Patent ID: 6294552
Filing Date: 2001-09-25
Classification: A61P,C07D,C07F

Abstract:
A method for the treatment of abnormal cell growth in a mammal which comprises administering to said mammal a therapeutically effective amount of a compound of formula 1 ##STR19##or a pharmaceutically acceptable salt, prodrug or solvate thereof wherein:the dashed line indicates that the bond between C-3 and C-4 of the quinolin-2-one ring is a single or double bond;R.sub.1 is selected from H, C.sub.1 -C.sub.10 alkyl, --(CR.sup.13 R.sup.14).sub.q C(O)R.sup.12, --(CR.sup.13 R.sup.14).sub.q C(O)OR.sup.15, --(CR.sup.13 R.sup.14).sub.q OR.sup.12, --(CR.sup.13 R.sup.14).sub.q SO.sub.2 R.sup.15, --(CR.sup.13 R.sup.14).sub.t (C.sub.3 -C.sub.10 cycloalkyl), --(CR.sup.13 R.sup.14).sub.t (C.sub.6 -C.sub.10 aryl), and --(CR.sup.13 R.sup.14).sub.t (4-10 membered heterocyclic), wherein t is an integer from 0 to 5 and q is an integer from 1 to 5, said cycloalkyl, aryl and heterocyclic R.sup.1 groups are optionally fused to a C.sub.6 -C.sub.10 aryl group, a C.sub.5 -C.sub.8 saturated cyclic group, or a 4-10 membered heterocyclic group; and the foregoing R.sup.1 groups, except H but including any optional fused rings referred to above, are optionally substituted by 1 to 4 R.sup.6 groups;R.sup.2 is halo, cyano, --C(O)OR.sup.15, or a group selected from the substituents provided in the definition of R.sup.12 ;each R.sup.3, R.sup.4, R.sup.5, R.sup.6, and R.sup.7 is independently selected from H, C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.10 alkenyl, halo, cyano, nitro, trifluoromethyl, trifluoromethoxy, azido, --OR.sup.12, --C(O)R.sup.12, --C(O)OR.sup.12, --NR.sup.13 C(O)OR.sup.15, --OC(O)R.sup.12, --NR.sup.13 SO.sub.2 R.sup.15, --SO.sub.2 NR.sup.12 R.sup.13, --NR.sup.13 C(O)R.sup.12, --C(O)NR.sup.12 R.sup.13, --NR.sup.12 R.sup.13, --CH.dbd.NOR.sup.12, --S(O).sub.j R.sup.12 wherein j is an integer from 0 to 2, --(CR.sup.13 R.sup.14).sub.t (C.sub.6 -C.sub.10 aryl), --(CR.sup.13 R.sup.14).sub.t (4-10 membered heterocyclic), --(CR.sup.13 R.sup.14).sub.t (C.sub.3 -C.sub.10 cycloalkyl), and --(CR.sup.13 R.sup.14).sub.t C.ident.CR.sup.16, and wherein in the foregoing R.sup.3, R.sup.4, R.sup.5, R.sup.6, and R.sup.7 groups t is an integer from 0 to 5; the cycloalkyl, aryl and heterocyclic moieties of the foregoing groups are optionally fused to a C.sub.6 -C.sub.10 aryl group, a C.sub.5 -C.sub.8 saturated cyclic group, or a 4-10 membered heterocyclic group; and said alkyl, alkenyl, cycloalkyl, aryl and heterocyclic groups are optionally substituted by 1 to 3 substituents independently selected from halo, cyano, nitro, trifluoromethyl, trifluoromethoxy, azido, --NR.sup.13 SO.sub.2 R.sup.15, --SO.sub.2 NR.sup.12 R.sup.13, --C(O)R.sup.12, --C(O)OR.sup.12, --OC(O)R.sup.12, --NR.sup.13 C(O)OR.sup.15, --NR.sup.13 C(O)R.sup.12, --C(O)NR.sup.12 R.sup.13, --OR.sup.12, --NR.sup.12 R.sup.13, --OR.sup.12, C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.10 alkenyl, C.sub.2 -C.sub.10 alkynyl, --(CR.sup.13 R.sup.14).sub.t (C.sub.6 -C.sub.10 aryl), and --(CR.sup.13 R.sup.14).sub.t (4-10 membered heterocyclic), wherein t is an integer from 0 to 5;R.sup.8 is H, --OR.sup.12, --NR.sup.12 R.sup.12, --NR.sup.12 C(O)R.sup.13, cyano, --C(O)OR.sup.13, --SR.sup.12, --(CR.sup.13 R.sup.14).sub.t (4-10 membered heterocyclic), wherein t is an integer from 0 to 5, or C.sub.1 -C.sub.6 alkyl, wherein said heterocyclic and alkyl moieties are optionally substituted by 1 to 3 R.sup.6 substituents;R.sup.9 is --(CR.sup.13 R.sup.14).sub.t (imidazolyl) wherein t is an integer from 0 to 5 and said imidazolyl moiety is optionally substituted by 1 or 2 R.sup.6 substituents;each R.sup.10 and R.sup.11 is independently selected from the substituents provided in the definition of R.sup.6 ;each R.sup.12 is independently selected from H, C.sub.1 -C.sub.10 alkyl, --(CR.sup.13 R.sup.14).sub.t (C.sub.3 -C.sub.10 cycloalkyl), --(CR.sup.13 R.sup.14).sub.t (C.sub.6 -C.sub.10 aryl), and --(CR.sup.13 R.sup.14).sub.t (4-10 membered heterocyclic), wherein t is an integer from 0 to 5; said cycloalkyl, aryl and heterocyclic R.sup.12 groups are optionally fused to a C.sub.6 -C.sub.10 aryl group, a C.sub.5 14 C.sub.8 saturated cyclic group, or a 4-10 membered heterocyclic group; and the foregoing R.sup.12 substituents, except H, are optionally substituted by 1 to 3 substituents independently selected from halo, cyano, nitro, trifluoromethyl, trifluoromethoxy, azido, --C(O)R.sup.13, --C(O)OR.sup.13, --OC(O)R.sup.13, --NR.sup.13 C(O)R.sup.14, --C(O)NR.sup.13 R.sup.14, --NR.sup.13 R.sup.14, hydroxy, C.sub.1 -C.sub.6 alkyl, and C.sub.1 -C.sub.6 alkoxy;each R.sub.13 and R.sub.14 is independently H or C.sub.1 -C.sub.6 alkyl, and where R.sup.13 and R.sup.14 are as --(CR.sup.13 R.sup.14).sub.q or (CR.sup.13 R.sup.14).sub.t each is independently defined for each iteration of q or t in excess of 1;R.sup.15 is selected from the substituents provided in the definition of R.sup.12 except R.sup.15 is not H;R.sup.16 is selected from the list of substituents provided in the definition of R.sup.12 and --SiR.sup.17 R.sup.18 R.sup.19 ;R.sup.17, R.sup.18 and R.sup.19 are each independently selected from the substituents provided in the definition of R.sup.12 except R.sup.17, R.sup.18 and R.sup.19 are not H; and provided that at least one of R.sup.3, R.sup.4 and R.sup.5 is --(CR.sup.13 R.sup.14).sub.t C.ident.CR.sup.16 wherein t is an integer from 0 to 5 and R.sup.13, R.sup.14, and R.sup.16 are as defined above, in combination with an anti-tumor agent selected from the group consisting of mitotic inhibitors, alkylating agents, anti-metabolites, intercalating antibiotics, growth factor inhibitors, cell cycle inhibitors, enzymes, topoisomerase inhibitors, biological response modifiers, anti-hormones, and anti-androgens.