Title of Invention

PYRROLODIHYDROISOQUINOLINES AS PDE10 INHIBITORS

Abstract The invention relates to novel pyrrolodihydroisoquinoline derivatives, which are efficatious inhibitors of PDE 10.
Full Text FORM 2
THE PATENT ACT 197 0
(39 of 1970)
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See Section 10, and rule 13)
TITLE OF INVENTION
PYRROLODIHYDROISOQUINOLINES AS PDE10 INHIBITORS

APPLICANT(S)
a) Name
b) Nationality
c) Address

ALTANA PHARMA AG
GERMAN Company
BYK-GULDEN-STRASSE 2,
7 8467 KONSTANZ,
GERMANY



PREAMBLE TO THE DESCRIPTION

GRANTED

The following specification particularly describes the invention and the manner in which it is to be performed : -


27-3-2008
27 MAR 2008

Field of application of the invention
The invention relates to novel pyrrolodihydroisoquinoline derivatives, which are used in the pharmaceutical industry for the production of pharmaceutical compositions. Prior Art
The International applications WO 02/48144, WO 03/014115, WO 03/014116, WO 03/014117 and WO 03/051877 disclose pyrrolodihydroisoquinoline derivatives with PDE10 inhibitory activity. The European application EP 1250923 discloses the use of selective PDE10 inhibitors in general, and papaverine in particular, for the treatment of certain neurologic and psychiatric disorders. Said European application is incorporated by reference into the specification of the present invention in its entirety for all purposes.
Additionally, the US application US 2003/0008806 likewise disclose the use of selective PDE10 inhibitors in general, and papaverine in particular, for the treatment of certain neurologic and psychiatric disorders; said US application is incorporated by reference into the specification of the present invention in its entirety for all purposes.
Yet additionally, the US application US 2003/0018047 also disclose the use of selective PDE10 inhibitors in general, and papaverine in particular, for the treatment of certain neurologic and psychiatric disorders; said US application is incorporated by reference into the specification of the present invention in its entirety for all purposes.
The US patent US 5965575 discloses pyrrolodihydroisoquinoline derivatives as 5HTIB antagonists. The International application WO 03/000269 disclose the use of PDEIOA inhibitors for the treatment of neurodegenerative diseases, especially Parkinson"s disease. Description of the invention
It has now been found that the pyrroloisoquinoline derivatives, which are described in greater details below, differ from prior art compounds by unanticipated, sophisticated, originative and effect-constitutive structural features and have surprising and particularly advantageous properties. The invention thus relates to compounds of formula I
R1 R4 R41
R8"
(I) in which Rl is halogen, nitro, amino, mono- or di-l-4C-alkylamino, l-4C-alkyl, hydroxyl, l-4C-alkoxy, 1-4C-
alkoxy-2-4C-a!koxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmerhoxy, or completely or
predominantly fluorine-substituted l-4C-alkoxy, R2 is hydrogen, halogen or l-4C-alkoxy, and R3 is hydrogen or l-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 l-2C-alkylenedioxy bridge, or Rl 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 Rl and R2 bound to the benzo ring moiety in ortho-position to each other together form a completely
or predominantly fluorine-substituted l-2C-alkylenedioxy bridge and R3 is hydrogen, R4 is hydrogen, fluorine, chlorine, l-4C-alkyl, trifluoromethyl, cyclopropyl, cyano, 1-4C-
alkoxycarbonyl or -CH2-O-R4II, in which R411 is hydrogen, l-4C-alkyl, l-4C-alkoxy-2-4-alkyl or l-4C-alkylcarbonyl, R41 is hydrogen or l-4C-alkyl, R5 is hydrogen, fluorine or l-4C-alkyl, and R51 is hydrogen or l-4C-alkyl, or
R4 is hydrogen, fluorine, chlorine or l-4C-alkyl, R41 is hydrogen or l-4C-alkyl, R5 is hydrogen, fluorine, l-4C-alkyl, trifluoromethyl, cyclopropyl, cyano, l-4C-alkoxycarbonyl or
-CH2-0-R511, in which R511 is hydrogen, l-4C-alkyl, l-4C-alkoxy-2-4-alkyl or l-4C-alkykarbonyl, and R51 is hydrogen or l-4C-alkyl, or
R4 and R5 together form a l-4C-alkylene bridge and R41 and R51 are both hydrogen, R6 is l-6C-alkyl, amino, formyl, or l-4C-alkyl substituted by R61, in which R61 is l-4C-alkoxycarbonyl, carboxyl, l-4C-alkoxy, hydroxyl, halogen or -N(R611)R612, in which R611 is hydrogen, l-4C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloaIkyl-l-4C-alkyl, and R612 is hydrogen or l-4C-alkyl, or R611 and R612 together and with inclusion of the nitrogen atom to which they are bound form a
radical Hetl, in which Hetl 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 a group consisting of nitrogen, oxygen and sulfur, and optionally substituted by R613 on a ring nitrogen atom, in which R613 is l-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-l-4C-alkyl, hydroxy-2-4C-alkyl, l-4C-alkoxy-2-
4C-alkyl, amino-2-4C-alkyl, mono- or di-l-4C-alkylammo-2-4C-aIkyl, 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 either
a monocyclic or fused bicyclic 5- to 10-membered heteroaryl radical comprising one to three
heteroatoms, each of which is selected from a group consisting of nitrogen, oxygen and sulfur,
or
a fused bicyclic 9- or 10-membered, partially saturated heterocyclic ring radical containing a
benzene ring and comprising one or two heteroatoms, each of which is selected from a group
consisting of nitrogen, oxygen and sulfur,
or
N-oxy-pyridyl,
R71 is hydroxyl, halogen, nitro, cyano, trifluoromethyl, l-4C-alkyl, l-4C-alkoxy, amino, mono- or di-l-4C-alkylamino, l-4C-alkylsulphonylamino, arylsulphonylamino, l-4C-a!koxycarbonyl, carboxyl, l-4C-alkylthio, aryloxy-2-4C-alkoxy, aryloxy-l-4C-alkyl, aryloxy, aryl-l-4C-alkoxy, aryl, l-4C-alkoxy-2-4C-alkoxy, l-4C-alkoxy-l-4C-alkyl, hydroxy-2-4C-alkoxy, amino-2-4C-alkoxy, mono- or di-l-4C-alkylamino-2-4C-alkoxy, completely or predominantly fluorine-substituted l-4C-alkoxy, mono- or di-l-4C-alkylaminocarbonyl, carbamoyl, tetrazolyl, or -N(H)S(0)2-N(R712)R713, in which
aryl is phenyl or R711-substituted phenyl, in which
R711 is halogen, l-4C-alkyl, l-4C-alkoxy, nitro or cyano,
R712 is l-4C-alkyl,
R713 is l-4C-alkyl, or
R712 and R713 together and with inclusion of the nitrogen atom to which they are bound form a radical Het3, in which
Het3 is pyrrolidin-1-yl, piperidin-1-yl or morpholin-4-yI,
R72 is halogen, l-4C-alkyl, 14C-alkoxy or l-4C-alkoxycarbonyl,
R73 is l-4C-alkyl or l-4C-alkoxy,
R74 is halogen, l-4C-alkyl, trifluoromethyl, l-4C-alkoxy, cyano, amino, mono- or di-l-4C-alkylamino, l-4C-alkoxycarbonyl, morpholino, carboxyl, nitro, phenyl, phenyloxy, phenyl-1-4C-alkyl, arylsulphonyl, l-4C-alkylsulphonyl, or -S(0)2-N(R712)R713,
R75 is l-4C-alkyl or halogen,
R76 is halogen, hydroxyl, l-4C-alkyl, l-4C-alkoxy, carboxyl or l-4C-alkoxycarbonyl,
R77 is l-4C-alkyl or l^C-alkoxy,
R8 is l-4C-alkyl, phenyl, 2-4C-alkinyl, cyano, -CH2-O-R8I, phenylcarbonyl, -C(0)-N(R82)R83 or -C(0)-OR9, in which
R81 is hydrogen, l-4C-alkyl, l-4C-alkoxy-2-4-alkyl or l-4C-alkylcarbonyl,
R82 is hydrogen, l-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-l-4C-alkyl, phenyl or phenyl-l-4C-alkyl, and
R83 is hydrogen or l-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
or N-(l-4C-alkyl)-piperazinyl,
R9 is hydrogen or l-4C-alkyl;
under the first provisio, 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 Rl- and/or R2- and/or R3-substituted benzo ring of the
dihydroisoquinoline moiety of the pyrrolodihydroisoquinoline scaffold shown in formula I is as
follows:

R"
in which
R" and R" can be bonded at any possible position of the benzo ring, and
R" is hydroxyl, l-4C-alkoxy or trifluoromethoxy,
R" is hydrogen or l-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(0)-OR9, in which
R9 is l-4C-alkyI; and under the second provisio, that, when R5and R51 are both hydrogen, then
R8 is other than phenyl, phenykarbonyl, -C(0)-N(R82) R83 or -C(0)-OR9, in which R82 is hydrogen, l-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-l-4C-alkyl, phenyl or phenyl-l-4C-
alkyl, R83 is hydrogen or l-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 or N-(l-4C-alkyl)-piperazinyl, and R9 is l-4C-alkyl;

and to the salts, stereoisomers, hydrates and hydrates of the salts of these compounds.
Compounds according to the present invention more worthy to be mentioned are those compounds
of formula I,
in which
Rl is hydroxyl, l-4C-alkoxy, l-4C-alkoxy-2-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy,
or completely or predominantly fluorine-substituted l-4C-alkoxy, R2 is hydrogen, halogen or l-4C-alkoxy, and R3 is l-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 l-2C-alkylenedioxy bridge, or Rl 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 Rl and R2 bound to the benzo ring moiety in ortho-position to each other together form a completely
or predominantly fluorine-substituted l-2C-alkylenedioxy bridge and R3 is hydrogen, and none of Rl, R2 and R3 is bound to the 10-position of the pyrrolo[2.1-a]isoquinoline ring, R4 is hydrogen or l-4C-alkyl, R41 is hydrogen or l-4C-alkyl,
R5 is hydrogen, l-4C-alkyl, cyano or l-4C-alkoxycarbonyl, and R51 is hydrogen or l-4C-alkyl, or
R4 and R5 together form a l-4C-alkylene bridge and R41 and R51 are both hydrogen, R6 is l-6C-alkyl, or l-4C-alkyl substituted by R61, in which R61 is l-4C-alkoxycarbonyI or -N(R611)R612, in which R611 is l-4C-alkyl, and R612 is l-4C-alkyl, or R611 and R612 together and with inclusion of the nitrogen atom to which they are bound form a
radical Hetl, in which Hetl is pyrrolidin-1-yl, piperidin-1-yl, morpholin-1-yl, or N-(l-4C-alkyl)-piperazinyl, R7 is Het2, R71- and/or R72- and/or R73-substituted phenyl, R74-substituted Het2, or naphthyl,
in which Het2 is either
a monocyclic or fused bicyclic 5- to 10-membered heteroaryl radical comprising one to three
heteroatoms, each of which is selected from a group consisting of nitrogen, oxygen and sulfur,
or

a fused bicyclic 9- or 10-membered, partially saturated heterocyclic ring radical containing a
benzene ring and comprising one or two heteroatoms, each of which is selected from a group
consisting of nitrogen, oxygen and sulfur,
or
N-oxy-pyridyl,
R71 is hydroxyl, halogen, rutro, cyano, trifluoromethyl, l-4C-alkyl, l-4C-alkoxy, amino, mono- or dI-4C-alkylamino, l-4C-alkylsulphonylamino, l-4C-alkoxycarbonyl, carboxyl, aryloxy, completely or predominantly fluorine-substituted l-4C-alkoxy, mono- or di-l-4C-alkylaminocarbonyl, carbamoyl, tetrazolyl, or -N(H)S(0)2-N(R712)R713, in which
aryl is phenyl or R711-substituted phenyl, in which
R711 is halogen or l-4C-alkyl,
R712 is l-4C-alkyl, and
R713 is l-4C-alkyl, or
R712 and R713 together and with inclusion of the nitrogen atom to which they are bound form a radical Het3, in which
Het3 is pyrrolidin-1-yl, piperidin-1-yl or morpholin-4-yl,
R72 is halogen, l-4C-alkyl or l-4C-alkoxy,
R73 is l-4C-alkyl or l-4C-alkoxy,
R74 is l-4C-alkyl, phenyl-1-4C-alkyl, arylsulphonyl, l-4C-alky!sulphonyI, or -S(0)2-N(R712)R713,
R8 is l-4C-alkyl, cyano, or -C(0)-OR9, in which
R9 is hydrogen or l-4C-alkyl;
under the first provisio, 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 Rl- and/or R2- and/or R3-substituted benzo ring of the dihydroisoquinoline moiety of the pyrrolodihydroisoquinoline scaffold shown in formula I is as follows:

R"
R" in which
R" and R" can be bonded at any possible position of the benzo ring, except the 10-position, and R" is hydroxyl, l-4C-alkoxy or trifluoromethoxy, R" is hydrogen or l-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(0)-OR9, in which
R9 is l-4C-alkyl; and under the second provisio, that, when R5and R51 are both hydrogen, then R8 is other than -C(0)-OR9, in which R9 is l-4C-alkyl;
and the salts, stereoisomers, hydrates and hydrates of the salts of these compounds. Compounds according to the present invention further more worthy to be mentioned are those compounds of formula I, in which
Rl is bound to the 8-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-4C-alkoxy, R2 is bound to the 7-position of the pyrrolo[2.1-a]isoquinoline ring, and is hydrogen, halogen or 1-
4C-alkoxy, R3 is bound to the 9-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-4C-alkoxy, R4 is hydrogen, R41 is hydrogen,
R5 is hydrogen, l-4C-alkyl, cyano or l-4C-alkoxycarbonyl, and R51 is hydrogen or l-4C-alkyl, or
R4 and R5 together form a 3-4C-alkylene bridge and R41 and R51 are both hydrogen, R6 is l-4C-alkyl, or l-4C-alkyl substituted by R61, in which R61 is l-4C-alkoxycarbonyl or -N(R611)R612, in which R611 and R612 together and with inclusion of the nitrogen atom to which they are bound form a
radical Hetl, in which Hetl is morpholin-1-yl, R7 is Het2, R71- and/ or R72- and/or R73-substituted phenyl, R74-substituted Het2, or naphthyl,
in which Het2 is either
a monocyclic or fused bicyclic 5- to 10-membered heteroaryl radical comprising one to three
heteroatoms, each of which is selected from a group consisting of nitrogen, oxygen and sulfur,
or

a fused bicyclic 9- or 10-membered, partially saturated heterocyclic ring radical containing a
benzene ring and comprising one or two heteroatoms, each of which is selected from a group
consisting of nitrogen, oxygen and sulfur,
or
N-oxy-pyridyl, R71 is hydroxyl, halogen, nitro, l-4C-alkyl, 1-4C-alkoxy, amino, mono- or di-l-4C-alkylamino, 1-4C-
alkylsulphonylamino, carboxyl, aryloxy, mono- or di-l-4C-alkylaminocarbonyl, carbamoyl,
tetrazolyl, or -N(H)S(0)2-N(R712)R713, in which aryl is phenyl or R711-substituted phenyl, in which R711 is halogen or l-4C-alkyl, R712 is l-4C-alkyl, and R713 is l-4C-alkyl, or R712 and R713 together and with inclusion of the nitrogen atom to which they are bound form a
radical Het3, in which Het3 is morpholin-4-yl, R72 is halogen, l-4C-alkyl or l-4C-alkoxy, R73 is l-4C-alkyl or l-4C-alkoxy,
R74 is l-4C-alkyl, phenyl-l-4C-alkyl, arylsulphonyl, l-4C-alkylsulphonyl, or -S(0)2-N(R712)R713, R8 is l-4C-alkyl, cyano, or -C(0)-OR9, in which R9 is hydrogen or l-4C-alkyl;
under the first provisio, 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 Rl- and/or R2- and/or R3-substituted benzo ring of the dihydroisoquinoline moiety of the pyrrolodihydroisoquinoline scaffold shown in formula I is as follows:
R"

in which
R" is l-4C-alkoxy, and
R" is l-4C-alkoxy,
and
b.) R4 is hydrogen, and R41 is hydrogen, and R5 is hydrogen, and R51 is hydrogen,
and

c.) R8 is -C(0)-0R9, in which
R9 is l-4C-alkyl; and under the second provisio, that, when R5and R51 are both hydrogen, then R8 is other than -C(0)-OR9, in which R9 is l-4C-alkyl;
and the salts, stereoisomers, hydrates and hydrates of the salts of these compounds. Compounds according to the present invention in particular worthy to be mentioned are those compounds of formula I, in which
either, in a first independent embodiment,
Rl is bound to the 8-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy, R2 is bound to the 7-position of the pyrrolo[2.1-a]isoquinoline ring, and is hydrogen, chlorine or
fluorine, R3 is bound to the 9-position of the pyrroIo[2.1-a]isoquinoline ring, and is l-2C-alkoxy, R4 is hydrogen, R41 is hydrogen,
R5 is hydrogen, l-2C-alkyl or cyano, and R51 is hydrogen, or
R4 and R5 together form a tetramethylene bridge and R41 and R51 are both hydrogen, R6 is l-2C-alkyl, or l-2C-alkyl substituted by R61, in which R61 is l-2C-alkoxycarbonyl or -N(R611)R612, in which R611 and R612 together and with inclusion of the nitrogen atom to which they are bound form a
radical Hetl, in which Hetl is morpholin-1-yl, R7 is naphthyl, 4-hydroxy-3,5-dimethylphenyl, 4-methoxy-3,5-dimethylphenyl, 4-carboxy-phenyl,
4-carbamoyl-phenyl, 2-methyl-4-hydroxy-phenyI, 4-amino-phenyl, 4-(2H-tetrazol-5-yl)-phenyl,
4-mopholino-sulphonylamino-phenyl, 4-methylsulphonylamino-phenyl, or 2-fluoro-3,4-
dimethoxy-phenyl,
pyridyl, indolyl, quinolinyl, indolinyl,
2-methyl-pyridin-4-yl, 3-methyl-pyridin-4-yl, or
N-(R74)-Het2, in which
Het2 is pyrrolyl or indolyl,
R74 is arylsulphonyl, l-2C-alkylsulphonyl, or -S(0)2-N(R712)R713, in which
aryl is phenyl, or R711-substituted phenyl, in which
R711 is l-2C-alkyl,
R712 is l-2C-alkyl,


R713 is l-2C-alkyl, or
R712 and R713 together and with inclusion of the nitrogen atom to which they are bound form a
radical Het3, in which Het3 is morpholin-4-yl, and R8 is cyano;
or, in a second independent embodiment,
Rl is bound to the 8-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy, R2 is bound to the 7-position of the pyrrolo[2.1-a]isoquinoline ring, and is hydrogen, chlorine or
fluorine, R3 is bound to the 9-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy, R4 is hydrogen, R41 is hydrogen, R5 is l-2C-alkyl or cyano, R51 is hydrogen, or
R4 and R5 together form a tetramethylene bridge and R41 and R51 are both hydrogen, R6 is l-2C-a!kyl, or l-2C-alkyl substituted by R61, in which R61 is l-2C-alkoxycarbonyl or -N(R611)R612, in which R611 and R612 together and with inclusion of the nitrogen atom to which they are bound form a
radical Hetl, in which Hetl is morpholin-1-yl, R7 is naphthyl, 4-hydroxy-3,5-dimethylphenyl, 4-methoxy-3,5-dimethylphenyl, 4-carboxy-phenyl,
4-carbamoyl-phenyl, 2-methyl-4-hydroxy-phenyI, 4-amino-phenyl, 4-(2H-tetrazol-5-yl)-phenyl,
4-mopholino-sulphonylamino-phenyl, 4-methylsulphonylamino-phenyl, or 2-fluoro-3,4-
dimethoxy-phenyl,
pyridyl, indolyl, quinolinyl, indolinyl,
2-methyl-pyridin-4-yl, 3-methyl-pyridin-4-yl, or
N-(R74)-Het2, in which Het2 is pyrrolyl or indolyl,
R74 is arylsulphonyl, l-2C-a!kylsulphonyl, or -S(0)2-N(R712)R713, in which aryl is phenyl, or R711-substituted phenyl, in which R711 is l-2C-alkyl, R712 is l-2C-alkyl, and R713 is l-2C-alkyl, or R712 and R713 together and with inclusion of the nitrogen atom to which they are bound form a
radical Het3, in which
Het3 is morpholin-4-yl, and
R8 is -C(0)-OR9, in which


R9 is l-2C-alkyl;
and the salts, stereoisomers, hydrates and hydrates of the salts of these compounds.
Compounds according to the present invention in further particular worthy to be mentioned are
those compounds of formula I,
in which
either, in a first independent embodiment,
Rl is bound to the 8-position of the pyrrolo[2.1-a]isoquinoline ring, and is methoxy,
R2 is bound to the 7-position of the pyrrolo[2.1-a]isoquinoline ring, and is hydrogen or fluorine,
R3 is bound to the 9-position of the pyrrolo[2.1-a]isoquinoline ring, and is methoxy,
R4 is hydrogen,
R41 is hydrogen,
R5 is hydrogen, methyl or cyano,
R51 is hydrogen,
R6 is methyl or 2-methoxycarbonylethyl,
R7 is 4-hydroxy-3,5-dimethylphenyl, 4-methoxy-3,5-dimethylphenyl, 4-carboxy-phenyl, 2-methyl-
4-hydroxy-phenyl, 4-amino-phenyl, 4-(2H-tetrazol-5-yl)-phenyl, 4-mopholino-sulphonylamino-
phenyl, 4-methylsulphonylamino-phenyl,
pyridyl, quinolinyl,
2-methyl-pyridin-4-yl, 3-methyl-pyridin-4-yl,
l-torylsulphonyl-pyrrol-3-yl, l-tolylsulphonyl-indol-3-yl, l-phenylsulphonyl-indol-3-yl, 1-
methylsulphonyl-indol-3-yl, l-dimethyIaminosulphonyl-indol-3-yl, or 1-morpholinosulphonyl-
indol-3-yl, and R8 is cyano;
or, in a second independent embodiment,
Rl is bound to the 8-position of the pyrrolo[2.1-a]isoquinoline ring, and is methoxy, R2 is bound to the 7-position of the pyrrolo[2.1-a]isoquinoline ring, and is hydrogen or fluorine, R3 is bound to the 9-position of the pyrrolo[2.1-a]isoquinoline ring, and is methoxy, R4 is hydrogen, R41 is hydrogen, R5 is methyl or cyano, R51 is hydrogen,
R6 is methyl or 2-methoxycarbonylethyl, R7 is 4-hydroxy-3,5-dimethylphenyl, 4-methoxy-3,5-dimethylphenyl, 4-carboxy-phenyl, 2-methyl-
4-hydroxy-phenyl, 4-amino-phenyl, 4-(2H-tetrazol-5-yl)-phenyl, 4-mopholino-sulphonylamino-
phenyl, 4-methylsulphonylamino-phenyl,
pyridyl, quinolinyl,
2-methyl-pyridin-4-yl, 3-methyl-pyridin-4-yl,

l-tolylsulphonyl-pyrroI-3-yl, l-toIylsulphonyI-indol-3-yl, l-phenylsulphonyl-indol-3-yl, 1-
methyIsulphonyl-indol-3-yl, l-dimethylaminosulphonyl-indol-3-yl, or 1-morpholinosulphonyl-
indol~3-yl, and R8 is -C(0)-OR9, in which R9 is ethyl;
and the salts, stereoisomers, hydrates and hydrates of the salts of these compounds. An interesting embodiment of the compounds according to the present invention refers to those compounds of formula I, in which Rl is bound to the 8-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy, such as e.g.
methoxy, R2 is bound to the 7-position of the pyrrolo[2.1-a]isoquinoline ring, and is chlorine or fluorine, R3 is bound to the 9-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy, such as e.g.
methoxy, and
R4 is hydrogen, R41 is hydrogen, R5 is l-2C-alkyl or cyano, R51 is hydrogen, and
R8 is -C(0)-OR9, in which R9 is l-2C-alkyl.
A more interesting embodiment of the compounds according to the present invention refers to those compounds of formula I, in which Rl is bound to the 8-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy, such as e.g.
methoxy, R2 is bound to the 7-position of the pyrrolo[2.1-a]isoquinoline ring, and is hydrogen, chlorine or
fluorine, R3 is bound to the 9-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy, such as e.g.
methoxy,
and
R4 is hydrogen,
R41 is hydrogen,
R5 is l-2C-alkyl or cyano,
R51 is hydrogen,
and
R8 is cyano.


Another more interesting embodiment of the compounds according to the present invention refers to
those compounds of formula I,
in which
Rl is bound to the 8-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy, such as e.g.
methoxy, R2 is bound to the 7-position of the pyrrolo[2.1-a]isoquinoline ring, and is chlorine or fluorine, R3 is bound to the 9-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy, such as e.g.
methoxy, and
R4 is hydrogen, R41 is hydrogen,
R5 is hydrogen, l-2C-alkyl or cyano, R51 is hydrogen, and
R8 is cyano.
Another more interesting embodiment of the compounds according to the present invention refers to those compounds of formula I, in which Rl is bound to the 8-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy, such as e.g.
methoxy, R2 is bound to the 7-position of the pyrrolo[2.1-a]isoquinoline ring, and is chlorine or fluorine, R3 is bound to the 9-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy, such as e.g.
methoxy, and
R4 is hydrogen, R41 is hydrogen, R5 is l-2C-alkyl or cyano, R51 is hydrogen, and
R8 is cyano.
A particular interesting embodiment of the compounds according to the present invention refers to those compounds of formula I, in which Rl is bound to the 8-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy, such as e.g.
methoxy, R2 is bound to the 7-position of the pyrrolo[2.1-a]isoquinoline ring, and is fluorine, R3 is bound to the 9-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy, such as e.g.
methoxy,


and
R4 is hydrogen,
R41 is hydrogen,
R5 is l-2C-alkyl or cyano, in particular methyl,
R51 is hydrogen,
and
R8 is cyano.
A variant (variant 1) of the present invention refers to those compounds of formula I, in which
Rl is halogen, nitro, amino, mono- or di-l-4C-alkylamino, l-4C-alkyl, hydroxyl, l-4C-alkoxy, 1-4C-
alkoxy-2-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy, or completely or
predominantly fluorine-substituted l-4C-alkoxy, R2 is hydrogen, halogen or l-4C-alkoxy, R3 is hydrogen or l-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 l-2C-alkylenedioxy bridge, or Rl 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 Rl and R2 bound to the benzo ring moiety in ortho-position to each other together form a completely
or predominantly fluorine-substituted l-2C-alkylenedioxy bridge and R3 is hydrogen, R4 is hydrogen, fluorine, chlorine, l-4C-alkyl, trifluoromethyl, cyclopropyl, cyano, 1-4C-
alkoxycarbonyl or -CH2-0-R411, in which R411 is hydrogen, l-4C-alkyl, l-4C-alkoxy-2-4-alkyl or l-4C-alkylcarbonyl, R41 is hydrogen or l-4C-alkyl, R5 is hydrogen, fluorine or l-4C-alkyl, R51 is hydrogen or l-4C-alkyl, or
R4 is hydrogen, fluorine, chlorine or l-4C-alkyl, R41 is hydrogen or l-4C-alkyl, R5 is hydrogen, fluorine, l-4C-alkyl, trifluoromethyl, cyclopropyl, cyano, l-4C-alkoxycarbonyl or
-CH2-0-R511, in which
R511 is hydrogen, l-4C-alkyl, l-4C-alkoxy-2-4-alkyl or l-4C-alkylcarbonyl,
R51 is hydrogen or l-4C-alkyl,
or
R4 and R5 together form a l-4C-alkylene bridge and R41 and R51 are both hydrogen,
R6 is l-6C-alkyl, amino, formyl, or l-4C-alkyl substituted by R61, in which
R61 is l-4C-alkoxycarbonyl, carboxyl, l-4C-alkoxy, hydroxyl, halogen or -N(R611)R612, in which


R611 is hydrogen, l-4C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkyl-l-4C-alkyl,
R612 is hydrogen or l-4C-alkyl, or
R611 and R612 together and with inclusion of the nitrogen atom to which they are bound form a radical Hetl, in which
Hetl 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 a group
consisting of nitrogen, oxygen and sulfur, and optionally substituted by R613 on a ring nitrogen atom,
in which
R613 is l-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-l-4C-alkyl, hydroxy-2-4C-alkyl, l-4C-alkoxy-2-4C-alkyl, amino-2-4C-alkyl, mono- or di-l-4C-alkylamino-2-4C-alkyl, formyl, pyridyl or pyrimidinyl,
R7 is phenyl, Het2, R71- and/or R72- and/or R73-substiruted 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 a group consisting of nitrogen, oxygen and sulfur,
R71 is hydroxyl, halogen, nitro, cyano, trifluoromethyl, l-4C-alkyl, l-4C-alkoxy, amino, mono- or di-l-4C-alkylamino, l-4C-alkylsulphonylamino, arylsulphonylamino, l-4C-alkoxycarbonyl, carboxyl, l-4C-alkylthio, aryloxy-2-4C-alkoxy, aryloxy-l-4C-alkyl, aryloxy, aryl-l-4C-alkoxy, aryl, l-4C-alkoxy-2-4C-alkoxy, l-4C-alkoxy-l-4C-alkyl, hydroxy-2-4C-alkoxy, amino-2-4C-alkoxy, mono- or di-l-4C-alkylamino-2-4C-alkoxy, or completely or predominantly fluorine-substituted l-4C-alkoxy, in which
aryl is phenyl or R711-substituted phenyl, in which
R711 is halogen, l-4C-alkyl, l-4C-alkoxy, nitro or cyano,
R72 is halogen, l-4C-alkyl, l-4C-alkoxy or l-4C-alkoxycarbonyl,
R73 is l-4C-alkyl or l-4C-alkoxy,
R74 is halogen, l-4C-alkyl, trifluoromethyl, l-4C-a!koxy, cyano, amino, mono- or di-l-4C-alkylamino, l-4C-alkoxycarbonyl, morpholino, carboxyl, nitro, phenyl or phenyloxy,
R75 is l-4C-alkyl or halogen,
R76 is halogen, hydroxyl, l-4C-alkyl, l-4C-alkoxy, carboxyl or l-4C-alkoxycarbonyl,
R77 is l-4C-alkyl or l-4C-alkoxy,
R8 is l-4C-alkyl, phenyl, 2-4C-alkinyl, cyano, -CH2-O-R8I, phenylcarbonyl, -C(0)-N(R82)R83 or -C(0)-OR9, in which
R81 is hydrogen, l-4C-alkyl, l-4C-alkoxy-2-4-alkyl or l-4C-alkylcarbonyl,
R82 is hydrogen, l-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-l-4C-alkyl, phenyl or phenyl-l-4C-alkyl,
R83 is hydrogen or l-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
or N-(l-4C-alkyl)-piperazinyl,
R9 is hydrogen or l-4C-alkyl;
under the first provisio, 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 Rl- and/or R2- and/or R3-substituted benzo ring of the
dihydroisoquinoline moiety of the pyrrolodihydroisoquinoline scaffold shown in formula I is as
follows:

