WATER SOLUBLE 4-AZAPODOPHYLLOTOXIN ANALOGS

摘要

The present invention relates to 4-azapodophyllotoxin analogs of formula (I) in which X, R1, R2, R3, R4 and Ar are as defined in claim 1, preferably a pharmaceutically acceptable salt thereof, optionally in the form of a solvate, a composition comprising said analogs, their use as medicament, in particular for the treatment of cancer, and a process for their preparation.;

主权项

1. Compound of formula (I): in which X represents —CH2— or —CH2CH2—; R1 and R4 are independently selected from the group consisting of H, halogen, C1-C4-alkyl; R2 and R3 are independently selected from the group consisting of H, OH, C1-C4 alkyl, C1-C4-alkoxy, C1-C4-alkylthio, halogen, trifluoromethyl, CN; or R2 and R3, taken together, form a bridging group selected from the group consisting of —(CH2)n- and —O—(CH2)m-O—, n being an integer between 3 and 4 and m being 1 or 2; Ar represents a phenyl or naphthyl group optionally substituted with one to four substituents independently selected from the group consisting of C1-C4-alkyl, OH, C1-C4-alkoxy, C1-C4-alkylthio, halogen, trifluoromethyl, CN, or a pharmaceutically acceptable salt thereof, and/or a solvate thereof.