NOVEL ISOCOUMARINE DERIVATIVES INHIBITING ANGIOGENESIS

摘要

PURPOSE: Provided are novel isocoumarine derivatives inhibiting angiogenesis, a preparation method thereof and a pharmaceutical composition comprising them. The isocoumarine derivatives, especially, 6, 8-dihydroxy-4-acetyl isocoumarine and 6, 8-dihydroxy-4-hydroxyacetyl isocoumarine are excellent in an inhibiting activity of the angiogenesis, therefore is useful in treating an angiogenic disease such as a cancer, a rheumatoid arthritis and diabetic retinopathy. CONSTITUTION: The novel isocoumarine derivative is represented by the following formula (1), wherein R1 is hydrogen, alkyl or allylalkyl; and R2 and R3, which may be the same or different, each represents hydrogen or alkyl. Also, 6, 8-dihydroxy-4-acetyl isocoumarine is represented by the following formula (2), wherein the compound is isolated from Sesquicillium mold strain Y70832. The preparation method of the compound comprises the steps of : extracting the mold strain Y70832 culture with acetone and ethyl acetate; separating the culture by a silica gel chromatography using a solvent mixed methylene chloride with methanol; further separating the culture by Sephadex LH 20 column chromatography using methanol as the solvent; and carrying out a high performance liquid chromatography (HPLC) using acetonitrile as the solvent.