R"
in which
R" and R" can be bonded at any possible position of the benzo ring, and
R" is hydroxyl, l-4C-alkoxy or trifluoromethoxy,
R" is hydrogen or l-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(0)-OR9, in which
R9 is l-4C-alkyl; and under the second provisio, that, when R5and R51 are both hydrogen, then
R8 is other than phenyl, phenylcarbonyl, -C(0)-N(R82)R83 or -C(0)-OR9, in which R82 is hydrogen, l-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-l-4C-alkyl, phenyl or phenyl-l-4C-
alkyl, R83 is hydrogen or l-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 or N-(l-4C-alkyl)-piperazinyl, and R9 is l-4C-alkyl;

and to the salts, stereoisomers, hydrates and hydrates of the salts of these compounds.
The invention further relates in a first aspect (aspect a) of variant 1 to compounds of formula I, in
which
in which
Rl is halogen, nitro, amino, mono- or di-l-4C-alkylamino, l-4C-alkyl, hydroxyl, l-4C-alkoxy, 1-4C-
alkoxy-2-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy, or completely or
predominantly fluorine-substituted l-4C-alkoxy, R2 is hydrogen, halogen or l-4C-alkoxy, R3 is hydrogen or l-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 l-2C-alkylenedioxy bridge, or Rl 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 Rl and R2 bound to the benzo ring moiety in ortho-position to each other together form a completely
or predominantly fluorine-substituted l-2C-alkylenedioxy bridge and R3 is hydrogen, R4 is hydrogen, fluorine, chlorine, l-4C-alkyl, trifluoromethyl, cyclopropyl, cyano, 1-4C-
alkoxycarbonyl or -CH2-0-R411, in which R411 is hydrogen, l-4C-alkyl, l-4C-alkoxy-2-4-alkyl or l-4C-alkylcarbonyl, R41 is hydrogen or l-4C-a!kyl, R5 is hydrogen, fluorine or l-4C-alkyl, R51 is hydrogen or l-4C-alkyl, or
R4 is hydrogen, fluorine, chlorine or l-4C-alkyl, R41 is hydrogen or l-4C-alkyl, R5 is hydrogen, fluorine, l-4C-alkyl, trifluoromethyl, cyclopropyl, cyano, l-4C-alkoxycarbonyl or
-CH2-0-R511, in which
R511 is hydrogen, l-4C-alkyl, l-4C-alkoxy-2-4-alkyl or l-4C-alkylcarbonyl,
R51 is hydrogen or l-4C-alkyl,
or
R4 and R5 together form a l-4C-alkylene bridge and R41 and R51 are both hydrogen,
R6 is l-6C-alkyl, amino, formyl, or l-4C-alkyl substituted by R61, in which
R61 is l-4C-alkoxycarbonyl, carboxyl, l-4C-alkoxy, hydroxyl, halogen or -N(R611)R612, in which
R611 is hydrogen, l-4C-alkyl, 3-70cydoalkyI or 3-7C-cycloalkyl-l-4C-alkyl,
R612 is hydrogen or l-4C-alkyl, or
R611 and R612 together and with inclusion of the nitrogen atom to which they are bound form a
radical Het l, in which


Het l 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 a group
consisting of nitrogen, oxygen and sulfur, and optionally substituted by R613 on a ring nitrogen atom,
in which
R613 is l-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-l-4C-alkyl, hydroxy-2-4C-alkyl, l-4C-alkoxy-2-4C-alkyl, amino-2-4C-alkyl, mono- or di-l-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 used "bicyclic 5 to 10-membered "heteroaryl radical comprising one to three heteroatoms, each of which is selected from a group consisting of nitrogen, oxygen and sulfur,
R71 is hydroxyl, halogen, nitro, cyano, trifluoromethyl, l-4C-alkyl, l-4C-alkoxy, amino, mono- or di-l-4C-alkylamino, l-4C-alkylsulphonylamino, arylsulphonylamino, l-4C-alkoxycarbonyl, carboxyl, l-4C-alkylthio, aryloxy-2-4C-alkoxy, aryloxy-l-4C-alkyl, aryloxy, aryl-l-4C-alkoxy, aryl, l-4C-alkoxy-2-4C-aIkoxy, l-4C-alkoxy-l-4C-alkyl, hydroxy-2-4C-alkoxy, amino-2-4C-alkoxy, mono- or di-l-4C-alKylamino-2-4C-alkoxy, or completely or predominantly fluorine-substituted l-4C-alkoxy, in which
aryl is phenyl or R711-substituted phenyl, in which
R711 is halogen, l-4C-alkyl, 14C-alkoxy, nitro or cyano,
R72 is halogen, l-4C-alkyl, l-4C-alkoxy or l-4C-alkoxycarbonyl,
R73 is l-4C-alkyl or l-4C-alkoxy,
R74 is halogen, l-4C-alkyl, trifluoromethyl, l-4C-alkoxy, cyano, amino, mono- or di-l-4C-alkylamino, l-4C-alkoxycarbonyl, morpholino, carboxyl, nitro, phenyl or phenyloxy,
R75 is l-4C-alkyl or halogen,
R76 is halogen, hydroxyl, l-4C-alkyl l-4C-alkoxy, carboxyl or l-4C-alkoxycarbonyl,
R77 is l-4C-alkyl or l-4C-alkoxy,
R8 is l-4C-alkyl, phenyl, 2-4C-alkinyl, cyano, -CH2-O-R8I, phenylcarbonyl or -C(0)-N(R82)R83, in which
R81 is hydrogen, l-4C-alkyl, l-40alkoxy-2-4-alkyl or l-4C-alkylcarbonyl,
R82 is hydrogen, l-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-l-4C-alkyl, phenyl or phenyM-4C-alkyl,
R83 is hydrogen or l-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
or N-(l-4C-alkyl)-piperazinyl,
under the provisio, that,
when R5and R51 are both hydrogen, then
R8 is other than phenyl, phenylcarbonyl or -C(0)-N(R82)R83, in which


R82 is hydrogen, l-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-l-4C-alkyl, phenyl or phenyl-l-4C-
alkyl, R83 is hydrogen or l-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 or N-(l-4C-alkyl)-piperazinyl,
and to the salts, stereoisomers, hydrates and hydrates of the salts of these compounds. The invention further relates in a second aspect (aspect b) of variant 1 to compounds of formula I, in which Rl is halogen, nitro, amino, mono- or di-l-4C-alkylamino, l-4C-alkyl, l-4C-alkoxy-2-4C-alkoxy, 3-
7C-cycloalkoxy, 3-7C-cycloalkylmethoxy, or completely or predominantly fluorine-substituted
l-4C-alkoxy, with the provisio that Rl is not trifluoromethoxy, R2 is hydrogen, halogen or l-4C-alkoxy, R3 is hydrogen or l-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 l-2C-alkylenedioxy bridge, or Rl 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 Rl and R2 bound to the benzo ring moiety in ortho-position to each other together form a completely
or predominantly fluorine-substituted l-2C-alkylenedioxy bridge and R3 is hydrogen, R4 is hydrogen, fluorine, chlorine, l-4C-alkyl, trifluoromethyl, cyclopropyl, cyano, 1-4C-
alkoxycarbonyl or -CH2-O-R4II, in which R411 is hydrogen, l-4C-alkyl, l-4C-alkoxy-2-4-alkyl or l-4C-alkylcarbonyl, R41 is hydrogen or l-4C-alkyl, R5 is hydrogen, fluorine or l-4C-alkyl, R51 is hydrogen or l-4C-alkyl, or
R4 is hydrogen, fluorine, chlorine or l-4C-alkyl, R41 is hydrogen or l-4C-alkyl, R5 is hydrogen, fluorine, l-4C-alkyl, trifluoromethyl, cyclopropyl, cyano, l-4C-alkoxycarbonyl or
-CH2-0-R511, in which R511 is hydrogen, l-4C-alkyl, l-4C-alkoxy-2-4-alkyl or l-4C-alkylcarbonyl, R51 is hydrogen or l-4C-alkyl, or
R4 and R5 together form a l-4C-alkylene bridge and R41 and R51 are both hydrogen,


R6 is l-6C-alkyl, amino, formyl, or l-4C-alkyl substituted by R61, in which
R61 is l-4C-alkoxycarbonyl, carboxyl, l-4C-alkoxy, hydroxyl, halogen or -N(R611)R612, in which
R611 is hydrogen, l-4C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkyM-4C-alkyl,
R612 is hydrogen or l-4C-alkyl, or
R611 and R612 together and with inclusion of the nitrogen atom to which they are bound form a radical Hetl, in which
Hetl 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 a group
consisting of nitrogen, oxygen and sulfur, and optionally substituted by R613 on a ring nitrogen atom,
in which
R613 is l-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-l-4C-alkyl, hydroxy-2-4C-alkyl, l-4C-alkoxy-2-4C-alkyl, amino-2-4C-alkyl, mono- or di-l-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 a group consisting of nitrogen, oxygen and sulfur,
R71 is hydroxyl, halogen, nitro, cyano, trifluoromethyl, l-4C-alkyl, l-4C-alkoxy, amino, mono- or di-l-4C-alkylamino, l-4C-alkylsulphonylamino, arylsulphonylamino, l-4C-alkoxycarbonyl, carboxyl, l-4C-alkylthio, aryloxy-2-4C-alkoxy, aryloxy-l-4C-alkyl, aryloxy, aryl-l-4C-alkoxy, aryl, l-4C-alkoxy-2-4C-alkoxy, l-4C-alkoxy-l-4C-alkyl, hydroxy-2-4C-alkoxy, amino-2-4C-alkoxy, mono- or di-l-4C-alkylamino-2-4C-alkoxy, or completely or predominantly fluorine-substituted l-4C-alkoxy, in which
aryl is phenyl or R711-substituted phenyl, in which
R711 is halogen, l-4C-alkyl, l-4C-alkoxy, nitro or cyano,
R72 is halogen, l-4C-alkyl, l-4C-alkoxy or l-4C-alkoxycarbonyl,
R73 is l-4C-alkyl or l-4C-alkoxy,
R74 is halogen, l-4C-alkyl, trifluoromethyl, l-4C-alkoxy, cyano, amino, mono- or di-l-4C-alkylamino, l-4C-alkoxycarbonyl, morpholino, carboxyl, nitro, phenyl or phenyloxy,
R75 is l-4C-alkyl or halogen,
R76 is halogen, hydroxyl, l-4C-alkyl, l-4C-alkoxy, carboxyl or l-4C-alkoxycarbonyl,
R77 is l-4C-alkyl or l-4C-alkoxy,
R8 is l-4C-alkyl, phenyl, 2-4C-alkinyl, cyano, -CH2-O-R81, phenylcarbonyl, -C(0)-N(R82)R83 or -C(0)-OR9, in which
R81 is hydrogen, l-4C-alkyI, l-4C-alkoxy-2-4-alkyl or l-4C-alkylcarbonyl,
R82 is hydrogen, l-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-l-4C-alkyl, phenyl or phenyl-l-4C-
alkyl,
R83 is hydrogen or l-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
or N-(l-4C-alkyl)-piperazinyl,
R9 is hydrogen or l-4C-alkyl,
under the provisio, that,
when R5and R51 are both hydrogen, then
R8 is other than phenyl, phenylcarbonyl, -C(0)-N(R82)R83 or -C(0)-OR9, in which
R82 is hydrogen, l-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycIoalkyl-l-4C-alkyl, phenyl or phenyl-l-4C-
alkyl, R83 is hydrogen or l-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 or N-(l-4C-alkyl)-piperazinyl, and R9 is l-4C-alkyl,
and to the salts, stereoisomers, hydrates and hydrates of the salts of these compounds. The invention further relates in a third aspect (aspect c) of variant 1 to compounds of formula I, in which Rl is halogen, nitro, amino, mono- or di-l-4C-alkylamino, l-4C-alkyl, hydroxyl, l-4C-alkoxy, 1-4C-
alkoxy-2-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy, or completely or
predominantly fluorine-substituted l-4C-alkoxy, R2 is halogen or l-4C-alkoxy, R3 is l-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 l-2C-alkylenedioxy bridge, R4 is hydrogen, fluorine, chlorine, l-4C-alkyl, trifluoromethyl, cyclopropyl, cyano, 1-4C-
alkoxycarbonyl or -CH2-0-R411, in which R411 is hydrogen, l-4C-alkyl, l-4C-alkoxy-2-4-alkyl or l-4C-alkylcarbonyl, R41 is hydrogen or l-4C-alkyl, R5 is hydrogen, fluorine or l-4C-alkyl, R51 is hydrogen or l-4C-alkyl, or
R4 is hydrogen, fluorine, chlorine or l-4C-alkyl, R41 is hydrogen or l-4C-alkyl, R5 is hydrogen, fluorine, l-4C-alkyl, trifluoromethyl, cyclopropyl, cyano, l-4C-alkoxycarbonyl or
-CH2-0-R511, in which R511 is hydrogen, l-4C-alkyl, l-4C-alkoxy-2-4-alkyl or l-4C-alkylcarbonyl,


R51 is hydrogen or l-4C-alkyl,
or
R4 and R5 together form a l-4C-alkylene bridge and R41 and R51 are both hydrogen,
R6 is l-6C-alkyl, amino, formyl, or l-4C-alkyl substituted by R61, in which
R61 is l-4C-alkoxycarbonyl, carbc"xyl, l-4C-alkoxy, hydroxyl, halogen or -N(R611)R612, in which
R611 is hydrogen, l-4C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkyl-l-4C-alkyl,
R612 is hydrogen or l-4C-alkyl, or
R611 and R612 together and with inclusion of the nitrogen atom to which they are bound form a radical Hetl, in which
Hetl is a 5- to 7-membered saturated neterocyclic ring radical comprising one nitrogen atom, to
which R611 and R612 are bound, and, optionally, one further heteroatom selected from a group
consisting of nitrogen, oxygen and sulfur, and optionally substituted by R613 on a ring nitrogen atom,
in which
R613 is l-4C-alkyl, 3-7C-cycloalkyL 3-7C-cycloalkyl-l-4C-alkyl, hydroxy-2-4C-alkyl, l-4C-alkoxy-2-4C-alkyl, amino-2-4C-alkyl, mono- or di-l-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 a group consisting of nitrogen, oxygen and sulfur,
R71 is hydroxyl, halogen, nitro, cyano, trifluoromethyl, l-4C-alkyl, l-4C-alkoxy, amino, mono- or di-l-4C-alkylamino, l-4C-alkylsulphonylamino, arylsulphonylamino, l-4C-alkoxycarbonyl, carboxyl, l-4C-alkylthio, aryloxy-2-4C-alkoxy, aryloxy-l-4C-alkyl, aryloxy, aryl-l-4C-alkoxy, aryl, l-4C-alkoxy-2-4C-aIkoxy, l-4C-alkoxy-l-4C-alkyl, hydroxy-2-4C-alkoxy, amino-2-4C-alkoxy, mono- or di-l-4C-alkylamino-2-4C-alkoxy, or completely or predominantly fluorine-substituted l-4C-alkoxy, in which
aryl is phenyl or R711-substituted phenyl, in which
R711 is halogen, l-4C-alkyl, l-4C-alkoxy, nitro or cyano,
R72 is halogen, l-4C-alkyl, l-4C-alkoxy or l-4C-alkoxycarbonyl,
R73 is l-4C-alkyl or l-4C-alkoxy,
R74 is halogen, l-4C-alkyl, trifluoromethyl, l-4C-alkoxy, cyano, amino, mono- or di-l-4C-alkylamino, l-4C-alkoxycarbonyl, morpholino, carboxyl, nitro, phenyl or phenyloxy,
R75 is l-4C-alkyl or halogen,
R76 is halogen, hydroxyl, l-4C-alKyl l-4C-alkoxy, carboxyl or l-4C-alkoxycarbonyl,
R77 is l-4C-alkyl or l-4C-alkoxy,
R8 is l-4C-alkyl, phenyl, 2-4C-alkinyl, cyano, -CH2-OR81, phenylcarbonyl, -C(0)-N(R82)R83 or -C(0)-OR9, in which
R81 is hydrogen, l-4C-alkyl, l-4C-alkoxy-2-4-alkyl or l-4C-aIkylcarbonyl,


R82 is hydrogen, l-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-l-4C-alkyl, phenyl or phenyl-l-4C-
alkyl, R83 is hydrogen or l-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 or N-(l-4C-alkyl)-piperazinyl, R9 is hydrogen or l-4C-alkyl, under the provisio, that, when R5and R51 are both hydrogen, then
R8 is other than phenyl, phenylcarbonyl, -C(0)-N(R82)R83 or -C(0)-OR9, in which R82 is hydrogen, l-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cydoalkyl-l-4C-alkyl, phenyl or phenyl-l-4C-
alkyl, R83 is hydrogen or l-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 or N-(l-4C-alkyl)-piperazinyl, and R9 is l-4C-alkyl,
and to the salts, stereoisomers, hydrates and hydrates of the salts of these compounds. The invention further relates in a fourth aspect (aspect d) of variant 1 to compounds of formula I, in which Rl is halogen, nitro, amino, mono- or di-l-4C-alkylamino, l-4C-alkyl, hydroxyl, l-4C-alkoxy, 1-4C-
alkoxy-2-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy, or completely or
predominantly fluorine-substituted l-4C-alkoxy, R2 is hydrogen, halogen or l-4C-alkoxy, R3 is hydrogen or l-4C-alkoxy, or R2 and R3 bound to the benzo ring moiety in ortho-position to each other together form a
l-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 l-2C-alkylenedioxy bridge, or Rl and R2 bound to the benzo ring moiety in ortho-position to each other together form a
l-2C-alkylenedioxy bridge and R3 is hydrogen, or Rl and R2 bound to the benzo ring moiety in ortho-position to each other together form a completely
or predominantly fluorine-substituted l-2C-alkylenedioxy bridge and R3 is hydrogen, R4 is fluorine, chlorine, l-4C-alkyl, trifluoromethyl, cyclopropyl, cyano, l-4C-alkoxycarbonyl or
-CH2-0-R411, in which
R411 is hydrogen, l-4C-alkyl, l-4C-alkoxy-2-4-alkyl or l-4C-alkylcarbonyl,
R41 is hydrogen or l-4C-alkyl,
R5 is hydrogen, fluorine or l-4C-alkyl,


R51 is hydrogen or l-4C-alkyl,
or
R4 is hydrogen, fluorine, chlorine or l-4C-alkyl,
R41 is hydrogen or l-4C-alkyl,
R5 is fluorine, l-4C-alkyl, trifluoromethyl, cyclopropyl, cyano, l-4C-alkoxycarbonyl or -CH2-O-R511, in which
R511 is hydrogen, l-4C-alkyl, l-4C-aIkoxy-2-4-alkyl or l-4C-alkylcarbonyl,
R51 is hydrogen or l-4C-alkyl,
or
R4 and R5 together form a l-4C-alkylene bridge and R41 and R51 are both hydrogen,
R6 is l-6C-alkyl, amino, formyl, or l-4C-alkyl substituted by R61, in which
R61 is l-4C-alkoxycarbonyl, carboxyl, l-4C-alkoxy, hydroxyl, halogen or -N(R611)R612, in which
R611 is hydrogen, l-4C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkyl-l-4C-alkyl,
R612 is hydrogen or l-4C-alkyl, or
R611 and R612 together and with inclusion of the nitrogen atom to which they are bound form a radical Hetl, in which
Hetl 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 a group consisting of nitrogen, oxygen and sulfur, and optionally substituted by R613 on a ring nitrogen atom, in which
R613 is l-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-l-4C-aIkyl, hydroxy-2-4C-alkyl, l-4C-alkoxy-2-4C-alkyl, amino-2-4C-alkyl, mono- or di-l-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, or 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 a group consisting of nitrogen, oxygen and sulfur,
R71 is hydroxyl, halogen, nitro, cyano, trifluoromethyl, l-4C-alkyl, l-4C-alkoxy, amino, mono- or di-l-4C-alkylamino, l-4C-alkylsulphonylamino, arylsulphonylamino, l-4C-alkoxycarbonyl, carboxyl, l-4C-alkylthio, aryloxy-2-4C-alkoxy, aryloxy-l-4C-alkyl, aryloxy, aryl-l-4C-alkoxy, aryl, l-4C-alkoxy-2-4C-alkoxy, l-4C-alkoxy-l-4C-alkyl, hydroxy-2-4C-alkoxy, amino-2-4C-alkoxy, mono- or di-l-4C-alkylamino-2-4C-alkoxy, or completely or predominantly fluorine-substituted l-4C-alkoxy, in which
aryl is phenyl or R711-substituted phenyl, in which
R711 is halogen, l-4C-alkyl, l-4C-alkoxy, nitro or cyano,
R72 is halogen, l-4C-alkyl, l-4C-alkoxy or l-4C-alkoxycarbonyl,
R73 is l-4C-alkyl or l-4C-alkoxy,

R74 is halogen, l-4C-alkyl, trifluoromethyl, l-4C-alkoxy, cyano, amino, mono- or di-l-4C-
alkylamino, l-4C-alkoxycarbonyl, morpholino, carboxyl, nitro, phenyl or phenyloxy, R75 is l-4C-alkyl or halogen,
R76 is halogen, hydroxyl, l-4C-alkyl, l-4C-alkoxy, carboxyl or l-4C-alkoxycarbonyl, R77 is l-4C-alkyl or l-4C-alkoxy, R8 is l-4C-alkyl, phenyl, 2-4C-alkinyl, cyano, -CH2-O-R81, phenylcarbonyl, -C(0)-N(R82)R83 or
-C(0)-OR9, in which R81 is hydrogen, l-4C-alkyl, l-4C-alkoxy-2-4-alkyl or l-4C-alkylcarbonyl, R82 is hydrogen, l-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-l-4C-alkyl, phenyl or phenyl-l~4C-
alkyl, R83 is hydrogen or l-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 or N-(l-4C-alkyl)-piperazinyl, R9 is hydrogen or l-4C-alkyl, under the provisio, that, when R5and R51 are both hydrogen, then
R8 is other than phenyl, phenylcarbonyl, -C(0)-N(R82)R83 or -C(0)-OR9, in which R82 is hydrogen, l-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-l-4C-alkyl, phenyl or phenyl-l-4C-
alkyl, R83 is hydrogen or l-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 or N-(l-4C-alkyl)-piperazinyl, and R9 is l-4C-alkyl,
and to the salts, stereoisomers, hydrates and hydrates of the salts of these compounds. The invention further relates in a fifth aspect (aspect e) of variant 1 to compounds of formula I, in which Rl is halogen, nitro, amino, mono- or di-l-4C-alkylamino, l-4C-alkyl, hydroxyl, l-4C-alkoxy, 14C-
alkoxy-2-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy, or completely or
predominantly fluorine-substituted l-4C-aIkoxy, R2 is hydrogen, halogen or l-4C-alkoxy, R3 is hydrogen or l-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 l-2C-alkylenedioxy bridge, or

Rl 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 Rl and R2 bound to the benzo ring moiety in ortho-position to each other together form a completely
or predominantly fluorine-substituted l-2C-alkylenedioxy bridge and R3 is hydrogen, R4 is hydrogen, fluorine, chlorine, l-4C-alkyl, trifluoromethyl, cyclopropyl, cyano, 1-4C-
alkoxycarbonyl or -CH2-O-R4H, in which R411 is hydrogen, l-4C-alkyl, l-4C-alkoxy-2-4-alkyl or l-4C-alkylcarbonyl, R41 is hydrogen or l-4C-alkyl, R5 is hydrogen, fluorine or l-4C-alkyl, R51 is hydrogen or l-4C-alkyl, or
R4 is hydrogen, fluorine, chlorine or l-4C-alkyl, R41 is hydrogen or l-4C-alkyl, R5 is hydrogen, fluorine, l-4C-alkyl, trifluoromethyl, cyclopropyl, cyano, l-4C-alkoxycarbonyl or
-CH2-0-R511, in which R511 is hydrogen, l-4C-alkyl, l-4C-alkoxy-2-4-alkyl or l-4C-aIkykarbonyl, R51 is hydrogen or l-4C-alkyl, or
R4 and R5 together form a l-4C-alkylene bridge and R41 and R51 are both hydrogen, R6 is l-6C-alkyl, amino, formyl, or l-4C-alkyl substituted by R61, in which R61 is l-4C-alkoxycarbonyl, carboxyl, l-4C-alkoxy, hydroxyl, halogen or -N(R611)R612, in which R611 is hydrogen, l-4C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloaIkyl-l-4C-alkyl, R612 is hydrogen or l-4C-alkyl, or R611 and R612 together and with inclusion of the nitrogen atom to which they are bound form a
radical Hetl, in which Hetl 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 a group consisting of nitrogen, oxygen and sulfur, and optionally substituted by R613 on a ring nitrogen atom, in which R613 is l-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-l-4C-alkyl, hydroxy-2-4C-alkyl, l-4C-alkoxy-2-
4C-alkyl, amino-2-4C-alkyl, mono- or di-l-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 a group consisting of nitrogen, oxygen and sulfur, R71 is hydroxyl, halogen, nitro, cyano, trifluoromethyl, l-4C-alkyl, l-4C-alkoxy, amino, mono- or
di-l-4C-alkylamino, l-4C-alkylsulphonylamino, arylsulphonylamino, l-4C-alkoxycarbonyl,


carboxyl, l-4C-alkylthio, aryloxy-2-4C-alkoxy, aryloxy-l-4C-alkyl, aryloxy, aryl-l-4C-alkoxy, aryl, l-4C-alkoxy-2-4C-alkoxy, l-4C-alkoxy-l-4C-alkyl, hydroxy-2-4C-alkoxy, amino-2-4C-alkoxy, mono- or di-l-4C-alkylamino-2-4C-alkoxy, or completely or predominantly fluorine-substituted l-4C-alkoxy, in which aryl is phenyl or R711-substituted phenyl, in which R711 is halogen, l-4C-alkyl, l-4C-alkoxy, nitro or cyano, R72 is halogen, l-4C-alkyl, l-4C-alkoxy or l-4C-alkoxycarbonyl, R73 is l-4C-alkyl or l-4C-alkoxy, R74 is halogen, l-4C-alkyl, trifluoromethyl, l-4C-alkoxy, cyano, amino, mono- or di-l-4C-
alkylamino, l-4C-alkoxycarbonyl, morpholino, carboxyl, nitro, phenyl or phenyloxy, R75 is l-4C-alkyl or halogen,
R76 is halogen, hydroxyl, l-4C-alkyl, l-4C-alkoxy, carboxyl or l-4C-alkoxycarbonyl, R77 is l-4C-alkyl or l-4C-alkoxy, R8 is carboxyl,
and to the salts, stereoisomers, hydrates and hydrates of the salts of these compounds. 1-4C-Alkyl represents a straight-chain or branched alkyl radical having 1 to 4 carbon atoms. Examples which may be mentioned are the butyl, isobutyl, sec-butyl, tert-butyl, propyl, isopropyl and preferably the ethyl and methyl radicals.
2-4C-Alkyl represents a straight-chain or branched alkyl radical having 2 to 4 carbon atoms. Examples which may be mentioned are the butyl, isobutyl, sec-butyl, tert-butyl, propyl, isopropyl and preferably the ethyl radical.
1-6C-Alkyl represents a straight-chain or branched alkyl radical having 1 to 6 carbon atoms. Examples which may be mentioned are the hexyl, isohexyl (4-methylpentyl), neohexyl (3,3-dimethylbutyl), pentyl, isopentyl (3-methylbutyl), neopentyl (2,2-dimethylpropyl), butyl, isobutyl, sec-butyl, tert-butyl, propyl, isopropyl, ethyl or methyl radicals.
l-4C-Alkoxy represents radicals which, in addition to the oxygen atom, contain a straight-chain or branched alkyl radical having 1 to 4 carbon atoms. Examples which may be mentioned are the butoxy, isobutoxy, sec-butoxy, tert-butoxy, propoxy, isopropoxy and preferably the ethoxy and methoxy radicals.
l-4C-Alkylthio represents radicals which, in addition to the sulfur atom, contain a straight-chain or branched alkyl radical having 1 to 4 carbon atoms. Examples which may be mentioned are the ethylthio and the methylthio radicals.
2-4C-Alkoxy represents radicals which, in addition to the oxygen atom, contain a straight-chain or branched alkyl radical having 2 to 4 carbon atoms. Examples which may be mentioned are the butoxy, isobutoxy, sec-butoxy, tert-butoxy, propoxy, isopropoxy and preferably the ethoxy radical. 3-7C-Cycloalkoxy represents cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy and cycloheptyloxy, of which cyclopropyloxy, cyclobutyloxy and cyclopentyloxy are preferred.

3-7C-Cycloalkyl represents cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl, of which cyclopropyl, cyclobutyl and cyclopentyl are preferred.
3-7C-Cycloalkylmethoxy represents cyclopropylmethoxy, cyclobutylmethoxy, cyclopentylmethoxy, cyclohexylmethoxy and cycloheptylmethoxy, of which cyclopropylmethoxy, cyclobutylmethoxy and cyclopentylmethoxy are preferred.
3-7C-Cycloalkyl-l-4C-alkyl represents one of the abovementioned l-4C-alkyl radicals, which is substituted by one of the abovementioned 3-7C-cycloalkyl radicals. Examples which may be mentioned are the cyclopropylmethyl, the cyclohexylethyl and the cyclohexylmethyl radicals. As completely or predominantly fluorine-substituted l-4C-alkoxy, for example, the 2,2,3,3,3-penta-fluoropropoxy, the perfluoroethoxy, the 1,2,2-trifluoroethoxy, in particular the 1,1,2,2-tetrafluoroethoxy, the 2,2,2-trifluoroethoxy, the trifluoromethoxy and preferably the difluoromethoxy radicals may be mentioned. "Predominantly" in this connection means that more than half of the hydrogen atoms of the l-4C-alkoxy radicals are replaced by fluorine atoms. l-4C-Alkoxy-2-4C-alkoxy represents one of the abovementioned 2-4C-alkoxy radicals, which is substituted by one of the abovementioned l-4C-alkoxy radicals. Examples which may be mentioned are the 2-methoxyethoxy, 2-ethoxyethoxy and the 2-isopropoxyethoxy radicals.
l-4C-Alkoxy-2-4C-alkyl represents one of the abovementioned 2-4C-alkyl radicals, which is substituted by one of the abovementioned l-4C-alkoxy radicals. Examples which may be mentioned are the 2-methoxyethyl and the 2-isopropoxyethyl radicals.
l-4C-Alkoxy-l-4C-alkyl stands for one of the abovementioned l-4C-alkyl radicals, which is substituted by one of the abovementioned l-4C-alkoxy radicals. Examples which may be mentioned are the 2-methoxyethyl and 2-isopropoxyethyl radicals.
l-2C-Alkylenedioxy represents, for example, the methylenedioxy [-O-CH2-O-] and the ethylenedioxy [-O-CH2-CH2-O-] radicals.
As completely or predominantly fluorine-substituted l-2C-alkylenedioxy bridge, for example, the difluoromefhylenedioxy [-O-CF2-O-] radical may be mentioned. "Predominantly" in this connection means that more than half of the hydrogen atoms of the l-4C-alkylenedioxy radical are replaced by fluorine atoms.
Phenyl-l-4C-alkyl stands for one of the abovementioned l-4C-alkyl radicals, which is substituted by a phenyl radical. Examples which may be mentioned are the phenethyl and the benzyl radicals. l-4C-Alkoxycarbonyl represents a radical which, in addition to the carbonyl group, contains one of the abovementioned l-4C-alkoxy radicals. Examples which may be mentioned are the methoxycarbonyl and ethoxycarbonyl radicals.
l-4C-Alkylcarbonyl represents a radical which, in addition to the carbonyl group, contains one of the abovementioned l-4C-alkyl radicals. An example which may be mentioned is the acetyl radical. 1-4C-Alkylene is a straight-chain alkylene radical such as, for example, the methylene (-CH2-) or, particularly, the trimethylene (-CH2-CH2-CH2-) or the tetramethylene (-CH2-CH2-CH2-CH2-) radical. Halogen within the meaning of the invention is bromine and, preferably, chlorine and fluorine.


