New stable, crystalline epipodophyllotoxin 4'-demethyl-4'-phosphate glucoside compound used as anticancer agent, e.g. for treating small cell lung cancer, neuroblastoma and lymphoma

摘要

Crystalline epipodophyllotoxin 4'-demethyl-4'-phosphate 2'',3''-bis-(pentafluorophenoxyacetyl)-4'',6''-ethylidene-beta -D-glucoside (I), as free base or hemiethanolate, is new. Crystalline epipodophyllotoxin 4'-demethyl-4'-phosphate 2'',3''-bis-(pentafluorophenoxyacetyl)-4'',6''-ethylidene-beta -D-glucoside, as free base or hemiethanolate (both characterized by X-ray diffraction diagrams given in the specification), of formula (I), are new. [Image] n : 0 or 0.5. An independent claim is included for the preparation of (I). ACTIVITY : Cytostatic. In tests in mice with implanted P388 leukemia, a single intraperitoneal injection of the crystalline hemiethanolate (I; n = 0.5) at 40 mg/kg or 160 mg/kg gave T/C values of 143% and 329%, respectively, compared with 100% (i.e. no effect) and 157% respectively for amorphous (I) at 40 mg/kg and 160 mg/kg. MECHANISM OF ACTION : Topoisomerase-1 inhibitor; Topoisomerase-2 inhibitor.