6-ETHER/THIOETHER-PURINES AS TOPOISOMERASE II CATALYTIC INHIBITORS AND THEIR USE IN THERAPY

摘要

The present invention relates to certain purines of the following formulae, which act as topoisomerase II catalytic inhibitors: wherein: J is independently: —H or —NR^N1R^N2; X is independently: —O—, or —S—; Q is independently: a covalent bond, C_1-7alkylene, C_2-7alkenylene, C_2-7alkynylene, C_3-7cycloalkylene, C_3-7cycloalkenylene, or C_3-7cycloalkynylene; T is independently: a group A¹ or a group A²; A¹ is independently: C_6-14carboaryl, C_4-14heteroaryl, C_3-12carbocyclic, or C_3-12heterocyclic; and is independently unsubstituted or substituted; A² is independently: —H, —CN, —OH, or —O(C═O)—C_1-7alkyl; R is independently —H or a nitrogen ring substituent: R⁸ is independently —H or a ring substituent; either: each of R^N1 and R^N2 is independently —H or a nitrogen substituent; or: R^N1 and R^N2 taken together with the nitrogen atom to which they are attached form a ring having from 3 to 7 ring atoms; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, N-oxides, chemically protected forms, and prodrugs thereof. These compounds are useful in combination with topoisomerase II poisons, such as anthracyclines and epipodophyllotoxins, in the treatment of proliferative conditions (e.g., cancer). These compounds are also useful in the treatment of tissue damage associated with extravasation of a topoisomerase II poison, such as an anthracycline or an epipodophyllotoxin.;