Hydroxy-2-4C-alkyl stands for one of the abovementioned 2-4C-alkyl radicals which is substituted by
a hydroxyl group. Examples which may be mentioned are the 2-hydroxyethyl and 3-hydroxypropyl
radicals.
Hydroxy-2-4C-alkoxy stands for one of the abovementioned 2-4C-alkoxy radicals which is substituted
by a hydroxyl group. Examples which may be mentioned are the 2-hydroxyethoxy and 3-
hydroxypropoxy radicals.
Amino-2-4C-alkyl stands for one of the abovementioned 2-4C-alkyl radicals which is substituted by
an amino group. Examples which may be mentioned are the 2-aminoethyl and 3-aminopropyl
radicals.
Amino-2-4C-alkoxy stands for one of the abovementioned 2-4C-alkoxy radicals which is substituted
by an amino group. Examples which may be mentioned are the 2-aminoethoxy and 3-aminopropoxy
radicals.
In addition to the nitrogen atom, mono- or di-l-4C-alkylamino radicals contain one or two of the
abovementioned l-4C-alkyl radicals. Di-l-4C-alkylamino is to be emphasized and here, in particular,
dimethyl-, diethyl- and diisopropylamino.
Mono- or Di-l-4C-alkylamino-2-4C-alkyl stands for one of the abovementioned 2-4C-alkyl radicals
which is substituted by one of the abovementioned mono- or di-l-4C-alkylamino radicals. Examples
which may be mentioned are the 2-dimethylaminoethyl and 3-dimethylaminopropyl radicals.
Mono- or Di-l-4C-alkylamino -2-4C-alkoxy stands for one of the abovementioned 2-4C-alkoxy
radicals which is substituted by one of the abovementioned mono- or di-l-4C-alkylamino radicals.
Examples which may be mentioned are the 2-dimethylaminoethoxy and 3-dimethylaminopropoxy
radicals.
l-4C-Alkylsulfonyl is a sulfonyl group to which one of the abovementioned l-4C-alkyl radicals is
bonded. An example is the methanesulfonyl radical (CH3SO2-).
l-4C-Alkylsulfonylamino is an amino group which is substituted by one of the abovementioned 1-4C-
alkylsulfonyl radicals. An example is the methanesulfonylamino radical (CH3SO2NH-).
Aryl radicals referred to herein, including those forming part of other groups or radicals, include
phenyl or R711-substituted phenyl radicals.
Aryloxy stands for phenoxy or R711-substituted phenoxy.
Aryl-l-4C-alkoxy stands for one of the abovementioned l-4C-alkoxy radicals, which is substituted by
one of the abovementioned aryl radicals. Examples which may be mentioned are the 2-arylethoxy
(e.g. phenethoxy) and the arylmethoxy (e.g. benzyloxy) radicals.
Aryloxy-2-4C-alkoxy stands for one of the abovementioned 2-4C-alkoxy radicals, which is substituted
by one of the abovementioned aryloxy radicals. An example which may be mentioned is the 2-
aryloxyethoxy (e.g. 2-phenoxyethoxy) radical.
Aryloxy-l-4C-alkyl stands for one of the abovementioned l-4C-alkyl radicals, which is substituted by
one of the abovementioned aryloxy radicals. Examples which may be mentioned are the 2-
aryloxyethyl (e.g. 2-phenoxyethyl) and the aryloxymethyl (e.g. phenoxymethyl) radicals.


Mono- or Di-l-4C-alkylaminocarbonyl radicals contain in addition to the carbonyl group one of the abovementioned mono- or di-l-4C-alkylamino radicals. Examples which may be mentioned are the N-methyl- the N,N-dimethyl-, the N-ethyl-, the N-propyl-, the N,N-diethyl- and the N-isopropylaminocarbonyl radical.
2-4C-Alkinyl is a straight chain or branched alkinyl radical having 2 to 4 carbon atoms. Examples are the 2-propinyl (propargyl) and the ethinyl radicals.
Hetl refers to 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 a group consisting of nitrogen, oxygen and sulfur, and optionally substituted by R613 on a ring nitrogen atom. Examples for Hetl include e.g. piperidin-1-yl, 4-methyl-piperidin-l-yl, 4-hydroxypiperidin-l-yl, morpholin-4-yl, pyrrolidin-1-yl, piperazin-1-yl, imidazolidin-1-yl, thiomorpholin-4-yl, homopiperidin-l-yl, homopiperazin-1-yl, 4-N-(l-4C-alkyl)-homopiperazin-l-yl or piperazinyl substituted on a ring nitrogen atom by R613 [4-N-(R613)-piperazin-l-yl] such as, for example, 4-N-(l-4C-alkyl)-piperazin-l-yl, 4-N-(hydroxy-2-4C-alkyl)-piperazin-l-yl, 4-N-(dimethylamino-2-4C-alkyl)-piperazin-1-yl, 4-N-(3-6C-cycloalkyl)-piperazin-l-yl, 4-N-formyl-piperazin-l-yl, 4-N-(pyridin-4-yl)-piperazin-1-yl, 4-N-(pyrimidin-2-yl)-piperazin-l-yl or 4-N-(3-6C-cycloalkylmethyl)-piperazin-l-yl. Het2 refers to a monocyclic or fused bicyclic 5 to 10-membered heteroaryl (heteroaromatic) radical comprising one to three heteroatoms, each of which is selected from a group consisting of nitrogen, oxygen and sulfur, and includes, for example, without being restricted to furanyl, thiophenyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, triazolyl, rhiadiazolyl, oxadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, benzo-fused analogues thereof, such as, for example, quinazolinyl, quinoxalinyl, cinnolinyl, quinolyl, isoquinolyl, indolyl, isoindolyl, indazolyl, benzothiophenyl, benzofuranyl, benzoxazolyl, benzothiazolyl or benzimidazolyl, or naphthyridinyl, phthalazinyl, imidazopyridinyl, purinyl, pteridinyl or imidazopyridazinyl. The monocyclic 5- to 6-membered radicals, such as, for example, furanyl, thiophenyl, pyrrolyl, pyrimidinyl and pyridinyl, and quinolinyl and indolyl are more worthy to be mentioned. In particular worthy to be mentioned are indolyl, quinolinyl and pyridinyl. In more particular worthy to be mentioned are quinolyl and pyridinyl, especially quinolin-4-yl and, particularly, pyridin-4-yl. Alternatively Het2 refers to a fused bicyclic 9- or 10-membered, partially saturated heterocyclic ring radical containing a benzene ring and comprising one or two heteroatoms, each of which is selected from a group consisting of nitrogen, oxygen and sulfur, and includes, for example, without being restricted to indolinyl, isoindolinyl, 1,2,3,4-tetrahydroquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl, 1,3-benzodioxolyl, 2,3-dihydro-l,4-benzodioxinyl or 2,3-dihydrobenzofuranyl.
N-(l-4C-alkyl)-piperazinyl stands for the piperazin-1-yl radical substituted by one of the abovementioned l-4C-alkyl radicals on the 4-N ring nitrogen atom. Naphthyl includes naphthalen-1-yl and naphthalen-2-yl.
The term Het2 includes all the possible isomeric forms thereof, in particular the positional isomers thereof. Thus, e.g. pyridinyl or pyridyl includes pyridin-2-yl, pyridin-3-yl and pyridin-4-yl.


Constituents which are substituted as described herein may be substituted, unless otherwise noted, at any possible position.
Thus, the substihients Rl, R2 and/or R3 may be attached, unless otherwise noted, at any position of the benzo moiety of the pyrrolodihydroisoquinoline ring.
The substihients R71, R72 and/or R73 of the compounds according to this invention can be each attached in the ortho, meta or para position with respect to the binding position in which the phenyl ring is bonded to the pyrrolo moiety of the pyrrolodihydroisoquinoline ring, whereby in an embodiment of the present invention the attachement in the meta or, in particular, in para position is to be emphasized.
Suitable salts for compounds of the formula I - depending on substitution - are all acid addition salts or all salts with bases. Particular mention may be made of the pharmacologically tolerable inorganic and organic acids and bases customarily used in pharmacy. Those suitable are, on the one hand, water-insoluble and, particularly, water-soluble acid addition salts with acids such as, for example, hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid, sulphuric acid, acetic acid, citric acid, D-gluconic acid, benzoic acid, 2-(4-hydroxybenzoyl)benzoic acid, butyric acid, sulphosalicylic acid, maleic acid, lauric acid, malic acid, fumaric acid, succinic acid, oxalic acid, tartaric acid, embonic acid, stearic acid, toluenesulphonic acid, methanesulphonic acid or 3-hydroxy-2-naphthoic acid, the acids being employed in salt preparation - depending on whether a mono- or polybasic acid is concerned and depending on which salt is desired - in an equimolar quantitative ratio or one differing therefrom.
On the other hand, salts with bases are - depending on substitution - also suitable. As examples of salts with bases are mentioned the lithium, sodium, potassium, calcium, aluminium, magnesium, titanium, ammonium, meglumine or guanidinium salts, here, too, the bases being employed in salt preparation in an equimolar quantitative ratio or one differing therefrom.
Pharmacologically intolerable salts, which can be obtained, for example, as process products during the preparation of the compounds according to the invention on an industrial scale, are converted into pharmacologically tolerable salts by processes known to the person skilled in the art. According to expert"s knowledge the compounds of the invention as well as their salts may contain, e.g. when isolated in crystalline form, varying amounts of solvents. Included within the scope of the invention are therefore all solvates and in particular all hydrates of the compounds of formula I as well as all solvates and in particular all hydrates of the salts of the compounds of formula I. Depending on substitution the compounds of formula I can be chiral compounds having, for example, chiral centers and/or chiral axes due to hindered rotation about single bonds. Chiral axes can be present in particular in those compounds according to the invention, in which R7 is a bicyclic ring, or a monocyclic ring substituted in the ortho position with respect to the binding position in which said monocyclic ring is bonded to the pyrrolo[2.1-a]isoquinoline ring system. The invention therefore includes all conceivable pure diastereomers and pure enantiomers and mixtures thereof in any mixing ratio including the racemates. The diastereomer mixtures can be separated into the


individual isomers by chromatographic processes. The enantiomers can be separated in a known manner (e.g. by chromatographic processes on chiral phases or by resolution).
A special subaspect (subaspect 1) of aspects a, b, c, d and e refers to compounds of formula I according to aspects a, b, c, d and e, in which
none of Rl, R2 and R3 is bound to the 10-position of the pyrrolo[2.1-a]isoquinoline ring.
R1,
Numbering:
(I)
A further special subaspect (subaspect 2) of aspects a, b, c and d refers to compounds of formula I
according to aspects a, b, c and d, in which
R8 is l-4C-alkyl, phenyl, 2-4C-alkinyl, cyano, -CH2-O-R81, phenylcarbonyl or -C(0)-N(R82)R83, in
which R81 is hydrogen, l-4C-alkyl, l-4C-alkoxy-2-4-alkyl or l-4C-alkylcarbonyl, R82 is hydrogen, l-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-l-4C-alkyl, phenyl or phenyl-l-4C-
alkyl, R83 is hydrogen or l-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 or N-(l-4C-alkyl)-piperazinyl. A further special subaspect (subaspect 3) of aspects a, b, c, d and e refers to compounds of formula I
according to aspects a, b, c, d and e, in which Rl is halogen, nitro, amino, mono- or di-l-4C-alkylamino, l-4C-alkyl, l-4C-alkoxy-2-4C-alkoxy, 3-
7C-cycloalkoxy, 3-7C-cycloalkylmethoxy, or completely or predominantly fluorine-substituted
l-4C-alkoxy, with the provisio that Rl is not trifluoromethoxy, R2 is hydrogen, halogen or l-4C-alkoxy, R3 is hydrogen or l-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 l-2C-alkylenedioxy bridge, or Rl 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 Rl and R2 bound to the benzo ring moiety in ortho-position to each other together form a completely
or predominantly fluorine-substituted l-2C-alkylenedioxy bridge and R3 is hydrogen.


A further special subaspect (subaspect 4) of aspects a, c, d and e refers to compounds of formula I
according to aspects a, c, d and e, in which
Rl is halogen, nitro, amino, mono- or di-l-4C-alkylamino, l-4C-alkyl, hydroxyl, l-4C-alkoxy, 1-4C-
alkoxy-2-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy, or completely or
predominantly fluorine-substituted l-4C-alkoxy, R2 is halogen or l-4C-alkoxy, R3 is l-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 l-2C-alkylenedioxy bridge. A further special subaspect (subaspect 5) of aspects a, b, c, d and e refers to compounds of formula I according to aspects a, b, c, d and e, in which R4 is fluorine, chlorine, l-4C-alkyl, trifluoromethyl, cyclopropyl, cyano, l-4C-alkoxycarbonyl or -
CH2-0-R411, in which R411 is hydrogen, l-4C-alkyl, l-4C-alkoxy-2-4-alkyl or l-4C-alkylcarbonyl, R41 is hydrogen or l-4C-alkyl, R5 is hydrogen, fluorine or l-4C-alkyl, R51 is hydrogen or l-4C-alkyl, or
R4 is hydrogen, fluorine, chlorine or l-4C-alkyl, R41 is hydrogen or l-4C-alkyl, R5 is fluorine, l-4C-alkyl, trifluoromethyl, cyclopropyl, cyano, l-4C-alkoxycarbonyl or -CH2-O-
R511, in which R511 is hydrogen, l-4C-alkyl, l-4C-alkoxy-2-4-alkyl or l-4C-alkylcarbonyl, R51 is hydrogen or l-4C-alkyl, or
R4 and R5 together form a l-4C-alkylene bridge and R41 and R51 are both hydrogen. A further special subaspect (subaspect 6) of aspects a, b, d and e refers to compounds of formula I according to aspects a, b, d and e, in which Rl is halogen, nitro, amino, l-4C-alkyl, l-4C-alkoxy-2-4C-aIkoxy, or completely or predominantly
fluorine-substituted l-4C-alkoxy, with the provisio that Rl is not trifluoromethoxy, R2 is hydrogen or l-4C-alkoxy, R3 is hydrogen or l-4C-alkoxy, or Rl and R2 bound to the benzo ring moiety in ortho-position to each other together form a completely
or predominantly fluorine-substituted l-2C-alkylenedioxy bridge and R3 is hydrogen.

A further special subaspect (subaspect 7) of said aspects a, c, d and e refers to compounds of formula I
according to aspects a, c, d and e, in which
Rl is halogen, nitro, amino, l-4C-alkyl, l-4C-alkoxy, l-4C-alkoxy-2-4C-alkoxy, or completely or
predominantly fluorine-substituted l-4C-alkoxy, R2 is l-4C-alkoxy, R3 is l-4C-alkoxy.
A further special subaspect (subaspect 8) of said aspects a, c, d and e refers to compounds of formula I according to aspects a, c, d and e, in which Rl is halogen, nitro, amino, l-4C-alkyl, l-4C-alkoxy, l^lC-alkoxy-2-4C-alkoxy, or completely or
predominantly fluorine-substituted l-4C-allcoxy, R2 is halogen, R3 is l-4C-alkoxy.
A further special subaspect (subaspect 9) of said aspects a, d and e refers to compounds of formula I according to aspects a, d and e, in which Rl is halogen, nitro, amino, l-4C-alkyl, l-4C-alkoxy, l-4C-alkoxy-2-4C-alkoxy, or completely or
predominantly fluorine-substituted l-4C-alkoxy, R2 is l-4C-alkoxy, R3 is hydrogen.
A further special subaspect (subaspect 10) of said aspects a, d and e refers to compounds of formula I according to aspects a, d and e, in which Rl is l-4C-alkoxy, R2 is l-4C-alkoxy, R3 is hydrogen.
A further special subaspect (subaspect 11) of said aspects a, d and e refers to compounds of formula I according to aspects a, d and e, in which Rl is halogen or l-2C-alkoxy, R2 is hydrogen or l-2C-alkoxy, R3 is l-2C-alkoxy.
A further special subaspect (subaspect 12) of said aspects a, c, d and e refers to compounds of formula I according to aspects a, c, d and e, in which Rl is l-2C-alkoxy, R2 is l-2C-alkoxy, R3 is l-2C-alkoxy.
Compounds according to subaspect 12 more worthy to be mentioned are those, in which none of Rl, R2 and R3 is bound to the 10-position of the pyrrolo[2.1-a]isoquinoline ring.
A further special subaspect (subaspect 13) of said aspects a, d and e refers to compounds of formula I according to aspects a, d and e, in which
Rl is l-2C-alkoxy,


R2 is hydrogen,
R3 is l-2C-alkoxy.
Compounds according to subaspect 13 more worthy to be mentioned are those, in which Rl is bound
to the 8-position and R3 is bound to the 9-position of the pyrrolo[2.1-a]isoquinoline ring, or those, in
which Rl is bound to the 9-position and R3 is bound to the 8-position of the pyrrolo[2.1-
ajisoquinoline ring.
A further special subaspect (subaspect 14) of said aspects a, b, d and e refers to compounds of formula
I according to aspects a, b, d and e, in which
Rl is halogen,
R2 is hydrogen,
R3 is l-2C-alkoxy,
Compounds according to subaspect 14 more worthy to be mentioned are those, in which Rl is bound
to the 8-position and R3 is bound to the 9-position of the pyrroIo[2.1-a]isoquinoline ring, or those, in
which Rl is bound to the 9-position and R3 is bound to the 8-position of the pyrrolo[2.1-
a]isoquinoline ring.
A further special subaspect (subaspect 15) of said aspects a, b, c, d and e refers to compounds of
formula 1 according to aspects a, b, c, d and e, in which
Rl is halogen,
R2 is l-2C-alkoxy,
R3 is l-2C-alkoxy.
Compounds according to subaspect 15 more worthy to be mentioned are those, in which none of Rl,
R2 and R3 is bound to the 10-position of the pyrrolo[2.1-a]isoquinoline ring.
A further special subaspect (subaspect 16) of said aspects a, b, c, d and e refers to compounds of
formula I according to aspects a, b, c, d and e, in which
Rl is halogen,
R2 is halogen,
R3 is l-2C-alkoxy.
Compounds according to subaspect 16 more worthy to be mentioned are those, in which none of Rl,
R2 and R3 is bound to the 10-position of the pyrrolo[2.1-a]isoquinoline ring.
A further special subaspect (subaspect 17) of said aspects a, b, c, d and e refers to compounds of
formula 1 according to aspects a, b, c, d and e, in which
Rl is halogen, nitro, l-4C-alkyl or l-4C-alkoxy-2-4C-alkoxy.
A further special subaspect (subaspect 18) of aspects a, b, c, d and e refers to compounds of formula I
according to aspects a, b, c, d and e, in which
Rl is chlorine or fluorine.
Compounds according to subaspect 18 more worthy to be mentioned are those, in which Rl is not
bound to the 10-position of the pyrrolo[2.1-a]isoquinoline ring.

A further special subaspect (subaspect 19) of aspects a, b, c, d and e refers to compounds of formula I according to aspects a, b, c, d and e, in which R4 is l-4C-alkyl, R41 is hydrogen or l-4C-aIkyl, R5 is hydrogen or l-4C-alkyl, R51 is hydrogen or l-4C-alkyl, or
R4 is hydrogen or l-4C-alkyl, R41 is hydrogen or l-4C-alkyl, R5 is l-4C-alkyl or l-4C-alkoxycarbonyl, R51 is hydrogen or l-4C-alkyl, or
R4 and R5 together form a 3-4C-alkyIene bridge and R41 and R51 are both hydrogen. A further special subaspect (subaspect 20) of aspects a, b, c, d and e refers to compounds of formula I according to aspects a, b, c, d and e, in which R4 is l-4C-alkyl, R41 is hydrogen or l-4C-alkyl, R5 is hydrogen, R51 is hydrogen, or
R4 is hydrogen, R41 is hydrogen,
R5 is l-4C-alkyl or l-4C-alkoxycarbonyl, R51 is hydrogen, or
R4 is hydrogen, R41 is hydrogen, R5 is l-4C-alkyl, R51 is l-4C-alkyl, or
R4 and R5 together form a 3-4C-alkylene bridge and R41 and R51 are both hydrogen. A further special subaspect (subaspect 21) of aspects a, b, c, d and e refers to compounds of formula I according to aspects a, b, c, d and e, in which either R4 is l-4C-alkyl, or R41 is l-4C-alkyl, or
R5 is l-4C-alkyl or l-4C-alkoxycarbanyl, or R51 is l-4C-alkyl, or
R4 and R5 together form a 3-4C-alkylene bridge and R41 and R51 are both hydrogen.


A further special subaspect (subaspect 22) of aspects a, b, c, d and e refers to compounds of formula I
according to aspects a, b, c, d and e, in which
R5 is l-4C-alkyl.
A further special subaspect (subaspect 23) of aspects a, b, c, d and e refers to compounds of formula I
according to aspects a, b, c, d and e, in which
R4 is hydrogen,
R41 is hydrogen,
R5 is l-4C-alkyl,
R51 is hydrogen.
A further special subaspect (subaspect 24) of aspects a, b, c, d and e refers to compounds of formula I
according to aspects a, b, c, d and e, in which
R4 is hydrogen,
R41 is hydrogen,
R5 is methyl or ethyl,
R51 is hydrogen.
A further special subaspect (subaspect 25) of aspects a, b, c, d and e refers to compounds of formula I
according to aspects a, b, c, d and e, in which
R4 is hydrogen,
R41 is hydrogen,
R5 is methyl,
R51 is hydrogen.
A further special subaspect (subaspect 26) of aspects a, b, c, d and e refers to compounds of formula I
according to aspects a, b, c, d and e, in which
R6 is l-6C-alkyI, or l-4C-alkyl substituted by R61, in which
R61 is l-4C-alkoxycarbonyl.
A further special subaspect (subaspect 27) of aspects a, b, c, d and e refers to compounds of formula I
according to aspects a, b, c, d and e, in which
R6 is methyl, ethyl or methoxycarbonylethyl.
A further special subaspect (subaspect 28) of aspects a, b, c, d and e refers to compounds of formula I
according to aspects a, b, c, d and e, in which
R6 is methyl.
A further special subaspect (subaspect 29) of aspects a, b, c, d and e refers to compounds of formula I
according to aspects a, b, c, d and e, in which
R6 is methoxycarbonylethyl.
A further special subaspect (subaspect 30) of aspects a, b, c, d and e refers to compounds of formula I
according to aspects a, b, c, d and e, in which
R7 is Het2, R74- and/or R75-substituted Het2, or hydroxy-dimethyl-phenyl, in which
Het2 is pyridinyl or quinolinyl,


R74 is halogen, l-4C-alkyl, trifluoromethyl, l-4C-alkoxy, cyano, amino, mono- or di-l-4C-
alkylamino, l-4C-alkoxycarbonyl, carboxyl, nitro, phenyl or phenyloxy, R75 is l-4C-alkyl.
Compounds according to subaspect 30 more worthy to be mentioned are those, in which R7 is Het2, R74- and/or R75-substituted Het2, or 4-hydroxy-3,5-dimethyIphenyl, in which Het2 is pyridin-4-yl or quinolin-4-yl, R74 is halogen, l-4C-alkyl, trifluoromethyl, l-4C-alkoxy, cyano, amino, mono- or di-l-4C-
alkylamino, l-4C-alkoxycarbonyl, carboxyl, nitro, phenyl or phenyloxy, R75 is l-4C-alkyl.
A further special subaspect (subaspect 31) of aspects a, b, c, d and e refers to compounds of formula I according to aspects a, b, c, d and e, in which R7 is pyridin-4-yl.
A further special subaspect (subaspect 32) of aspects a, b, c, d and e refers to compounds of formula I according to aspects a, b, c, d and e, in which R7 is 2,6-dimethylpyridin-4-yl.
A further special subaspect (subaspect 33) of aspects a, b, c, d and e refers to compounds of formula I according to aspects a, b, c, d and e, in which R7 is quinolin-4-yl.
A further special subaspect (subaspect 34) of aspects a, b, c and d refers to compounds of formula I according to aspects a, b, c and d, in which R8 is l-4C-alkyl, phenyl, 2-4C-alkinyl, cyano, -CH2-0-R81, phenylcarbonyl or -C(0)-N(R82)R83, in
which R81 is hydrogen, l-4C-alkyl, l-4C-alkoxy-2-4-alkyl or l-4C-alkylcarbonyl, R82 is hydrogen, l-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-l-4C-alkyl, phenyl or phenyl-l-4C-
alkyl, R83 is hydrogen or l-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 or N-(l-4C-alkyl)-piperazinyl.
A further special subaspect (subaspect 35) of aspects a, b, c and d refers to compounds of formula I according to aspects a, b, c and d, in which
R8 is phenyl, cyano, phenylcarbonyl or -C(0)-N(R82)R83, in which R82 is hydrogen, l-4C-alkyl, 3-7C-cycloalkyl or phenyl, R83 is hydrogen or l-4C-alkyl, or
R82 and R83 together and with inclusion of the nitrogen atom, to which they are bound, form a pyrrolidinyl ring.
A further special subaspect (subaspect 36) of aspects a, b, c and d refers to compounds of formula I according to aspects a, b, c and d, in which


R51 is hydrogen,
or
R4 and R5 together form a 3-4C-alkylene bridge and R41 and R51 are both hydrogen,
R6 is l-6Galkyl or l-4C-alkyl substituted by R61, in which
R61 is l-4C-alkoxycarbonyl,
R7 is phenyl, Het2, R71- and/or R72- and/ or R73-substituted phenyl, R74- and/or R75-substituted
Het2, or naphthyl, in which Het2 is a heteroaryl radical selected from the group consisting of furanyl, thiophenyl, pyrrolyl,
pyridinyl, quinolyl, indolyl, benzothiophenyl and benzofuranyl, R71 is hydroxyl, halogen, nitro, trifluoromethyl, l-4C-alkyI, l-4C-alkoxy, amino, mono- or di-l-4C-
alkylamino, l-4C-aIkylsulphonylamino, tolylsulphonylamino or aryloxy, in which aryl is R711-substituted phenyl, in which R711 is halogen,
R72 is l-4C-alkyl, l-4C-alkoxy or l-4C-alkoxycarbonyl, R73 is l-4C-alkyl or l-4C-alkoxy,
R74 is l-4C-alkyl, trifluoromethyl, l-4C-alkoxy, l-4C-alkoxycarbonyl, nitro, phenyl or phenyloxy, R75 is l-4C-alkyl,
R8 is phenyl, cyano, phenylcarbonyl or -C(0)-N(R82)R83, in which R82 is hydrogen, l-4C-alkyl, 3-7C-cycloalkyl or phenyl, R83 is hydrogen or l-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 and piperidinyl; under the provisio, that, when R5and R51 are both hydrogen, then
R8 is other than phenyl, phenylcarbonyl or -C(0)-N(R82)R83, in which R82 is hydrogen, l-4C-alkyl, 3-7C-cycIoalkyI or phenyl, R83 is hydrogen or l-4C-alkyI, 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 and piperidinyl; and the salts, stereoisomers, hydrates and hydrates of the salts of these compounds. Compounds according to aspect a in particular worthy to be mentioned are those of formula 1, in which
Rl is chlorine, fluorine, nitro, amino, methyl, methoxy, methoxyethoxy or difluoromethoxy, R2 is hydrogen or methoxy, R3 is hydrogen or methoxy, or Rl and R2 bound to the benzo ring moiety in ortho-position to each other together form a
difluoromethylenedioxy bridge and R3 is hydrogen, and none of Rl, R2 and R3 is bound to the 10-position of the pyrrolo[2.1-a]isoquinoline ring,


R4 is hydrogen or methyl,
R41 is hydrogen or methyl,
R5 is hydrogen,
R51 is hydrogen,
or
R4 is hydrogen,
R41 is hydrogen,
R5 is hydrogen or methyl,
R51 is hydrogen or methyl,
or
R4 is hydrogen,
R41 is hydrogen,
R5 is methoxycarbonylethyl,
R51 is hydrogen,
or
R4 and R5 together form a tetramethylene (-CH2-CH2-CH2-CH2-) bridge and R41 and R51 are both
hydrogen, R6 is methyl, ethyl or methoxycarbonylethyl,
R7 is phenyl, Het2, R71- and/or R72- and/or R73-substituted phenyl, or naphthyl, in which Het2 is indolyl, pyridinyl or quinolyl,
R71 is hydroxyl, chlorine, methoxy, dimethylamino, or aryloxy, in which aryl is R7ll-substituted phenyl, in which R711 is chlorine,
R72 is methyl, tert-butyl or methoxy, R73 is methyl, tert-butyl or methoxy,
R8 is phenyl, cyano, phenylcarbonyl or -C(0)-N(R82)R83, in which R82 is hydrogen, methyl, ethyl, iso-propyl, iso-butyl, cyclohexyl, cyclopropyl or phenyl, R83 is hydrogen or methyl, or R82 and R83 together and with inclusion of the nitrogen atom, to which they are bound, form a
pyrrolidinyl radical; under the provisio, that, when R5and R51 are both hydrogen, then
R8 is other than phenyl, phenylcarbonyl or -C(0)-N(R82)R83, in which R82 is hydrogen, methyl, ethyl, iso-propyl, iso-butyl, cyclohexyl, cyclopropyl or phenyl, R83 is hydrogen or methyl, or R82 and R83 together and with inclusion of the nitrogen atom, to which they are bound, form a
pyrrolidinyl radical;
and the salts, stereoisomers, hydrates and hydrates of the salts of these compounds.


