CA2469385A1 - Substituted 4-phenyltetrahydroisoquinolines, process for their preparation, their use as medicament, and medicament containing them - Google Patents

Substituted 4-phenyltetrahydroisoquinolines, process for their preparation, their use as medicament, and medicament containing them Download PDF

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CA2469385A1
CA2469385A1 CA002469385A CA2469385A CA2469385A1 CA 2469385 A1 CA2469385 A1 CA 2469385A1 CA 002469385 A CA002469385 A CA 002469385A CA 2469385 A CA2469385 A CA 2469385A CA 2469385 A1 CA2469385 A1 CA 2469385A1
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methyl
tetrahydro
dichloro
isoquinolin
phenyl
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Armin Hofmeister
Uwe Heinelt
Hans-Jochen Lang
Markus Bleich
Klaus Wirth
Michael Gekle
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Sanofi Aventis Deutschland GmbH
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    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
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    • C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
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    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

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Abstract

The invention relates to compounds of formula (I), wherein R1 - R9 which have the meaning as cited in the claims, are extremely suitable as antihypertensives for reducing or preventing ischemically induced injuries, as medicaments for operative intervention for the treatment of ischemics of the nervous system, strokes and swelling of the brain, shocks, disturbed respiratory functions, for the treatment of snorers, as a laxative, as agents against ectopic parasites, for the prevention of gallstones, as antiatherosclerotic agents, agents against diabetic late complications, cancer, fibrotic diseases, endothelial dysfunctions, organ hypertrophia and hyperplasia. Said compounds are also inhibitors of the cellular sodium-proton-antiporters, they influence serum lipoproteins and can be used in the prophylaxis of and for the regression of atherosclerotic alterations.

Description

Description Substituted 4-phenyltetrahydroisoquinolines, process for their preparation, their use as medicament, and medicament containing them The invention relates to compounds of the formula I
R9~ ~ ~~R7 N
R3 / ~R5 in which the meanings are:
R1, R2, R3 and R4 independently of one another H, F, CI, Br, I, CN, N02, OH, NH2, CaH2a+1, CqqH2qq_1, OCbH2b+1, COOR10, OCOR10, COR10 or Ox-(CH2)y-phenyl;
a and b in the groups CaH2a+1 and OCbH2b+1 independently of one another 1, 2, 3, 4, 5, 6, 7 or 8, it being possible for one or more H atoms to be replaced by F atoms;
qq 3, 4, 5, 6, 7 or 8, it being possible for one or more H atoms to be replaced by F atoms;
R10 H or CcH2c+1;
c 1, 2, 3, 4, 5, 6, 7 or 8, it being possible for one or more H
atoms to be replaced by F atoms, x zero or 1;
y zero, 1, 2, 3 or 4;
where the phenyl ring in the group Ox-(CH2)y-phenyl is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, CI, Br, CN, N02, OH, NH2 or CdH2d+1 d 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms, or R1, R2, R3 and R4 independently of one another heteroaryl, it being possible for zero, 1, 2, 3 or 4 N atoms, zero or 1 oxygen atom or zero or 1 S atom to be present as ring atoms;
or R1, R2, R3 and R4 ~ 10 independently of one another CONR11 R12 or NR11 R12;
R11 and R12 independently of one another H, CeH2e+1, CrrH2rr-1;
a 1,2,3,4,5,6,7or8, rr 3, 4, 5, 6, 7, or 8, it being possible for one or more H~ atoms in the groups CeH2e+1 and CrrH2rr-1 to be replaced by F atoms and for one or more CH2 groups to be replaced by O or NR13;
R13 H or CfH2f+1 f 1, 2, 3 or 4, it being possible for one or more H
atoms to be replaced by F atoms;
or R13 and a CH2 group of R11 or R12 together with the N atom to which they are bonded a 5- or 6-membered ring;
or R11 and R12 together with the N atom to which they are bonded a 5-, 6- or 7-membered ring;
or R11 and R12 independently of one another COR14, CSR14 or S02R14;
R14 CgH2g+1;
g 1, 2, 3, 4, 5, 6, 7 or 8, it being possible for one or more H atoms to be replaced by F atoms, and it being possible for one or more CH2 groups to be replaced by O or NR13, or R1, R2, R3 and R4 independently of one another -Oh-SOj-R15, with h zero or 1;
j zero, 1 or 2;
R15 CkH2k+1, OH, OCIH21+1 or NR17R18;
k 1, 2, 3, 4, 5, 6, 7 or 8, it being possible for one or more H
atoms to be replaced by F atoms;
I 1, 2, 3, 4, 5, 6, 7 or 8, it being possible for one or more H
atoms to be replaced by F atoms;
R17 and R18 independently of one another H or CmH2m+1 m 1, 2, 3, 4, 5, 6, 7 or 8, it being possible for one or more H atoms in the group CmH2m+1 to be replaced by F
atoms and for one or more CH2 groups to be replaced by O, CO, CS or NR19;
R19 H or CnH2n+1;
n 1, 2, 3 or 4;
it being possible for one or more H atoms in CnH2n+1 to be replaced by F atoms;
or R17 and R18 together with the N atom to which they are bonded a 5-, 6- or 7-membered ring;
or R19 and a CH2 group of R17 or R18 together with the N atom to which they are bonded a 5- or 6-membered ring;
but where R2 must always not be equal to H, R5 H, CPH2p+1, CssH2ss-1, COR20 or S02R20;
p 1, 2, 3, 4, 5, 6, 7 or 8, ss 3, 4, 5, 6, 7 or 8, R20 CqH2q+1;
q 1, 2, 3, 4, 5, 6, 7 or 8, it being possible for one or more H atoms in the groups CpH2p+1, CssH2ss-1 and CqH2q+1 to be replaced by F atoms and for one or more CH2 groups to be replaced by O or NR21;
R21 H or CrH2r+1;
r 1, 2, 3 or 4;
it being possible for one or more H atoms in CrH2r+1 to be replaced by F atoms;
R6 H, F, CI, Br, I, CSH2s+1, CddH2dd-1~ OH, OCtH2t+1 or OCOR22;
sandt independently of one another 1, 2, 3, 4, 5, 6, 7 or 8;
dd 3, 4, 5, 6, 7 or 8, it being possible for one or more H atoms in CsH2s+1 ~ CddH2dd-1 and OCtH2t+1 to be replaced by F atoms;
R22 CuH2u+1;
a 1, 2, 3 or 4;
it being possible for one or more H atoms in CuH2u+1 to be replaced by F atoms;
R7, R8 and R9 independently of one another -Ov-SOw-R23;
v zero or 1;
w zero, 1 or 2;
R23 C~nH2nn+1~ CmmH2mm-1, OH, OCppH2pp+1 or NR25R26;
nn and pp independently of one another 1, 2, 3, 4, 5, 6, 7 or 8, mm 3, 4, 5, 6, 7 or 8, it being possible for one or more H atoms in CnnH2nn+1 CmmH2mm-1 and OCppH2pp+1 to be replaced by F atoms;
R25 and R26 independently of one another H, CN or CZH2z+1, CzzH2zz-1 5 z 1, 2, 3, 4, 5, 6, 7 or 8;
zz 3, 4, 5, 6, 7 or 8, it being possible for one or more H
atoms to be replaced by F atoms and, in CZH2z+1, it being possible for one or more H atoms to be replaced by F atoms and it being possible for one or more CH2 groups to be replaced by O, CO, CS
or NR27;
R27 H or CaaH2aa+1 as 1, 2, 3 or 4;
it being possible for one or more H atoms in CaaH2aa+1 to be replaced by F atoms;
or R25 and R26 together with the N atom to which they are bonded a 5-, 6- or 7-membered ring, or R27 and a CH2 group of R25 or R26 together with the N atom to which they are bonded a 5- or 6-membered ring;
or R7, R8 and R9 independently of one another NR32COR30, NR32CSR30 or NR32SObbR30;
R30 H, CccH2cc+1 ~ CyyH2yy-1 ~ pYrrolidinyl or piperidinyl, in which rings a CH2 group may be replaced by O or NR33;
R32 and R33 independently of one another H or ChH2h+1 bb 2 or 3;
cc 1, 2, 3, 4, 5, 6, 7 or 8;
yy 3, 4, 5, 6, 7 or 8;
h 1, 2, 3, 4, 5, 6, 7 or 8, it being possible for one or more H atoms in ChH2h+1 to be replaced by F
atoms, and it being possible for one or more H atoms in the groups CccH2cc+1 and CyyH2yy_1 to be replaced by F atoms and for one or more CH2 groups to be replaced by NR31 and for a CH2 group to be replaced by O;
R31 H, CkkH2kk+1, COR65 or S02R65;
kk 1, 2, 3, or 4;
it being possible for one or more H atoms to be replaced by F
atoms, R65 H, C~H2~+1;
xx 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
or R31 forms together with a CH2 group of R30 a 5-, 6- or 7-membered ring;
or R30 a 5- or 6-membered heteroaryl with 1, 2, 3 or 4 N atoms, zero or 1 S
atoms and zero or 1 O atoms, which is unsubstituted or substituted by up to three substituents selected from the group consisting of F, CI, Br, I, CooH2oo+1 ~ NR70R71;
R70 and R71 independently of one another H, CuuH2uu+1 and COR72;
R72 H, CvvH2vv+1 00, uu and w independently of one another 1, 2, 3, 4, 5, 6, 7 or 8;
it being possible for one or more H atoms in the groups CooH2oo+1 ~ CuuH2uu+1 or CvvH2vv+1 to be replaced by F atoms;
or R7, R8 and R9 independently of one another H, F, CI, Br, I, N02, CN, OH, NH2, CeeH2ee+1 C~,~,H2~_1, OC~H2~+1, NR40R41, CONR40R41, COOR42, COR42 or OCOR42, ee and ff independently of one another 1, 2, 3, 4, 5, 6, 7 or 8;
ww 3, 4, 5, 6, 7 or 8;
it being possible for one or more H atoms in the groups CeeH2ee+1 C~,,~,,H2~_1 and OC~H2~+1 to be replaced by F atoms;
R40 and R41 H,CttH2tt+1 or C(NH)NH2;
tt 1, 2, 3, 4, 5, 6, 7 or 8;
it being possible for one or more H atoms in the group CttH2tt+1 to be replaced by F atoms and for one or more CH2 groups to be replaced by O or NR44;
R44 H or CggH2gg+1;
gg 1, 2, 3, 4, 5, 6, 7 or 8;
it being possible for one or more H atoms in the group CggH2gg+1 to be replaced by F atoms, and it being possible for R44 together with a (CH2) group of R40 or R41 and the N atom to which they are jointly bonded to form a 5- or 6-membered ring, or R40 and R41 with the N atom to which they are bonded a 5- or 6-membered ring;
R42 H or ChhH2hh+1 hh 1, 2, 3, 4, 5, 6, 7 or 8;
it being possible for one or more H atoms in the group ChhH2hh+1 to be replaced by F atoms;
but where two substituents from the group of R7, R8 and R9 may not simultaneously be OH or OCH3 and where at least one of the radicals R7, R8 or R9 must be selected from the group consisting of CONR40R41, -OvSON,R23, NR32COR30, NR32CSR30 and NR32SObbR30;
and the pharmaceutically acceptable salts and trifluoroacetates thereof.
Preference is given to compounds of the formula I in which the meanings are:
R1, R2, R3 and R4 independently of one another, H, F, CI, Br, I, CN, N02, OH, NH2, CaH2a+1 cycloalkyl with 3, 4, 5 or 6 C atoms, OCbH2b+1, COOR10;
a and b independently of one another 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
R10 H or CcH2c+1;
c 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
or R1, R2, R3 and R4 ~ 20 independently of one another 5- or 6-membered heteroaryl selected from the group consisting of pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thiazolyl and oxazolyl;
or R1, R2, R3 and R4 independently of one another CONR11 R12 or NR11 R12;
R11 and R12 independently of one another H, CeH2e+1, CrrH2rr-1;
a 1, 2, 3 or 4, rr 3, 4, 5 or 6, it being possible for one or more H atoms in the groups CeH2e+1 and CrrH2rr-1 to be replaced by F atoms or R11 and R12 independently of one another hydroxyethyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, pyrrolidinoethyl, N-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl;
or R11 and R12 together with the N atom to which they are bonded a pyrrolidine, piperidine, N-methylpiperazine, piperazine or morpholine ring;
or R11 and R12 independently of one another COR14, CSR14, CONHR14, CSNHR14 or S02R14;
R14 CgH2g+1;
g 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
or R1, R2, R3 and R4 independently of one another OS03H, S03H, S02R15, with R15 CkH2k+1, OCIH21+1 or NR17R18;
k 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
I 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
R17 and R18 independently of one another H, CmH2m+1, in which the first CH2 group bonded to the nitrogen is replaced by CO and the second CH2 group is replaced by NR19;
m 1, 2, 3, 4 or 5, it being possible for one or more H
atoms in the group CmH2m+1 to be replaced by F
atoms;

