANÉE TRÈS ÉLEVÉ
  申请人：TECHFIELDS BIOCHEM CO LTD

  公开号：WO2008041054A1

  公开（公告）日：2008-04-10

  [EN] The novel positively charged pro-drugs of prostaglandins, prostacyclins and related compounds in the general formula (2) 'Structure 2' were designed and synthesized. The compounds of the general formula (2) 'Structure 2' indicated above can be prepared from protected prostaglandins, prostacyclins, and related compounds, by reaction with suitable alcohols, thiols, or amines and coupling reagents, such as N, N'-Dicyclohexylcarbodiimide, N, N'-Diisopropylcarbodiimide, O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate, O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate, Benzotriazol-1-yl-oxy-tris (dimethylamino)phosphonium hexafluorophosphate, et al. The positively charged amino groups of these pro-drugs not only largely increases the solubility of the drugs in water, but also bonds to the negative charge on the phosphate head group of membranes and pushes the pro-drug into the cytosol. The results suggest that the pro-drugs diffuse through human skin ~1000 times faster than do prostaglandins, prostacyclins, and related compounds. In plasma, more than 90% of these pro-drugs can change back to the parent drugs in a few minutes. The prodrugs can be used medicinally in treating any prostaglandins, prostacyclins, and related compounds-treatable conditions in humans or animals. The prodrugs can be administered transdermally for any kind of medical treatments and avoid most of the side effects of prostaglandins, prostacyclins, and related compounds. Controlled transdermal administration systems of the prodrug enable prostaglandins, prostacyclins, and related compounds to reach constantly optimal therapeutic blood levels to increase effectiveness and reduce the side effects of prostaglandins, prostacyclins, and related compounds. Another great benefit of transdermal administration of these pro-drugs is that administering medication, especially to children, will be much easier.
  [FR] La présente invention concerne la conception et la synthèse de promédicaments innovants de prostaglandines, de prostacyclines et de composés analogues, positivement chargés, répondant à la formule générale (2) 'Structure 2'. Les composés de formule générale (2) 'Structure 2' mentionnés ci-dessus peuvent être préparés à partir de prostaglandines, de prostacyclines et de composés analogues protégés par une réaction avec des alcools, des thiols ou des amines appropriés et des réactifs de couplage, tels que le N,N'-dicyclohexylcarbodiimide, le N,N'-diisopropylcarbodiimide, le tétrafluoroborate de O-(benzotriazol-1-yl)-N,N,N',N'-tétraméthyluronium, l'hexafluorophosphate de O-(benzotriazol-1-yl)-N,N,N',N'-tétraméthyluronium, l'hexafluorophosphate de benzotriazol-1-yl-oxy-tris (diméthylamino) phosphonium, etc. Les groupes amino positivement chargés de ces promédicaments non seulement augmentent fortement la solubilité des médicaments dans l'eau, mais ils se lient aussi à la charge négative sur le groupe phosphate de tête des membranes et ils poussent le promédicament dans le cytosol. Les résultats suggèrent que les promédicaments se diffusent à travers la peau humaine ~ 1000 fois plus rapidement que les prostaglandines, les prostacyclines et les composés analogues. Dans le plasma, plus de 90 % de ces promédicaments peuvent se retransformer en médicaments parents en quelques minutes. Les promédicaments peuvent être utilisés médicalement pour traiter n'importe quelle affection pouvant être traitée par les prostaglandines, les prostacyclines et les composés analogues chez les humains ou les animaux. Les promédicaments peuvent être administrés par voie transdermique pour n'importe quelle sorte de traitement médical et ils évitent la plupart des effets secondaires des prostaglandines, des prostacyclines et des composés analogues. Les systèmes d'administration transdermique contrôlée du promédicament permettent aux prostaglandines, aux prostacyclines ou aux composés analogues de rester à des taux sanguins thérapeutiques constamment optimaux afin d'augmenter l'efficacité et de réduire les effets secondaires des prostaglandines, des prostacyclines et des composés analogues. Un autre grand avantage de l'administration transdermique de ces promédicaments est qu'ils faciliteront beaucoup l'administration des médicaments, en particulier aux enfants.
• JOHNSON, D. M.;TAYLOR, W. F., J. PHARM. SCI., 1984, 73, N 10, 1414-1417
  作者：JOHNSON, D. M.、TAYLOR, W. F.

  DOI：——

  日期：——