Compounds according to aspect b more worthy to be mentioned are those of formula I, in which
Rl is halogen, nitro, amino, l-4C-alkyl, l-4C~alkoxy-2-4C-alkoxy, or completely or predominantly
fluorine-substituted l-4C-alkoxy, with the provisio that Rl is not trifluoromethoxy, R2 is hydrogen or l-4C-alkoxy, R3 is hydrogen or l-4C-alkoxy, or Rl and R2 bound to the benzo ring moiety in ortho-position to each other together form a completely
or predominantly fluorine-substituted l-2C-alkylenedioxy bridge and R3 is hydrogen, R4 is hydrogen or l-4C-a!kyl, R41 is hydrogen or l-4C-alkyl, R5 is hydrogen, R51 is hydrogen, or
R4 is hydrogen, R41 is hydrogen, R5 is hydrogen or l-4C-alkyl, R51 is hydrogen or l-4C-alkyl, or
R4 is hydrogen, R41 is hydrogen, R5 is l-4C-alkoxycarbonyl, R51 is hydrogen, or
R4 and R5 together form a 3-4C-alkylene bridge and R41 and R51 are both hydrogen, R6 is l-6C-alkyl, formyl, or l-4C-alkyI substituted by R61, in which R61 is l-4C-alkoxycarbonyl, R7 is phenyl, Het2, R71- and/or R72- and/ or R73-substituted phenyl, R74- and/or R75-substituted
Het2, or naphthyl, in which Het2 is a heteroaryl radical selected from the group consisting of furanyl, thiophenyl, pyrrolyl,
pyridinyl, quinolyl, indolyl, benzothiophenyl and benzofuranyl, R71 is hydroxyl, halogen, nitro, trifluoromethyl, l-4C-alkyl, l-4C-alkoxy, amino, mono- or di-l-4C-
alkylamino, l-4C-alkylsulphonylamino, tolylsulphonylamino or aryloxy, in which aryl is R711-substituted phenyl, in which R711 is halogen,
R72 is l-4C-alkyl, l-4C-alkoxy or l-4C-alkoxycarbonyl, R73 is l-4C-aIkyI or l-4C-alkoxy, R74 is l~4C-alkyl, trifluoromethyl, l-4C-alkoxy, l-4C-alkoxycarbonyl, nitro, phenyl or phenyloxy,
R75 is l-4C-alkyl,


R8 is phenyl, cyano, phenykarbonyl, -C(0)-N(R82)R83 or -C(0)-OR9, in which
R82 is hydrogen, l-4C-aIkyl, 3-7C-cycloalkyl or phenyl,
R83 is hydrogen or l-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 and piperidinyl, R9 is l-4C-alkyl; under the provisio, that, when R5and R51 are both hydrogen, then
R8 is other than phenyl, phenykarbonyl, -C(0)-N(R82)R83 or -C(0)-OR9, in which R82 is hydrogen, l-4C-alkyl, 3-7C-cycloalkyl or phenyl, R83 is hydrogen or l-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 and piperidinyl, R9 is 14C-alkyl;
and the salts, stereoisomers, hydrates and hydrates of the salts of these compounds. Compounds according to aspect b in particular worthy to be mentioned are those of formula I, in which
Rl is chlorine, fluorine, nitro, amino, methyl, methoxyethoxy or difluoromethoxy, R2 is hydrogen or methoxy, R3 is hydrogen or methoxy, or Rl and R2 bound to the benzo ring moiety in ortho-position to each other together form a
difluoromethylenedioxy bridge and R3 is hydrogen, and none of Rl, R2 and R3 is bound to the 10-position of the pyrrolo[2.1-a]isoquinoline ring, R4 is hydrogen or methyl, R41 is hydrogen or methyl, R5 is hydrogen, R51 is hydrogen, or
R4 is hydrogen, R41 is hydrogen, R5 is hydrogen or methyl, R51 is hydrogen or methyl, or
R4 is hydrogen, R41 is hydrogen, R5 is methoxycarbonyl, R51 is hydrogen,
or


R4 and R5 together form a tetramethylene (-CH2-CH2-CH2-CH2-) bridge and R41 and R51 are both
hydrogen, R6 is methyl, ethyl or methoxycarbonylethyl,
R7 is phenyl, Het2, R71- and/ or R72- and/or R73-substituted phenyl, or naphthyl, in which Het2 is indolyl, pyridinyl or quinolyl,
R71 is hydroxyl, chlorine, methoxy, dimethylamino, or aryloxy, in which aryl is R711-substituted phenyl, in which R711 is chlorine,
R72 is methyl, tert-butyl or methoxy, R73 is methyl, tert-butyl or methoxy,
R8 is phenyl, cyano, phenylcarbonyl, -C(0)-N(R82)R83 or -C(0)-OR9, in which R82 is hydrogen, methyl, ethyl, iso-propyl, iso-butyl, cyclohexyl, cyclopropyl or phenyl, R83 is hydrogen or methyl, or R82 and R83 together and with inclusion of the nitrogen atom, to which they are bound, form a
pyrrolidinyl radical, R9 is methyl or ethyl; under the provisio, that, when R5and R51 are both hydrogen, then
R8 is other than phenyl, phenylcarbonyl, -C(0)-N(R82)R83 or -C(0)-OR9, in which R82 is hydrogen, methyl, ethyl, iso-propyl, iso-butyl, cyclohexyl, cyclopropyl or phenyl, R83 is hydrogen or methyl, or R82 and R83 together and with inclusion of the nitrogen atom, to which they are bound, form a
pyrrolidinyl radical, R9 is methyl or ethyl;
and the salts, stereoisomers, hydrates and hydrates of the salts of these compounds. Compounds according to aspect c more worthy to be mentioned are those of formula I, in which Rl is halogen, nitro, amino, l-4C-alkyl, l-4C-alkoxy, l-4C-alkoxy-2-4C-alkoxy, or completely or
predominantly fluorine-substituted l-4C-alkoxy,
R2 is l-4C-aIkoxy,
R3 is l-4C-alkoxy,
R4 is hydrogen or l-4C-alkyl,
R41 is hydrogen or l-4C-alkyl,
R5 is hydrogen,
R51 is hydrogen,
or
R4 is hydrogen,
R41 is hydrogen,
R5 is hydrogen or l-4C-alkyl,


R51 is hydrogen or l-4C-aIkyl,
or
R4 is hydrogen,
R41 is hydrogen,
R5 is l-4C-alkoxycarbonyl,
R51 is hydrogen,
or
R4 and R5 together form a 3-4C-alkylene bridge and R41 and R51 are both hydrogen,
R6 is l-6C-aIkyl or l-4C-alkyl substituted by R61, in which
R61 is l-4C-alkoxycarbonyl,
R7 is phenyl, Het2, R71- and/or R72- and/or R73-substituted phenyl, R74- and/or R75-substituted
Het2, or naphthyl, in which Het2 is a heteroaryl radical selected from the group consisting of furanyl, thiophenyl, pyrrolyl,
pyridinyl, quinolyl, indolyl, benzothiophenyl and benzofuranyl, R71 is hydroxyl, halogen, nitro, trifluoromethyl, l-4C-alkyl, l-4C-alkoxy, amino, mono- or di-l-4C-
alkylamino, l-4C-alkylsulphonylamino, tolylsulphonylamino or aryloxy, in which aryl is R711-substituted phenyl, in which R711 is halogen,
R72 is l-4C-alkyl, l-4C-alkoxy or l-4C-alkoxycarbonyl, R73 is l-4C-alkyl or 14C-alkoxy,
R74 is l-4C-alkyl, trifluoromethyl, l-4C-alkoxy, l-4C-alkoxycarbonyl, nitro, phenyl or phenyloxy, R75 is l-4C-alkyl,
R8 is phenyl, cyano, phenylcarbonyl, -C(0)-N(R82)R83 or -C(0)-OR9, in which R82 is hydrogen, l-4C-alkyl, 3-7C-cycloalkyl or phenyl, R83 is hydrogen or l-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 and piperidinyl, R9 is l-4C-alkyl; under the provisio, that, when R5and R51 are both hydrogen, then
R8 is other than phenyl, phenylcarbonyl, -C(0)-N(R82)R83 or -C(0)-OR9, in which R82 is hydrogen, l-4C-alkyl, 3-7C-cycloalkyl or phenyl, R83 is hydrogen or l-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 and piperidinyl, R9 is l-4C-alkyl; and the salts, stereoisomers, hydrates and hydrates of the salts of these compounds.

Compounds according to aspect c in particular worthy to be mentioned are those of formula I, in
which
Rl is chlorine, fluorine, nitro, amino, methyl, methoxy, methoxyethoxy or difluoromethoxy,
R2 is methoxy,
R3 is methoxy,
and none of Rl, R2 and R3 is bound to the 10-position of the pyrrolo[2.1-a]isoquinoline ring,
R4 is hydrogen or methyl,
R41 is hydrogen or methyl,
R5 is hydrogen,
R51 is hydrogen,
or
R4 is hydrogen,
R41 is hydrogen,
R5 is hydrogen or methyl,
R51 is hydrogen or methyl,
or
R4 is hydrogen,
R41 is hydrogen,
R5 is methoxycarbonyl,
R51 is hydrogen,
or
R4 and R5 together form a tetramethylene (-CH2-CH2-CH2-CH2-) bridge and R41 and R51 are both
hydrogen, R6 is methyl, ethyl or methoxycarbonylethyl,
R7 is phenyl, Het2, R71- and/or R72- and/or R73-substituted phenyl, or naphthyl, in which Het2 is indolyl, pyridinyl or quinolyl,
R71 is hydroxyl, chlorine, methoxy, dimethylamino, or aryloxy, in which aryl is R711-substituted phenyl, in which R711 is chlorine,
R72 is methyl, tert-butyl or methoxy, R73 is methyl, tert-butyl or methoxy,
R8 is phenyl, cyano, phenylcarbonyl, -C(0)-N(R82)R83 or -C(0)-OR9, in which R82 is hydrogen, methyl, ethyl, iso-propyl, iso-butyl, cyclohexyl, cyclopropyl or phenyl, R83 is hydrogen or methyl, or R82 and R83 together and with inclusion of the nitrogen atom, to which they are bound, form a
pyrrolidinyl radical,
R9 is methyl or ethyl;
under the provisio, that,


when R5and R51 are both hydrogen, then
R8 is other than phenyl, phenylcarbonyl, -C(0)-N(R82)R83 or -C(0)-OR9, in which
R82 is hydrogen, methyl, ethyl, iso-propyl, iso-butyl, cyclohexyl, cyclopropyl or phenyl,
R83 is hydrogen or methyl, or
R82 and R83 together and with inclusion of the nitrogen atom, to which they are bound, form a
pyrrolidinyl radical, R9 is methyl or ethyl;
and the salts, stereoisomers, hydrates and hydrates of the salts of these compounds. Compounds according to aspect d more worthy to be mentioned are those of formula I, in which Rl is halogen, nitro, amino, l-4C-alkyl, l-4C-alkoxy, l-4C-alkoxy-2-4C-a!koxy, or completely or
predominantly fluorine-substituted l-4C-alkoxy, R2 is hydrogen or l-4C-alkoxy, R3 is hydrogen or l-4C-alkoxy, or Rl and R2 bound to the benzo ring moiety in ortho-position to each other together form a completely
or predominantly fluorine-substituted l-2C-alkylenedioxy bridge and R3 is hydrogen, R4 is l-4C-alkyl, R41 is hydrogen or l-4C-alkyl, R5 is hydrogen, R51 is hydrogen, or
R4 is hydrogen, R41 is hydrogen, R5 is l-4C-alkyl, R51 is hydrogen or l-4C-alkyl, or
R4 is hydrogen, R41 is hydrogen, R5 is l-4C-alkoxycarbonyl, R51 is hydrogen, or
R4 and R5 together form a 3-4C-alkylene bridge and R41 and R51 are both hydrogen, R6 is l-6C-alkyl or l-4C-alkyl substituted by R61, in which R61 is l-4C-alkoxycarbonyl, R7 is phenyl, Het2, R71- and/or R72- and/or R73-substituted phenyl, R74- and/or R75-substituted
Het2, or naphthyl, in which Het2 is a heteroaryl radical selected from the group consisting of furanyl, thiophenyl, pyrrolyl,
pyridinyl, quinolyl, indolyl, benzothiophenyl and benzofuranyl,

R71 is hydroxyl, halogen, nitro, trifluoromethyl, l-4C-alkyl, l-4C-alkoxy, amino, mono- or di-l-4C-
alkylamino, l-4C-alkylsulphonylamino, tolylsulphonylamino or aryloxy, in which aryl is R711-substituted phenyl, in which R711 is halogen,
R72 is l-4C-alkyl, l-4C-alkoxy or l-4C-alkoxycarbonyl, R73 is l-4C-alkyl or l-4C-alkoxy,
R74 is l-4C-alkyl, trifluoromethyl, l-4C-alkoxy, l-4C-alkoxycarbonyl, nitro, phenyl or phenyloxy, R75 is l-4C-alkyl,
R8 is phenyl, cyano, phenylcarbonyl, -C(0)-N(R82)R83 or -C(0)-OR9, in which R82 is hydrogen, l-4C-alkyl, 3-7C-cycloalkyl or phenyl, R83 is hydrogen or l-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 and piperidinyl, R9 is l-4C-alkyl; under the provisio, that, when R5and R51 are both hydrogen, then
R8 is other than phenyl, phenylcarbonyl, -C(0)-N(R82)R83 or -C(0)-OR9, in which R82 is hydrogen, l-4C-alkyl, 3-7C-cycloalkyl or phenyl, R83 is hydrogen or l-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 and piperidinyl, R9 is l-4C-alkyl;
and the salts, stereoisomers, hydrates and hydrates of the salts of these compounds. Compounds according to aspect d in particular worthy to be mentioned are those of formula I, in which
Rl is chlorine, fluorine, nitro, amino, methyl, methoxy, methoxyethoxy or difluoromethoxy, R2 is hydrogen or methoxy, R3 is hydrogen or methoxy, or Rl and R2 bound to the benzo ring moiety in ortho-position to each other together form a
difluoromethylenedioxy bridge and R3 is hydrogen,
and none of Rl, R2 and R3 is bound to the 10-position of the pyrrolo[2.1-a]isoquinoline ring,
R4 is methyl,
R41 is hydrogen or methyl,
R5 is hydrogen,
R51 is hydrogen,
or
R4 is hydrogen,
R41 is hydrogen,


R5 is methyl,
R51 is hydrogen or methyl,
or
R4 is hydrogen,
R41 is hydrogen,
R5 is methoxycarbonyl,
R51 is hydrogen,
or
R4 and R5 together form a tetramethylene (-CH2-CH2-CH2-CH2-) bridge and R41 and R51 are both
hydrogen, R6 is methyl, ethyl or methoxycarbonylethyl,
R7 is phenyl, Het2, R71- and/or R72- and/or R73-substituted phenyl, or naphthyl, in which Het2 is a heteroaryl radical selected from the group consisting of furanyl, thiophenyl, pyrrolyl,
pyridinyl, quinolyl, indolyl, benzothiophenyl and benzofuranyl, R71 is hydroxyl, chlorine, methoxy, dimethylamino, or aryloxy, in which aryl is R711-substituted phenyl, in which R711 is chlorine,
R72 is methyl, tert-butyl or methoxy, R73 is methyl, tert-butyl or methoxy,
R8 is phenyl, cyano, phenylcarbonyl, -C(0)-N(R82)R83 or -C(0)-OR9, in which R82 is hydrogen, methyl, ethyl, iso-propyl, iso-butyl, cyclohexyl, cyclopropyl or phenyl, R83 is hydrogen or methyl, or R82 and R83 together and with inclusion of the nitrogen atom, to which they are bound, form a
pyrrolidinyl radical, R9 is methyl or ethyl; under the provisio, that, when R5and R51 are both hydrogen, then
R8 is other than phenyl, phenylcarbonyl, -C(0)-N(R82)R83 or -C(0)-OR9, in which R82 is hydrogen, methyl, ethyl, iso-propyl, iso-butyl, cyclohexyl, cyclopropyl or phenyl, R83 is hydrogen or methyl, or R82 and R83 together and with inclusion of the nitrogen atom, to which they are bound, form a
pyrrolidinyl radical, R9 is methyl or ethyl;
and the salts, stereoisomers, hydrates and hydrates of the salts of these compounds. A special interest in the compounds according to this invention refers to those compounds of formula I which are included -within the scope of this invention- by one or, when possible, by more of the following special embodiments:

A special embodiment (embodiment 1) of the compounds according to this invention refers to those
compounds of formula I, in which
R8 is -C(0)-OR9, in which
R9 is l-4C-alkyl.
Another special embodiment (embodiment 2) of the compounds according to this invention refers to
those compounds of formula I, in which
R8 is cyano.
Another special embodiment (embodiment 3) of the compounds according to this invention refers to
those compounds of formula I, in which
R4 is hydrogen, and
R41 is hydrogen.
Another special embodiment (embodiment 4) of the compounds according to this invention refers to
those compounds of formula I, in which
R5 is l-4C-alkyl, cyano or l-4C-alkoxycarbonyl, and
R51 is hydrogen.
Another special embodiment (embodiment 5) of the compounds according to this invention refers to
those compounds of formula I, in. which
R4 is hydrogen,
R41 is hydrogen,
R5 is cyano; or, in particular, l-4C-alkyl, such as e.g. l-2C-alkyl, especially methyl; and
R51 is l-4C-alkyl, such as e.g. l-2C-alkyl, especially methyl; or, in particular hydrogen.
Another special embodiment (embodiment 6) of the compounds according to this invention refers to
those compounds of formula I, in which
R5 is l-4C-alkyl, such as e.g. l-2C-alkyl, in particular methyl, and
R51 is hydrogen.
Another special embodiment (embodiment 7) of the compounds according to this invention refers to
those compounds of formula I, in which
R4 is hydrogen,
R41 is hydrogen,
R5 is l-4C-alkyl, such as e.g. l-2C-alkyl, in particular methyl, and
R51 is hydrogen.
Another special embodiment (embodiment 8) of the compounds according to this invention refers to
those compounds of formula I, in which
R4 is hydrogen,
R41 is hydrogen,
R5 is cyano, and
R51 is hydrogen.

Another special embodiment (embodiment 9) of the compounds according to this invention refers to
those compounds of formula I, in which
none of Rl, R2 and R3 is bound to the 10-position of the pyrroIo[2.1-a]isoquinoline ring.
Another special embodiment (embodiment 10) of the compounds according to this invention refers to
those compounds of formula I, in which
none of Rl and R2 is bound to the 7- or 10-position of the pyrrolo[2.1-a]isoquinoline ring, and
R3 is hydrogen.
Another special embodiment (embodiment 11) of the compounds according to this invention refers to
those compounds of formula I, in which
none of Rl and R3 is bound to the 7- or 10-position of the pyrroIo[2.1-a]isoquinoline ring, and
none of Rl and R3 is hydrogen, and
R2 is bound to the 7-position of the pyrrolo[2.1-a]isoquinoline ring.
Another special embodiment (embodiment 12) of the compounds according to this invention refers to
those compounds of formula I, in which
Rl is l-4C-alkoxy, l-4C-alkoxy-2-4C-alkoxy, 3-7C-cycloalkoxy or 3-7C-cycloalkylmethoxy,
in particular
Rl is l-2C-alkoxy, l-2C-alkoxy-3-4C-alkoxy, 3-5C-cycloalkoxy or 3-5C-cycloalkylmethoxy,
in more particular
Rl is l-2C-alkoxy, such as e.g. methoxy.
Another special embodiment (embodiment 13) of the compounds according to this invention refers to
those compounds of formula I, in which
R2 is chlorine, or, in particular fluorine.
Another special embodiment (embodiment 14) of the compounds according to this invention refers to
those compounds of formula I, in which
R3 is l-4C-alkoxy, in particular l-2C-alkoxy, such as e.g. methoxy.
Another special embodiment (embodiment 15) of the compounds according to this invention refers to
those compounds of formula I, in which
Rl is l-4C-alkoxy, l-4C-alkoxy-2-4C-alkoxy, 3-7C-cycloalkoxy or 3-7C-cycloalkylmethoxy,
R2 is l-4C-alkoxy,
R3 is hydrogen, and
none of Rl and R2 is bound to the 7- or 10-position of the pyrrolo[2.1-a]isoquinoline ring.
Another special embodiment (embodiment 16) of the compounds according to this invention refers to
those compounds of formula I, in which
Rl is bound to the 8-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-4C-alkoxy, such as e.g.
l-2C-alkoxy, R2 is bound to the 9-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-4C-alkoxy, such as e.g.
l-2C-alkoxy, and
R3 is hydrogen.


Another special embodiment (embodiment 17) of the compounds according to this invention refers to
those compounds of formula I, in which
Rl is l-4C-alkoxy, l-4C-alkoxy-2-4C-alkoxy, 3-7C-cycloalkoxy or 3-7C-cycloalkylmethoxy,
R2 is halogen, and
R3 is l-4C-alkoxy.
Another special embodiment (embodiment 18) of the compounds according to this invention refers to
those compounds of formula I, which are from formulae la or lb shown below.
Another special embodiment (embodiment 19) of the compounds according to this invention refers to
those compounds of formula I, in which
Rl is l-2C-alkoxy, l-2C-alkoxy-2-3C-alkoxy, 3-5C-cycloalkoxy or 3-5C-cycIoaIkylmethoxy,
R2 is halogen, such as e.g. chlorine or fluorine,
R3 is l-2C-alkoxy,
and none of Rl, R2 and R3 is bound to the 10-position of the pyrrolo[2.1-a]isoquinoline ring.
Another special embodiment (embodiment 20) of the compounds according to this invention refers to
those compounds of formula I, in which
Rl is l-2C-alkoxy, l-2C-alkoxy-2-3C-alkoxy, 3-5C-cycloalkoxy or 3-5C-cycloalkyImethoxy,
R2 is bound to the 7-position of the pyrrolo[2.1-a]isoquinoline ring, and is chlorine or fluorine,
R3 is l-2C-alkoxy,
and none of Rl and R3 is bound to the 10-position of the pyrrolo[2.1-a]isoquinoline ring.
Another special embodiment (embodiment 21) of the compounds according to this invention refers to
those compounds of formula I, in which
Rl is bound to the 8-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy, such as e.g.
methoxy, R2 is bound to the 7-position of the pyrrolo[2.1-a]isoquinoline ring, and is chlorine or fluorine, and R3 is bound to the 9-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy, such as e.g.
methoxy.
Another special embodiment (embodiment 22) of the compounds according to this invention refers to
those compounds of formulae la or lb as shown below, in which
as a first alternative,
Rl is hydrogen,
R2 is chlorine or fluorine,
R3 is methoxy or ethoxy,
or, as a second alternative,
Rl is hydrogen,
R2 is methoxy or ethoxy,
R3 is methoxy or ethoxy,
or, as a third alternative,
Rl is methoxy or ethoxy,

R2 is chlorine or fluorine,
R3 is methoxy or ethoxy,
or, as a fourth alternative,
Rl is chlorine or fluorine,
R2 is methoxy or ethoxy,
R3 is methoxy or ethoxy,
or, as a fifth alternative,
Rl is methoxy or ethoxy,
R2 is methoxy or ethoxy,
R3 is methoxy or ethoxy.
Another special embodiment (embodiment 23) of the compounds according to this invention refers to
those compounds of formula I, in which
R7 is naphthyl (such as e.g. naphthalen-1-yl), or R71- and/or R72- and/or R73-substituted phenyl,
such as, for example,
4-hydroxy-3,5-dimethyIphenyl, 4-methoxy-3,5-dimethylphenyl, 4-carboxy-phenyl, 4-
carbamoyl-phenyl, 2-methyl-4-hydroxy-phenyl, 4-amino-phenyl, 4-(2H-tetrazol-5-yl)-phenyl, 4-
mopholino-sulphonylamino-phenyl, 4-methylsulphonylamino-phenyl, or 2-fluoro-3,4-
dimethoxy-phenyl. Another special embodiment (embodiment 24) of the compounds according to this invention refers to those compounds of formula I, in which either
R7 is Het2, 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 a group consisting of nitrogert, oxygen and sulfur,
and which optionally contains a benzene ring,
or
a fused bicyclic 9- or 10-membered, partially saturated heterocyclic ring radical containing a
benzene ring and comprising one or two heteroatoms, each of which is selected from a group
consisting of nitrogen, oxygen and sulfur,
or
N-oxy-pyridyl; such as, for example,
pyridyl, indolyl, quinolinyl, or indolinyl,
e.g. pyridin-4-yl, indol-3-yl, indol-5-yl, quinolin-4-yl, N-oxy-pyridin-4-yl, or indolin-5-yl; or
R7 is R74-substituted Het2, in which Het2 has one of the meanings as defined afore,
R74 is l-4C-alkyl, arylsulphonyl, l-4C-alkylsulphonyl, or -S(0)2-N(R712)R713, in which


aryl is phenyl, or R711-substituted phenyl, in which
R711 is l-4C-alkyl,
R712 isl-4C-alkyl,
R713 is l-4C-aIkyl, or
R712 and R713 together and with inclusion of the nitrogen atom to which they are bound form a
radical Het3, in which Het3 is pyrrolidin-1-yl, piperidin-1-yl or morpholin-4-yl; such as, for example,
l-tolylsulphonyl-pyrrol-3-yl, l-tolylsulphonyl-indol-3-yl, l-phenylsulphonyl-indol-3-yl, 1-
methylsulphonyl-indol-3-yl, 2-methyl-pyridin-4-yl, 3-methyl-pyridin-4-yl, 1-
dimethylaminosulphonyl-indol-3-yl, l-morpholinosulphonyl-indol-3-yl. Another special embodiment (embodiment 25) of the compounds according to this invention refers to those compounds of formula I, in which R7 is 4-hydroxy-3,5-dimethylphenyl.
Another special embodiment (embodiment 26) of the compounds according to this invention refers to those compounds of formula I, in which R7 is Het2, in which Het2 is a fused bicyclic 9- or 10-membered heteroaryl radical comprising one to three heteroatoms,
each of which is selected from a group consisting of nitrogen, oxygen and sulfur, which
optionally contains a benzene ring,
such as e.g. quinolyl or indolyl.
Another special embodiment (embodiment 27) of the compounds according to this invention refers to
those compounds of formula I, in which
R6 is l-4C-alkyl, such as e.g. methyl.
Another special embodiment (embodiment 28) of the compounds according to this invention refers to
those compounds of formula I, in which
R6 is l-4C-alkyl substituted by l-4C-alkoxycarbonyl, such as e.g. 2-methoxycarbonyl-ethyl.
Another special embodiment (embodiment 29) of the compounds according to this invention refers to
those compounds of formula I, in which
Rl is l-2C-alkoxy, l-2C-alkoxy-2-3C-alkoxy, 3-5C-cycloalkoxy, or 3-5C-cycloalkylmethoxy,
R2 is chlorine or fluorine,
R3 is l-2C-alkoxy,
and none of Rl, R2 and R3 is bound to the 10-position of the pyrrolo[2.1-a]isoquinoline ring,
and
R4 is hydrogen,
R41 is hydrogen,
R5 is hydrogen, l-2C-alkyl or cyano,
R51 is hydrogen,


and
R8 is cyano;
in particular
Rl is bound to the 8-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-aIkoxy,
R2 is bound to the 7-position of the pyrrolo[2.1-a]isoquinoline ring, and is chlorine or fluorine,
R3 is bound to the 9-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy,
and
R4 is hydrogen,
R41 is hydrogen,
R5 is hydrogen, l-2C-alkyl or cyano,
R51 is hydrogen,
and
R8 is cyano;
in more particular
Rl is bound to the 8-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy, such as e.g.
methoxy, R2 is bound to the 7-position of the pyrrolo[2.1-a]isoquinoline ring, and is fluorine, R3 is bound to the 9-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy, such as e.g.
methoxy, and
R4 is hydrogen, R41 is hydrogen, R5 is methyl, R51 is hydrogen, and
R8 is cyano.
Another special embodiment (embodiment 30) of the compounds according to this invention refers to those compounds of formula I, in which
Rl is l-2C-alkoxy, l-2C-alkoxy-2-3C-alkoxy, 3-5G-cycloalkoxy, or 3-5C-cycloalkylmethoxy, R2 is hydrogen, R3 is l-2C-alkoxy,
and none of Rl and R2 is bound to the 7- or 10-position of the pyrrolo[2.1-a]isoquinoline ring, and
R4 is hydrogen, R41 is hydrogen,
R5 is hydrogen, l-2C-alkyl or cyano, R51 is hydrogen,
and


R8 is cyano;
in particular
Rl is bound to the 8-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy,
R2 is hydrogen,
R3 is bound to the 9-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy,
and
R4 is hydrogen,
R41 is hydrogen,
R5 is hydrogen, l-2C-alkyI or cyano,
R51 is hydrogen,
and
R8 is cyano;
in more particular
Rl is bound to the 8-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy, such as e.g.
methoxy, R2 is hydrogen, R3 is bound to the 9-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy, such as e.g.
methoxy,
and
R4 is hydrogen,
R41 is hydrogen,
R5 is methyl,
R51 is hydrogen,
and
R8 is cyano.
Another special embodiment (embodiment 31) of the compounds according to this invention refers to
those compounds of formula I, in which
Rl is l-2C-alkoxy, l-2C-alkoxy-2-3C-alkoxy, 3-5C-cycloalkoxy, or 3-5C-cycloalkylmethoxy,
R2 is chlorine or fluorine,
R3 is l-2C-alkoxy,
and none of Rl, R2 and R3 is bound to the 10-position of the pyrrolo[2.1-a]isoquinoline ring,
and
R4 is hydrogen,
R41 is hydrogen,
R5 is hydrogen, l-2C-alkyl or cyano,
R51 is hydrogen,
and
R6 is l-2C-alkyl or 2-methoxycarbonylethyl,


and
R8 is cyano;
in particular
Rl is bound to the 8-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy,
R2 is bound to the 7-position of the pyrrolo[2.1-a]isoquinoline ring, and is chlorine or fluorine,
R3 is bound to the 9-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy,
and
R4 is hydrogen,
R41 is hydrogen,
R5 is hydrogen, l-2C-aIkyI or cyano,
R51 is hydrogen,
and
R6 is l-2C-alkyl or 2-methoxycarbonylethyl,
and
R8 is cyano;
in more particular
Rl is bound to the 8-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy, such as e.g.
methoxy,
R2 is bound to the 7-position of the pyrrolo[2.1-a]isoquinoline ring, and is fluorine,
R3 is bound to the 9-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy, such as e.g.
methoxy, and
R4 is hydrogen,
R41 is hydrogen,
R5 is methyl,
R51 is hydrogen,
and
R6 is methyl,
and
R8 is cyano.
Another special embodiment (embodiment 32) of the compounds according to this invention refers to
those compounds of formula Ia as shown below, in which
R2 is methoxy,
R3 is methoxy,
R4 is hydrogen,
R41 is hydrogen,
R51 is hydrogen,


and in which the following combinations 1.) to 75.) of the substituent meanings for Rl, R5, R6 and R8 shown in Table X apply:
Table X:

Rl R5 R6 R8
1.) hydrogen methyl Methyl cyano
2-) hydrogen methyl Methyl ethoxycarbonyl
3.) hydrogen methyl 2-methoxycarbonylethyl cyano
4.) hydrogen methyl 2-methoxycarbonylethyl ethoxycarbonyl
5-) hydrogen hydrogen Methyl cyano
6.) hydrogen hydrogen 2-methoxycarbonylethyl cyano
7-) fluorine methyl Methyl cyano
8.) fluorine methyl Methyl ethoxycarbonyl
9) fluorine methyl 2-methoxycarbonylethyl cyano
10.) fluorine methyl 2-methoxycarbonylethyl ethoxycarbonyl
11.) fluorine hydrogen Methyl cyano
12.) fluorine hydrogen 2-methoxycarbonylethyl cyano
13.) fluorine hydrogen Methyl ethoxycarbonyl
14.) fluorine hydrogen 2-methoxycarbonylethyl ethoxycarbonyl
15.) hydrogen cyano Methyl cyano
16.) hydrogen cyano Methyl ethoxycarbonyl
17.) hydrogen cyano 2-methoxycarbonylethyl cyano
18.) hydrogen cyano 2-methoxycarbonylethyl ethoxycarbonyl
19.) fluorine cyano Methyl cyano
20.) fluorine cyano Methyl ethoxycarbonyl
21.) fluorine cyano 2-methoxycarbonylethyl cyano
22.) fluorine cyano 2-methoxycarbonylethyl ethoxycarbonyl
23.) chlorine methyl Methyl cyano
24.) chlorine methyl Methyl ethoxycarbonyl
25.) chlorine methyl 2-methoxycarbonylethyl cyano
26.) chlorine methyl 2-methoxycarbonylethyl ethoxycarbonyl
27.) chlorine hydrogen Methyl cyano
28.) chlorine hydrogen 2-methoxycarbonylethyl cyano
29.) chlorine hydrogen Methyl ethoxycarbonyl
30.) chlorine hydrogen 2-methoxycarbonylethyl ethoxycarbonyl
31.) chlorine cyano Methyl cyano
32.) chlorine cyano Methyl ethoxycarbonyl
33.) chlorine cyano 2-methoxycarbonylethyl cyano
34.) chlorine cyano 2-methoxycarbonylethyl ethoxycarbonyl
35.) hydrogen methyl Methyl methoxycarbonyl
36.) hydrogen methyl 2-methoxycarbonylethyl methoxycarbonyl
37.) fluorine methyl Methyl methoxycarbonyl
38.) fluorine methyl 2-methoxycarbonylethyl methoxycarbonyl
39.) fluorine hydrogen Methyl methoxycarbonyl
40.) fluorine hydrogen 2-methoxycarbonylethyl methoxycarbonyl
41.) hydrogen cyano Methyl methoxycarbonyl
42.) hydrogen cyano 2-methoxycarbonylethyl methoxycarbonyl
43.) fluorine cyano Methyl methoxycarbonyl
44.) fluorine cyano 2-methoxycarbonylethyl methoxycarbonyl
45.) chlorine methyl Methyl methoxycarbonyl
46.) chlorine methyl 2-methoxycarbonylethyl methoxycarbonyl
47.) chlorine hydrogen Methyl methoxycarbonyl
48.) chlorine hydrogen 2-methoxycarbonylethyl methoxycarbonyl
49.) chlorine cyano Methyl methoxycarbonyl