R19 H or CnH2n+1 n 1, 2, 3 or 4;
it being possible for one or more H atoms in CnH2n+1 to be replaced by F atoms;
5 or R17 and R18 together with the N atom to which they are bonded a 5- or 6-membered ring;
but where R2 must always not be equal to H, 10 R5 H, CpH2p+1;
p 1, 2, 3 or 4;
it being possible for one or more H atoms in CpH2p+1 to be replaced by F atoms;
R6 H, CSH2s+1, OCtH2t+1 or OCOR22;
sandt independently of one another 1, 2, 3 or 4;
it being possible for one or more H atoms in CSH2s+1 and OCtH2t+1 to be replaced by F atoms;
R22 CuH2u+1 a 1, 2, 3 or 4;
it being possible for one or more H atoms in CuH2u+1 to be replaced by F atoms;
R7, R8 and R9 independently of one another OS03H, S03H or S02R23;
R23 CnnH2nn+1 ~ CmmH2mm-1 ~ OCppH2pp+1 or NR25R26;
nn and pp independently of one another 1, 2, 3, 4 or 5, mm 3, 4, 5 or 6, it being possible for one or more H atoms in CnnH2nn+1 CmmH2mm-1 and OCppH2pp+1 to be replaced by F atoms;
R25 and R26 independently of one another H, CN, CZH2z+1, in which the first CH2 group bonded to the nitrogen is replaced by CO or CS and the second CH2 is replaced by NR27;
z 1, 2, 3, 4, 5 or 6;
it being possible for one or more H atoms in CZH2z+1 to be replaced by F atoms;
R27 H or CaaH2aa+1 as 1, ~2, 3 or 4;
it being possible for one or more H atoms in CaaH2aa+1 to be replaced by F atoms;
or R25 and R26 together with the N atom to which they are bonded a 5- or 6-membered ring;
or R27 and a CH2 group of R25 or R26 together with the N atom to which they are bonded a 5- or 6-membered ring;
or R7, R8 and R9 independently of one another NR32COR30, NR32CSR30 or NR32S02R30;
R30 H, OH, CccH2cc+1 ~ CyyH2yy-1 ~ PYrrolidinyl or piperidinyl, in which rings a C!-i2 group may be replaced by O or NR33;
R32 and R33 independently of one another H or ChH2h+1;
cc 1, 2, 3, 4, 5, 6, 7 or 8;
yy 3, 4, 5 or 6;
h 1, 2, 3 or 4;
if being possible for one or more H atoms in ChH2h+1 to be replaced by F
atoms, and it being possible for one or more H atoms in the groups CccH2cc+1 and CyyH2yy_1 to be replaced by F atoms and for one or more CH2 groups to be replaced by NR31 and for a CH2 group to be replaced by O;
R31 H, CkkH2kk+1 ~ COR65 or S02R65;
kk 1, 2, 3, or 4;
it being possible for one or more H atoms to be replaced by F atoms, R65 H, CxxH2xx+1;
xx 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
or R31 together with a CH2 group of R30 and the N atom to which they are jointly bonded form a 5- or 6-membered ring;
or R30 a 5- or 6-membered heteroaromatic system selected from the group consisting of pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thienyl, thiazolyl and oxazolyl, which are unsubstituted or substituted by up to three substituents selected from the group consisting of F, CI, Br, I, Coof~2oo+1~ NR70R71, R70 and R71 ~ 20 independently of one another H, CuuH2uu+1 or COR72;
R72 H, CvvH2vv+1 oo, uu and w independently of one another 1, 2, 3 or 4;
it being possible for one or more H atoms in the groups CooH2oo+1 ~ CuuH2uu+1 or CvvH2vv+1 to be replaced by F
atoms;
or R7, R8 and R9 independently of one another H, F, CI, Br, I, N02, CN, OH, NH2, CeeH2ee+1.
CN,~,H2N,v,-1, OC~H2~+1, NR40R41, CONR40R41, COOR42, COR42 or OCOR42;
ee and ff independently of one another 1, 2, 3 or 4;
ww 3, 4, 5 or 6, it being possible for one or more H atoms in the groups CeeH2ee+1 C~H2~"N,_1 and OC~H2~+1 to be replaced by F atoms;
R40 and R41 H, CttH2tt+1 or C(NH)NH2;
tt 1, 2, 3, 4, 5, 6, 7 or 8;
it being possible for one or more H atoms in the group CttH2tt+1 to be replaced by F atoms;
or R40 and R41 to be selected independently of one another hydroxyethyl, , N,N-dimethylaminoethyl, N,N-diethylaminoethyl, pyrrolidinoethyl, N-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl;
or R40 and R41 together with the N atom to which they are bonded form a ring selected from the group consisting of pyrrolidine, piperidine, N-methyl-piperazine, piperazine and morpholine;
R42 H or ChhH2hh+1 hh 1, 2, 3 or 4;
it being possible for one or more H atoms in the group ChhH2hh+1 to be replaced by F atoms;
but where two substituents from the group of R7, R8 and R9 may not simultaneously be OH or OCH3 and where at least one of the radicals R7, R8 or R9 must be selected from the group consisting of CONR40R41, -O~SO~",R23, NR32COR30, NR32CSR30 and NR32SObbR30;
and the pharmaceutically acceptable salts and trifluoroacetates thereof.
Particular preference is given to compounds of the formula I in which the meanings are:
R1, R2, R3 and R4 independently of one another H, F, CI, Br, OH, NH2, CaH2a+1, cycloalkyl with 3, 4, 5 or 6 C atoms, OCbH2b+1.
a and b in the groups CaH2a+1 and OCbH2b+1 independently of one another 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
or R1, R2, R3 and R4 independently of one another NR11 R12;
R11 and R12 independently of one another H, CeH2e+1, CrrH2rr-1;
a 1, 2, 3 or 4, rr 3, 4, 5 or 6, it being possible for one or more H atoms in the groups CeH2e+1 and CrrH2rr-1 to be replaced by F
2p atoms;
or R11 and R12 together with the N atom to which they are bonded form a ring selected from the group consisting of pyrrolidine, piperidine, N-methylpiperazine, piperazine and morpholine;
or R11 and R12 independently of one another COR14, CSR14, CONHR14, CSNHR14 or S02R14;
R14 CgH2g+1;

