-11- Benzoaphenazin-11-carboxamide derivatives and their use as joint inhibitors of topomerase I and II

摘要

Described herein are benzo [a] phenazinyl-11-carboxamide derivative compounds of formula I or pharmaceutically acceptable salts thereof.;Formula I;In the above formula (I);R^OneTo R⁴Are each the same or different and are hydrogen, halogen, hydroxyl, substituted or unsubstituted C_One-C₆Alkoxy, heteroaryloxy, substituted or unsubstituted C_One-C₆Alkyl, nitro, cyano, azido, amide oxime, CO₂R¹⁰, CON (R¹²)₂, OCON (R¹²), SR¹⁰, SOR¹¹, SO₂R¹¹, SO₂N (R¹²)₂, N (R¹²)₂, NR¹⁰SO₂R¹¹, N (SO₂R¹¹)₂, NR¹⁰(CH₂)_nCN, NR¹⁰COR¹¹, OCOR¹¹And COR¹⁰;;R⁵To R⁷Are each the same or different and are hydrogen, halogen, hydroxy, C_One-C₆Alkoxy, C_One-C₆Alkyl, SR¹⁰And N (R¹²)₂;;Q is (i) substituted or unsubstituted C_One-C₆Alkyl, (ii) hydroxy (provided that such a hydroxy group is not on any of the N atoms adjacent to Q in formula I), (iii) CO₂R¹⁰Or (iv) CON (R¹²)₂ RTI ID = 0.0 C_One-C₆Alkylene;;R⁸And R⁹Are each the same or different and are each hydrogen or C_One-C₆Alkyl, or R⁸And R⁹Together with the nitrogen atom to which they are attached form a saturated 5-or 6-membered N-containing heterocyclic ring which may contain one additional heteroatom selected from O, N and S, or R⁸And R⁹Is an alkylene chain optionally interrupted by O, N or S which is attached to the carbon atom of the alkylene moiety represented by Q and forms a saturated 5-or 6-membered N-containing heterocyclic ring as defined above ,;R¹⁰, R¹¹, R¹²And n are as defined in claim 1,;R^OneTo R⁴/RTI is not hydrogen.;These compounds are inhibitors of topoisomerase I and / or topoisomerase II and can be used to treat tumors, including tumors that express MDR.