50.) chlorine cyano 2-methoxycarbonylethyl methoxycarbonyl
51.) hydrogen methyl Ethyl cyano
52.) hydrogen methyl Ethyl ethoxycarbonyl
53.) hydrogen hydrogen Ethyl cyano
54.) fluorine methyl Ethyl cyano
55.) fluorine methyl Ethyl ethoxycarbonyl
56.) fluorine hydrogen Ethyl cyano
57.) fluorine hydrogen Ethyl ethoxycarbonyl
58.) hydrogen cyano Ethyl cyano
59.) hydrogen cyano Ethyl ethoxycarbonyl
60.) fluorine cyano Ethyl cyano
61.) fluorine cyano Ethyl ethoxycarbonyl
62.) chlorine methyl Ethyl cyano
63.) chlorine methyl Ethyl ethoxycarbonyl
64.) chlorine hydrogen Ethyl cyano
65.) chlorine hydrogen Ethyl ethoxycarbonyl
66.) chlorine cyano Ethyl cyano
67.) chlorine cyano Ethyl ethoxycarbonyl
68.) hydrogen methyl Ethyl methoxycarbonyl
69.) fluorine methyl Ethyl methoxycarbonyl
70.) fluorine hydrogen Ethyl methoxycarbonyl
71.) hydrogen cyano Ethyl methoxycarbonyl
72.) fluorine cyano Ethyl methoxycarbonyl
73.) chlorine methyl Ethyl methoxycarbonyl
74.) chlorine hydrogen Ethyl methoxycarbonyl
75.) chlorine cyano Ethyl methoxycarbonyl
whereby those combinations, in which R8 is cyano, are more worthy to be mentioned, and
whereby those combinations, in which R8 is cyano and R5 is other than hydrogen, are further more
worthy to be mentioned, and
whereby the combinations 1 to 7,16,24 and 35 are to be emphasized, and
whereby the combinations 1,3,5,6 and 7 are more to be emphasized, and
whereby the combination 7 is in particular to be emphasized.
Another special embodiment (embodiment 33) of the compounds according to this invention refers to
those compounds of formula I, in which
Het2 is a fused bicyclic 9- or 10-membered, partially saturated heterocyclic ring radical containing a
benzene ring and comprising one or two heteroatoms, each of which is selected from a group
consisting of nitrogen, oxygen and sulfur,
or
N-oxy-pyridyl. Another special embodiment (embodiment 34) of the compounds according to this invention refers to those compounds of formula I, in which R71 is mono- or di-l-4C-alkylaminocarbonyl, carbamoyl, tetrazolyl, or -N(H)S(0)2-N(R712)R713, in
which R712 is l-4C-alkyl, R713 is l-4C-alkyl, or

R712 and R713 together and with inclusion of the nitrogen atom to which they are bound form a
radical Het3, in which Het3 is pyrrolidin-l-yl, piperidin-l-yl or morpholin-4-yl.
Another special embodiment (embodiment 34) of the compounds according to this invention refers to those compounds of formula I, in which
R74 is phenyl-l-4C-alkyl, arylsulphonyl, l-4C-alkylsulphonyl, or -S(0)2-N(R712)R713, in which R712 is l-4C-alkyl, R713 is l-4C-alkyl, or R712 and R713 together and with inclusion of the nitrogen atom to which they are bound form a
radical Het3, in which Het3 is pyrrolidin-1-yl, piperidin-l-yl or morpholin-4-yl.
A notable embodiment (embodiment a) of variant 1 the present invention includes compounds of formula I, in which Rl is halogen, nitro, amino, mono- or di-l-4C-aIkyIamino, l~4C-alkyl, hydroxyl, l-4C-alkoxy, 1-4C-
alkoxy-2-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy, or completely or
predominantly fluorine-substituted l-4C-alkoxy, R2 is hydrogen, halogen or l-4C-alkoxy, R3 is hydrogen or l-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 l-2C-alkylenedioxy bridge, or Rl 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 Rl and R2 bound to the benzo ring moiety in ortho-position to each other together form a completely
or predominantly fluorine-substituted l-2C-alkylenedioxy bridge and R3 is hydrogen, R4 is hydrogen, R41 is hydrogen, R5 is hydrogen or l-4C-alkyl, R51 is hydrogen,
R6 is l-6C-alkyl, amino, formyl, or l-4C-alkyl substituted by R61, in which R61 is l-4C-alkoxycarbonyl, carboxyl, l-4C-alkoxy, hydroxyl, halogen or -N(R611)R612, in which R611 is hydrogen, l-4C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkyl-l-4C-alkyl, R612 is hydrogen or l-4C-alkyl, or R611 and R612 together and with inclusion of the nitrogen atom to which they are bound form a
radical Hetl, in which Hetl 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 a group


consisting of nitrogen, oxygen and sulfur, and optionally substituted by R613 on a ring nitrogen atom,
in which
R613 is lAC-alkyl 3-7C-cydoalkyl, 3-7C-cydoa]kyJ-l-4C-alkyl, hydroxy-2-4C-alkyl, l-4C-alkoxy-2-4C-alkyl, amino-2-4C-alkyl, mono- or di-l-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 a group consisting of nitrogen, oxygen and sulfur,
R71 is hydroxyl, haiogen, nitro, cyano, trifluoromethyl, l-4C-aIkyf, l-4C-a!koxy, amino, mono- or di-l-4C-alkylamino, l-4C-alkylsulphonylamino, arylsulphonylamino, l-4C-alkoxycarbonyl, carboxyl, l-4C-alkylthio, aryloxy-2-4C-alkoxy, aryloxy-l-4C-alkyl, aryloxy, aryl-l-4C-alkoxy, aryl, l-4C-alkoxy-2-4C-alkoxy, l-4C-alkoxy-l-4C-alkyl, hydroxy-2-4C-alkoxy, amino-2-4C-alkoxy, mono- or di-l-4C-alkylamino-2-4C-alkoxy, or completely or predominantly fluorine-substituted l-4C-alkoxy, in which
aryl is phenyl or R711-substituted phenyl, in which
R711 is halogen, l-4C-alkyl, l-4C-alkoxy, nitro or cyano,
R72 is halogen, l-4C-alkyl, l-4C-alkoxy or l-4C-alkoxycarbonyl,
R73 is l-4C-aIkyl or l-4C-alkoxy,
R74 is halogen, l-4C-alkyl, trifluoromethyl, l-4C-a!koxy, cyano, amino, mono- or di-l-4C-alkylamino, l-4C-alkoxycarbonyl, morpholino, carboxyl, nitro, phenyl or phenyloxy,
R75 is l-4C-alkyl or halogen,
R76 is halogen, hydroxyl, l-4C-alkyl, l-4C-alkoxy, carboxyl or l-4C-alkoxycarbonyl,
R77 is l-4C-alkyl or l-4C-alkoxy,
R8 is cyano,
and the salts, stereoisomers, hydrates and hydrates of the salts of these compounds.
A further notable embodiment (embodiment b) of variant 1 of the present invention includes
compounds of formula I, in which
Rl is halogen, nitro, amino, mono- or di-l-4C-alkylamino, l-4C-alkyl, hydroxyl, l-4C-alkoxy, 1-4C-alkoxy-2-4C-alkoxy, 3-7C-cycioalkoxy, 3-7C-cycloaikyImethoxy, or completely or predominantly fluorine-substituted l-4C-alkoxy,
R2 is hydrogen, halogen or l-4C-alkoxy,
R3 is hydrogen or l-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 l-2C-alkylenedioxy bridge, or

Rl 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
Rl and R2 bound to the benzo ring moiety in ortho-position to each other together form a completely or predominantly fluorine-substituted l-2C-alkylenedioxy bridge and R3 is hydrogen,
R4 is hydrogen,
R41 is hydrogen,
R5 is l-2C-alkyl,
R51 is hydrogen, or
R4 and R5 together form a tetramethylene (-CH2-CH2-CH2-CH2-) bridge and R41 and R51 are both hydrogen,
R6 is l-6C-alkyl, amino, formyl, or l-4C-alkyl substituted by R61, in which
R61 is l-4C-alkoxycarbonyl, carboxyl, l-4C-alkoxy, hydroxyl, halogen or -N(R611)R612, in which
R611 is hydrogen, l-4C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkyl-l-4C-alkyl,
R612 is hydrogen or l-4C-aIkyl, or
R611 and R612 together and with inclusion of the nitrogen atom to which they are bound form a radical Hetl, in which
Hetl 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 a group
consisting of nitrogen, oxygen and sulfur, and optionally substituted by R613 on a ring nitrogen atom,
in which
R613 is l-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-l-4C-alkyl, hydroxy-2-4C-alkyl, l-4C-alkoxy-2-4C-alkyl, amino-2-4C-alkyl, mono- or di-l-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 a group consisting of nitrogen, oxygen and sulfur,
R71 is hydroxyl, halogen, nitro, cyano, trifluoromethyl, l-4C-alkyl, l-4C-alkoxy, amino, mono- or di-l-4C-alkylamino, l-4C-alkylsu!phonylamino, arylsulphonylamino, l-4C-alkoxycarbonyl, carboxyl, l-4C-alkylthio, aryloxy-2-4C-alkoxy, aryloxy-l-4C-alkyl, aryloxy, aryl-l-4C-alkoxy, aryl, l-4C-alkoxy-2-4C-alkoxy, l-4C-alkoxy-l-4C-alkyl, hydroxy-2-4C-alkoxy, amino-2-4C-alkoxy, mono- or di-l-4C-alkylamino-2-4C-alkoxy, or completely or predominantly fluorine-substituted l-4C-alkoxy, in which
aryl is phenyl or R711-substituted phenyl, in which
R711 is halogen, l-4C-alkyl, l-4C-alkoxy, nitro or cyano,
R72 is halogen, l-4C-alkyl, l-4C-alkoxy or l-4C-alkoxycarbonyl,
R73 is l-4C-alkyl or l-4C-alkoxy,

R74 is halogen, l-4C-alkyl, trifluoromethyl, l-4C-alkoxy, cyano, amino, mono- or di-l-4C-alkylamino, l-4C-alkoxycarbonyl, morpholino, carboxyl, nitro, phenyl or phenyloxy,
R75 is l-4C-alkyl or halogen,
R76 is halogen, hydroxyl, l-4C-alkyl, l-4C-alkoxy, carboxyl or l-4C-alkoxycarbonyl,
R77 is l-4C-alkyl or l-4C-alkoxy,
R8 is l-4C-alkyl, phenyl, 2-4C-alkinyl, cyano, -CH2-OR81, phenylcarbonyl, -C(0)-N(R82)R83 or -C(0)-OR9, in which
R81 is hydrogen, l-4C-alkyl, l-4C-alkoxy-2-4-alkyl or l-4C-alkylcarbonyl,
R82 is hydrogen, l-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-l-4C-alkyl, phenyl or phenyl-l-4C-alkyl,
R83 is hydrogen or l-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
or N-(l-4C-alkyl)-piperazinyl,
R9 is hydrogen or l-4C-alkyl,
and the salts, stereoisomers, hydrates and hydrates of the salts of these compounds.
A special subclass of embodiment b includes compounds of formulae la or lb



R4 R41
R4 R41


in which,
as a first alternative,
Rl is hydrogen,
R2 is chlorine or fluorine,
R3 is methoxy or ethoxy,
or, as a second alternative,
Rl is hydrogen,
R2 is methoxy or ethoxy,
R3 is methoxy or ethoxy,
or, as a third alternative,
Rl is methoxy or ethoxy,
R2 is chlorine or fluorine,
R3 is methoxy or ethoxy,
or, as a fourth alternative,
Rl is chlorine or fluorine,
R2 is methoxy or ethoxy,

(la)

(lb)

R3 is methoxy or ethoxy,
or, as a fifth alternative,
Rl is methoxy or ethoxy,
R2 is methoxy or ethoxy,
R3 is methoxy or ethoxy,
R4 is hydrogen,
R41 is hydrogen,
R5 is ethyl or, in particular, methyl,
R51 is hydrogen,
R6 is methyl, ethyl or methoxycarbonylethyl,
R7 is Het2, R74- and/or R75-substituted Het2, or hydroxy-dimethyl-phenyl, in which
Het2 is pyridinyl or quinolinyl,
R74 is halogen, l-4C-alkyI, trifluoromethyl, l-4C-aIkoxy, cyano, amino, mono- or di-l-4C-
alkylamino, l-4C-alkoxycarbonyl, carboxyl, nitro, phenyl or phenyloxy, R75 is l-4C-alkyl. R8 is -C(0)-OR9, in which R9 is l-4C-alkyl,
and the salts, stereoisomers, hydrates and hydrates of the salts of these compounds. Compounds according to embodiments a or b more worthy to be mentioned are compounds of formula I, in which Rl is halogen or l-4C-alkoxy, R2 is hydrogen, halogen or l-4C-alkoxy, R3 is l-4C-alkoxy, R4 is hydrogen, R41 is hydrogen, R5 is l-2C-alkyl, R51 is hydrogen,
R6 is l-6C-alkyl, amino, formyl, or l-4C-alkyl substituted by R61, in which R61 is l-4C-alkoxycarbonyl, carboxyl, l-4C-alkoxy, hydroxyl, halogen or -N(R611)R612, in which R611 is hydrogen, l-4C-aIkyl, 3-7C-cycloalkyl or 3-7C-cycloalkyl-l-4C-alkyl, R612 is hydrogen or l-4C-alkyl, or R611 and R612 together and with inclusion of the nitrogen atom to which they are bound form a
radical Hetl, in which Hetl 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 a group consisting of nitrogen, oxygen and sulfur, and optionally substituted by R613 on a ring nitrogen atom, in which

R613 is l-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-l-4C-alkyl, hydroxy-2-4C-alkyl, l-4C-alkoxy-2-4C-alkyl, amino-2-4C-alkyl, mono- or di-l-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 a group consisting of nitrogen, oxygen and sulfur,
R71 is hydroxyl, halogen, nitro, cyano, trifluoromethyl, l-4C-alkyl, l-4C-alkoxy, amino, mono- or di-l-4C-alkylamino, l-4C-alkylsulphonylamino, arylsulphonylamino, l-4C-alkoxycarbonyl, carboxyl, l-4C-alkylthio, aryloxy-2-4C-aikoxy, aryloxy-l-4C-alkyl, aryloxy, aryl-l-4C-alkoxy, aryl, l-4C-alkoxy-2-4C-alkoxy, l-4C-alkoxy-l-4C-alkyl, hydroxy-2-4C-alkoxy, amino-2-4C-alkoxy, mono- or di-l-4C-alkylamino-2-4C-alkoxy, or completely or predominantly fluorine-substituted l-4C-alkoxy, in which
aryl is phenyl or R711-substituted phenyl, in which
R711 is halogen, l-4C-alkyl, l-4C-alkoxy, nitro or cyano,
R72 is halogen, l-4C-alkyl, l-4C-alkoxy or l-4C-alkoxycarbonyl,
R73 is l-4C-alkyl or l-4C-alkoxy,
R74 is halogen, l-4C-alkyl, trifluoromethyl, l-4C-alkoxy, cyano, amino, mono- or di-l-4C-alkylamino, l-4C-alkoxycarbonyl, morpholino, carboxyl, nitro, phenyl or phenyloxy,
R75 is l-4C-alkyl or halogen,
R76 is halogen, hydroxyl, l-4C-alkyl, l-4C-alkoxy, carboxyl or l-4C-alkoxycarbonyl,
R77 is l-4C-alkyl or l-4C-alkoxy,
R8 is cyano,
and the salts, stereoisomers, hydrates and hydrates of the salts of these compounds.
Compounds according to embodiments a or b in particular worthy to be mentioned are compounds
of formulae la or lb,
in which,
as a first alternative,
Rl is hydrogen,
R2 is chlorine or fluorine,
R3 is methoxy or ethoxy,
or, as a second alternative,
Rl is hydrogen,
R2 is methoxy or ethoxy,
R3 is methoxy or ethoxy,
or, as a third alternative,
Rl is methoxy or ethoxy,
R2 is chlorine or fluorine,


8. (4aRS,8aRS)-cis-2-(4-hydroxy-3,5-dimethyl-phenyl)-10,ll-dimethoxy-3-methyl-4a/5,6,7,8,8a-hexahydro-pyrrolo[2,l-f]phenanthridine-l-carboxylic acid ethyl ester
9. (5RS)-3-Ethyl-2-(4-hydroxy-3,5-dimethyl-phenyl)-8,9-dimethoxy-5-methyl-5,6-dihydro-pyrrolo[2,l-a]isoquinoIine-l-carboxylic acid ethyl ester
10. (5RS)-8,9-Dimethoxy-3,5-dimethyl-2-(3,4,5-trimethoxy-phenyl)-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carboxyIic acid ethyl ester
11. (5RS)-8,9-Dimethoxy-3,5-dimethyl-2-naphthalen-l-yl-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-1-carboxylic acid ethyl ester
12. (4aRS,8aRS)-cis-10,11-Dimethoxy-3-methyl-2-naphthalen-l-yl-4a,5/6,7/8,8a-hexahydro-pyrrolo[2,l-f]phenanthridine-l-carboxylic acid ethyl ester
13. (4aRS,8aRS)-cis-10,ll-Dimethoxy-3-methyl-2-quinoIin-4-yl-4a,5,6/7,8/8a-hexahydro-pyrrolo[2,l-f]phenanthridine-l-carboxylic acid ethyl ester
14. (4aR,8aR)-10,ll-Dimethoxy-3-methyl-2-quinolin-4-yl-4a,5,6/7,8,8a-hexahydro-pyrrolo[2,l-f]phenanthridine-l-carboxylic acid ethyl ester
15. (4aR,8aR)-10,11-Dimethoxy-3-methyl-2-naphrhalen-l-yl-4a,5,6,7,8,8a-hexahydro-pyrrolo[2/l-f]phenanthridine-l-carboxylic acid ethyl ester
16. (4aR,8aR)-2-(4-Hydroxy-3,5-dimethyl-phenyl)-10,H-dimethoxy-3-methyl-4a,5,6/7,8,8a-hexahydro-pyrrolo[2,l-f]phenanthridine-l-carboxylic acid ethyl ester
17. (5RS)-5-Ethyl-8,9-dimethoxy-3-methyl-2-naphthalen-l-yl-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carboxylic acid ethyl ester
18. (5RS)-2-(4-Hydroxy-3,5-dimethyl-phenyl)-7,8,9-trimethoxy-3,5-dimethyl-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carboxylic acid ethyl ester
19. 2-(4-Hydroxy-3,5-dimethyl-phenyl)-8,9-dimethoxy-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-1,5-dicarboxyIic acid 1-ethyl 5-methyl ester
20. (5RS)-8,9-Dimethoxy-3-(2-methoxycarbonyl-ethyl)-5-methyl-2-naphthalen-l-yl-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carboxylic acid ethyl ester
21. 2-(4-Hydroxy-3,5-dimethyl-phenyl)-8,9-dimethoxy-3-methyl-5,6-dihydro-pyrollo[2,l-a]isoquinoline-l-carbonitrile
22. 8,9-Dimethoxy-3-methyl-2-naphrhalen-l-yl-5,6-dihydro-pyrrolo[24-a]isoquinoline-l-carbonitrile
23. 8,9-Dimethoxy-3-methyl-2-quinolin4-yl-5,6-dihydro-pyrrolo[24-a]isoquinoline-l 24. 2-(lH-Indol-3-yl)-8,9-dimethoxy-3-methyl-5,6-dihydro-pyrrolo[2/l-a]isoquinoline-l-carbonitrile
25. 2-(3,5-Di-tert-butyl-4-hydroxy-phenyl)-8,9-dimethoxy-3-methyl-5,6-dihydro-pyrrolo[2,l-a] isoquinoline-1 -carboni trile

26. 8,9-Dimemoxy-3,5-dimemyl-2-pyridm-4-yl-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carbonitrile
27. 3-[l-Cyano-2-(4-hydroxy-3,5-dimethyl)-8,9-dimethoxy-5-methyl-5/6-dihydro-pyrrolo[2,l-a]isoquinolin3-yl]-propionic acid methyl ester
28. 2-(4-Hydroxy-3,5-dimethyl-phenyl)-8,9-dimethoxy-3,5-dimethyl-5,6-dihydro-pyrrolo[2,l-a] isoquinoline-1 -carboni trile
or a salt, stereoisomer, hydrate or hydrate of a salt thereof.
As further exemplary compounds according to this invention may be mentioned any compound
selected from the group consisting of those compounds individualized and listed as Examples 29 to
69 in the following examples, or a salt, stereoisomer, hydrate or hydrate of a salt thereof.
As exemplary compounds according to this invention the following compounds of formula Ic, and
the salts, stereoisomers, hydrates or hydrates of the salts thereof,

H H CH30
(Ic)
are notably to be mentioned by means of the substituent meanings for R5, R6 and R7 in the following Tables Al, A2, A3 and A4: Table Al:





as well as compound 30 and compound 42.
The following compounds of formula Id or le, and the salts, stereoisomers, hydrates or hydrates of
the salts thereof,

H H
CH,0

(Id) ((e)
may also be mentioned as exemplary compounds according to this invention by means of the substituent meanings for R5, R6 and R7 in the following Tables Bl, B2, B3 and B4: Table Bl:




The compounds according to the present invention can be prepared, for example, in an art-known manner, or in a manner described and shown as follows, or as disclosed in WO 02/48144, WO 03/014115, WO 03/014116, WO 03/014117 or WO 03/051877, or as described by way of example in the following examples, or analogously or similarly thereto.


(I)
As shown in the scheme above, in a first reaction step compounds of formula VIII, in which Rl, R2, R3, R4, R41, R5 and R51 have the meanings indicated above, are reacted with compounds of formula VII, in which R8 has the meanings indicated above and L is a suitable leaving group, for example chlorine or an acyloxy radical (e.g. the R8-CH2-C(0)-0- radical), to give in the presence of a suitable organic or inorganic base corresponding compounds of formula VI.
Alternatively, compounds of formula VI are also accessible from compounds of formula VIII, in which Rl, R2, R3, R4, R41, R5 and R51 have the meanings indicated above, and compounds of formula VII, in which R8 has the meanings indicated above and L is hydroxyl, by reaction with amide bond linking reagents known to the person skilled in the art. Exemplary amide bond linking reagents known to the person skilled in the art which may be mentioned are, for example, the carbodiimides (e.g. dicyclohexylcarbodiimide or, preferably, l-ethyI-3-(3-dimethylaminopropyl)carbodiimide hydrochloride), azodicarboxylic acid derivatives (e.g. diethyl azodicarboxylate), uronium salts [e.g. 0-(benzotriazol-l-yl)-N,N,N",N"-tetramethyluronium terafluoroborate or 0-(benzotriazol-lyl)-N,N,N,N"-tetramthyl-uronium-hexafluorophosphate] and N,N"-carbonyldiimidazole. In the scope of this invention preferred amide bond linking reagents are uronium salts and, particularly, carbodiimides, preferably, l-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride. Said reactions are carried out under conditions known to the person skilled in the art or as described exemplarily in the following examples.
As shown in the next step, compounds of the formula IV, in which Rl, R2, R3, R4, R41, R5, R51 and R8 have the meanings indicated above, can be obtained by cyclocondensation of corresponding compounds of the formula VI. Said cyclocondensation reaction is carried out in a manner habitual per

se to the person skilled in the art or as described by way of example in the following examples, according to Bischler-Napieralski (e.g. as described in J. Chem. Soc, 1956, 4280-4282) in the presence of a suitable condensing or dehydrating agent, such as, for example, polyphosphoric acid, phosphorus pentachloride, phosphorus pentoxide or phosphorus oxychloride, in a suitable inert solvent, e.g. in a chlorinated hydrocarbon such as chloroform, or in a cyclic hydrocarbon such as toluene or xylene, or another inert solvent such as acetonitrile, or without further solvent using an excess of condensing agent, at reduced temperature, or at room temperature, or at elevated temperature or at the boiling temperature of the solvent or condensing agent used. Compounds of formula IV are converted either with compounds of formulae II, in which R7 has the meanings given above, and III, in which R6 is l-6C-alkyl or l-4C-alkyl substituted by 1-4C-alkoxycarbonyl, or with compounds of formula V, in which R7 has the meanings given above and R6 is l-6C-alkyl or l-4C-alkyI substituted by l-4C-alkoxycarbonyl, optionally in a one pot synthesis and suitably in the presence of an inorganic or organic base (in particular a cyclic amine, e.g. piperidine) into the corresponding compounds of formula I.
Said conversion can be carried out as known to the skilled person or as described in the following examples or analogously or similarly thereto.
Compounds of formulae VIII, VII, III and II are commercially available or can be obtained in a manner known to the skilled person from his/her expert knowledge and/or from literature. Compounds of formula V are known or are accessible by reaction of compounds of formula II with compounds of formula III in the presence of a suitable organic or inorganic base in a manner customary per se to the skilled person.
Compounds of formula I obtained can be converted into further compounds of formula I by methods known to one of ordinary skill in the art. More specifically, for example, from compounds of the formula I, in which
a.) R8, R61, R71, R74 or R76 are an ester group, the corresponding acids can be obtained by acidic or, particularly, alkaline hydrolysis;
b.) R8 is an ester group, the corresponding reduced forms thereof (e.g. the hydroxymethyl or methyl radicals) can be obtained by selective reduction reactions;
c.) R8 is a hydroxymethyl group obtainable according b.), the corresponding ester or ether derivatives -CH2-O-R81 can be obtained by esterification or etherification reactions;
d.) R8 is an ester or carboxyl group, the corresponding amides can be obtained by amidifcation reactions;
e.) R6 is l-4C-aIkyl, particularly methyl, the corresponding halogenated, preferably chlorinated, groups can be obtained by halogenation reaction, particularly by reaction with a chlorination reagent such as sulfuryl chloride, thionyl chloride or N-chlorosuccinimide;
f.) R6 is l-4C-alkyl substituted by halogen obtainable according e.), the corresponding derivatized l-4C-alkyl radicals substituted by l-4C-alkoxy, hydroxyl, halogen or -

N(R611)R612 can be obtained by nucleophilic substitution reactions with suitable
nucleophiles; g.) R6 is l-4C-alkyl substituted by hydroxyl obtainable according f.), the corresponding
derivatized l-4C-aIkyl radicals substituted by l-4C-alkoxycarbonyl can be obtained by
oxidation and esterification reactions under suitable conditions; h.) R6 is methyl, the corresponding oxidized forms thereof (e.g. the hydroxymethyl or formyl
radicals) can be obtained stepwise or directly by selective oxidation reactions (e.g. with the
aid of manganese dioxide to obtain the formyl radicals); i.) R6 is formyl obtainable according h.), the corresponding aminated compounds can be
obtained by reductive amination reaction; j.) R6 is hydroxymethyl obtainable according h.), the corresponding fluorine compounds can be
obtained by fluorination reaction; k.) R6 is methyl, the corresponding amino compounds can be obtained by nitration reaction and
subsequential reduction of the nitro compounds obtained. The methods mentioned under a.) to k.) are expediently carried out analogously to the methods known to the person skilled in the art or as described by way of example in the following examples. It is moreover known to the person skilled in the art that if there are a number of reactive centers on a starting or intermediate compound it may be necessary to block one or more reactive centers temporarily by protective groups in order to allow a reaction to proceed specifically at the desired reaction center. A detailed description for the use of a large number of proven protective groups is found, for example, in "Protective Groups in Organic Synthesis" by T. Greene and P. Wuts (John Wiley & Sons, Inc. 1999, 3rd Ed.) or in "Protecting Groups (Thieme Foundations Organic Chemistry Series N Group" by P. Kocienski (Thieme Medical Publishers, 2000). The isolation and purification of the substances according to the invention is carried out in a manner known per se, e.g. by distilling off the solvent in vacuo and recrystallizing the resulting residue from a suitable solvent or subjecting it to one of the customary purification methods, such as, for example, column chromatography on suitable support material.
Salts are obtained by dissolving the free compound in a suitable solvent (e.g. a ketone, such as acetone, methyl ethyl ketone or methyl isobutyl ketone, an ether, such as diethyl ether, tetrahydrofuran or dioxane, a chlorinated hydrocarbon, such as methylene chloride or chloroform, or a low molecular weight aliphatic alcohol such as ethanol or isopropanol) which contains the desired acid or base, or to which the desired acid or base is then added. The salts are obtained by filtering, reprecipitating, precipitating with a nonsolvent for the addition salt or by evaporating the solvent. Salts obtained can be converted by alkalization or by acidification into the free compounds, which in turn can be converted into salts. In this way, pharmacologically intolerable salts can be converted into pharmacologically tolerable salts.
The person skilled in the art knows on the basis of his/her knowledge and on the basis of those synthesis routes, which are shown and described within the description of this invention, how to find other possible synthesis routes for compounds of the formula I. All these other possible synthesis routes are also part of this invention. Having described the invention in detail, the scope of the present invention is not limited only to those described characteristics or embodiments. As will be apparent to persons skilled in the art,

modifications, variations and adaptations to the described invention can be made on the base of the
disclosure (e.g. the explicite, implicite or inherent disclosure) of the present invention without
departing from the spirit and scope of this invention.
The following examples serve to illustrate the invention in greater detail without restricting it.
Likewise, further compounds of the formula I, whose preparation is not explicitly described, can also
be prepared in an analogous manner or in a manner familiar per se to the person skilled in the art
using customary process techniques.
In the examples, m.p. stands for melting point, h for hour(s), min for minutes, cone, for concentrated,
satd. for saturated, MS for mass spectrum, M for molecular ion.
Unless otherwise noted, if the exemplary compounds mentioned expressis verbis herein contain a
chirality center, they are desribed illustratively as racemic mixtures herein, without restricting this
invention thereto.
The compounds mentioned in the examples as well as their salts and stereoisomers are a preferred
subject of the invention.
Examples
Final products
1. 2-(4-Hydroxy-3,5-dimethyl-phenyl)-8,9-dimethoxy-3,5,5-trimethyl-5,6-dihydro-pyrrolo[2,l-
a]isoquinoIine-l-carboxylic acid ethyl ester
Analogously to a procedure described by Meyer in Liebigs Ann. Chem. 1981, 9, 1534-1544, (6,7-dimethoxy-3,3-dimethyl-3,4-dihydro-2H-isoquinolin-l-ylidene)-aceric acid ethyl ester (compound AT) is reacted with nitro ethane and 4-hydroxy-3,5-dimethyl benzaldehyde to afford the title compound. MS (M+H) = 464.1; m.p. = 210 - 213 °C
The following examples (Examples 2-20) can be prepared in analogy to example 1 using the appropriate starting compound selected from the group consisting of the compounds Al to A9. All aldehydes used are commercially available or can be prepared in analogy to published procedures. If nitro propane or 4-nitro butyric acid methyl ester is used instead of nitroethane, 3-ethyl-5,6-dihydro-pyrrolo[2,l-a]isoquinolines and 3-methoxycarbonylethyl-5,6-dihydro-pyrrolo[2,l-a]isoquinolines (e.g. 3-(8,9-dimethoxy-5,6-dihydro-pyrrolo[2,l-a]isoquinolin-3-yl)propionic methyl esters), respectively are obtained.
2. 8,9-Dimethoxy-3,5,5-trimethyl-2-(3,4,5-trimethoxy-phenyl)-5,6-dihydro-pyrrolo[2,l-
a]isoquinoline-l-carboxylic acid ethyl ester
MS (M+H) = 510.4; m.p. = 52-56 °C
3. 2-[3-(4-Chloro-phenoxy)-phenyl]-8,9-dimethoxy-3,5,5-trimethyl-5,6-dihydro-pyrrolo[2,l-
a]isoquinoline-l-carboxylic acid ethyl ester
MS (M+H) = 546.2; m.p. = 61-64 °C
4. 2-(3-Dimethylamino-phenyl)-8,9-dimethoxy-3,5,5-trimethyl-5,6-dihydro-pyrrolo[2,l-
a]isoquinoline-l-carboxyIic acid ethyl ester
MS (M+H) = 463.1; m.p. = 101 -102 °C


