Pharmaceutical compounds

摘要

A compound which is a benzo[a]phenazine-11-carboxamide derivative of formula (I) wherein each of R¹ to R⁴, which are the same or different, is selected from hydrogen, halogen, hydroxyl, C₁-C₆ alkoxy which is unsubstituted or substituted, heteroaryloxy, C₁-C₆ alkyl which is unsubstituted or substituted, nitro, cyano, azido, amidoxime, CO₂R¹⁰, CON(R¹²)₂, OCON(R¹²), SR¹⁰, SOR¹¹, SO₂R¹¹, SO₂N(R¹²)₂, N(R¹²)₂, NR¹⁰SO₂R¹¹, N(SO₂R₁₁)₂ NR¹⁰(CH₂)_nCN, NR¹⁰COR¹¹, OCOR¹¹ or COR¹⁰; each of R⁵ to R⁷, which are the same or different, is selected from hydrogen, halogen, hydroxy, C₁-C₆ alkoxy, C₁-C₆ alkyl, SR¹⁰ and N(R¹²)₂; Q is C₁-C₆ alkylene which is unsubstituted or substituted by (i) C₁-C₆ alkyl which is unsubstituted or substituted, (ii) hydroxy, provided that the hydroxy group is not alpha to either of the N atoms adjacent to Q in formula (I), (iii) CO₂R¹⁰, or (iv) CON(R¹²); R⁸ and R⁹, which are the same or different, are each hydrogen or C₁-C₆ alkyl, or R⁸ and R⁹ together with the nitrogen atom to which they are attached form a saturated 5- or 6-membered N-containing heterocyclic ring which may include one additional heteroatom selected from O, N and S, or one of R⁸ and R⁹ is an alkylene chain optionally interrupted by O, N or S, which is attached to a carbon atom on the alkylene chain represented by Q to complete a saturated 5- or 6-membered N-containing heterocyclic ring as defined above; R¹⁰ is hydrogen, C₁-C₆ alkyl, C₃-C₆ cycloalkyl, benzyl or phenyl; R¹¹ is C₁-C₆ alkyl, C₃-C₆ cycloalkyl, benzyl or phenyl; each R¹², which are the same or different, is hydrogen, C₁-C₆ alkyl cycloalkyl, benzyl or phenyl, or the two R¹² groups form, together with the nitrogen atom to which they are attached a 5- or 6-membered saturated N-containing heterocyclic ring which may include 1 or 2 additional heteroatoms selected from O, N and S; and n is 1, 2 or 3; or a pharmaceutically acceptable salt thereof; with the proviso that at least one of R¹ to R⁴ is other than hydrogen. These compounds are inhibitors of topoisomerase I and/or topoisomerase II and can be used to treat tumours, including tumours which express MDR.