g 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
or R1, R2, R3 and R4 5 independently of one another OS03H, S03H, S02R15;
R15 CkH2k+1 or NR17R18;
k 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
R17 and R18 10 independently of one another H or CmH2m+1 m 1, 2, 3, 4 or 5, it being possible for one or more H
atoms in the group CmH2m+1 to be replaced by F
atoms;
or 15 R17 and R18 together with the N atom to which they are bonded a 5- or 6-membered ring;
but where R2 must always not be equal to H;
R5 methyl or trifluoromethyl;
R6 H;
R7, R8 and R9 independently of one another OS03H, S03H or S02R23;
R23 CnnH2nn+1 or NR25R26;
nn 1,2,3,4or5, it being possible for one or more H atoms in CnnH2nn+1 to be replaced by F atoms;
R25 and R26 independently of one another H, CN or CZH2z+1, in which the first CH2 group bonded to the nitrogen is replaced by CO or CS and the second CH2 is replaced by NR27;
z 1, 2, 3, 4, 5 or 6;
it being possible for one or more H atoms in CzH2z+1 to be replaced by F atoms;
R27 H or CaaH2aa+1 as 1, 2, 3 or 4;
it being possible for one or more H atoms in CaaH2aa+1 to be replaced by F atoms;
or R25 and R26 together with the N atom to which they are bonded a 5- or 6-membered ring, or R27 and a CH2 group of R25 or R26 together with the N atom to which they are bonded a 5- or 6-membered ring;
or R7, R8 and R9 independently of one another NR32COR30, NR32CSR30 or NR32S02R30;
R30 H, OH, CccH2cc+1 ~ CyyH2yy-1 ~ pYrrolidinyl or piperidinyl, in which rings a CH2 group may be replaced by O or NR33;
R32 and R33 H, methyl or CF3;
cc 1, 2, 3, 4, 5, 6, 7 or 8;
yy 3, 4, 5 or 6;
it being possible for one or more H atoms in the groups CccH2cc+1 and CyyH2yY_1 to be replaced by F atoms and for one or more CH2 groups to be replaced by NR31 and for a CH2 group to be replaced by O;
R31 H, methyl, ethyl, CF3, CH2CF3, acetyl, propionyl, methanesulfonyl or ethanesulfonyl;
or R31 together with a CH2 group of R30 and the N atom to which they are jointly bonded form a 5- or 6-membered ring;
or R30 pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thiazolyl or oxazolyl, which are unsubstituted or substituted by a maximum of 3 substituents selected from the group consisting of F, CI, methyl, ethyl, trifluoromethyl, NH2, NHacetyl;
or R7, R8 and R9 independently of one another H, F, CI, OH, NH2, CeeH2ee+1 ~ CwwH2ww-1 OC~H2~+1, NR40R41, CONR40R41, COOR42 or OCOR42, ee and ff independently of one another 1, 2, 3 or 4;
ww 3, 4, 5 or 6, it being possible for one or more H atoms in the groups CeeH2ee+1 C"~,N,H2~,~,,-1 and OC~H2~+1 to be replaced by F atoms;
R40 and R41 H, CttH2tt+1 or C(NH)NH2 tt 1, 2, 3 or 4; , it being possible for one or more H atoms in the group CttH2tt+1 to be replaced by F atoms;
or R40 and R41 independently of one another hydroxyethyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, pyrrolidinoethyl, N-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl;
or R40 and R41 together with the N atom to which they are bonded a pyrrolidine, piperidine, N-methylpiperazine, piperazine or morpholine ring;
R42 H or ChhH2hh+1 hh 1, 2, 3 or 4;
it being possible for one or more H atoms in the group ChhH2hh+1 to be replaced by F atoms;
but where two substituents from the group of R7, R8 and R9 may not simultaneously be OH or OCH3 and where at least one of the radicals R7, R8 or R9 must be selected from the group consisting of CONR40R41, -OvSO~",R23, NR32COR30, NR32CSR30 and NR32SObbR30;
and the pharmaceutically acceptable salts and trifluoroacetates thereof.
Very particular preference is given to compounds of the formula I in which the meanings are:
R1, R2, R3 and R4 independently of one another H, F, CI, Br, OH, NH2, CaH2a+1, cycloalkyl with 3, 4, 5 or 6 C atoms, OCbH2b+1;
a and b in the groups CaH2a+1 and OCbH2b+1 independently of one another 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
or R1, R2, R3 and R4 independently of one another NR11 R12;
R11 and R12 independently of one another H, CeH2e+1, CrrH2rr-1;
a 1, 2, 3 or 4, rr 3, 4, 5 or 6, it being possible for one or more H atoms in the groups CeH2e+1 and CrrH2rr-1 to be replaced by F
atoms;
or R11 and R12 together with the N atom to which they are bonded form a ring selected from the group consisting of pyrrolidine, piperidine, N-methylpiperazine, piperazine and morpholine;
or R11 and R12 independently of one another COR14, CSR14, CONHR14, CSNHR14 or S02R14;
R14 C9H2g+1;
g 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
or R1, R2, R3 and R4 independently of one another OS03H, S03H, S02R15;
R15 CkH2k+1 or NR17R18;
k 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
R17 and R18 independently of one another H or CmH2m+1 m 1, 2, 3, 4 or 5, it being possible for one or more H
atoms in the group CmH2m+1 to be replaced by F
atoms;
or R17 and R18 together with the N atom to which they are bonded a 5- or 6-membered ring;
but where R2 must always not be equal to H;
R5 methyl or trifluoromethyl;
R6 H;
R7, R8 and R9 independently of one another OS03H, S03H or S02R23;
R23 CnnH2nn+1 or NR25R26;

nn 1, 2, 3, 4 or 5, it being possible for one or more H atoms in CnnH2nn+1 to be replaced by F atoms;
R25 and R26 5 independently of one another H, CN or CZH2z+~ , in which the first CH2 group bonded to the nitrogen is replaced by CO or CS and the second CH2 is replaced by NR27;
z 1, 2, 3, 4, 5 or 6;
it being possible for one or more H atoms in CZH2z+1 10 to be replaced by F atoms;
R27 H or CaaH2aa+1:
as 1, 2, 3 or 4;
it being possible for one or more H atoms in CaaH2aa+1 to be replaced by F atoms;
15 or R25 and R26 together with the N atom to which they are bonded a 5- or 6-membered ring, or 20 R27 and a CH2 group of R25 or R26 together with the N atom to which they are bonded a 5- or 6-membered ring;
or R7, R8 and R9 independently of one another NR32COR30, NR32CSR30 or NR32S02R30;
R30 H, OH, CccH2cc+1 ~ CyyH2yy-1 ~ pYrrolidinyl or piperidinyl, in which rings a CH2 group may be replaced by O or NR33;
R32 and R33 H, methyl or CF3;
cc 1, 2, 3, 4, 5, 6, 7 or 8;
yy 3, 4, 5, 6;
it being possible for one or more H atoms in the groups CccH2cc+1 and CyyH2yy_1 to be replaced by F atoms and for one or more CH2 groups to be replaced by NR31 and for a CH2 group to be replaced by O;
R31 H, methyl, ethyl, CF3, CH2CFg, acetyl, propionyl, methanesulfonyl or ethanesulfonyl;
or R31 together with a CH2 group of R30 and the N atom to which they are jointly bonded form a 5- or 6-membered ring;
or R30 pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thiazolyl or oxazolyl, which are unsubstituted or substituted by a maximum of 3 substituents selected from the group consisting of F, CI, methyl, ethyl, trifluoromethyl, NH2, NHacetyl;
or R7, R8 and R9 independently of one another H, F, CI, OH, NH2, CeeH2ee+1 ~ CwwH2ww-1 OCttH2tt+1, NR40R41, CONR40R41, COOR42 or OCOR42, ee and ff independently of one another 1, 2, 3 or 4;
ww 3, 4, 5 or 6, it being possible for one or more H atoms in the groups CeeH2ee+1 C~"~,H2~,N,_1 and OCttH2tt+1 to be replaced by F atoms;
R40 and R41 H, CttH2tt+1 or C(NH)NH2;
tt 1, 2, 3 or 4;
it being possible for one or more H atoms in the group CttH2tt+1 to be replaced by F atoms;
or R40 and R41 independently of one another hydroxyethyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, pyrrolidinoethyl, N-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl;
or R40 and R41 together with the N atom to which they are bonded a pyrrolidine, piperidine, N-methylpiperazine, piperazine or morpholine ring;
R42 H or ChhH2hh+1 hh 1, 2, 3 or 4;
it being possible for one or more H atoms in the group ChhH2hh+1 to be replaced by F atoms;
but where two substituents from the group of R7, R8 and R9 may not simultaneously be OH or OCH3 and where at least one of the radicals R7, R8 or R9 must be selected from the group consisting of -OvSO~,R23, NR32COR30, NR32CSR30 and NR32SObbR30;
and the pharmaceutically acceptable salts and trifluoroacetates thereof.
Very particular specific preference is given to compounds 1) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
2) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide;
3) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide;
4) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N,N-dimethyl-benzenesulfonamide;
5) 4-(4-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline;
6) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid;
7) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-ethyl-benzamide;
8) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-propyl-benzamide;
9) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N-(2-dimethylamino-ethyl)-benzamide;
10) 6,8-dichloro-2-methyl-4-(4-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline;
11) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-diethyl-amine 12) 6,8-dichloro-2-methyl-4-(4-piperidin-1-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline;
13) 6,8-dichloro-2-methyl-4-(4-pyrrolidin-1-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline;
14) 6,8-dichloro-2-methyl-4-[4-(4-methyl-piperazin-1-yl)-phenyl]-1,2,3,4-tetrahydro-isoquinoline;
15) 6,8-dichloro-2-cyclopropyl-4-phenyl-1,2,3,4-tetrahydroisoquinoiine;
16) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine;
17) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-propylurea;
18) 1-[4-(fj,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-thiourea;
19) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
20) N-[4-(6-methanesulfonyl-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
21) N-[4-(2,6,8-trimethyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
22) N-[4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
23) N-[4-(8-chloro-2-methyl-6-pyrrolidin-1-yl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
24) N-[4-(8-chloro-2-methyl-6-morpholin-4-yl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
25) N-f4-[8-chloro-2-methyl-6-(4-methyl-piperazin-1-yl)-1,2,3,4-tetrahydro-isoquinolin-4-yl]-phenyl}-acetamide;
26) N-{4-[8-chloro-6-(cyclopropylmethyl-amino)-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl]-phenyl}-aretamide;
27) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoic acid;
28) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-N-methyl-benzamide;
29) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N-ethyl-2-hydroxy-benzamide;
30) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N-(2-dimethylamino-ethyl)-2-hydroxy-benzamide;
31) N-[5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoyl]-guanidine;
32) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
33) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine;
34) 2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine;
35) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;
36) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;
37) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]pentanamide;
38) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-isobutyramide;
39) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2-dimethyl-propionamide;
40) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclopropanecarboxamide;
41) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin- 4-yl)-phenyl]-cyclobutanecarboxamide;
42) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclopentanecarboxamide;
43) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2,2-trifluoro-acetamide;
44) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-acetylpiperidine-4-carboxamide;
45) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-nicotinamide;
46) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methane-sulfonamide;
47) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)- phenyl]-ethanesulfonamide;
48) N',N'-dimethylamino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide;
5 49) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;
50) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;
51 ) N-[3-(~6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-10 pentanamide;
52) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-isobutyramide;
53) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2-dimethyl-propionamide;
15 54) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclopropanecarboxamide;
55) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclobutanecarboxamide;
56) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-20 cyclopentanecarboxamide;
57) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2,2-trifluoro-acetamide;
58) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-acetylpiperidine-4-carboxamide;
25 59) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-nicotinamide;
60) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methane-sulfonamide;
61) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)- phenyl]-ethanesulfonamide;
62) N',N'-dimethylamino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide;

63) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl)-propionamide;
64) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;
65) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pentanamide;
66) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl)-isobutyramide;
67) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2-dimethyl-propionamide;
68) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclopropanecarboxamide;
69) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)- phenyl]-cyclobutanecarboxamide;
70) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclopentanecarboxamide;
71 ) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2,2-trifluoro-acetamide;
72) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl)-1-acetylpiperidine-4-carboxamide;
73) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methane-sulfonamide;
74) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)- phenyl]-ethanesulfonamide;
75) N',N'-dimethylamino-N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide;
76) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
77) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-thiourea;
78) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;

79) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-thiourea;
80) N-{5-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylsulfamoyl]-4-methyl-thiazol-2-yl}-acetamide;
81) N-{5-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylsulfamoyl]-4-methyl-thiazol-2-yl}-acetamide;
82) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,2-dimethyl-1 H-imidazole-4-sulfonamide;
83) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,2-dimethyl-1 H-imidazole-4-sulfonamide;
84) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-5-chloro-1,3-dimethyl-1 H-pyrazole-4-sulfonamide;
85) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-5-chloro-1,3-dimethyl-1 H-pyrazole-4-sulfonamide;
86) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-5-bromo-thiophene-2-sulfonamide;
87) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl],-5-bromo-thiophene-2-sulfonamide;
88) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-C,C,C-trifluoro-methanesulfonamide;
89) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-C,C,C-trifluoro-methanesulfonamide;
90) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2,2-trifluoroethanesulfonamide;
91 ) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2,2-trifluoro-ethanesulfonamide;
92) N-ethyl-N'-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonylurea;
93) 2-chloro-5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide;
94) 2-methyl-4-phenyl-6,8-bis-trifluoromethyl-1,2,3,4-tetrahydro-isoquinoline;

95) 2-amino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
96) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2-methylamino-acetamide;
97) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2-dimethylamino-acetamide;
98) 2-amino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;
99) 2-amino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;
100) 2,6-diamino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-hexanamide;
101) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrolidine-2-carboxamide;
102) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-isonicotinamide;
103) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrole-3-carboxamide;
104) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrole-2-carboxamide;
105) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methyl-piperidine-4-carboxamide;
106) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,4-dimethyl-1 H-pyrrole-2-carboxamide;
107) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-nitro-1 H-pyrrole-2-carboxamide;
108) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,5-dimethyl-1 H-pyrrole-3-carboxamide;
109) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-imidazole-4-carboxamide;
110) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonyl-piperidine-4-carboxamide;

111) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3,5-dimethyl-1 H-pyrazole-4-carboxamide;
112) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrazole-4-carboxamide;
113) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-trifluoromethyl-1 H-pyrazole-4-carboxamide;
114) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2-methylamino-acetamide;
115) N-[3-(~,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-dimethylamino-acetamide;
116) 2-amino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;
117) 2-amino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;
118) 2,6-diamino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-hexanamide;
119) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrolidine-2-carboxamide;
120) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-isonicotinamide;
121 ) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrole-3-carboxamide;
122) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrole-2-carboxamide;
123) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methyl-piperidine-4-carboxamide;
124) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,4-dimethyl-1 H-pyrrole-2-carboxamide;
125) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-nitro-1 H-pyrrole-2-carboxamide;
126) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,5-dimethyl-1 H-pyrrole-3-carboxamide;

127) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-imidazole-4-carboxamide;
128) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methanesu Ifonyl-piperid ine-4-carboxamide;
5 129) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3,5-dimethyl-1 H-pyrazole-4-carboxamide;
130) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrazole-4-carboxamide;
131) N-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-~ 10 3-trifluoromethyl-1 H-pyrazole-4-carboxamide;
132) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-thiourea;
133) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-thiourea;
15 134) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-thiourea;
135) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-dimethyl-a rea;
136) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-methyl-20 piperazine-1-carboxamide;
137) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-piperidine-1-carboxamide;
138) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-morpholine-4-carboxamide;
25 139) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrolidine-1-carboxamide;
140) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-diethyl-urea;
141) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-30 urea;
142) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;

143) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(tetrahydro-furan-3-yl)-urea;
144) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(tetrahydro-pyran-4-yl)-urea;
145) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methyl-1-( 1-methyl-piperidin-4-yl)-urea;
146) 3-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-(3-dimethylamino-propyl)-1-methyl-urea;
147) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-(2-dimethylamino-ethyl)-1-methyl-urea;
148) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-(3-dimethylamino-propyl)-urea;
149) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-methoxy-ethyl)-urea;
150) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-pyridin-3-yl-a rea;
151) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-pyridin-4-yl-urea;
152) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-methyl-piperazine-1-carboxamide;
153) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-urea;
154) 3-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea;
155) 3-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-d iethyl-a rea;
156) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-piperidine-1-carboxamide;
157) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-morpholine-4-carboxamide;
158) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrolidine-1-carboxamide;

159) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl}-urea;
160) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-methyl-piperazine-1-carboxamide;
161) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrolidine-1-carboxamide;
162) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-urea;
163) 3-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-d imethyl-urea;
164) 3-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-diethyl-urea;
165) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;
166) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-piperidine-1-carboxamide;
167) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-morpholine-4-carboxam'ide;
168) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-formamide;
169) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amine;
170) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,3-dimethyl-urea;
171) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-4-methyl-piperazine-1-carboxamide;
172) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,3,3-trimethyl-urea;
173) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-piperidine-1-carboxamide;
174) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-morpholine-4-carboxamide;

175) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-pyrrolidine-1-carboxamide;
176) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-1-methyl-urea;
177) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3,3-d iethyl-1-methyl-urea;
178) N-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-formamide;
179) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amine;
180) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-pyrrolidine-1-carboxamide;
181) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-piperidine-1-carboxamide;
182) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,3,3-trimethyl-urea;
183) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,3-dimethyl-urea;
184) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-morpholine-4-carboxamide;
185) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-4-methyl-piperazine-1-carboxamide;
186) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-1-methyl-urea;
187) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3,3-d iethyl-1-methyl-urea;
188) 2-dimethylamino-ethyl [3-(fi,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
189) 2-dimethylamino-ethyl [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
190) 2-dimethylamino-ethyl [2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;

191) methyl [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
192) ethyl [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
193) isopropyl [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
194) 2,2-dimethyl-propyl [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
195) methyl [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
196) isopropyl [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
197) 2,2-dimethyl-propyl [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
198) ethyl [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
199) (R)-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylJ-methanesulfonamide;
200) (S)-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonamide;
201 ) (R)-1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
202) (S)-1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
203) N-[3-(6,8-difluoro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
204) 4-(3-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoline;
205) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-hydroxy-ethyl)-urea;
206) ethyl 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoate;
207) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid.
and the pharmaceutically acceptable salts thereof.