(5RS)- (4-Hydroxy-3,5-dimethyl-phenyl)-8,9-dimethoxy-3,5-dimethyl-5,6-dihydro-pyrrolo[2,l-
a]isoquinoline-l-carboxylic acid ethyl ester
MS (M+H) = 450.2; m.p. = 158 ~ 161 °C
(5RS)-5-Ethyl-2-(4-hydroxy-3,5-dimethyl-phenyl)-8,9-dimethoxy-3-rnethyl-5,6-dihydro-
pyrrolo[2,l-a]isoquinoline-l-carboxylic acid ethyl ester
MS (M+H) = 464.1; m.p. = 164 - 166 °C
(5RS)-2-Chlorophenyl-5-ethyl-8,9-dimethoxy-3-methyl-5,6-dihydro-pyrrolo[2,l-
a]isoquinoline-l-carboxylic acid ethyl ester
MS (M+H) = 454.2; m.p. = 121 -124 °C
(4aRS,8aRS)-cis-2-(4-hydroxy-3,5-dimethyl-phenyl)-10/ll-dimethoxy-3-methyl-4a,5,6,7,8,8a-
hexahydro-pyrrolo[2/l-f]phenanthridine-l-carboxylic acid ethyl ester
MS (M+H) = 490.2; m.p. = 186 - 192 °C
(5RS)-3-Erhyl-2-(4-hydroxy-3,5-dimethyl-phenyl)-8,9-dimethoxy-5-methyl-5,6-dihydro-
pyrrolo[2,l-a]isoquinoline-l-carboxylic acid ethyl ester
MS (M+H) = 464.1; m.p. = 188 -190 °C
(5RS)-8,9-Dimethoxy-3/5-dimethyl-2-(3/4,5-trimethoxy-phenyl)-5,6-dihydro-pyrrolo[2/l-
a]isoquinoline-l-carboxylic acid ethyl ester
MS (M+H) = 496.0; m.p. = 116 - 118 °C
(5RS)-8,9-Dimethoxy-3,5-dimethyl-2-naphthalen-l-yl-5,6-dihydro-pyrrolo[24-a]isoquinoline-
1-carboxylic acid ethyl ester
MS (M+H) = 456.1; m.p. = 184 °C
(4aRS/8aRS)-cis-10,ll-Dimethoxy-3-methyl-2-naphthalen-l-yl-4a,5,6,7,8,8a-hexahydro-
pyrrolo[2,l-flphenanthridine-l-carboxylic acid ethyl ester
MS (M+H) = 496.1; m.p. = 189 -191 °C
(4aRS,8aRS)-cis-10,ll-Dimethoxy-3-methyl-2-quinolin-4-yl-4a,5,6,7,8,8a-hexahydro-
pyrroIo[2,l-f]phenanthridine-l-carboxyIic acid ethyl ester
MS (M+H) = 497.3; m.p. = 153 -157 °C
(4aR,8aR)-10,ll-Dimemoxy-3-memyl-2-qxririolin-4-yl-4a/5,6,7,8,8a-hexahydro-pyrrolo[2,l-
f]phenanthridine-l-carboxyIic acid ethyl ester
MS (M+H) = 497.3; oil
(4aR/8aR)-10/ll-Dimethoxy-3-methyl-2-naphthaIen-l-yl-4a,5/6/7,8,8a-hexahydro-pyrrolo[2,l-
f]phenanthridine-l-carboxylic acid ethyl ester
MS (M+H) = 496.1; m.p. = 212 - 216 °C
(4aR,8aR)-2-(4-Hydroxy-3;5-dimethyl-phenyl)-10,ll-dimethoxy-3-methyl4a,5,6,7,8,8a-
hexahydro-pyrrolo[2,l-f]phenanthridine-l-carboxylic acid ethyl ester
MS (M+H) = 490.2; m.p. = 203 - 206 °C
(5RS)-5-Ethyl-8,9-dimethoxy-3"methyl-2-naphthalen-l-yl-5,6-dihydro-pyrrolo[2,l-
a]isoquinoline-l-carboxylic acid ethyl ester


MS (M+H) = 470.1; oil
18. (5RS)-2-(4-Hydroxy-3,5-dimethyl-phenyI)-7/8,9-trimethoxy-3,5-dimethyl-5/6-dihydro-
pyrrolo[2,l-a]isoquinoline-l-carboxylic acid ethyl ester
MS (M+H) = 480.0; m.p. = 144 °C
19. 2-(4-Hydroxy-3,5-dimemyl-phenyl)-8,9-dimemoxy-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-
1,5-dicarboxylic acid 1-ethyl 5-methyl ester
MS (M+H) = 494.1; m.p. =92-97 °C
20. (5RS)-8/9-Dimethoxy-3-(2-methoxycarbonyl-ethyl)-5-methyl-2-naphthalen-l-yl-5/6-dihydro-
pyrrolo[2,l-a]isoquinoline-l-carboxylic acid ethyl ester
MS (M+H) = 528.1; m.p. =56-59 °C
21. 2-(4-Hydroxy-3,5-dimethyl-phenyl)-8,9-dimethoxy-3-methyl-5,6-dihydro-pyrollo[2,l"
a]isoquinoline-l-carbonitrile
Analogously to the procedure described for Example 1, (6,7-dimethoxy-3,4-dihydro-2H-isoquinolin-l-ylidene)-acetonitrile (compound A8) is reacted with nitro ethane and 4-hydroxy-3,5-dimethyl benzaldehyde to afford 2-(4-hydroxy-3,5-dimethyl-phenyl)-8,9-dimethoxy-3-methyl-5,6-dihydro-pyrollo[2,l-a]isoquinoline-l-carbonitrile as a colorless solid of m.p. 285 - 287 °C The mass spectrum shows the molecular peak M+H at 388.5 Da.
The following examples (Nos. 22-28) can be prepared in analogy to example 21 using the appropriate starting compound A8 or A9. All aldehydes used are commercially available or can be prepared in analogy to published procedures. If nitro propane or 4-nitro butyric acid methyl ester is used instead of nitroethane, 3-ethyl-5,6-dihydro-pyrrolo[2,l-a]isoquinolines and 3-methoxycarbonylethyl-5,6-dihydro-pyrrolo[2,l-a]isoquinolines, respectively are obtained.
22. 8,9-Dimemoxy-3-methyl-2-naphthalen-l-yl-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-
carbonitrile
MS (M+H) = 395.2; m.p. = 226 - 229 °C
23. 8,9-Dimemoxy-3-methyl-2-quinolin -yl-5,6-dihydro-pyrrolo[24-a]isoquinoline-l-carbonitrile MS (M+H) = 396.3; m.p. = 239 - 243 °C
24. 2-(lH-Indol-3-yl)-8,9-dimethoxy-3-methyl-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carbonitrile
MS (M+H) = 384.3; m.p. = 304 - 307 °C
25. 2-(3,5-Di-tert-butyl-4-hydroxy-phenyl)-8,9-dimethoxy-3-methyl-5/6-dihydro-pyrrolo[2,l-
a]isoquinoline-l-carbonitrile
MS (M+H) = 473.1; m.p. = 250 - 252 °C
26. 8,9-Dimethoxy-3,5-dimethyl-2-pyridin-4-yl-5,6-dihydro-pyrrolo[2/l-a]isoquinoline-l-
carbonitrile
MS (M+H) = 360.3; m.p. = 253 - 254 °C

27. 3-[l-Cyano-2-(4-hydroxy-3,5-dimethyl)-8,9-dimethoxy-5-methyl-5,6-dihydro-pyrrolo[2,l-a]isoquinolin3-yl]-propionic acid methyl ester MS (M+H) = 475.2; m.p. = 208 - 209 °C
28. 2-(4-Hydroxy-3,5-dimethyl-phenyl)-8,9-dimethoxy-3,5-dimethyl-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carbonitrile
MS (M+H) = 403.2; m.p. = 268 - 270 °C The following examples (Nos. 29-59) can be prepared in analogy to example 21 using the appropriate starting compound, which can be prepared in an art-known manner, or analogously or similarly as described for A8 or A9. All aldehydes used are commercially available or can be prepared in analogy to published procedures. If nitro propane or 4-nitro butyric acid methyl ester is used instead of nitroethane, 3-ethyl-5/6-dihydro-pyrrolo[2,l-a]isoquinolines and 3-methoxycarbonylethyl-5,6-dihydro-pyrrolo[2,l-a]isoquinolines, respectively are obtained.
29. 3-(l-Cyano-8,9-dimethoxy-2-pyridin-4-yl-5,6-dihydro-pyrrolo[2,l-a]isoquinolin-3-yl)-
propionic acid methyl ester
MS (M+H) = 417.9; m.p. = 191 -193 "C
30. 7-Fluoro-2-(4-hydroxy-3,5-dimethyl-phenyl)-8,9-dimethoxy-3,5-dimethyl-5,6-dihydro-
pyrrolo[2,l-a]isoquinoline-l-carbonitrile
MS (M+H) = 421.2; m.p. = 166 - 168 °C
31. 3-(l-Cyano-8,9-dimethoxy-2-quinolin-4-yl-5,6-dihydro-pyrrolo[2/l-a]isoquinolin-3-yl)-
propionic acid methyl ester
MS (M+H) = 467.9; m.p. = 232 - 234 °C
32. 3-[l-Cyano-2-(4-hydroxy-3,5-dimethyl-phenyl)-8,9-dimethoxy-5,6-dihydro-pyrrolo[2,l-
a]isoquinolin-3-yl]-propionic acid methyl ester
MS (M+H) = 461.0; m.p. = 217 - 219 °C
33. 8,9-Dimethoxy-2-(4-methoxy-3,5-dimethyl-phenyl)-3,5-dimethyI-5,6-dihydro-pyrroIo[2,l-
a]isoquinoline~l-carbonitriIe
MS (M+H) = 417.3;
34. 2-(lH-mdol-5-yl)-8/9-dimethoxy-3-methyl-5,6-dihydro-pyrrolo[2yl-a]isoquinoline-l-
carbonitrile
MS (M+H) = 384.3;
35. 8,9-Dimethoxy-2-(4-methoxy-3,5-dimethyl-phenyl)-3-methyl-5,6-dihydro-pyrrolo[2,l-
a]isoquinoline-l-carbonitrile
MS (M+H) = 403.3;
36. 2-(l-Benzyl-2,3-dihydro-lH-indol-5-yl)-8,9-dimethoxy-3-methyl-5/6-dihydro-pyrrolo[2/l-
a]isoquinoIine-l-carbonitrile
MS (M+H) = 476.1;
37. 8,9-Dimethoxy-3,5-dimethyl-2-[l-(toluene-4-sulfonyl)-lH-pyrrol-3-yl]-5,6-dihydro-
pyrrolo[2/l-a]isoquinoline-l-carbonitrile

MS (M+H) = 502.1;
38. 8,9-Dimethoxy-3,5-dimethyl-2-[l-(toluene-4-sulfonyl)-lH-indol-3-yl]-5/6-dihydro-pyrrolo[2,l-
a]isoquinoline-l-carbonitrile
MS (M+H) = 569.0;
39. 2-(l-Benzenesulfonyl-lH-indol-3-yl)-8,9-dimethoxy-3,5-dimethyl-5,6-dihydro-pyrrolo[2,l-
a]isoquinoline-l-carbonitrile
MS (M+H) = 537.7;
40. 2-(l-Methanesulfonyl-lH-indol-3-yl)-8,9-dimethoxy-3,5-dimethyl-5,6-dihydro-pyrrolo[2,l-
a]isoquinoline-l-carbonitrile
MS (M+H) = 475.8; m.p. = 219 - 221 °C
41. 8,9-Dimethoxy-3,5-dimethyl-2-(l-oxy-pyridin-4-yl)-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-
carbonitrile
MS (M+H) = 375.8; m.p. = 279 - 282 °C
42. 7-Fluoro-8,9-dimethoxy-3,5-dimethyl-2-[l-(toluene-4-sulfonyl)-lH-iiidol-3-yl]-5,6-dihydro-
pyrrolo[2,l-a]isoquinoline-l-carbonitrile
MS (M+H) = 587.0;
43. 2-(2,3-Dihydro-lH-indol-5-yl)-8,9-dimethoxy-3-methyl-5,6-dihydro-pyrrolo[2,l-
a]isoquinoline-l-carbonitrile
MS (M+H) = 386.3;
44. 2-(4-Hydroxy-3,5-dimethyl-phenyl)-8,9-dimethoxy-5-methyl-3-rnorpholin-4-ylmethyl-5,6-
dihydro-pyrrolo[2,l-a]isoquinoline-l-carbonitrile
m.p. = 228 - 230 °C
45. 8/9-Dimethoxy-3/5-dimethyl-2-(2-methyl-pyridin-4-yl)-5,6-dihydro-pyrrolo[2,l-
a]isoquinoline-l-carbonitrile
MS (M+H) = 374.2; m.p. = 187 - 189 °C
46. 8,9-Dimethoxy-3,5-dimethyl-2-(4-mtro-pheny])-5,6-dihydro-pyrrolo[24-a]isoquinoline-l-
carbonitrile
MS (M+H) = 403.7; m.p. = 206 - 207 °C
47. 4-(l-Cyano-8,9-dimethoxy-3/5-dimethyl-5,6-dihydro-pyrrolo[2/l-a]isoquinolin-2-yl)-ben2oic
acid
MS (M+H) = 402.7; m.p. = 287 - 289 °C
48. 2-(4-Amino-phenyl)-8,9-dimethoxy-3,5-dimethyl-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-
carbonitrile
MS (M+H) = 374.1; m.p. = 237 - 239 °C
49. 8,9-Dimethoxy-3,5-dimethyl-2-(3-methyl-pyridin-4-yl)-5,6-dihydro-pyrroIo[2,l-
a]isoquinoline-l-carbonitrile
MS (M+H) = 374.5; m.p. = 232 - 233 °C

50. 4-(l-Cyano-8-ethoxy-9-methoxy-3,5-dimethyl-5,6-dihydro-pyrrolo[2,l-a]isoquinolin-2-yl)-
benzoic acid
MS (M+H) = 417.2; m.p. = 274 - 277 °C
51. 2-(4-Hydroxy-2-methyl-phenyl)-8/9-dimethoxy-3,5-dimethyl-5,6-dihydro-pyrrolo[2,l-
a]isoquinoline-l-carbonitrile
MS (M+H) = 389.1; m.p. = 228 - 230 °C
52. 4-(l-Cyano-8,9-dimethoxy-3,5-dimethyl-5,6-dihydro-pyrrolo[2,l-a]isoquinolin-2-yl)-
benzamide
m.p. = 228 - 230 °C
53. 8-Ethoxy-2-(4-hydroxy-3,5-dimethyl-phenyl)-9-methoxy-3,5-dimethyl-5,6-dihydro-
pyrrolo[2,l-a]isoquinoline-l-carbonitrile
MS (M+H) = 417.2; m.p. = 232 - 234 °C
54. 3-(l-Cyano-8,9-dimethoxy-3,5-dimethyl-5,6~dihydro-pyrrolo[2,l-a]isoquinolin-2-yl)-indole-l-
sulfonic acid dimethylamide
MS (M+H) = 505.2; m.p. = 236 - 237 °C
55. 8,9-Dimethoxy-3,5-dimethyl-2-(2-methyl-l-oxy-pyridin-4-yl)-5,6-dihydro-pyrrolot2,l-
a] isoquinoline-1 -carbonitrile
MS (M+H) = 390.1; m.p. = 265 - 268 °C
56. 8,9-Dimethoxy-3/5-dimethyl-2-[l-(morpholine-4-sulfonyl)-lH-indol-3-yl]-5,6-dihydro-
pyrrolo[2,l-a]isoquinoline-l-carbonitrile
MS (M+H) = 574.1; m.p. = 210 - 212 °C
57. 8/9-Dimethoxy-3,5-dimethyl-2-[4-(2H-tetrazol-5-yl)-phenyl]-5,6-dihydro-pyrrolo[2,l-
a]isoquinoline-l-carbonitrile
MS (M+H) = 427.2; m.p. = 204 - 207 °C
58. Morpholine-4-sulfonic acid [4-(l-cyano-8,9-dimethoxy-3,5-dimethyl-5,6-dihydro-pyrrolo[2,l-
a]isoquinolin-2-yl)-phenyl]-amide
MS (M+H) = 523.1; m.p. = 223 - 225 °C
59. N-[4-(l-Cyano-8,9-dimethoxy-3,5-dimethyl-5,6-dihydro-pyrrolo[2,l-a]isoquinolin-2-yl)-
phenyl]-methanesulfonamide
MS (M+H) = 452.1; m.p. = 257 - 259 °C The following examples (Examples 60-67) can be prepared in analogy to example 1 using the appropriate starting compound, which can be prepared in an art-known manner, or analogously or similarly as described for compounds Al to A9. All aldehydes used are commercially available or can be prepared in analogy to published procedures. If nitro propane or 4-nitro butyric acid methyl ester is used instead of nitroethane, 3-ethyl-5,6-dthydro-pyrrolo[2,l-a]isoquinolines and 3-methoxycarbonylethyl-5,6-dihydro-pyrrolo[2,l-a]isoquinolines, respectively are obtained.
60. 5-Ethyl-2-(2-fluoro-3,4-dimethoxy-phenyl)-8,9-dimethoxy-3-methyl-5/6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carboxylic acid ethyl ester

MS (M+H) = 498.1;
61. 7-Chloro-8,9-dimethoxy-3,5-dimethyl-2-pyridin-4-yl-5/6-dihydro-pyrrolo[2/l-a]isoquinoline-
1-carboxylic acid ethyl ester
MS (M+H) = 441.3;
62. 7-Chloro-2-(4-hydroxy-3,5-dimethyl-phenyl)-8,9-dimethoxy-3,5-dimethyl-5,6-dihydro-
pyrrolo[2,l-a]isoquinoline-l-carboxylic acid ethyl ester
MS (M+H) = 484.0;
63. 7,8,9-Trimethoxy-3,5-dimethyl-2-pyridin-4-yl-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-
carboxylic acid ethyl ester
MS (M+H) = 437.3;
64. 8,9-Dimethoxy-3-(2-methoxycarbonyl-ethyl)-5-methyl-2-quinolin-4-yl-5,6-dihydro-
pyrrolo[2,l-a]isoquinoline-l-carboxylic acid ethyl ester
MS (M+H) = 529.3;
65. 2-(4-Hydroxy-3,5-dimethyl-phenyl)-8,9-dimethoxy-3,5-dimethyl-5,6-dihydro-pyrrolo[2,l-
a]isoquinoline-l-carboxylic acid methyl ester
MS (M+H) = 435.9; m.p. = 177 -179 °C
66. 8,9-Dimethoxy-3,5-dimethyl-2-[l-(toluene-4-sulfonyI)-lH-indol-3-yI]-5,6-dihydro-pyrroIo[2,l-
a]isoquinoline-l-carboxylic acid methyl ester
MS (M+H) = 584.9; m.p. = 177 - 179 °C
67. 5-Cyano-2-(4-hydroxy-3,5-dimethyl-phenyl)-8,9-dimethoxy-3-methyl-5,6-dihydro-pyrrolo[2,l-
a]isoquinoline-l-carboxylic acid ethyl ester
MS (M+H) = 461.0;
68. 4-(8,9-Dimethoxy-l/3-dimethyl-5/6-dihydro-pyrrolo[2,l-a]isoquinolin-2-yl)-2,6-dimethyl-
phenol
MS (M+H) = 377.9; m.p. = 183 - 185 °C
The title compound can be obtained via an analogous synthesis route as described for the
Examples herein.
69. 8,9-Dimethoxy-3-(2-methoxycarbonyI-ethyl)-5-methyl-2-quinoIin-4-yl-5,6-dihydro-
pyrrolo[2,l-a]isoquinoline-l-carboxylic add ethyl ester
MS (M+H) = 407.9; m.p. = 176 -177 °C
The title compound can be obtained from the corresponding ester compound, which is
accessible analogously as described in Example 1 herein, by art-known saponification
reaction. Examplary compounds of formula Ic mentioned as Examples 70-139 in Tables Al to A4 can be prepared analogously or similarly to the described examples.
Examplary compounds of formulae Id or le can be also prepared analogously or similarly to the described examples.

Starring compounds
Al (3RS)-(6,7-Dimethoxy-3-methyl-3,4-dihydro-2H-isoquinolin-l-ylidene)-acetic acid ethyl ester
The title compound can be obtained by a Bischler-Napieralski reaction (Ber. 1893, 26,1903) using N-
{2-[4-methoxy-3-(2-methoxy-ethoxy)-phenyl]-ethyl}-malonamic acid ethyl ester (compound Bl) as the
starting material.
The following 3,4-Dihydro-l(2H)-isoquinolinylidene-derivatives A2 to A9 and also further relevant,
non-explicitly described similar compounds can be prepared according to an analogous procedure
using the appropriate starting compound B2 to B8, or an appropriate analogous compound:
A2 (3RS)-(3-Ethyl-6,7-dimerhoxy-3,4-dihydro-2H-isoquinolin-l-ylidene)-acetic acid ethyl ester
A3 ((4aR,10bR)-8,9-Dimethoxy-l,3,4,4a,5,10b-hexyhydro-2H-phenanthridin-6-ylidene)-acetic acid
ethyl ester A4 ((4aRS,10bRS)-cis-8,9-Dimethoxy-l,3,4,4a,5,10b-hexyhydro-2H-phenanthridin-6-yIidene)-
acetic acid ethyl ester A5 l-Erhoxycarbonylmethylene-6,7-dimethoxy-l,2,3,4-tetrahydro-isoquinolie-3-carboxylic acid
methyl ester A6 (3RS)-(5,6,7-Trimethoxy-3-methyI-3,4-dihydro-2H-isoquinoIin-l-ylidene)-acetic acid ethyl
ester A7 (6,7-Dimethoxy-3,3-dimethyl-3,4-dihydro-2H-isoquinolin-l-ylidene)-acetic acid ethyl ester
The compound A19 is commercially available. A8 (6,7-Dimethoxy-3,4-dihydro-2H-isoquinolin-l-ylidene)-acetonitrile
The compound A8 can be prepared analogously to the above-described synthesis of
compound Al using the starting compound B7. A9 (6,7-Dimethoxy-3-methyl-3,4-dihydro-2H-isoquinolin-l-ylidene)-acetonitrile
The compound A9 can be prepared analogously to the above-described synthesis of
compound Al using the starting compound B8.
Bl N-[(RS)-2-(3,4-Dimethoxy-phenyl)-l-methyl-ethyl]-malonamic acid ethyl ester
The title compound can be prepared by a reaction of (RS)-2-(3,4-Dimethoxy-phenyl)-l-methyl-ethylamine (compound CI) with ethyl maloyl chloride in analogy to procedures in the literature (e.g. Benovsky et al., Tetrahedron Lett. 1997,38,8475-8478).
The following amides B2 to B8 can be synthesized according an analogous procedure:
B2 N-[(RS)-l-(3,4-Dimethoxy-benzyl)-propyl]-malonamic acid ethyl ester
B3 N-[(lR,2R)-2-(3,4-Dimethoxy-phenyl)-cycIohexyl]-malonamic acid ethyl ester
B4 N-[(lRS,2RS)-cis-2-(3,4-Dimethoxy-phenyl)-cyclohexyl]-malonamic acid ethyl ester
B5 3-(3,4-Dimethoxy-phenyl)-2-(2-ethoxycarbonyl-ethanoylamino)-propionic acid methyl ester
B6 N-[(RS)-l-Methyl-2-(2,3,4-trimethoxy-phenyl)-ethyl]malonamic acid ethyl ester B7 2-Cyano-N-[2-(3,4-dimethoxy-phenyl)-ethyl]-acetamide
A solution of 10.0 g (55.1 mmol) of 2-(3,4-dimethoxy-phenyl)-ethylamine and 9.36 g (82.7 mmol) of ethyl cyano acetate is stirred at 100 °C for 15 h. The mixture is cooled to room temperature. The


precipitate is filtered off and recrystallized from ethanol. 9.44 g (38.0 mmol, 60 %) of 2-cyano-N-[2-(3,4-dimethoxy-phenyl)-ethyl]-acetamide are obtained as a beige solid. MS (M+H) = 249.0, m.p. = 113-115 °C.
B8 2-Cyano-N-[2-(3,4-dimethoxy-phenyl)-l-methyl-ethyl]-acetamide
Compound B8 can be prepared analogously to the synthesis of compound B7.
The appropriate starting compounds for the preparation of the compounds Bl to B8 are commercially available, or can be prepared as described below in the synthesis of the compound CI or analogously or similarly thereto, or can be obtained in analogy to published procedures, e.g. the substituted 2-phenethyl amines can be prepared starting from the corresponding benzaldehydes (see also Shepard et al., J. Org. Chem. 1952,17,568).
CI (RS)-2-(3,4-Dimethoxy-phenyl)-l-methyl-ethylamine
The title compound can be prepared by a sequence described by Shepard et al. in J. Org. Chem. 1952, 17,568.
Commercial utility Commercial applicability
Intracellular levels of the second messengers cAMP and cGMP are regulated by both their rates of synthesis by cyclases and their hydrolysis by phosphodiesterases. Of the 11 phosphodiesterase (PDE) isoenzymes which are presently known, PDE10 was described for the first time in 1999 (Soderling SH, Bayuga SJ, Beavo JA. Isolation and characterization of a dual-substrate phosphodiesterase gene family: PDEIOA. Proc Natl Acad Sci USA. 1999 Jun 8;96(12):7071-6; Fujishige K, Kotera J, Michibata H, Yuasa K, Takebayashi S, Okumura K, Omori K. Cloning and characterization of a novel human phosphodiesterase that hydrolyzes both cAMP and cGMP (PDEIOA). J Biol Chem. 1999 Jun 25;274(26):18438-45; Loughney K, Snyder PB, Uher L, Rosman GJ, Ferguson K, Florio VA. Isolation and characterization of PDEIOA, a novel human 3", 5"-cyclic nucleotide phosphodiesterase. Gene. 1999 Jun 24;234(1):109-17). The first gene of this new PDE subfamily was designated PDEIOA and the first splice variant was described as PDE10A1, according to the current nomenclature. Due to alternative splicing, other splice variants of PDEIOA exist and have been described in the subsequent years (Kotera J, Fujishige K, Yuasa K, Omori K. Characterization and phosphorylation of PDE10A2, a novel alternative splice variant of human phosphodiesterase that hydrolyzes cAMP and cGMP. Biochem Biophys Res Commun. 1999 Aug ll;261(3):551-7; Fujishige K, Kotera J, Omori K. Striatum- and testis-specific phosphodiesterase PDEIOA isolation and characterization of a rat PDEIOA. Eur J Biochem. 1999 Dec;266(3):1118-27; Fujishige K, Kotera J, Yuasa K, Omori K. The human phosphodiesterase PDEIOA gene genomic organization and evolutionary relatedness with other PDEs containing GAF domains. Eur J Biochem. 2000 Oct;267(19):5943-51). PDEIOA has been described as a cyclic nucleotide phosphodiesterase exhibiting properties of a cAMP PDE and a cAMP-inhibited cGMP PDE. Individual representatives of the PDE10 isoenzyme are characterized by being particularly prominently expressed in specific areas of the brain (striatum, putamen, caudate nucleus, cerebellum, thalamus), in testis, in the thyroid gland, in the pituitary gland, in kidney and in placenta.


