发明名称 |
Synthesis of combretastatin A-2 prodrugs |
摘要 |
The original synthesis of combretastatin A-2 (1a) was modified to provide an efficient scale-up procedure for obtaining this antineoplastic stilbene. Subsequent conversion to a useful prodrug was accomplished by phosphorylation employing in situ formation of dibenzylchlorophosphite followed by cleavage of the benzyl ester protective groups with bromotrimethylsilane to afford phosphoric acid intermediate 11. The latter was immediately treated with sodium methoxide to complete a practical route to the disodium phosphate prodrug (2a). The phosphoric acid precursor (11) of phosphate 2a was employed in a parallel series of reactions to produce a selection of metal and ammonium cation prodrug candidates. Each of the phosphate salts (2a-q) was evaluated with respect to relative solubility behavior, cancer cell growth inhibition, and antimicrobial activity.
|
申请公布号 |
US7105695(B2) |
申请公布日期 |
2006.09.12 |
申请号 |
US20040499848 |
申请日期 |
2004.06.21 |
申请人 |
ARIZONA BOARD OF REGENTS, ACTING FOR AND ON BEHALF OF ARIZONA STATE UNIVERSITY |
发明人 |
PETTIT GEORGE R.;MOSER BRYAN R. |
分类号 |
A61K31/665;C07F9/02;A61K31/36;A61P9/00;A61P35/00;A61P43/00;C07C43/23;C07F9/12;C07F9/655 |
主分类号 |
A61K31/665 |
代理机构 |
|
代理人 |
|
主权项 |
|
地址 |
|