Exceptionally particular preference is given to compounds from the group of 1) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
5 2) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide;
3) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide;
4) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-thiourea;
5) 1-[4-(5,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-10 urea;
6) N-[4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
7) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
15 8) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;
9) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-acetyl-piperidine-4-carboxamide;
10) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methane-20 sulfonamide;
11 ) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-ethanesulfonamide;
12) N',N'-dimethylamino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide;
25 13) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;
14) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;
15) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-30 isobutyramide;
16) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclopropanecarboxamide;

17) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclobutanecarboxamide;
18) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2,2-trifluoro-acetamide;
19) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-acetyl-piperidine-4-carboxamide;
20) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-nicotinamide;
21 ) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methane-sulfonamide;
22) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-ethanesulfonamide;
23) N',N'-dimethylamino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide;
24) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclopropanecarboxamide;
25) N-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-acetyl-piperidine-4-carboxamide;
26) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
27) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-thiourea;
28) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
29) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-thiourea;
30) N-{5-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylsulfamoyl]-4-methyl-thiazol-2-yl}-acetamide;
31 ) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,2-dimethyl-1 H-imidazole-4-sulfonamide;
32) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-C,C,C-trifluoro-methanesulfonamide;

33) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-C,C,C-trifluoro-methanesulfonamide;
34) N-ethyl-N'-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonylurea;
35) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2-dimethylamino-acetamide;
36) 2,6-diamino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-hexanamide;
37) N-[4-(~,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrole-3-carboxamide;
38) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methyl-piperidine-4-carboxamide;
39) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methanesulfonyl-piperidine-4-carboxamide;
40) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1 H-pyrazole-carboxamide;
41) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2-methylamino-acetamide;
42) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2-dimethylamino-acetamide;
43) 2-amino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;
44) 2-amino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;
45) 2,6-diamino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-hexanamide;
46) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methyl-piperidine-4-carboxamide;
47) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-imidazole-4-carboxamide;
48) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methanesulfonyl-piperidine-4-carboxamide;
49) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3,5-dimethyl-1 H-pyrazole-4-carboxamide;
50) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrazole-carboxamide;
51) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea;
52) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-methyl-piperazine-1-carboxamide;
53) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-piperidine-1-carboxamide;
54) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-morpholine-4-carboxamide;
55) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrolidine-1-carboxamide;
56) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-diethyl-urea;
57) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-urea;
58) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;
59) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(tetrahyd ro-fu ra n-3-yl )-a rea;
60) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(tetrahydro-pyran-4-yl)-urea;
61 ) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methyl-1-(1-methyl-piperidin-4-yl)-urea;
62) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-(3-dimethylamino-propyl)-1-methyl-urea;
63) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-(2-dimethylamino-ethyl)-1-methyl-urea;
64) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(3-diethylamino-propyl)-urea;
65) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-methoxy-ethyl)-urea;
66) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-pyridin-3-yl )-a rea;
67) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-pyridin-4-yl-urea;
68) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-methyl-piperazine-1-carboxamide;
69) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-urea;
70) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-d imethylamino-ethyl )-a rea;
71 ) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-methyl-piperazine-1-carboxamide;
72) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-urea;
73) 3-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea;
74) 3-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-diethyl-urea;
75) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;
76) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-morpholine-4-carboxamide;
77) N-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-formamide;
78) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-formamide;
79) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,3,3-trimethyl-urea;
80) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,3-dimethyl-urea;
81 ) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-morpholine-4-carboxamide;
82) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-4-methyl-piperazine-1-carboxamide;
5 83) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-1-methyl-urea;
84) 2-dimethylamino-ethyl [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl )-phenyl]-carbamate;
85) 2-dimethylamino-ethyl [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-~ 10 yl)-phenyl]-carbamate;
86) 2-dimethylamino-ethyl [2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
87) methyl [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
15 88) (R or S)-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonamide;
89) (R or S)-1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
90) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-20 hydroxy-ethyl)-urea;
and the pharmaceutically acceptable salts thereof.
The invention further encompasses the use of the compounds of the formula I
for producing a medicament for the treatment of disorders which can be influenced by 25 inhibition of the sodium-proton exchanger of subtype III (NHE3), in which the meanings are:
R1, R2, R3 and R4 independently of one another H, F, CI, Br, I, CN, N02, OH, NH2, CaH2a+1, CqqH2qq_1, OCbH2b+1, COOR10, OCOR10, COR10 or Ox-(CH2)Yphenyl;
30 a and b in the groups CaH2a+1 and OCbH2b+1 independently of one another 1, 2, 3, 4, 5, 6, 7 or 8, it being possible for one or more H atoms to be replaced by F atoms;
qq 3, 4, 5, 6, 7 or 8, it being possible for one or more H atoms to be replaced by F atoms;
R10 H or CcH2c+1;
c 1, 2, 3, 4, 5, 6, 7 or 8, it being possible for one or more H
atoms to be replaced by F atoms, x zero or 1;
y zero, 1, 2, 3 or 4;
where the phenyl ring in the group Ox-(CH2)y-phenyl is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, CI, Br, CN, N02, OH, NH2 or CdH2d+1 d 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms, or R1, R2, R3 and R4 independently of one another heteroaryl, it being possible for zero, 1, 2, 3 or 4 N atoms, zero or 1 oxygen atom or zero or 1 S atom to be present as ring atoms;
or R1, R2, R3 and R4 independently of one another CONR11 R12 or NR11 R12;
R11 and R12 independently of one another H, CeH2e+1, CrrH2rr-1;
a 1, 2, 3, 4, 5, 6, 7 or 8, rr 3, 4, 5, 6, 7, or 8, it being possible for one or more H atoms in the groups CeH2e+1 and CrrH2rr-1 to be replaced by F atoms and for one or more CH2 groups to be replaced by O or NR13;

R13 H or CfH2f+1;
f 1, 2, 3 or 4, it being possible for one or more H
atoms to be replaced by F atoms;
or R13 and a CH2 group of R11 or R12 together with the N atom to which they are bonded a 5- or 6-membered ring;
or R11 and R12 together with the N atom to which they are bonded a 5-, 6- or 7-membered ring;
or R11 and R12 independently of one another COR14, CSR14 or S02R14;
R14 CgH2g+1;
g 1, 2, 3, 4, 5, 6, 7 or 8, it being possible for one or more H atoms to be replaced by F atoms, and it being possible for one or more CH2 groups to be replaced by O or NR13, or R1, R2, R3 and R4 independently of one another -Oh-SOj-R15, with h zero or 1;
j zero, 1 or 2;
R15 CkH2k+1, OH, OCIH21+1 or NR17R18;
k 1, 2, 3, 4, 5, 6, 7 or 8, it being possible for one or more H
atoms to be replaced by F atoms;
I 1, 2, 3, 4, 5, 6, 7 or 8, it being possible for one or more H
atoms to be replaced by F atoms;
R17 and R18 independently of one another H or CmH2m+1 m 1, 2, 3, 4, 5, 6, 7 or 8, it being possible for one or more H atoms in the group CmH2m+1 to be replaced by F
atoms and for one or more CH2 groups to be replaced by O, CO, CS or NR19;
R19 H or CnH2n+1 n 1, 2, 3 or 4;
it being possible for one or more H atoms in CnH2n+1 to be replaced by F atoms;
or R17 and R18 together with the N atom to which they are bonded a 5-, 6- or 7-membered ring;
or R19 and a CH2 group of R17 or R18 together with the N atom to which they are bonded a 5- or 6-membered ring;
R5 H, CpH2p+1, CssH2ss-1, COR20 or S02R20;
p 1, 2, 3, 4, 5, 6, 7 or 8, ss 3, 4, 5, 6, 7 or 8, it being possible for one or more H atoms in CpH2p+1 and CssH2ss-1 to be replaced by F atoms ~ , R20 CqH2q+1;
q 1, 2, 3, 4, 5, 6, 7 or 8, it being possible for one or more H atoms in CqH2q+1 to be replaced by F atoms and for one or more CH2 groups to be replaced by O or N R21;
R21 H or CrH2r+1 r 1, 2, 3 or 4;
it being possible for one or more H atoms in CrH2r+1 to be replaced by F atoms;
R6 H, F, CI, Br, I, CSH2s+~, CddH2dd-1, OH, OCtH2t+1 or OCOR22;
s and t independently of one another 1, 2, 3, 4, 5, 6, 7 or 8;
dd 3, 4, 5, 6, 7 or 8, it being possible for one or more H atoms in CsH2s+1, CddH2dd-1 and OCtH2t+1 to be replaced by F atoms;
R22 CuH2u+1;
a 1,2,3or4;
it being possible for one or more H atoms in CuH2u+1 to be replaced by F atoms;
R7, R8 and R9 independently of one another -Ov-SOw-R23;
v zero or 1;
w zero, 1 or 2;
R23 CnnH2nn+1 ~ CmmH2mm-1, OH, OCppH2pp+1 or NR25R26;
nn and pp independently of one another 1, 2, 3, 4, 5, 6, 7 or 8, mm 3, 4, 5, 6, 7 or 8, it being possible for one or more H atoms in CnnH2nn+1 CmmH2mm-1 and OCppH2pp+1 to be replaced by F atoms;
R25 and R26 independently of one another H, CN or CZH2z+1, C~H2u_1;
~ 20 z 1, 2, 3, 4, 5, 6, 7 or 8;
zz 3, 4, 5, 6, 7 or 8, it being possible for one or more H
atoms to be replaced by F atoms and, in CZH2z+1, it being possible for one or more H atoms to be replaced by F atoms and it being possible for one or more CH2 groups to be replaced by O, CO, CS
or NR27;
R27 H or CaaH2aa+1 as 1, 2, 3 or 4;
it being possible for one or more H atoms in CaaH2aa+1 to be replaced by F atoms;
or R25 and R26 together with the N atom to which they are bonded a 5-, 6- or 7-membered ring, or 5 R27 and a CH2 group of R25 or R26 together with the N atom to which they are bonded a 5- or 6-membered ring;
or R7, R8 and R9 independently of one another NR32COR30, NR32CSR30 or NR32SObbR30;
10 R30 H, CccH2cc+1 ~ CyyH2yy-1 ~ PYrrolidinyl or piperidinyl, in which rings a CH2 group may be replaced by O or NR33;
R32 and R33 independently of one another H or ChH2h+1 bb 2 or 3;
cc 1, 2, 3, 4, 5, 6, 7 or 8;
15 yy 3, 4, 5, 6, 7 or 8;
h 1, 2, 3, 4, 5, 6, 7 or 8, it being possible for one or more H atoms in ChH2h+1 to be replaced by F
atoms, and it being possible for one or more H atoms in the groups CccH2cc+1 and CyyH2yy_1 to be replaced by F atoms and for one or more 20 (CH2) groups to be replaced by NR31 and for a (CH2) group to be replaced by O;
R31 H, CkkH2kk+1, COR65 or S02R65;
kk 1, 2, 3, or 4;
it being possible for one or more H atoms to be replaced by F
25 atoms, R65 H, CxxH2xx+1 xx 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
or 30 R31 forms together with a CH2 group of R30 a 5-, 6- or 7-membered ring;
or R30 a 5- or 6-mernbered heteroaryl with 1, 2, 3 or 4 N atoms, zero or 1 S
atoms and zero or 1 O atoms, which is unsubstituted or substituted by up to three substituents selected from the group consisting of F, CI, Br, I, CooH2oo+1 ~ NR70R71;
R70 and R71 independently of one another H, CuuH2uu+1 and COR72;
R72 H, CvvH2vv+1 00, uu and vv independently of one another 1, 2, 3, 4, 5, 6, 7 or 8;
it being possible for one or more H atoms in the groups CooH2oo+1. CuuH2uu+1 or C~,~,H2vv+1 to be replaced by F atoms;
or R7, R8 and R9 independently of one another H, F, CI, Br, I, N02, CN, OH, NH2, CeeH2ee+1 C~"~,H2N,N,_1, OC~H2~+1, NR40R41, CONR40R41, COOR42, COR42 or OCOR42, ee and ff independently of one another 1, 2, 3, 4, 5, 6, 7 or 8;
ww 3,4,5,6,7or8;
it being possible for one or more H atoms in the groups CeeH2ee+1 CN,~"H2~,N,_1 and OCffH2~+1 to be replaced by F atoms;
R40 and R41 H, CttH2tt+1 or C(NH)NH2;
tt 1, 2, 3, 4, 5, 6, 7 or 8;
it being possible for one or more H atoms in the group CttH2tt+1to be replaced by F atoms and for one or more CH2 groups to be replaced by O or NR44;

