发明名称 |
SELF-ASSEMBLED TAXO-DIPERPENOID NANOSTRUCTURES |
摘要 |
Onium salts of taxo-diterpenoid-C<n>,2-O-aza-arenes form water soluble self-assembling nanostructures above a critical aggregation concentration. The onium salt of aza-arene includes a delocalized charge which renders derivatized taxo-diterpenoids amphoteric, enhances their solubility in water, and promotes self-assembly of water soluble nanostructures, e.g., helical fibular structures and spherical micellular structures. These same onium salts of taxo-diterpenoid-C<n>,2-O-aza-arenes are employed as water soluble prodrugs. For example, taxol-2'-methylpyridinium tosylate (MPT) is characterized by an elevated aqueous solubility, rapid activation by serum protein, good stability in most other aqueous solutions, formation of a protein: taxol intermediate and good retention within the circulatory system. The toxicity of the activated form is comparable or greater than underivatized taxol. Furthermore, taxol-2'-MPT can be synthesized by a simple one step reaction between taxol and 2-fluoro-1-MPT. The invention is applicable to taxol and taxol memetics having hydroxyls that are reactive with onium salts of 2-halogenated-aza-arenes. For example, taxol, C-2 substituted taxol and Taxotere each have reactive hydroxyls at the 2' and 7 positions. The invention is also applicable to a wide array of 2-halogenated-aza-arenes. |
申请公布号 |
WO9518613(A1) |
申请公布日期 |
1995.07.13 |
申请号 |
WO1995US00538 |
申请日期 |
1995.01.11 |
申请人 |
THE SCRIPPS RESEARCH INSTITUTE;NICOLAOU, K., C.;WRASIDLO, WOLFGANG;GUY, RODNEY, K.;PITSINOS, EMMANUEL |
发明人 |
NICOLAOU, K., C.;WRASIDLO, WOLFGANG;GUY, RODNEY, K.;PITSINOS, EMMANUEL |
分类号 |
A61K31/335;A61K31/337;A61P35/00;C07D305/14;C07D405/12;C07D405/14;C07D407/12;C07D409/12;C07D409/14;C07D411/12;C07D411/14;C07D413/12;C07D417/12;C07D417/14 |
主分类号 |
A61K31/335 |
代理机构 |
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代理人 |
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主权项 |
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地址 |
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