自己会合タキソ-ジテルペノイドナノ構造

Title:

自己会合タキソ-ジテルペノイドナノ構造

Document Type and Number:

Japanese Patent JP3778929

Kind Code:

B2

Abstract:

Onium salts of taxo-diterpenoid-Cn,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-Cn,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.

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Inventors:

Nicolau, K. C.
Rasidro, Wolfgang
Guy, Rodney K.
Pitosinos, Emmanuel

Application Number:

JP51871595A

Publication Date:

May 24, 2006

Filing Date:

January 11, 1995

Export Citation:

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Assignee:

THE SCRIPPS RESEARCH INSTITUTE

International Classes:

C07D305/14; A61K31/335; A61K31/337; A61P35/00; A61P43/00; C07D405/12; C07D405/14; C07D407/12; C07D409/12; C07D409/14; C07D411/12; C07D411/14; C07D413/12; C07D417/12; C07D417/14

Foreign References:

EP0537905A1

Other References:

Mukaiyama, T., Angewandte Chemie, 1979年,vol.91, pp.798-812

Attorney, Agent or Firm:

Shoichi Okuyama
Arihara Koichi
Matsushima Tetsuo
Kazuo Yoshii
Okimoto Kazuaki
Noriaki Nagahama
Atsushi Kokubun

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