R44 H or CggH2gg+1;
gg 1, 2, 3, 4, 5, 6, 7 or 8;
it being possible for one or more H atoms in the group CggH2gg+1 to be replaced by F atoms, or R40 and R41 with the N atom to which they are bonded a 5- or 6-membered ring;
R42 H or ChhH2hh+1 hh 1, 2, 3, 4, 5, 6, 7 or 8;
it being possible for one or more H atoms in the group ChhH2hh+1 to be replaced by F atoms;
and the pharmaceutically acceptable salts thereof.
Preference is given to the use of compounds of the formula I, in which the meanings are:
R1, R2, R3 and R4 independently of one another, H, F, CI, Br, I, CN, N02, OH, NH2, CaH2a+1 cycloalkyl with 3, 4, 5 or 6 C atoms, OCbH2b+1, COOR10;
a and b independently of one another 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
R10 H or CcH2c+1;
c 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
or R1, R2, R3 and R4 independently of one another 5- or 6-membered heteroaryl selected from the group consisting of pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thiazolyl and oxazolyl;
or R1, R2, R3 and R4 independently of one another CONR11 R12 or NR11 R12;
R11 and R12 independently of one another H, CeH2e+1, CrrH2rr-1;
a 1, 2, 3 or 4, rr 3, 4, 5 or 6, it being possible for one or more H atoms in the groups CeH2e+1 and CrrH2rr-1 to be replaced by F atoms or R11 and R12 independently of one another hydroxyethyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, pyrrolidinoethyl, N-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl;
or R11 and R12 together with the N atom to which they are bonded a pyrrolidine, piperidine, N-methylpiperazine, piperazine or morpholine ring;
or R11 and R12 independently of one another COR14, CSR14, CONHR14, CSNHR14 or S02R14;
R14 CgH2g+1;
g 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
or R1, R2, R3 and R4 independently of one another OS03H, S03H, S02R15, or R15 CkH2k+1, OCIH21+1 or NR17R18;
k 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;

I 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
R17 and R18 independently of one another H, CmH2m+1, in which the first CH2 group bonded to the nitrogen is replaced by CO and the second CH2 group is replaced by NR19;
m 1, 2, 3, 4 or 5, it being possible for one or more H
atoms in the group CmH2m+1 to be replaced by F
atoms;
R19 H or CnH2n+1 n 1, 2, 3 or 4;
it being possible for one or more H atoms in CnH2n+1 to be replaced by F atoms;
or R17 and R18 together with the N atom to which they are bonded a 5- or 6-membered ring;
R5 H, CpH2p+1, CssH2ss-~1 p 1, 2, 3 or 4;
ss 3, 4, 5 or 6, it being possible for one or more H atoms in CpH2p+1 and CssH2ss-1 to be replaced by F atoms;
R6 H, CSH2s+1, OCtH2t+1 or OCOR22;
sandt independently of one another 1, 2, 3 or 4;
it being possible for one or more H atoms in CSH2s+1 and OCtH2t+1 to be replaced by F atoms;
R22 CuH2u+1~
a 1, 2, 3 or 4;
it being possible for one or more H atoms in CuH2u+1 to be replaced by F atoms;

R7, R8 and R9 independently of one another OS03H, S03H or S02R23;
R23 CnnH2nn+1 ~ CmmH2mm-1, OCppH2pp+1 or NR25R26;
nn and pp 5 independently of one another 1, 2, 3, 4 or 5, mm 3, 4, 5 or 6, it being possible for one or more H atoms in CnnH2nn+1 CmmH2mm-1 and OCppH2pp+1 to be replaced by F atoms;
R25 and R26 10 independently of one another H, CN, CzH2z+1, in which the first CH2 group bonded to the nitrogen is replaced by CO or CS and the second CH2 is replaced by NR27;
z 1, 2, 3, 4, 5 or 6;
it being possible for one or more H atoms in CZH2z+1 15 to be replaced by F atoms;
R27 H or CaaH2aa+1 as 1, 2, 3 or 4;
it being possible for one or more H atoms in CaaH2aa+1 to be replaced by F atoms;
20 or R25 and R26 together with the N atom to which they are bonded a 5- or 6-membered ring;
or 25 R27 and a CH2 group of R25 or R26 together with the N atom to which they are bonded a 5- or 6-membered ring;
or R7, R8 and R9 independently of one another NR32COR30, NR32CSR30 or NR32S02R30;