Increased expression levels in a broad variety of tumor cell lines and tissues, namely of the lung, breast, pancreas, brain, prostate and ovar indicates that PDE10 may play an important role in tumor cell growth and/or survival under conditions of elevated cAMP and/or cGMP generation. Increased expression levels and activities of PDE10A have been also found in testis suggesting that PDE10A may contribute to spermatogenesis (Fujishige K et al., Eur J Biochem. 1999, 266:1118-27). Certain PDE inhibitors, namely e.g. PDE3 or PDE11A inhibitors, are known to augment glucose-induced insulin secretion and thus may be useful for treating diabetes (see e.g. WO 03/077949). The compounds according to the invention have miscellaneous valuable pharmacological properties which make them commercially utilizable.
Thus, for example, the compounds according to this invention are PDE inhibitors. Yet thus, for example, the compounds according to the invention are potent PDE10 inhibitors, some of which are apparently selective (by >100 fold) among other PDE isoenzymes, whereby these selective compounds are particularly preferred in the context of the present invention. The compounds according to the invention therefore can be employed as therapeutic agents for the treatment or prophylaxis of diseases in human and veterinary medicine.
Due to their potent and selective PDE10 inhibitory activity, the compounds according to the present invention may be, in a first facet of the present invention, of potential value in treating disorders of the central nervous system, in particular neurologic and psychiatric disorders, for example those mentioned in EP 1250923 and/or, in more particular, psychotic disorders, anxiety disorders, mood disorders or episodes, drug addiction, movement disorders or disorders comprising deficient cognition as a symptom (e.g. dementia, Parkinson"s disease or Alzheimer"s disease). Furthermore, the compounds according to the present invention may be, in a second facet of the present invention, of potential value in treating certain disorders of the central nervous system, in particular neurologic and psychiatric disorders, for example those mentioned generically, specifically or exemplarily in EP 1250923, US 2003/0008806 and/or US 2003/0018047, such as, for example, anxiety or psychotic disorders, movement disorders, obsessive/compulsive disorders, drug addictions, cognition deficiency disorders, mood disorders or mood episodes, or neurodegenerative disorders.
In this context, examples of anxiety disorders, which may be treated by the compounds according to the present invention, include, without being limited thereto, panic disorder, agoraphobia, a specific phobia, social phobia, obsessive-compulsive disorder, post-traumatic stress disorder, acute stress disorder, or generalized anxiety disorder.
Examples of psychotic disorders, which may be treated by the compounds according to the present invention, include, without being limited thereto, schizophrenia (for example of the paranoid, disorganized, catatonic, undifferentiated, or residual type), schizophreniform disorder, schizoaffective disorder (for example of the delusional type or the depressive type), delusional disorder, substance-induced psychotic disorder (for example psychosis induced by alcohol,

amphetamine, cannabis, cocaine, hallucinogens, inhalants, opioids, or phencyclidine), personality
disorder of the paranoid type, or personality disorder of the schizoid type.
Examples of movement disorders, which may be treated by the compounds according to the present
invention, include, without being limited thereto, Parkinson"s disease, or restless leg syndrome.
Examples of obsessive/ compulsive disorders, which may be treated by the compounds according to
the present invention, include, without being limited thereto, Tourette"s syndrome, or other tic
disorders.
Examples of drug addictions, which may be treated by the compounds according to the present
invention, include, without being limited thereto, an alcohol, amphetamine, cocaine, or opiate
addiction.
Examples of cognition deficiency disorders, which may be treated by the compounds according to the
present invention, include, without being limited thereto, Alzheimer"s disease, multi-infarct dementia,
alcoholic dementia or other drug-related dementia, dementia associated with intracranial tumors or
cerebral trauma, dementia associated with Huntington"s disease or Parkinson"s disease, or AIDS-
related dementia, delirium, amnestic disorder, post-traumatic stress disorder, mental retardation, a
learning disorder, for example reading disorder, mathematics disorder, or a disorder of written
expression, attention-deficit/ hyperactivity disorder, or age-related cognitive decline.
Examples of mood disorders or mood episodes, which may be treated by the compounds according to
the present invention, include, without being limited thereto, a major depressive episode of the mild,
moderate or severe type, a manic or mixed mood episode, a hypomanic mood episode, a depressive
episode with a typical features, a depressive episode with melancholic features, a depressive episode
with catatonic features, a mood episode with postpartum onset, post-stroke depression, major
depressive disorder, dysthymic disorder, minor depressive disorder, premenstrual dysphoric
disorder, post-psychotic depressive disorder of schizophrenia, a major depressive disorder
superimposed on a psychotic disorder such as delusional disorder or schizophrenia, a bipolar
disorder (for example bipolar I disorder, bipolar II disorder), or cyclothymic disorder.
Examples of neurodegenerative disorders, which may be treated by the compounds according to the
present invention, include, without being limited thereto, Parkinson"s disease, Huntington"s disease,
dementia (for example Alzheimer"s disease, multi-infarct dementia, AIDS-related dementia, or Fronto
temperal Dementia), neurodegeneration associated with cerebral trauma, neurodegeneration
associated with stroke, neurodegeneration associated with cerebral infarct, hypoglycemia-induced
neurodegeneration, neurodegeneration associated with epileptic seizure, neurodegeneration
associated with neurotoxin poisoning, or multi-system atrophy.
Yet in this context, the compounds according to the present invention may be of potential value for
treating diseases or conditions, in which abnormal function of the basal ganglia has been implicated.
Thus, abnormal function of the basal ganglia may be involved in disregulated motoric, appetitive
and/or cognitive processes. Exemplary neuropsychiatric conditions, in which abnormal function of
the basal ganglia has been implicated, are mentioned e.g. in EP 1250923, US 2003/0008806 and/or US


2003/0018047, such as e.g. psychosis, attention-deficit/hyperactivity disorder (ADHD) and related attentional disorders, depression, obsessive conpulsive disorders including Tourette"s syndrome and other tic disorders, and substance abuse. Several neurological disorders including Parkinson"s disease, restless leg syndrom and Huntington"s disease can be also linked to basal ganglia dysfunction.
Still yet in this context, the compounds according to the present invention may be of potential value for improving cognition, powers of concentration, learning skills or hypermesia, in particular if the disorder is a symptom of dementia.
Yet furthermore, the compounds according to the present invention may be, in a third facet of the present invention, of potential value for regulating fertility, e.g. via reducing spermatogenesis and/or via reducing sperm motility.
Still yet furthermore, the compounds according to the present invention may be, in a fourth facet of the present invention, of potential value for treating diabetes, such as, for example, typ II diabetes, e.g. via augmenting glucose-induced insulin secretion.
A special interest in the compounds according to the present invention lies in their use in therapy of schizophrenia.
Another special interest in the compounds according to the present invention lies in their use in the therapy of psychotic disorders.
Another special interest in the compounds according to the present invention lies in their use in the therapy of drug addictions.
The invention further relates to a method for treating mammals, including humans, which/who are suffering from one of the abovementioned diseases and/or disorders. The method is characterized by the fact that a pharmacologically active and therapeutically effective and tolerated quantity of one or more of the compounds according to the invention is administered to the affected mammal. The invention further relates to a method for treating mammals, in particular humans, which/who are suffering from one of the abovementioned diseases and/or disorders comprising the step of administering to said ill mammal a pharmaceutically acceptable composition according to the present invention.
The invention further relates to the compounds according to the invention for use in the treatment or prophylaxis of diseases, in particular said diseases and/or disorders.
The invention likewise relates to the use of the compounds according to the invention in the manufacture of pharmaceutical compositions which are employed for the treatment of said diseases or disorders.
The invention further relates to pharmaceutical compositions for the treatment or prophylaxis of the said diseases and/or disorders, which pharmaceutical compositions comprise one or more of the compounds according to the invention.
The present invention further relates to pharmaceutical compositions comprising one or more of the compounds according to this invention and a pharmaceutically acceptable carrier or diluent.


The present invention further relates to combinations comprising one or more of the compounds according to this invention and pharmaceutically acceptable auxiliaries, excipients or vehicles, e.g. for use in the treatment of those conditions mentioned above.
The present invention further relates to the use of the compounds according to this invention for the production of pharmaceutical compositions which can be used use in therapy of disorders responsive to inhibiting of PDE, such as e.g. PDE10.
The present invention further relates to compounds according to this invention having PDE, particularly PDE10, inhibiting properties.
The present invention further relates to pharmaceutical combinations or compositions according to this invention having PDE10 inhibiting properties.
The invention further relates to the use of a pharmaceutical composition comprising one or more of the compounds according to this invention as sole active ingredient(s) and a pharmaceutically acceptable carrier or diluent in the manufacture of pharmaceutical products for therapy, amelioration or prophylaxis of the illnesses, diseases, disorders or conditions mentioned above. In addition, the present invention further relates to a method for regulating fertility in a mammal, including human, comprising administering one or more compounds according to this invention to said mammal in need thereof.
In further addition, the present invention further relates to the use of the compounds according to this invention for inhibiting spermatogenesis and/ or inhibiting sperm motility in a mammal, including human.
In yet further addition, the present invention further relates to the use of the compounds according to this invention for regulating fertility in a mammal, including human.
The invention furthermore relates to a commercial product which consists of a customary secondary packaging means, a primary packaging means (for example an ampoule or a blister pack) which contains a pharmaceutical composition, and, if desired, a patient information leaflet, with the pharmaceutical composition exhibiting an antagonistic effect toward type 10 cyclic nucleotide phosphodiesterases (PDE10) and leading to the attenuation of the symptoms of diseases and/or disorders which are associated with type 10 cyclic nucleotide phosphodiesterases, and with reference being made, on the secondary packaging means and/or on the patient information leaflet of the commercial product, to the suitability of the pharmaceutical composition for use in the prophylaxis or treatment of diseases and/or disorders which are associated with type 10 cyclic nucleotide phosphodiesterases, and with the pharmaceutical composition comprising one or more compounds according to this invention. The secondary packaging means, the primary packaging means containing the pharmaceutical composition and the patient information leaflet otherwise correspond to what the skilled person would regard as being the standard for drugs of this nature. The pharmaceutical compositions according to this invention are produced using methods with which the skilled person is familiar. When employed in pharmaceutical compositions, the compounds according to the invention (= active compounds) are either used as such or, preferably, in


combination with suitable pharmaceutical auxiliaries or formulating agents, for example in the form
of tablets, coated (e.g. sugar-coated) tablets, capsules, caplets, suppositories, patches (e.g. as TTS),
plasters, emulsions, suspensions, gels or solutions, with the content of active compound
advantageously being between 0.1 and 95%, and where, by the appropriate choice of the auxiliaries, a
pharmaceutical administration form (e.g. a delayed release form or an enteric form) exactly suited to
the active compound and/ or to the desired onset of action can be achieved.
The person skilled in the art is familiar, on the basis of his/her knowledge, with auxiliaries, vehicles,
formulating agents, carriers, diluents, adjuvants or excipients which are suitable to be used for the
desired pharmaceutical formulations, preparations or compositions. Beside solvents, gel-forming
agents, suppository bases, tablet auxiliaries and other active carriers, it is possible to use, for example,
antioxidants, dispersants, emulsifiers, antifoams, flavor corrigents, preservatives, solubilizers,
colorants or, in particular, permeation promoters and complexing agents (e.g. cyclodextrines).
The administration of the pharmaceutical compositions according to the invention may be performed
in any of the generally accepted modes of administration available in the art. Illustrative examples of
suitable modes of administration include intravenous, inhalative, oral, nasal, parenteral, topical,
transdermal and rectal delivery. Oral or intravenous delivery are preferred.
The pharmaceutical compositions according to the invention are prepared by processes known per se.
For producing the drugs, the compounds according to the invention (= active compounds) are
preferably mixed with suitable pharmaceutical auxiliary substances and further processed into
suitable medicinal formulations. Suitable medicinal formulations which may be mentioned by way of
example are powders, emulsions, suspensions, sprays, oils, ointments, greasy ointments, creams,
pastes, gels and solutions.
The required dosage of the active compounds according to this invention can vary depending on the
mode of administration, the particular condition to be treated and the effect desired. In general,
satisfactory results are indicated to be obtained systemically at daily dosages of from about 0.01 to
about 100 mg/kg body weight, conveniently administered, for example, in divided doses up to four
times a day or in retard form.
The optimal dose and manner of administration of the active compounds necessary in each case can
easily be determined by any person skilled in the art on the basis of his/her expert knowledge.
Depending upon the particular disease, to be treated or prevented, additional therapeutic active
agents, which are normally administered to treat or prevent that disease, may optionally be
coadministered separately, simultaneously, sequentially or chronologically staggered with the
compounds according to this invention. As used herein, additional therapeutic agents that are
normally administered to treat or prevent a particular disease are known as appropriate for the
disease being treated.
The person skilled in the art is aware on the base of his/her expert knowledge of the total daily
dosage(s) of the additional therapeutic agent(s) coadministered. Said total daily dosage(s) can vary
within a wide range.


Biological investigations
Methods to determine the activity and selectivity of a phosphodiesterase inhibitor are known to the
person skilled in the art. In this connection it may be mentioned, for example, the methods described
by Thompson et al. (Adv Cycl Nucl Res 10: 69-92,1979), Giembycz et al. (Br J Pharmacol 118:1945-
1958,1996) and the phosphodiesterase scintillation proximity assay of Amersham Pharmacia Biotech.
Inhibiting the activity of PDE10A
The PDE10A is cloned into pCR2.1-Topo (Invitrogen) via PCR from human whole brain cDNA using
primers OZ 353 (5"- ACCATGTTGACAGATGAAAAAGTGAAGGC -3") and OZ 317 (5"-
TCAATCTTCAGATGCAGCTGCC -3"). The ORF encoding for the PDE10A is cut with EcoRV and
BamHI and subcloned into Smal and Bgl II of the expression vector pBP9 (Clontech). The encoded
protein represents the PDE10A1 (GenBank Acc.-# AB020593) truncated at its N-terminus at aa 14.
The recombinant baculoviruses are prepared by means of homologous recombination in Sf9 insect
cells. The expression plasmids are cotransfected with Bac-N-Blue (Invitrogen) or Baculo-Gold DNA
(Pharmingen) using a standard protocol (Pharmingen). Wildtype virus-free recombinant virus
supernatants are selected using plaque assay methods. After that, high-titre virus supernatants are
prepared by amplifying 3 times. PDE10A1 is expressed in Sf21 cells by infecting 2x10* cells/ml with
an MOI (multiplicity of infection) between 1 and 10 in serum-free SF900 medium (Life Technologies,
Paisley, UK). Cells are cultured at 28CC, typically for 48 hours, after which they are pelleted for 5-10
min at 1000 g and 4°C. In spinner flasks, cells are cultured at a rotational speed of 75 rpm. The SF21
insect cells are resuspended, at a concentration of approx. lxlO7 cells/ml, in ice-cold (4°C
homogenization buffer (20 mM Tris, pH 8.2, containing the following additions: 140 mM NaCl, 3.8
mM KC1, 1 mM EGTA, 1 mM MgCl2, 10 mM (J-mercaptoethanol, 2 mM benzamidine, 0.4 mM
Pefabloc, 10 µM leupeptin, 10 uM pepstatin A, 5 µM trypsin inhibitor) and disrupted by
ultrasonication on ice. The homogenate is then centrifuged for 10 min at 1000 g (4 °C) and the
supernatant is stored at - 80 °C until subsequent use (see below). The protein content is determined by
the Bradford method (BioRad, Munich) using BSA as the standard.
The PDE10A activity is inhibited by said compounds in a modified SPA (scintillation proximity assay)
test, supplied by Amersham Pharmacia Biotech (see procedural instructions "Phosphodiesterase
[3H]cAMP SPA enzyme assay, code TRKQ 7090"), carried out in 96-well microtitre plates (MTPs). The
test volume was 100 µl and contained 20 mM Tris buffer (pH 7.4), 0.1 mg of BSA (bovine serum
albumin)/ml, 5 mM Mg2+, 0.5 uM cAMP (including about 50,000 cpm of [3H]cAMP), 1 ul of the
respective substance dilution in DMSO and sufficient recombinant PDE10A1 (lOOOxg supernatant, see
above) to ensure that 15-20% of cAMP was converted under said experimental conditions. After a
preincubation of 5 min at 37°C, the reaction is started by adding a substrate (cAMP) and the assays
are incubated for a further 15 min; after that, they are stopped by adding SPA beads (50 ul). In
accordance with the manufacturer"s instructions, the SPA beads have previously been resuspended in
water and diluted 1:3 (v/v) and added to IBMX (3 mM). After the beads have been sedimented
(>30min), the MTPs are analyzed in commercially available measuring appliances and the


corresponding IC50 values of the compounds for the inhibition of PDEIOA activity are determined
from concentration-effect curves by means of non-linear regression.
Representative inhibitory values [inhibitory concentration as -loglCso (mol/1)] which are determined
for the compounds according to the invention are shown in the following table 1, in which the
numbers of the compounds correspond to the numbers of the examples.
Particular interesting compounds according to this invention are those compounds mentioned in
table 1 below. Table 1: Inhibition of PDEIOA activity

Compounds -log ICso
5,6,8, 9,11,12,13,18, 20,21, 23,24,26 to 35,37 to 54,56 to 62,64 to 67 The inhibitory values of the mentioned Examples lie in the range from 7.01 to 9.58

We Claim;
1. Compounds of formula I

(I) in which
Rl is halogen, nitro, amino, mono- or di-l-4C-alkylamino, l-4C-alkyl, hydroxyl, l-4C-alkoxy, 1-4C-
alkoxy-2-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloaIkylmethoxy, or completely or
predominantly fluorine-substituted l-4C-alkoxy, R2 is hydrogen, halogen or l-4C-alkoxy, and R3 is hydrogen or l~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 l-2C-alkylenedioxy bridge, or Rl 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 Rl and R2 bound to the benzo ring moiety in ortho-position to each other together form a completely
or predominantly fluorine-substituted l-2C-alkylenedioxy bridge and R3 is hydrogen, R4 is hydrogen, fluorine, chlorine, l-4C-alkyl, trifluoromethyl, cyclopropyl, cyano, 1-4C-
alkoxycarbonyl or -CH2-0-R411, in which R411 is hydrogen, l-4C-alkyl, l-4C-alkoxy-2-4-alkyl or l-4C-alkylcarbonyl, R41 is hydrogen or l-4C-alkyl, R5 is l-4C-alkyl, and R51 is hydrogen or l-4C-alkyl, or
R4 is hydrogen, fluorine, chlorine or l-4C-alkyl, R41 is hydrogen or l-4C-alkyl, R5 is l-4C-alkyl, cyano, or l-4C-alkoxycarbonyl and R51 is hydrogen or l-4C-alkyl,
R6 is l-6C-alkyl, amino, formyl, or l-4C-alkyl substituted by R61, in which R61 is l-4C-alkoxycarbonyl, carboxyl, l-4C-alkoxy, hydroxyl, halogen or -N(R611)R612, in which R611 is hydrogen, l-4C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkyl-l-4C-alkyl, and R612 is hydrogen or l-4C-alkyl, or R611 and R612 together and with inclusion of the nitrogen atom to which they are bound form a
radical Hetl, in which


Hetl is a 5- to 7-rnembered saturated heterocyclic ring radical comprising one nitrogen atom, to
which R611 and R612 are bound, and, optionally, one further heteroatom selected from a group
consisting of nitrogen, oxygen and sulfur, and optionally substituted by R613 on a ring nitrogen atom,
in which
R613 is l-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-l-4C-alkyl, hydroxy-2-4C-alkyl, 1-4C alkoxy-2-
4C-alkyl, amino-2-4C-alkyl, mono- or di-l-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 either
a monocyclic or fused bicyclic 5- to 10-membered heteroaryl radical comprising one to three
heteroatoms, each of which is selected from a group consisting of nitrogen, oxygen and sulfur,
or
a fused bicyclic 9- or 10-membered, partially saturated heterocyclic ring radical containing a
benzene ring and comprising one or two heteroatoms, each of which is selected from a group
consisting of nitrogen, oxygen and sulfur,
or
N-oxy-pyridyl,
R71 is hydroxyl, halogen, nitro, cyano, trifluoromethyl, l-4C-alkyl, l-4C-alkoxy, amino, mono- or di-l-4C-alkylamino, l-4C-alkylsulphonylamino, arylsulphonylamino, l-4C-alkoxycarbonyl, carboxyl, l-4C-alkylthio, aryIoxy-2-4C-alkoxy, aryloxy-l-4C-alkyl, aryloxy, aryl-l-4C-alkoxy, aryl, l-4C-alkoxy-2-4C-alkoxy, l-4C-alkoxy-l-4C-alkyl, hydroxy-2-4C-alkoxy, amino-2-4C-alkoxy, mono- or di~l-4C-alkylamino-2-4C-aIkoxy, completely or predominantly fluorine-substituted l-4C-alkoxy, mono- or di-l-4C-alkylaminocarbonyl, carbamoyl, tetrazolyl, or -N(H)S(0)2-N(R712)R713, in which
aryl is phenyl or R711-substituted phenyl, in which
R711 is halogen, l-4C-alkyl, l-4C-alkoxy, nitro or cyano,
R712 is l-4C-alkyl, and
R713 is l-4C-alkyI, or
R712 and R713 together and with inclusion of the nitrogen atom to which they are bound form a radical Het3, in which
Het3 is pyrrolidin-1-yl, piperidin-1-yl or morpholin-4-yl,
R72 is halogen, l-4C-alkyl, l-4C-alkoxy or l-4C-alkoxycarbonyl,
R73 is l-4C-alkyl or l-4C-alkoxy,
R74 is halogen, l-4C-alkyl, trifluoromethyl, l-4C-alkoxy, cyano, amino, mono- or di-l-4C-alkylamino, l-4C-alkoxycarbonyl, morpholino, carboxyl, nitro, phenyl, phenyloxy, phenyl-1-4C-alkyl, arylsulphonyl, l-4C-alkylsulphonyl, or -S(0)2-N(R712)R713,
R75 is l-4C-alkyl or halogen,
R76 is halogen, hydroxyl, l-4C-alkyl, l-4C-alkoxy, carboxyl or l-4C-alkoxycarbonyl,


R77 is l-4C-alkyl or l-4C-alkoxy,
R8 is l-4C-alkyl, phenyl 2-4C-alkinyl, cyano, -CH2-O-R8I, phenylcarbonyl, -C(0)-N(R82)R83 or
-C(0)-OR9, in which R81 is hydrogen, 1 -4C-alkyl, 1 -4C-alkoxy-2-4-alky 1 or 1 -4C-alkylcarbonyl, R82 is hydrogen, l-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-l-4C-alkyl, phenyl or phenyl-l-4C-
alkyl, and R83 is hydrogen or l-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 or N-(l-4C-alkyl)-piperazinyl, R9 is hydrogen or l-4C-alkyl;
and the salts, stereoisomers, hydrates and hydrates of the salts of these compounds. 2. Compounds of formula I as claiemd in claim 1, in which Rl is hydroxyl, l-4C-alkoxy, l-4C-alkoxy-2-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy,
or completely or predominantly fluorine-substituted l-4C-alkoxy, R2 is hydrogen, halogen or l-4C-alkoxy, and R3 is l-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 l-2C-alkylenedioxy bridge, or Rl 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 Rl and R2 bound to the benzo ring moiety in ortho-position to each other together form a completely
or predominantly fluorine-substituted l-2C-alkylenedioxy bridge and R3 is hydrogen, and none of Rl, R2 and R3 is bound to the 10-position of the pyrrolo[2.1-a]isoquinoline ring, R4 is hydrogen or l-4C-alkyl, R41 is hydrogen or l-4C-alkyl, R5 is l-4C-alkyl, cyano or l-4C-alkoxycarbonyl, and R51 is hydrogen or l-4C-alkyl,
R6 is l-6C-alkyl, or l-4C-alkyl substituted by R61, in which R61 is l-4C-alkoxycarbonyl or -N(R611)R612, in which R611 is l-4C-alkyl, and R612 is l-4C-alkyl, or R611 and R612 together and with inclusion of the nitrogen atom to which they are bound form a
radical Hetl, in which Hetl is pyrrolidin-1-yl, piperidhvl-yl, morpholin-1-yl, or N-(l-4C-alkyl)-piperazinyl,


R7 is Het2, R71- and/or R72- and/or R73-substituted phenyl, R74-substituted Het2, or naphthyl,
in which Het2 is either
a monocyclic or fused bicyclic 5- to 10-membered heteroaryl radical comprising one to three
heteroatoms, each of which is selected from a group consisting of nitrogen, oxygen and sulfur,
or
a fused bicyclic 9- or 10-membered, partially saturated heterocyclic ring radical containing a
benzene ring and comprising one or two heteroatoms, each of which is selected from a group
consisting of nitrogen, oxygen and sulfur,
or
N-oxy-pyridyl, R71 is hydroxyl, halogen, nitro, cyano, trifluoromethyl, l-4C-alkyl, l-4C~alkoxy, amino, mono- or
di-l-4C-alkylamino, l-4C-alkylsulphonylamino, l-4C-alkoxycarbonyl, carboxyl, aryloxy,
completely or predominantly fluorine-substituted l-4C-alkoxy, mono- or di-l-4C-
alkylaminocarbonyl, carbamoyl, tetrazolyl, or -N(H)S(0)2-N(R712)R713, in which aryl is phenyl or R711-substituted phenyl, in which R711 is halogen or l-4C-alkyI, R712 is l-4C-alkyl, and R713 is l-4C-alkyI, or R712 and R713 together and with inclusion of the nitrogen atom to which they are bound form a
radical Het3, in which Het3 is pyrrolidin-1-yl, piperidin-1-yl or morpholin-4-yl, R72 is halogen, l-4C-alkyl or l-4C-alkoxy, R73 is l-4C-alkyl or l-4C-alkoxy,
R74 is l-4C-alkyl, phenyl-l-4C-alkyl, arylsulphonyl, l-4C-alkylsulphonyl, or -S(0)2-N(R712)R713, R8 is l-4C-alkyl, cyano, or -C(0)-OR9, in which R9 is hydrogen or l-4C-alkyl;
and the salts, stereoisomers, hydrates and hydrates of the salts of these compounds. 3. Compounds of formula I as claiimed in claim 1, in which
Rl is bound to the 8-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-4C-alkoxy, R2 is bound to the 7-position of the pyrrolo[21-a]isoquinoline ring, and is hydrogen, halogen or 1-
4C-alkoxy,
R3 is bound to the 9-position of the pyrrolo[21-a]isoquinoline ring, and is l-4C-alkoxy,
R4 is hydrogen,
R41 is hydrogen,
R5 is l-4C-alkyl, cyano or l-4C-alkoxycarbonyl, and
R51 is hydrogen or l-4C-alkyl,


R6 is l-4C-alkyl, or l-4C-alkyl substituted by R61, in which
R61 is l-4C-alkoxycarbonyl or -N(R611)R612, in which
R611 and R612 together and with inclusion of the nitrogen atom to which they are bound form a
radical Hetl, in which Hetl is morpholin-1-yl, R7 is Het2, R71- and/or R72- and/or R73-substituted phenyl, R74-substituted Het2, or naphthyl,
in which Het2 is either
a monocyclic or fused bicyclic 5- to 10-membered heteroaryl radical comprising one to three
heteroatoms, each of which is selected from a group consisting of nitrogen, oxygen and sulfur,
or
a fused bicyclic 9- or 10-membered, partially saturated heterocyclic ring radical containing a
benzene ring and comprising one or two heteroatoms, each of which is selected from a group
consisting of nitrogen, oxygen and sulfur,
or
N-oxy-pyridyl, R71 is hydroxyl, halogen, nitro, l-4C-alkyl, l-4C-alkoxy, amino, mono- or di-l-4C-alkylamino, 1-4C-
alkylsulphonylamino, carboxyl, aryloxy, mono- or di-l-4C-alkylaminocarbonyl, carbamoyl,
tetrazolyl, or -N(H)S(0)2-N(R712)R713, in which aryl is phenyl or R711-substituted phenyl, in which R711 is halogen or l-4C-aIkyI, R712 is l-4C-alkyl, and R713 is l-4C-alkyl, or R712 and R713 together and with inclusion of the nitrogen atom to which they are bound form a
radical Het3, in which Het3 is morpholin-4-yl, R72 is halogen, l-4C-alkyl or l-4C-alkoxy, R73 is l-4C-alkyl or l-4C-alkoxy,
R74 is l-4C-alkyl, phenyl-l-4C-alkyl, arylsulphonyl, l-4C-alkylsulphonyl, or -S(0)2-N(R712)R713, R8 is l-4C-alkyl, cyano, or -C(0)-OR9, in which R9 is hydrogen or l-4C-alkyl;
and the salts, stereoisomers, hydrates and hydrates of the salts of these compounds. 4. Compounds of formula I as claimed in claim 1, in which
either, in a first independent embodiment,
Rl is bound to the 8-posiuon of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy, R2 is bound to the 7-position of the pyrrolo[2.1-a]isoquinoline ring, and is hydrogen, chlorine or
fluorine,


R3 is bound to the 9-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy,
R4 is hydrogen,
R41 is hydrogen,
R5 is l-2C-alkyl or cyano, and
R51 is hydrogen,
R6 is l-2C-alkyl, or l-2C-alkyl substituted by R61, in which
R61 is l-2C-alkoxycarbonyl or -N(R611)R612, in which
R611 and R612 together and with inclusion of the nitrogen atom to which they are bound form a
radical Hetl, in which Hetl is morpholin-1-yl, R7 is naphthyl, 4-hydroxy-3,5-dimethylphenyl, 4-methoxy-3,5-dimethylphenyl, 4-carboxy-phenyl,
4-carbamoyl-phenyl, 2-methyl-4-hydroxy-phenyl, 4-amino-phenyl, 4-(2H-tetrazol-5-yl)-phenyl,
4-morpholino-suIphonylamino-phenyI, 4-methylsuIphonylamino-phenyI, or 2-fluoro-3,4-
dimethoxy-phenyl,
pyridyl, indolyl, quinolinyl, indolinyl,
2-methyl-pyridin-4-yl, 3-methyl-pyridin-4-yl, or
N-(R74)-Het2, in which Het2 is pyrrolyl or indolyl,
R74 is arylsulphonyl, l-2C-alkylsulphonyl, or -S(0)2-N(R712)R713, in which aryl is phenyl, or R711-substituted phenyl, in which R711 is l-2C-alkyl, R712 is l-2C-alkyl, and R713 is l-2C-alkyl, or R712 and R713 together and with inclusion of the nitrogen atom to which they are bound form a
radical Het3, in which Het3 is morpholin-4-yl, and R8 is cyano;
or, in a second independent embodiment,
Rl is bound to the 8-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy, R2 is bound to the 7-position of the pyrrolo[2.1-a]isoquinoline ring, and is hydrogen, chlorine or
fluorine, R3 is bound to the 9-position of the pyrroIo[2.1-a]isoquino!ine ring, and is l-2C-alkoxy, R4 is hydrogen, R41 is hydrogen, R5 is l-2C-alkyl or cyano, and R51 is hydrogen, R6 is l-2C-alkyl, or l-2C-alkyl substituted by R61, in which
R61 is l-2C-alkoxycarbonyl or -N(R611)R612, in which


