Novel pyrrolodihydroisoquinolines useful in the treatment of cancer

A compound of formula I

• in which
• R1 is halogen, nitro, amino, mono- or di-1-4C-alkylamino, 1-4C-alkyl, hydroxyl, 1-4C-alkoxy, 1-4C-alkoxy-2-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy, or completely or predominantly fluorine-substituted 1-4C-alkoxy,
• R2 is hydrogen, halogen or 1-4C-alkoxy, and
• R3 is hydrogen or 1-4C-alkoxy, or
• R2 and R3 bound to the benzo ring moiety in ortho-position to each other together form a 1-2C-alkylenedioxy bridge, or
• R2 and R3 bound to the benzo ring moiety in ortho-position to each other together form a completely or predominantly fluorine-substituted 1-2C-alkylenedioxy bridge, or
• R1 and R2 bound to the benzo ring moiety in ortho-position to each other together form a 1-2C-alkylenedioxy bridge and R3 is hydrogen, or
• R1 and R2 bound to the benzo ring moiety in ortho-position to each other together form a completely or predominantly fluorine-substituted 1-2C-alkylenedioxy bridge and R3 is hydrogen,
• R4 is hydrogen, fluorine, chlorine, 1-4C-alkyl, trifluoromethyl, cyclopropyl, cyano, 1-4C-alkoxycarbonyl or —CH2—O—R411, in which
• R411 is hydrogen, 1-4C-alkyl, 1-4C-alkoxy-2-4-alkyl or 1-4C-alkylcarbonyl,
• R41 is hydrogen or 1-4C-alkyl,
• R5 is hydrogen, and
• R51 is hydrogen,
• or
• R4 is hydrogen, fluorine, chlorine or 1-4C-alkyl,
• R41 is hydrogen or 1-4C-alkyl,
• R5 is hydrogen, and
• R51 is hydrogen,
• R6 is 1-6C-alkyl, amino, formyl, or 1-4C-alkyl substituted by R61, in which
• R61 is 1-4C-alkoxycarbonyl, carboxyl, 1-4C-alkoxy, hydroxyl, halogen or —N(R611)R612, in which
• R611 is hydrogen, 1-4C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkyl-1-4C-alkyl, and
• R612 is hydrogen or 1-4C-alkyl, or
• R611 and R612 together and with inclusion of the nitrogen atom to which they are bound form a radical Het1, in
• which
• Het1 is a 5- to 7-membered saturated heterocyclic ring radical comprising one nitrogen atom, to which R611 and R612 are bound, and, optionally, one further heteroatom selected from the group consisting of nitrogen, oxygen and sulfur, and optionally substituted by R613 on a ring nitrogen atom, in which
• R613 is 1-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-1-4C-alkyl, hydroxy-2-4C-alkyl, 1-4C-alkoxy-2-4C-alkyl, amino-2-4C-alkyl, mono- or di-1-4C-alkylamino-2-4C-alkyl, formyl, pyridyl or pyrimidinyl,
• R7 is phenyl, Het2, R71- and/or R72- and/or R73-substituted phenyl, R74- and/or R75-substituted Het2, naphthyl, or R76- and/or R77-substituted naphthyl, in which
• Het2 is a monocyclic or fused bicyclic 5 to 10-membered heteroaryl radical comprising one to three heteroatoms, each of which is selected from the group consisting of nitrogen, oxygen and sulfur,
• R71 is hydroxyl, halogen, nitro, cyano, trifluoromethyl, 1-4C-alkyl, 1-4C-alkoxy, amino, mono- or di-1-4C-alkylamino, 1-4C-alkylsulphonylamino, arylsulphonylamino, 1-4C-alkoxycarbonyl, carboxyl, 1-4C-alkylthio, aryloxy-2-4C-alkoxy, aryloxy-1-4C-alkyl, aryloxy, aryl-1-4C-alkoxy, aryl, 1-4C-alkoxy-2-4C-alkoxy, 1-4C-alkoxy-1-4C-alkyl, hydroxy-2-4C-alkoxy, amino-2-4C-alkoxy, mono- or di-1-4C-alkylamino-2-4C-alkoxy, or completely or predominantly fluorine-substituted 1-4C-alkoxy, in which
• aryl is phenyl or R711-substituted phenyl, in which
• R711 is halogen, 1-4C-alkyl, 1-4C-alkoxy, nitro or cyano,
• R72 is halogen, 1-4C-alkyl, 1-4C-alkoxy or 1-4C-alkoxycarbonyl,
• R73 is 1-4C-alkyl or 1-4C-alkoxy,
• R74 is halogen, 1-4C-alkyl, trifluoromethyl, 1-4C-alkoxy, cyano, amino, mono- or di-1-4C-alkylamino, 1-4C-alkoxycarbonyl, morpholino, carboxyl, nitro, phenyl or phenyloxy,
• R75 is 1-4C-alkyl or halogen,
• R76 is halogen, hydroxyl, 1-4C-alkyl, 1-4C-alkoxy, carboxyl or 1-4C-alkoxycarbonyl,
• R77 is 1-4C-alkyl or 1-4C-alkoxy,
• R8 is phenyl, phenylcarbonyl, —C(O)—N(R82)R83 or —C(O)—OR9, in which
• R82 is hydrogen, 1-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-1-4C-alkyl, phenyl or phenyl-1-4C-alkyl, and
• R83 is hydrogen or 1-4C-alkyl, or
• R82 and R83 together and with inclusion of the nitrogen atom, to which they are bound, form a heterocyclic ring radical selected from the group consisting of pyrrolidinyl, piperidinyl, morpholinyl and N-(1-4C-alkyl)-piperazinyl,
• R9 is 1-4C-alkyl,
• or a salt, stereoisomer, hydrate or hydrate of a salt thereof;
• under the proviso that this subgroup of compounds of formula I, wherein the combination of all of the following restrictions a.) to c.) apply, is thereof disclaimed:
• a.) the substitution pattern of the left R1- and/or R2- and/or R3-substituted benzo ring of the dihydroisoquinoline moiety of the pyrrolodihydroisoquinoline scaffold shown in formula I is as follows:
• in which
• R′ and R″ can be bonded at any possible position of the benzo ring, and
• R′ is hydroxyl, 1-4C-alkoxy or trifluoromethoxy,
• R″ is hydrogen or 1-4C-alkoxy,
• or R′ and R″ bound to the benzo ring moiety in ortho-position to each other together form a 1-2C-alkylenedioxy bridge,
• and
• b.) R4 is hydrogen, and
• R41 is hydrogen, and
• R5 is hydrogen, and
• R51 is hydrogen,
• and
• c.) R8 is —C(O)—OR9, in which
• R9 is 1-4C-alkyl.