R30 H, OH, CccH2cc+1 ~ CyyH2yy-1 ~ PYrrolidinyl or piperidinyl, in which rings a CH2 group may be replaced by O or NR33;
R32 and R33 independently of one another H or ChH2h+1;
cc 1, 2, 3, 4, 5, 6, 7 or 8;
yy 3, 4, 5 or 6;
h 1, 2, 3 or 4;
it being possible for one or more H atoms in ChH2h+1 to be replaced by F
atoms, and it being possible for one or more H atoms in the groups CccH2cc+1 and CyyH2yy_1 to be replaced by F atoms and for one or more (CH2) groups to be replaced by NR31 and for a (CH2) group to be replaced by O;
R31 H, CkkH2kk+1. COR65 or S02R65;
kk 1, 2, 3, or 4;
it being possible for one or more H atoms to be replaced by F atoms, R65 H, C~H2~+1;
xx 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
a or R31 together with a CH2 group or R30 and the N atom to which they are jointly bonded form a 5- or 6-membered ring;
or R30 a 5- or 6-membered heteroaromatic system selected from the group consisting of pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thienyl, thiazolyl and oxazolyl, which are unsubstituted or substituted by up to three substituents selected from the group consisting of F, CI, Br, I, CooH2oo+1, NR70R71, R70 and R71 independently of one another H, CuuH2uu+1 or COR72;
R72 H, CvvH2vv+1 oo, uu and w independently of one another 1, 2, 3 or 4;
it being possible for one or more H atoms in the groups CooH2oo+1 ~ CuuH2uu+1 or C~~H2~,~,+1 to be replaced by F
atoms;
or R7, R8 and R9 independently of one another H, F, CI, Br, I, N02, CN, OH, NH2, CeeH2ee+1 C~,~,,H2~,,~"_1, OC~H2~+1, NR40R41, CONR40R41, COOR42, COR42 or OCOR42;
ee and ff independently of one another 1, 2, 3 or 4;
ww 3, 4, 5 or 6, it being possible for one or more H atoms in the groups CeeH2ee+1.
CN,~,H2~,~"_1 and OC~H2~+1 to be replaced by F atoms;
R40 and R41 H, CttH2tt+1 or C(NH)NH2;
tt 1,2,3,4,5,6,7or8;
it being possible for one or more H atoms in the group CttH2tt+1 to be replaced by F atoms;
or R40 and R41 to be selected independently of one another hydroxyethyl, , N,N-dimethylaminoethyl, N,N-diethylaminoethyl, pyrrolidinoethyl, N-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl;
or R40 and R41 together with the N atom to which they are bonded form a ring selected from the group consisting of pyrrolidine, piperidine, N-methyl-piperazine, piperazine and morpholine;
R42 H or ChhH2hh+1 hh 1, 2, 3 or 4;
it being possible for one or more H atoms in the group ChhH2hh+1 to be replaced by F atoms;
and the pharmaceutically acceptable salts thereof.
Particular preference is given to the use of compounds of the formula I in which the meanings are:
R1, R2, R3 and R3 independently of one another H, F, CI, Br, OH, NH2, CaH2a+1, cycloalkyl with 3, 4, 5 or 6 C atoms, OCbH2b+1;
a and b in the groups CaH2a+1 and OCbH2b+1 independently of one another 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
or R1, R2, R3 and R4 independently of one another NR11 R12; 3 R11 and R12 independently of one another H, CeH2e+1, CrrH2rr-1;
a 1, 2, 3 or 4, rr 3, 4, 5 or 6, it being possible for one or more H atoms in the groups CeH2e+1 and CrrH2rr-1 to be replaced by F
atoms;
or R11 and R12 together with the N atom to which they are bonded form a ring selected from the group consisting of pyrrolidine, piperidine, N-methylpiperazine, piperazine and morpholine;
or R11 and R12 independently of one another COR14, CSR14, CONHR14, CSNHR14 or S02R14;
R14 CgH2g+1;
g 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
or R1, R2, R3 and R4 independently of one another OS03H, S03H, S02R15;
R15 CkH2k+1 or NR17R18;
k 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
R17 and R18 independently of one another H or CmH2m+1;
m 1, 2, 3, 4 or 5, it being possible for one or more H
atoms in the group CmH2m+1 to be replaced by F
atoms;
or R17 and R18 . 20 together with the N atom to which they are bonded a 5- or 6-membered ring;
R5 H, CPH2p+1, CssH2ss-1;
p 1, 2, 3 or 4;
ss 3, 4, 5 or 6, it being possible for one or more H atoms in CPH2p+1 and CssH2ss-1 to be replaced by F atoms;
R6 H, CH3;
R7, R8 and R9 independently of one another OS03H, S03H or S02R23;
R23 CnnH2nn+1 or NR25R26;
nn 1, 2, 3, 4 or 5, it being possible for one or more H atoms in CnnH2nn+1 to be replaced by F atoms;
R25 and R26 independently of one another H, CN or CZH2z+1, in which the 5 first CH2 group bonded to the nitrogen is replaced by CO or CS and the second CH2 is replaced by NR27;
z 1, 2, 3, 4, 5 or 6;
it being possible for one or more H atoms in CZH2z+1 to be replaced by F atoms;
10 R27 H or CaaH2aa+1 as 1, 2, 3 or 4;
it being possible for one or more H atoms in CaaH2aa+1 to be replaced by F atoms;
or 15 R25 and R26 together with the N atom to which they are bonded a 5- or 6-membered ring, or R27 and a CH2 group of R25 or R26 together with the N atom 20 to which they are bonded a 5- or 6-membered ring;
or R7, R8 and R9 independently of one another NR32COR30, NR32CSR30 or NR32S02R30;
R30 H, OH, CccH2cc+1, CyyH2yy_1 ~ PYrrolidinyl or piperidinyl, in which 25 rings a CH2 group may be replaced by O or NR33;
R32 and R33 H, CH3 or CF3;
cc 1,2,3,4,5,6,7or8;
yy 3, 4, 5 or 6;

it being possible for one or more H atoms in the groups CccH2cc+1 and CyyH2yy_1 to be replaced by F atoms and for one or more (CH2) groups to be replaced by NR31 and for a (CH2) group to be replaced by O;
R31 H, methyl, ethyl, CFg, CH2CF3, acetyl, propionyl, methanesulfonyl or ethanesulfonyl;
or R31 together with a CH2 group of R30 and the N atom to which they are jointly bonded form a 5- or 6-membered ring;
or R30 pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thiazolyl or oxazolyl, which are unsubstituted or substituted by a maximum of 3 substituents selected from the group consisting of F, CI, methyl, ethyl, trifluoromethyl, NH2, NHacetyl;
or R7, R8 and R9 independently of one another H, F, CI, OH, NH2, CeeH2ee+1 ~ CwwH2ww-1 OCttH2tt+1, NR40R41, CONR40R41, COOR42 or OCOR42, ee and ff independently of one another 1, 2, 3 or 4;
ww 3, 4, 5 or 6, it being possible for one or more H atoms in the groups CeeH2ee+1 C~,,~,H2",,~,,_1 and OC~H2tt+1 to be replaced by F atoms;
R40 and R41 H, CttH2tt+1 or C(NH)NH2;
tt 1, 2, 3 or 4;
it being possible for one or more H atoms in the group CttH2tt+1 to be replaced by F= atoms;
or R40 and R41 independently of one another hydroxyethyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, pyrrolidinoethyl, N-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl;
or R40 and R41 together with the N atom to which they are bonded a pyrrolidine, piperidine, N-methylpiperazine, piperazine or morpholine ring;
R42 H or ChhH2hh+1 hh 1, 2, 3 or4;
it being possible for one or more H atoms in the group ChhH2hh+1 to be replaced by F atoms;
and the pharmaceutically acceptable salts thereof.
Very particular preference is given to the use of compounds selected from the group consisting of 1 ) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]=
acetamide;
2) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide;
3) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide;
4) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N,N-dimethyl-benzenesulfonamide;
5) 4-(4-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline;
6) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid;
7) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-ethyl-benzamide;
8) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-propyl-benzamide;
9) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N-(2-dimethylamino-ethyl)-benzamide;
10) 6,8-dichloro-2-methyl-4-(4-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline;
11 ) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-diethyl-amine 12) 6,8-dichloro-2-methyl-4-(4-piperidin-1-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline;
13) 6,8-dichloro-2-methyl-4-(4-pyrrolidin-1-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline;

14) 6,8-dichloro-2-methyl-4-[4-(4-methyl-piperazin-1-yl)-phenyl]-1,2,3,4-tetrahydro-isoquinoline;
15) 6,8-dichloro-2-cyclopropyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline;
16) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine;
17) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-propylurea;
18) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-thiourea;
19) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-a rea;
20) N-[4-(6-methanesulfonyl-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
21) N-[4-(2,6,8-trimethyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
22) N-[4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
23) N-[4-(8-chloro-2-methyl-5-pyrrolidin-1-yl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
24) N-[4-(8-chloro-2-methyl-6-morpholin-4-yl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
25) N-{4-[8-chloro-2-methyl-6-(4-methyl-piperazin-1-yl)-1,2,3,4-tetrahydro-isoquinolin-4-yl]-phenyl}-acetamide;
26) N-{4-[8-chloro-6-(cyclopropylmethyl-amino)-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl]-phenyl}-acetamide;
27) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoic acid;
28) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-N-methyl-benzamide;
29) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N-ethyl-2-hydroxy-benzamide;
30) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N-(2-dimethylamino-ethyl)-2-hydroxy-benzamide;

31 ) N-[5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoyl]-guanidine;
32) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
33) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine;
34) 2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine;
35) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;
36) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;
37) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]pentanamide;
38) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-isobutyramide;
39) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2-dimethyl-propionamide;
40) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclopropanecarboxamide;
41) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclobutanecarboxamide;
42) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclopentanecarboxamide;
43) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2,2-trifluoro-acetamide;
44) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-acetylpiperidine-4-carboxamide;
45) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-nicotinamide;
46) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methane-sulfonamide;
47) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)- phenyl]-ethanesulfonamide;

48) N',N'-dimethylamino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl)-sulfamide;
49) N-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;
5 50) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;
51 ) N-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pentanamide;
52) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-10 isobutyramide;
53) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2-dimethyl-propionamide;
54) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl)-cyclopropanecarboxamide;
15 55) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclobutanecarboxamide;
56) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]
cyclopentanecarboxamide;
57) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2,2-20 trifluoro-acetamide;
58) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-acetylpiperidine-4-carboxamide;
59) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-nicotinamide;
25 60) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methane-sulfonamide;
61) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)- phenyl]-ethanesulfonamide;
62) N',N'-dimethylamino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-30 yl)-phenyl]-sulfamide;
63) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;

64) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;
65) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pentanamide;
66) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-isobutyramide;
67) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2-dimethyl-propionamide;
68) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclopropanecarboxamide;
69) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)- phenyl]-cyclobutanecarboxamide;
70) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclopentanecarboxamide;
71) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2,2-trifluoro-acetamide;
72) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-acetylpiperidine-4-carboxamide;
73) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methane-sulfonamide;
74) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)- phenyl]-ethanesulfonamide;
75) N',N'-dimethylamino-N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide;
76) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
77) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-thiourea;
78) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
79) 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-thiourea;

