Zhejiang Dade Pharmaceutical Group Co., Ltd.

Weiping Shen

Jianguo Wang

Jianping Wang

Fei Wang

Feng Qian

Hongmei Jin

The invention disclosed a total synthesis process of novel ethoxy combretastatins and their prodrugs. Combretastatins are chemically modified by ethoxy substituted on the 4'-position of their B aryl ring and are converted to be their soluble prodrugs of phosphate or their inner salt of phosphorylcholine by modifying the hydroxyl on the 3&#x2032;-position of their B aryl ring. Similarly, 3&#x2032;-amino combretastatin is 4&#x2032;-ethoxy chemically modified and further side chain of amino acid can be introduced to the amino to form soluble prodrug of amino acidamide. The structure of the said compound is showed as formula (I). Ethoxy combretastatins possess potent tubulin polymerization inhibitory activity and can be used for the treatment of inhibiting tumor or neovascular. 

Preparation and the use of ethoxy combretastatins and their prodrugs

Combretastatin derivatives of formula (I), preparation and use thereof are disclosed, wherein: Ris alkyl with 1-8 carbon atoms and 1-17 fluorine atoms, R is amino, substituted amino, hydroxyl, nitro, halo, alkyloxy, phosphate or amino acid side chain. Said derivatives have a capability to inhibit the polymerization of microtubules and are useful in treatment against tumor and neovascularization.

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Shanghai, China

Weiping Shen