R611 and R612 together and with inclusion of the nitrogen atom to which they are bound form a
radical Hetl, in which Hetl is morpholin-1-yl, R7 is naphthyl, 4-hydroxy-3,5-dimethylphenyl, 4-methoxy-3,5-dimethylphenyl, 4-carboxy-phenyl,
4-carbamoyl-phenyl, 2-methyl-4-hydroxy-phenyl, 4-amino-phenyl, 4-(2H-tetrazol-5-yl)-phenyl,
4-morpholino-sulphonylamino-phenyl, 4-methylsuIphonylamino-phenyl, or 2-fluoro-3,4-
dimethoxy-phenyl,
pyridyl, indolyl, quinolinyl, indolinyl,
2-methyl-pyridin~4-yl, 3-methyl-pyridin-4-yl, or
N-(R74)-Het2, in which Het2 is pyrrolyl or indolyl,
R74 is arylsulphonyl, l-2C-alkylsulphonyl, or -S(0)2-N(R712)R713, in which aryl is phenyl, or R711-substituted phenyl, in which R711 is l-2C-alkyl, R712 is l-2C-alkyl, and R713 is l-2C-alkyl, or R712 and R713 together and with inclusion of the nitrogen atom to which they are bound form a
radical Het3, in which Het3 is morpholin-4-yl, and R8 is -C(0)-OR9, in which R9 is l-2C-alkyl;
and the salts, stereoisomers, hydrates and hydrates of the salts of these compounds. 5. Compounds of formula I as claiemd in claim 1, in which
either, in a first independent embodiment,
Rl is bound to the 8-position of the pyrrolo[2.1-a]isoquinoline ring, and is methoxy, R2 is bound to the 7-position of the pyrrolo[2.1-a]isoquinoline ring, and is hydrogen or fluorine, R3 is bound to the 9-position of the pyrrolo[2.1-a]isoquinoline ring, and is methoxy, R4 is hydrogen, R41 is hydrogen, R5 is methyl or cyano, R51 is hydrogen,
R6 is methyl, ethyl or 2-methoxycarbonylethyl, R7 is 4-hydroxy-3,5-dimethylphenyl, 4-methoxy-3,5-dimethylphenyl, 4-carboxy-phenyl, 2-methyl-
4-hydroxy-phenyl, 4-amino-phenyl, 4-(2H-tetrazol-5-yl)-phenyl, 4-morpholino-
sulphonylamino-phenyl, 4-methylsulphonylamino-phenyl, pyridyl, quinolinyl, 2-
methyl-pyridin-4-yl, 3-methyl-pyridin-4-yl, l-tolylsulphonyl-pyrrol-3-yl, 1-tolylsulphonyl-

indol-3-yl, l-phenylsulphonyl-indol-3-yl, l-methylsulphonyl-indol-3-yI, 1-
dimethylaminosulphonyl-indol-3-yl, or l-morpholinosulphonyl-indol-3-yl, and
R8 is cyano;
or, in a second independent embodiment,
Rl is bound to the 8-position of the pyrrolo[2.1-a]isoquinoline ring, and is methoxy,
R2 is bound to the 7-position of the pyrrolo[2.1-a]isoquino!ine ring, and is hydrogen or fluorine,
R3 is bound to the 9-position of the pyrrolo[2.1-a]isoquinoline ring, and is methoxy,
R4 is hydrogen,
R41 is hydrogen,
R5 is methyl or cyano,
R51 is hydrogen,
R6 is methyl, ethyl or 2-methoxycarbonylethyl,
R7 is 4-hydroxy-3,5-dimethylphenyl, 4-methoxy-3,5-dimethylphenyl, 4-carboxy-phenyl, 2-methyl-
4-hydroxy-phenyl, 4-amino-phenyl, 4-(2H-tetrazol-5-yl)-phenyl, 4-morpholino-
sulphonylamino-phenyl, 4-methylsulphonylamino-phenyl, pyridyl, quinolinyl, 2-methyl-pyridin-4-yl, 3-methyI-pyridin-4-yl, l-tolylsulphonyl-pyrrol-3-yl, l-tofylsulphonyl-indol-3-yI, 1-phenylsulphonyl-indol-3-yl, l-methylsulphonyI-indol-3-yl, l-dimethylaminosulphonyl-indol-3-yl, or l-morpholinosulphonyl-indol-3-yl, and
R8 is -C(0)-OR9, in which
R9 is methyl or ethyl;
and the salts, stereoisomers, hydrates and hydrates of the salts of these compounds.
6. Compounds of formula I as claiemd in claim 1,
in which
Rl is bound to the 8-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy, such as e.g. methoxy,
R2 is bound to the 7-position of the pyrrolo[21-a]isoquinoline ring, and is fluorine,
R3 is bound to the 9-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy, such as e.g. methoxy,
R4 is hydrogen,
R41 is hydrogen,
R5 is methyl or cyano,
R51 is hydrogen,
R6 is methyl, ethyl or 2-methoxycarbonylethyl,
R7 is 4-hydroxy-3,5-dimethyIphenyI, 4-methoxy-3,5-dimethylphenyl, 4-carboxy-phenyl, 2-methyI-
4-hydroxy-phenyl, 4-amino-phenyl, 4-(2H-tetrazol-5-yl)-phenyl, 4-morpholino-
sulphonylamino-phenyl, 4-methylsulphonylamino-phenyl, pyridyl, quinolinyl, 2-methyl-pyridin-4-yl, 3-methyl-pyridin-4-yl, l-tolylsulphonyl-pyrrol-3-yl, l-tolylsulphonyl-indol-3-yl,


l-phenylsulphonyl-indol-3-yl,l-methylsulphonyl4ndol-3-yl, 1-dimethylaminosulphonyl-indol-
3-yl, or l-morpholinosulphonyl-indol-3-yl, R8 is cyano; and the salts, stereoisomers, hydrates and hydrates of the salts of these compounds.
7. Compounds of formula I as claimed in claim 1,
in which
Rl is bound to the 8-position of the pyrrolo[2.1-a]isoquinoline ring, and is methoxy,
R2 is bound to the 7-position of the pyrrolo[2.1-a]isoquinoline ring, and is fluorine,
R3 is bound to the 9-position of the pyrrolo[2.1-a]isoquinoline ring, and is methoxy,
R4 is hydrogen,
R41 is hydrogen,
R5 is methyl,
R51 is hydrogen,
R6 is methyl,
R7 is 4-hydroxy-3,5-dimethylphenyl, 4-methoxy-3,5-dimethylphenyl, 4-carboxy-phenyl, 2-methyl-
4-hydroxy-phenyl, 4-amino-phenyl, 4-(2H-tetrazol-5-yl)-phenyl, 4-morpholino-
sulphonylamino-phenyl, 4-methylsulphonylamino-phenyl, pyridyl, quinolinyl, 2-methyl-pyridin-4-yl, 3-methyl-pyridin-4-yl, l-tolylsulphonyl-pyrrol-3-yl, l-tolylsulphonyl-indol-3-yl, l-phenylsulphonyl-indol-3-yl, l-methylsulphonyl-indol-3-yl, 1-dimethylaminosulphonyl-indol-3-yl, or l-morpholinosulphonyl-indol-3-yl,
R8 is cyano;
and the salts, stereoisomers, hydrates and hydrates of the salts of these compounds.
8. Compounds of formula I as claimed in claim 1,
in which
Rl is halogen or l-2C-alkoxy,
R2 is hydrogen or l-2C-alkoxy,
R3 is l-2C-alkoxy,
R4 is hydrogen,
R41 is hydrogen,
R5 is l-2C-alkyl,
R51 is hydrogen,
R6 is methyl, ethyl or methoxycarbonylethyl,
R7 is phenyl, Het2, R71- and/or R72- and/or R73-substituted phenyl, or naphthyl, in which
Het2 is a heteroaryl radical selected from the group consisting of furanyl, thiophenyl, pyrrolyl,
pyridinyl, quinolyl, indolyl, benzothiophenyl and benzofuranyl, R71 is hydroxyl, chlorine, methoxy, dimethylamino, or aryloxy, in which aryl is R711-substituted phenyl, in which R711 is chlorine,


R72 is methyl, tert-butyl or methoxy,
R73 is methyl, tert-butyl or methoxy,
R8 is cyano,
and the salts, stereoisomers, hydrates and hydrates of the salts of these compounds.
9. Compounds as claimed in claim 1, which are from formulae la or lb,


R3
R 2
R 1

R 4 R4 1



(la)

(lb)

in which,
as a first alternative,
Rl is hydrogen,
R2 is chlorine or fluorine,
R3 is methoxy or ethoxy,
or, as a second alternative,
Rl is hydrogen,
R2 is methoxy or ethoxy,
R3 is methoxy or ethoxy,
or, as a third alternative,
Rl is methoxy or ethoxy,
R2 is chlorine or fluorine,
R3 is methoxy or ethoxy,
or, as a fourth alternative,
Rl is chlorine or fluorine,
R2 is methoxy or ethoxy,
R3 is methoxy or ethoxy,
or, as a fifth alternative,
Rl is methoxy or ethoxy,
R2 is methoxy or ethoxy,
R3 is methoxy or ethoxy,
R4 is hydrogen,
R41 is hydrogen,
R5 is methyl,
R51 is hydrogen,
R6 is methyl, ethyl or methoxycarbonylethyl,
R7 is Het2, R75-substituted Het2, or 4-hydroxy-3,5-dimethyl-phenyl, in which
Het2 is pyridinyl or quinolinyl,


R75 is l-4C-alkyl,
R8 is cyano,
and the salts, stereoisomers, hydrates and hydrates of the salts of these compounds.
10. Compounds as claimed in any of the preceding claims 1 to 9,
in which
Rl is bound to the 8-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy, such as e.g.
methoxy, R2 is bound to the 7-position of the pyrrolo[2.1-a]isoquinoline ring, and is hydrogen, chlorine or
fluorine, R3 is bound to the 9-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy, such as e.g.
methoxy, and
R4 is hydrogen, R41 is hydrogen, R5 is l-2C-alkyl or cyano, R51 is hydrogen, and
R8 is cyano, and the salts, stereoisomers, hydrates and hydrates of the salts of these compounds.
11. Compounds as claimed in any of the claims 1 to 9,
in which
Rl is bound to the 8-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy, such as e.g.
methoxy, R2 is bound to the 7-position of the pyrrolo[2.1-a]isoquinoline ring, and is chlorine or fluorine, R3 is bound to the 9-position of the pyrrolo[2.1-a]isoquinoline ring, and is l-2C-alkoxy, such as e.g.
methoxy, and
R4 is hydrogen, R41 is hydrogen, R5 is l-2C-alkyl or cyano, R51 is hydrogen, and
R8 is cyano, and the salts, stereoisomers, hydrates and hydrates of the salts of these compounds.
12. A compound as claimed in any of the claims 1 to 9,
wherein said compound is from formula la as defined in claim 9, in which R2 is methoxy,
R3 is methoxy,


R4 is hydrogen,
R41 is hydrogen,
R51 is hydrogen,
and in which Rl, R5, R6 and R8 have any one of the meanings 1.) to 54.) specified in the following
table:

Rl R5 R6 R8
!) hydrogen Methyl Methyl cyano
2-) hydrogen Methyl Methyl ethoxycarbonyl
3.) hydrogen Methyl 2-methoxycarbonylethyl cyano
4.) hydrogen Methyl 2-methoxycarbonylethyl ethoxycarbonyl
5.) fluorine Methyl Methyl cyano
6.) fluorine Methyl Methyl ethoxycarbonyl
7-) fluorine Methyl 2-methoxycarbonylethyl cyano
8.) fluorine Methyl 2-methoxycarbonylethyl ethoxycarbonyl
9-) hydrogen Cyano Methyl cyano
10.) hydrogen Cyano Methyl ethoxycarbonyl
11.) hydrogen Cyano 2-methoxycarbonylethyl cyano
12.) hydrogen Cyano 2-methoxycarbonylethyl ethoxycarbonyl
13.) fluorine Cyano Methyl cyano
14.) fluorine Cyano Methyl ethoxycarbonyl
15.) fluorine Cyano 2-methoxycarbonylethyl cyano
16) fluorine Cyano 2-methoxycarbonylethyl ethoxycarbonyl
17.) chlorine methyl Methyl cyano
18.) chlorine methyl Methyl ethoxycarbonyl
19.) chlorine methyl 2-methoxycarbonylethyl cyano
20.) chlorine methyl 2-methoxycarbonylethyl ethoxycarbonyl
21.) chlorine Cyano Methyl cyano
22.) chlorine Cyano Methyl ethoxycarbonyl
23.) chlorine Cyano 2-methoxycarbonylethyl cyano
24.) chlorine Cyano 2-methoxycarbonylethyl ethoxycarbonyl
25.) hydrogen methyl Methyl methoxycarbonyl
26.) hydrogen methyl 2-methoxycarbonylethyl methoxycarbonyl
27.) fluorine methyl Methyl methoxycarbonyl
28.) fluorine methyl 2-methoxycarbonylethyl methoxycarbonyl
29.) hydrogen Cyano Methyl methoxycarbonyl
30.) hydrogen Cyano 2-methoxycarbonylethyl methoxycarbonyl
31.) fluorine Cyano methyl methoxycarbonyl
32.) fluorine Cyano 2-methoxycarbonylethyl methoxycarbonyl
33.) chlorine methyl methyl methoxycarbonyl
34.) chlorine methyl 2-methoxycarbonylethyl methoxycarbonyl
35.) chlorine Cyano methyl methoxycarbonyl
36.) chlorine Cyano 2-methoxycarbonylethyl methoxycarbonyl
37.) hydrogen methyl ethyl cyano
38.) hydrogen methyl ethyl ethoxycarbonyl
39.) fluorine methyl ethyl cyano
40.) fluorine methyl ethyl ethoxycarbonyl
41.) hydrogen Cyano ethyl cyano
42.) hydrogen Cyano ethyl ethoxycarbonyl
43.) fluorine Cyano ethyl cyano
44.) fluorine Cyano ethyl ethoxycarbonyl
45.) chlorine methyl ethyl cyano
46.) chlorine methyl ethyl ethoxycarbonyl
47.) chlorine Cyano ethyl cyano
48.) chlorine Cyano ethyl ethoxycarbonyl
49.) hydrogen methyl ethyl methoxycarbonyl
50.) fluorine methyl ethyl methoxycarbonyl
51.) hydrogen Cyano ethyl methoxycarbonyl
52.) fluorine Cyano ethyl methoxycarbonyl
53.) chlorine methyl ethyl methoxycarbonyl
54.) chlorine Cyano ethyl methoxycarbonyl
or a salt, stereoisomer, hydrate or hydrate of a salt of this compound.
13. A compound as claimed in claim 1, which is selected from the group consisting of:
1. 2-(4-Hydroxy-3,5-dimethyl-phenyl)-8/9-dimethoxy-3,5,5-trimethyl-5,6-dihydro-pyrroIo[2,l-a]isoquinoline-l-carboxylic acid ethyl ester
2. 8,9 -Dimethoxy-3,5,5 -trimethyl-1-2-(3,4,5-trimethoxy-phenyl)5,6-dihydro-pyrroIo[2,1 a]isoquinoline-l-carboxylic acid ethyl ester
3. 2-[3-(4-Chloro-phenoxy)-phenyl]-8,9-dimethoxy-3,5,5-trimethyl-5,6-dihydro-pyiTolo[2,l-a]isoquinoline-l-carboxylic acid ethyl ester
4. 2-(3-Dimethylamino-phenyl)-8,9-dimethoxy-3,5,5-trimethyl-5,6-dihydro-pyrrolo[2/l-a]isoquinoline-l-carboxylic acid ethyl ester
5. (5RS)-(4-Hydroxy-3,5-dimethyl-phenyl)-8,9-dimethoxy-3,5-dimethyl-5/6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carboxylic acid ethyl ester
6. (5RS)-5-Ethyl-2-(4-hydroxy-3/5-dimethyl-phenyl)-8/9-dimethoxy-3-methyl-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carboxyIic acid ethyl ester
7. (5RS)-2-ailoro-5-ethyl-8,9-dimethoxy-3-methy]-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carboxylic acid ethyl ester
8. (4aRS,8aRS)-cis-2-(4-hydroxy-3,5-dimethyl-phenyl)-10,n-dimethoxy-3-methyl-4a,5,6,7,8,8a-hexahydro-pyrrolo[2,l-f]phenanthridine-l-carboxylic acid ethyl ester
9. (5RS)-3-Ethyl-2-(4-hydroxy-3,5-dimethyI-phenyl)-8,9-dimethoxy-5-methyl-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carboxylic acid ethyl ester
10. (5RS)-8,9-Dimethoxy-3,5-dimethyl-2-(3,4,5-trimethoxy-phenyl-5,6-dihydro-pyrrolo[2,1 a]isoquinoline-l-carboxylic acid ethyl ester
11. (5RS)-8,9-Dimethoxy-3,5-dimethyl-2-naphthalen-l-yl-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-1-carboxylic acid ethyl ester
12. (4aRS,8aRS)-cis-10/ll-Dimethoxy-3-methyl-2-naphthalen-l-yl-4a/5,6,7,8/8a-hexahydro-pyrro!o[2,l-f]phenanthridine-l-carboxyIic acid ethyl ester
13. (4aRS/8aRS)-cis-10,ll-Dimethoxy-3-methyll-2-quinolin-4-yl-4a,5,6,7,8,8a-hexahydro-pyrrolo[2,l-f]phenanthridine-l-carboxylic acid ethyl ester
14. (4aR,8aR)-10,ll-Dimethoxy-3-methyl-2-quinolin-4-yl-4a,5,6,7,8,8a-hexahydro-pyrrolo[2,l-f]phenanthridine-l-carboxylic acid ethyl ester
15. (4aR,8aR)-10, 11-Dimethoxy-3-methyl-2-naphthalen-l-yl-4a,5,6,7,8,8a-hexahydro-pyrrolo[2,l-f]phenanthridine-l-carboxylic acid ethyl ester


16. (4aR,8aR)-2-(4-Hydroxy-3,5-dimethyl-phenyl)-10,H-dimethoxy-3-methyl-4a/5,6,7/8/8a-hexahydro-pyrrolo[2,l-f]phenanthridine-l-carboxylic acid ethyl ester
17. (5RS)-5-Ethyl-8,9-dimethoxy-3-methyl-2-naphthalen-l-yl-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carboxylic acid ethyl ester
18. (5RS)-2-(4-Hydroxy-3,5dimethyl-phenyl)-7/8,9-trimethoxy-3,5-dirnethyl-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carboxylic acid ethyl ester
19. (5RS)-8/9-Dimethoxy-3-(2-methoxycarbonyl-ethyl)-5-methyl-2-naphthalen-l-yl-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carboxylic acid ethyl ester
20. 8,9-Dimethoxy-3,5-dimethyl-2-pyridin-4-yl-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carbonitrile
21. 3-[l-Cyano-2-(4-hydroxy-3,5-dimethyl)-8,9-dimethoxy-5-methyl-5,6-dihydro-pyrrolo[2,l-a]isoquinolin3-yl]-propionic acid methyl ester
22. 2-(4-Hydroxy-3,5-dimethyl-phenyl)-8,9-dimethoxy-3/5-dimethyl-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l -carbonitrile
or a salt, stereoisomer, hydrate or hydrate of a salt thereof.
14. A compound as claimed in claim 1, which is selected from the group consisting of:
1. 2-(4-Hydroxy-3,5-dimethyl-phenyl)-8,9-dimethoxy-3,5,5-trimethyl-5,6-dihydro-pyrroIo[2,l-a]isoquinoline-l-carboxylic acid ethyl ester
2. 8,9-Dimethoxy-3,5,5-trimethyI-2-(3,4,5-trimethoxy-phenyl)-5,6-dihydro-pyrrolo[2,l-oc]isoquinoline-l-carboxy]ic acid ethyl ester
3. 2-[3-(4-Chloro-phenoxy)-phenyl]-8,9-dimethoxy-3,5,5-trimethyl-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carboxylic acid ethyl ester
4. 2-(3-Dimethylamino-phenyl)-8,9-dimethoxy-3,5,5-trimethyl-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carboxylic acid ethyl ester
5. (5RS)- (4-Hydroxy-3,5-dimethyl-phenyl)-8,9-dimethoxy-3,5-dimethyl-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carboxylic acid ethyl ester
6. (5RS)-5-Ethyl-2-(4-hydroxy-3,5-dimethyl-phenyl)-8/9-dimethoxy-3-methyl-5/6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carboxyIic acid ethyl ester
7. (5RS)-2-Chloro-5-ethyl-8,9-dimethoxy"3-methyl-5,6-dihydro-pyrrolo[2/l-a]isoquinoline-l-carboxylic acid ethyl ester
8. (4aRS/8aRS)-cis-2-(4-hydroxy-3,5-dimethyl"phenyl)-10,ll-dimethoxy-3-methyl-4aA6,7,8,8a-hexahydro-pyrrolo[2,l-f]phenanthridine-l-carboxylic acid ethyl ester
9. (5RS)-3-Ethyl-2-(4-hydroxy-3,5-dimethyl-phenyl)-8,9-dimethoxy-5-methyl-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carboxylic acid ethyl ester
10. (5RS)-8,9-Dimethoxy-3,5-dimethyl-2-(3,4,5-trimethoxy-phenyl)-5,6-dihydrcKpyrrolo[2,l-a]isoquinoline-l-carboxylic acid ethyl ester
11. (5RS)-8,9-Dimethoxy-3,5-dimerhyl-2-naphthalen-l-yl-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-
1-carboxylic acid ethyl ester


12. (4aRS,8aRS)-cis-10,ll-Dimethoxy-3-methyl-2-naphthalen-l-yI-4a,5,6,7,8,8a-hexahydro-pyrrolo[2,l-f]phenanthridine-l-carboxylic add ethyl ester
13. (4aRS,8aRS)-cis-10,H-Dimethoxy-3-methyl-2-quinolin-4-yl-4a,5,6,7/8,8a-hexahydro-pyrrolo[2,l-f]phenanthridine-l-carboxylic add ethyl ester
14. (4aR,8aR)-1041-Dimethoxy-3-methyl-2-quinolin-4-yl-4a,5/6/7,8/8a-hexahydro-pyrrolo[2,l-f]phenanthridine-l-carboxylic add ethyl ester
15. (4aR,8aR)-10,ll-Dimethoxy-3-methyl-2-naphthalen-l-yl-4a,5,6,7,8,8a-hexahydro-pyrrolo[2,l-f]phenanthridine-l-carboxylic add ethyl ester
16. (4aR,8aR)-2-(4-Hydroxy-3,5-dimethyI-phenyl)-10,ll-dimethoxy-3-methyl-4a/5,6,7.8,8a-hexahydro-pyrrolo[2,l-flphenanthridine-l-carboxylic add ethyl ester
17. (5RS)-5-Ethyl-8,9-dimethoxy-3-methyl-2-naphthalen-l-yl-5,6-dihydro-pyrroIo[2,l-a]isoquinoline-l-carboxylic add ethyl ester
18. (5RS)-2-(4-Hydroxy-3,5-dJrnethyl-phenyl)-7,8,9-trimethoxy-3,5-dimethyl-5,6-dihydro-pyrrolo[2/l-a]isoquinoline-l-carboxylic add ethyl ester
19. 2-(4-Hydroxy-3,5-dimethyl-phenyl)-8,9-dimethoxy-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-1,5-dicarboxylic acid 1-ethyl 5-methyl ester
20. (5RS)-8,9-Dimethoxy-3-(2-methoxycarbonyl-ethyl)-5-methyl-2-naphthalen-l-yl-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carboxylic add ethyl ester
21. 8,9-Dimethoxy-3,5-dimethyl-2-pyridin-4-yl-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carbonitrile
22. 3-[l-Cyano-2-(4-hydroxy"3,5-dimethyI)-8,9-dimethoxy-5-methyI-5,6-dihydro-pyrrolo[2,l-a]isoquinolin3-yl]-propionic add methyl ester
23. 2-(4-Hydroxy-3,5-dimethyl-phenyl)-8,9-dimethoxy-3,5-dimethyl-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carbonitrile
24. 7-Fluoro-2-(4-hydroxy-3,5-dimethyl-phenyl)-8,9-dimethoxy-3,5-dimethyl-5/6-dihydro-pyrrolo[2,l-a]isoquinoline-l -carbonitrile
25. 8,9-Dimethoxy-2-(4-methoxy-3,5-dimethyl-phenyl)-3,5-dimethyl-5,6-dihydro-pyrrolot2,l-a]isoquinoline-l-carbonitrile
26. 8,9-Dimethoxy-3,5-dimethyl-2-[l-(toluene-4-sulfonyl)-lH-pyrrol-3-yI]-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carbonitrile
27. 8,9-Dirnethoxy-3/5-dimethyl-2-[l-(toluene-4-sulfonyl)-lH-indol-3-yl]-5,6-dihydro-pyrrolo[2,l-a]isoquinoline~l-carbonitrile
28. 2-(l-Benzenesulfonyl-lH-indol-3-yl)-8/9-dimethoxy-3/5-dimethyl-5/6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carbonitrile
29. 2-(l-Methanesulfonyl-lH-indol-3-yl)-8,9-dimethoxy-3,5-dimerhyl-5/6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carbonitrile
30. 8,9-Dimethoxy-3,5-dimethyl-2-(l-oxy-pyridin-4-yl)-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-
carbonitrile


31. 7-Fluoro-8,9-dimethoxy-3,5-dimeihyl-2-[l-(toluene-4-sulfonyl)-lH-indol-3-yl]-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carbonitrile
32. 2-(4-Hydroxy-3/5-dimethyl-phenyl)-8,9-dimethoxy-5-methyl-3-morphoIin-4-ylmethyl-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carbonitrile
33. 8,9-Dimethoxy-3,5-dimethyl-2-(2-methyl-pyridin-4-yI)-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carbonitrile
34. 8,9-Dimethoxy-3,5-dimethyl-2-(4-nitro-phenyl)-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carbonitrile
35. 4-(l-Cyano-8,9-dimethoxy-3,5-dimethyl-5,6-dihydro-pyrrolo[2,l-a]isoquinolin-2-yl)-benzoic acid
36. 2-(4-Amino-phenyl)-8,9-dimethoxy-3,5-dimethyl-5/6-dihydro-pyrrolo[2,l-a]isoqtiinoline-l-carbonitrile
37. 8,9-Dimethoxy-3,5-dimethyl-2-(3-methyl-pyridin-4-yl)-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carbonitrile
38. 4-(l-Cyano-8-ethoxy-9-methoxy-3,5-dimethyl-5/6-dihydro-pyrrolo[2,l-a]isoquinolin-2-yl)-benzoic acid
39. 2-(4-Hydroxy-2-methyl-phenyl)-8,9-dimethoxy-3,5-dimethyl-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carbonitrile
40. 4-(l-Cyano-8,9-dimethoxy-3/5-dimethyl-5/6-dihydro-pyrrolo[2,l-a]isoquinolin-2-yl)-benzamide
41. 8-Ethoxy-2-(4-hydroxy-3,5-dimethyl-phenyl)-9-methoxy-3,5-dimethyl-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carbonitrile
42. 3-(l-Cyano-8,9-dirnethoxy-3,5-dimethyl-5,6-dihydro-pyrrolo[2,l-a]isoquinolin-2-yl)-indole-l-sulfonic acid dimethylamide
43. 8,9-Dimethoxy-3,5-dimethyl-2-(2-methyl-l-oxy-pyridin-4-yl)-5,6-dihydro-pyrrolo[2,l-a] isoquinoline-1 -carbonitrile
44. 8,9-Dimethoxy-3/5-dimethyl-2-[l-(morpholine-4-sulfonyl)-lH-indol-3-yl]-5/6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carbonitrile
45. 8,9-Dimethoxy-3,5-dimethyl-2-[4-(2H-tetrazoI-5-yl)-phenyl]-5,6-dihydro-pyrroIo[2,l-a]isoquinoIine-l -carbonitrile
46. Morpholine-4-sulfonic acid [4-(l-cyano-8,9-dimethoxy-3,5-dimethyl-5,6-dihydro-pyrrolo[2,l-a]isoquinolin-2-yl)-phenyl]-amide
47. N-[4-(l-Cyano-8,9-dimethoxy-3,5-dimethyl-5,6-dihydro-pyrrolo[2,l-a]isoquinolin-2-yl)-phenyl]-methanesulfonamide
48. 5-Ethyl-2-(2-fluoro-3,4-dimethoxy-phenyl)-8,9-dimethoxy-3-methyl-5,6-dihydro-pyrrolo[24-a]isoquinoline-l-carboxylic acid ethyl ester
49. 7-Chloro-8,9-dimethoxy-3,5-dimethyl-2-pyridin-4-yl-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-
l-carboxylic acid ethyl ester


50. 7-Chloro-2-(4-hydroxy-3,5-dimethyl-phenyl)-8,9-dimethoxy-3,5-dimethyI-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carboxylic acid ethyl ester
51. 7,8,9-Trimethoxy-3,5-dimethyl-2-pyridin-4-yl-5,6-dihydro-pyrrolo[2,l-a]isoqiiinoline-l-carboxylic acid ethyl ester
52. 8/9-Dimethoxy-3-(2-methoxycarbonyl-ethyl)-5-methyl-2-quinolin-4-yl-5/6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carboxylic acid ethyl ester
53. 2-(4-Hydroxy-3,5-dimethyl-phenyl)-8,9-dimethoxy-3,5-dimethyl-5,6-dihydro-pyrrolo[2,l-a]isoquinoline-l-carboxylic acid methyl ester
54. 8,9-Dimethoxy-3,5-dimethyl-2-[l-(toluene-4-suIfonyl)"lH-indol-3-yl]-5,6-dihydro-pyrrolot2,l-a]isoquinoline-l-carboxylic acid methyl ester
55. 5-Cyano-2-(4-hydroxy-3,5-dimethyl-phenyl)-8,9-dimethoxy-3-methyl-5,6-dihydro-pyrrolo[2,l-ajisoquinoline-l-carboxylic acid ethyl ester
or a salt, stereoisomer, hydrate or hydrate of a salt thereof.
Dated this 23rd day of January, 2006.
HIRAL CHANDRAKANT JOSHI AGENT FOR ALTANA PHARMA AG

Documents:

83-MUMNP-2006--CORRESPONDENCE(19-11-2008).pdf

83-MUMNP-2006--GENERAL POWER OF ATTORNEY(19-11-2008).pdf

83-mumnp-2006-abstract(27-3-2008).pdf

83-mumnp-2006-abstract(complete)-(23-1-2006).pdf

83-mumnp-2006-abstract(granted)-(25-8-2008).pdf

83-mumnp-2006-cancelled pages(27-3-2006).pdf

83-mumnp-2006-claims(complete)-(23-1-2006).pdf

83-mumnp-2006-claims(granted)-(25-8-2008).pdf

83-mumnp-2006-correspondence 1(17-6-2010).pdf

83-MUMNP-2006-CORRESPONDENCE 1(19-11-2008).pdf

83-MUMNP-2006-CORRESPONDENCE 2(17-6-2010).pdf

83-mumnp-2006-correspondence 2(8-2-2006).pdf

83-mumnp-2006-correspondence(17-6-2010)).pdf

83-MUMNP-2006-CORRESPONDENCE(19-11-2008).pdf

83-MUMNP-2006-CORRESPONDENCE(27-3-2008).pdf

83-mumnp-2006-correspondence(ipo)-(5-11-2008).pdf

83-mumnp-2006-description(complete)-(23-1-2006).pdf

83-mumnp-2006-description(granted)-(25-8-2008).pdf

83-mumnp-2006-form 1(23-1-2006).pdf

83-mumnp-2006-form 1(27-3-2008).pdf

83-mumnp-2006-form 1(8-2-2006).pdf

83-mumnp-2006-form 13(19-11-2008).pdf

83-mumnp-2006-form 13-(19-11-2008).pdf

83-mumnp-2006-form 2(complete)-(23-1-2006).pdf

83-mumnp-2006-form 2(granted)-(25-8-2008).pdf

83-mumnp-2006-form 2(granted)-(27-3-2008).doc

83-mumnp-2006-form 2(title page)-(complete)-(23-1-2006).pdf

83-mumnp-2006-form 2(title page)-(granted)-(25-8-2008).pdf

83-mumnp-2006-form 3(27-3-2008).pdf

83-mumnp-2006-form 5(23-1-2006).pdf

83-mumnp-2006-form 5(27-3-2008).pdf

83-mumnp-2006-mark copy(27-3-2008).pdf

83-mumnp-2006-power of attorney(19-11-2008).pdf

83-mumnp-2006-power of attorney(23-01-2006).pdf

83-mumnp-2006-specification(amended)-(27-3-2008).pdf

83-mumnp-2006-wo international publication report(23-1-2006).pdf

83-mumnp-2007-cancelled pages(27-3-2008).pdf

83-mumnp-2007-claims(granted)-(27-3-2008).doc

83-mumnp-2007-claims(granted)-(27-3-2008).pdf

83-mumnp-2007-correspondence(27-3-2008).pdf

83-mumnp-2007-correspondence(ipo)-(23-5-2008).pdf

83-mumnp-2007-form 1(27-3-2003).pdf

83-mumnp-2007-form 18(30-6-2006).pdf

83-mumnp-2007-form 2(granted)-(27-3-2008).pdf

83-mumnp-2007-form 3(23-1-2006).pdf

83-mumnp-2007-form 3(27-3-2003).pdf

83-mumnp-2007-form 5(27-3-2003).pdf

83-mumnp-2007-form-pct-isa-210(23-1-2006).pdf

83-mumnp-2007-power of attorney(23-1-2006).pdf


Patent Number 222777
Indian Patent Application Number 83/MUMNP/2006
PG Journal Number 39/2008
Publication Date 26-Sep-2008
Grant Date 25-Aug-2008
Date of Filing 23-Jan-2006
Name of Patentee ALTANA PHARMA AG
Applicant Address Byk-Gulden-Str. 2, 78467 Konstanz.
Inventors:
# Inventor's Name Inventor's Address
1 MATTHIAS VENNEMANN LEINERSTR. 20 78462 KONSTANZ.
2 THOMAS BAR BERGRAMAWEG 31 78333 STOCKACH.
3 THOMAS MAIER PANORAMAWEG 31 78333 STOCKACH
4 ULRICH GRADLER FICHTERSTR. 15 69126 HEIDELBERG.
5 JURGEN BRAUNGER DORFWIESENWEG 26 78465 KONSTANZ.
6 PETER GIMMNICH. SONNENBUHLSTR. 58 7864 KONSTANZ
7 GIANLUCA QUINTINI EICHHORNSTR.51 78464 KONSTANZ
8 PAOLA CIPETTI 12, ROUTE DES TOMAINS 67120 ALTRO.
9 JEAN-MARIE CONTRERAS 7D, RUE DE LA COTE D' AZUR 67100 STRASBOURG.
10 PROF. CAMILLE GEORGES WERGES WERMUTH
PCT International Classification Number C07D 471/04
PCT International Application Number PCT/EP04/051307
PCT International Filing date 2003-06-30
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 03014424.0 2003-06-30 EUROPEAN UNION