Heterocyclic cytotoxic agents

A compound of formula I:

• wherein
• R1, R2 and R3 are each individually hydrogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, nitro, hydroxy, NRgRh, COORk, ORm, or halo;
• or R1 and R2 taken together are methylenedioxy and R3 is hydrogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, nitro, hydroxy, NRgRh, COORK, ORm, or halo;
• or R2 and R3 taken together are methylenedioxy and R1 is hydrogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, nitro, hydroxy, NRgRh, COORk, ORm, or halo;
• R4 is oxy, (C1-C6)alkyl, or is absent;
• R5 is hydrogen, hydroxy, or (C1-C6)alkyl;
• R6, R7 and R8 are each individually hydrogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, nitro, hydroxy, NRgRh, COORk, ORm, or halo;
• or R6 and R7 taken together are methylenedioxy and R8 is hydrogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, nitro, hydroxy, NRgRh, COORk, ORm, or halo;
• or R7 and R8 taken together are methylenedioxy and R6 is hydrogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, nitro, hydroxy, NRgRh, C(═O)Rk, COORk, ORm, or halo;
• each bond represented by ————— is individually present or absent;
• X is C(Ra)(Rb) or NRc;
• Y is C(Rd)(Re) or NRf;
• if present, Ra and Rb are each independently hydrogen or (C1-C6)alkyl if the bond between the 11- and 12-positions represented by ————— is absent;
• or Ra is hydrogen or (C1-C6)alkyl and Ra is absent if the bond between the 11- and 12-positions represented by ————— is present;
• if present, Rc and Rf are each independently hydrogen or (C1-C6)alkyl if the bond between the 11- and 12-positions represented by ————— is absent;
• or Rc and Rf are each independently (C1-C6)alkyl or absent if the bond between the 11- and 12-positions represented by ————— is present;
• if present, Rd and Re are each independently hydrogen or (C1-C6)alkyl if the bond between the 11- and 12-positions represented by ————— is absent;
• or Rd is hydrogen or (C1-C6)alkyl and Re is absent if the bond between the 11- and 12-positions represented by ————— is present;
• each Rg and Rh is independently hydrogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, (C1-C6)alkanoyl, aryl, aryl(C1-C6)alkyl, aryloxy, or aryl(C1-C6)alkoxy;
• or Rg and Rh together with the nitrogen to which they are attached are pyrrolidino, piperidino, morpholino, or thiomorpholino;
• each Rk is independently hydrogen, or (C1-C6)alkyl;
• and
• each Rm is independently (C1-C6)alkanoyl, aryl, or aryl(C1-C6)alkyl;
• wherein any (C1-C6)alkyl, (C3-C6)cycloalkyl, or (C1-C6)alkoxy of R1, R2, R3, R6, R7, R8, or Rk is optionally substituted on carbon with 1, 2, or 3 substituents independently selected from hydroxy, halo, NRnRp, (C3-C6)cycloalkyl, or (C1-C6)alkoxy;
• wherein each Rn and Rp is independently hydrogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, or (C1-C6)alkanoyl;
• or Rn and Rp together with the nitrogen to which they are attached are pyrrolidino, piperidino, morpholino, or thiomorpholino;
• wherein any aryl is optionally be substituted with 1, 2, or 3 substituents independently selected from hydroxy, halo, nitro, trifluoromethyl, trifluoromethoxy, carboxy, amino, (C1-C6)alkyl, (C3-C6)cycloalkyl, and (C1-C6)alkoxy;
• provided that at least one of R2 and R8 is hydrogen, methyl, nitro, hydroxy, amino, fluoro or chloro;
• or at least one of R2 and R8 forms part of a methylenedioxy;
• and
• provided that R1-R3 and R6-R8 are not all hydrogen;
• provided the compound is not 9-methylbenzo[i]phenanthridine;
• 1-chloro-2-methoxybenzo[i]phenanthridine;
• 2-methoxybenzo[i]phenanthridine;
• 2,3-methylenedioxy-8,9-methylenedioxybenzo[i]phenanthridine;
• 5,8-dimethylbenzo[i]phenanthridine;
• 2-methoxy-5-methylbenzo[i]phenanthridine;
• 2-methoxy-5,8-dimethyl benzo[i]phenanthridine;
• 5,6-dihydro-9-methylbenzo[i]phenanthridine;
• or 1-chloro-2-methoxy-5,6-dihydrobenzo[i]phenanthridine;
• or a pharmaceutically acceptable salt thereof.