80) N-{5-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylsulfamoyl]-4-methyl-thiazol-2-yl}-acetamide;
81 ) N-{5-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylsulfamoyl]-4-methyl-thiazol-2-yl}-acetamide;
82) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,2-dimethyl-1 H-imidazole-4-sulfonamide;
83) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,2-dimethyl-1 H-imidazole-4-sulfonamide;
84) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-5-chloro-1,3-dimethyl-1 H-pyrazole-4-sulfonamide;
85) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-5-chloro-1,3-dimethyl-1 H-pyrazoVe-4-sulfonamide;
86) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-5-bromo-thiophene-2-sulfonamide;
87) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-5-bromo-thiophene-2-sulfonamide;
88) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-C,C,C-trifluoro-methanesulfonamide;
89) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-C,C,C-trifluoro-methanesulfonamide;
90) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2,2-trifluoroethanesulfonamide;
91 ) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2,2-trifluoro-ethanesulfonamide;
92) N-ethyl-N'-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonylurea;
93) 2-chloro-5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide;
94) 2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinolin-8-ylamine;
95) 6,8-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
96) 4-(8-amino-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenol;
97) 8-methoxy-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
98) 2-(8-amino-2-ethyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenol;
99) 2-(8-amino-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenol-;
100) 5-(8-amino-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-methoxy-phenol;
101 ) 2-methyl-8-nitro-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
102) 4-(8-amino-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzene-1,2-diol;
103) 2,8-dimethyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
104) 4-(3,4-dichloro-phenyl)-2-methyl-1,2,3,4-tetrahydro-isoquinoline;
105) 4-(3,4-dichloro-phenyl)-2-methyl-1,2,3,4-tetrahydro-isoquinolin-8-ylamine;
106) 4-(2,4-dichloro-phenyl)-2-methyl-1,2,3,4-tetrahydro-isoquinolin-8-ylamine;
107) 4-(3-chloro-phenyl)-2-methyl- 1,2,3,4-tetrahydro-isoquinolin-8-ylamine;
108) 2,4-dimethyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
109) 2-butyl-4-phenyl-1,2,3,4-tetrahydro-isoquinolin-8-ylamine;
110) N-(2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinolin-8-yl)-acetamide;
111 ) 7-chloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
112) 8-chloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
113) 2,6-dimethyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
114) 6-chloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
115) 6-methoxy-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
116) 2-ethyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
117) 2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
118) 6,8-dichloro-2-ethyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
119) 4-(4-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoline;
120) 2-methyl-4-phenyl-6,8-bis-trifluoromethyl-1,2,3,4-tetrahydro-isoquinoline;
121) 6,8-dichloro-2-isopropyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
122) 5,8-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
123) 6,8-dichloro-4-(4-fluoro-phenyl)-2-methyl-1,2,3,4-tetrahydro-isoquinoline;
124) 6,8-dichloro-2-methyl-4-p-tolyl-1,2,3,4-tetrahydro-isoquinoline;
125) 5,6-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
126) 6,7-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
127) 8-bromo-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
128) 6,8-dichloro-4-(4-chloro-phenyl)-2-methyl-1,2,3,4-tetrahydro-isoquinoline;
129) 6,8-dichloro-2-cyclopropyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
130) 2-amino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl}-phenyl]-acetamide;
131 ) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methylamino-acetamide;
132) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-dimethylamino-acetamide;
133) 2-amino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;
134) 2-amino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;
135) 2,6-diamino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-hexanamide;
136) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrolidine-2-carboxamide;
137) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-isonicotinamide;
138) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrole-3-carboxamide;
139) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrole-2-carboxamide;
140) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methyl-piperidine-4-carboxamide;
141) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,4-dimethyl-1 H-pyrrole-2-carboxamide;
142) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-nitro-1 H-pyrrole-2-carboxamide;
143) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,5-dimethyl-1 H-pyrrole-3-carboxamide;
144) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-imidazole-4-carboxamide;
145) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonyl-piperidine-4-carboxamide;
146) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3,5-dimethyl-1 H-pyrazole-4-carboxamide;
147) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrazole-4-carboxamide;
5 148) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-trifluoromethyl-1 H-pyrazole-4-carboxamide;
149) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methylamino-acetamide;
150) N[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2-10 dimethylamino-acetamide;
151) 2-amino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylJ-propionamide;
152) 2-amino-N-(3-(6,8-dichlora-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylJ-butyramide;
15 153) 2,6-diamino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-hexanamide;
154) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrolidine-2-carboxamide;
155) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylJ-20 isonicotinamide;
156) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrole-3-carboxamide;
157) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrole-2-carboxamide;
25 158) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methyl-piperidine-4-carboxamide;
159) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,4-dimethyl-1 H-pyrrole-2-carboxamide;
160) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-nitro-30 1 H-pyrrole-2-carboxamide;
161) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,5-dimethyl-1 H-pyrrole-3-carboxamide;

162) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-imidazole-4-carboxamide;
163) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonyl-piperidine-4-carboxamide;
164) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3,5-dimethyl-1 H-pyrazole-4-carboxamide;
165) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrazole-4-carboxamide;
166) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-~ 10 trifluoromethyl-1 H-pyrazole-4-carboxamide;
167) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-thiourea;
168) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-thiourea;
169) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-thiourea;
170) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea;
171) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-methyl-piperazine-1-carboxamide;
172) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-piperidine-1-carboxamide;
173) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-morpholine-4-carboxamide;
174) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrolidine-1-carboxamide;
175) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-diethyl-urea;
176) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-urea;
177) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-a rea;

178) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-(tetrahyd ro-fu ran-3-yl )-a rea;
179) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-(tetrahyd ro-pyran-4-yl)-a rea;
180) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methyl-1-(1-methyl-piperidin-4-yl)-urea;
181) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-(3-dimethylamino-propyl)-1-methyl-urea;
182) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-(2-dimethylamino-ethyl)-1-methyl-urea;
183) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(3-dimethylamino-propyl)-urea;
184) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-methoxy-ethyl)-urea;
185) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-pyridin-3-yl-urea;
186) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-pyridin-4-yl-urea;
187) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-methyl-piperazine-1-carboxamide;
188) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-urea;
189) 3-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea;
190) 3-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-diethyl-urea;
191) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-piperidine-1-carboxamide;
192) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-morpholine-4-carboxamide;
193) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrolidine-1-carboxamide;

194) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;
195) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-methyl-piperazine-1-carboxamide;
196) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrolidine-1-carboxamide;
197) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-urea;
198) 3-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-~ 10 dimethyl-urea;
199) 3-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-diethyl-urea;
200) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;
201 ) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-piperidine-1-carboxamide;
202) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl];
morpholine-4-carboxamide;
203) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-formamide;
204) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amine;
205) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,3-dimethyl-urea;
206) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-4-methyl-piperazine-1-carboxamide;
207) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,3,3-trimethyl-urea;
208) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl)-methyl-piperidine-1-carboxamide;
209) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl morpholine-4-carboxamide;

210) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-pyrrolidine-1-carboxamide;
211 ) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-1-methyl-urea;
212) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3,3-diethyl-1-methyl-urea;
213) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-formamide;
214) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amine;
215) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-pyrrolidine-1-carboxamide;
216) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-piperidine-1-carboxamide;
217) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,3,3-trimethyl-urea;
218) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,3-dimethyl-urea;
219) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-morpholine-4-carboxamide;
220) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-4-methyl-piperazine-1-carboxamide;
221) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-1-methyl-urea;
222) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3,3-diethyl-1-methyl-urea;
223) 2-dimethylamino-ethyl [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
224) 2-dimethylamino-ethyl [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
225) 2-dimethylamino-ethyl [2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;

226) methyl [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
227) ethyl [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
5 228) isopropyl [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
229) 2,2-dimethyl-propyl [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
230) methyl [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-10 carbamate;
231 ) isopropyl [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
232) 2,2-dimethyl-propyl [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
15 233) ethyl [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
234) (R)-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonamide;
235) (S)-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-20 methanesulfonamide;
236) (R)-1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-a rea;
237) (S)-1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
25 238) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
239) 4-(3-bromo-phenyl)-6,8-dichloro-methyl-1,2,3,4-tetrahydro-isoquinoline;
240) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl)-3-(2-hydroxy-ethyl)-urea;
30 241 ) ethyl 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoate;
242) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid.

and the pharmaceutically acceptable salts thereof.
Exceptionally particular preference is given to the use of compounds selected from the group consisting of 1 ) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylJ-acetamide;
2) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide;
3) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide;
4) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahjrdro-isoquinolin-4-yl)-benzoic acid;
5) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-ethyl-benzamide;
6) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-propyl-benzamide;
7) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N-(2-dimethylamino-ethyl)-benzamide;
8) 6,8-dichloro-2-methyl-4-(4-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline;
9) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine;
10) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-thiourea;
11 ) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
12) N-[4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
13) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoic acid;
14) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N-(2-dimethylamino-ethyl)-2-hydroxy-benzamide;
15) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
16) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine;
17) 2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine;
18) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylJ-propionamide;

19) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-acetyl-piperidine-4-carboxamide;
20) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methane-sulfonamide;
21 ) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-ethanesulfonamide;
22) N',N'-dimethylamino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide;
23) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;
24) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;
25) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-isobutyramide;
26) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclopropanecarboxamide;
27) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclobutanecarboxamide;
28) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2,2-trifluoro-acetamide;
29) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-acetyl-piperidine-4-carboxamide;
30) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-nicotinamide;
31 ) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methane-sulfonamide;
32) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-ethanesulfonamide;
33) N',N'-dimethylamino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide;
34) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclopropanecarboxamide;

35) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-acetyl-piperidine-4-carboxamide;
36) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
37) 1-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-thiourea;
38) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
39) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-thiourea;
40) N-f5-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylsulfamoyl]-4-methyl-thiazol-2-yl}-acetamide;
41 ) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,2-dimethyl-1 H-imidazole-4-sulfonamide;
42) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-C,C,C-trifluoro-methanesulfonamide;
43) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-C,C,C-trifluoro-methanesulfonamide;
44) N-ethyl-N'-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonylurea;
45) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2-dimethylamino-acetamide;
46) 2,6-diamino N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-hexanamide;
47) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1 H-pyrrole-3-carboxamide;
48) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methyl-piperidine-4-carboxamide;
49) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methanesulfonyl-piperidine-4-carboxamide;
50) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyazole-4-carboxamide;

51 ) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methylamino-acetamide;
52) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2-dimethylamino-acetamide;
53) 2-amino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;
54) 2-amino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;
55) 2,6-diamino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-~ 10 phenyl]-hexanamide;
56) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methyl-piperidine-4-carboxamide;
57) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-imidazole-4-carboxamide;
58) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methanesulfonyl-piperidine-4-carboxamide;
59) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3,5-dimethyl-1 H-pyrazole-4-carboxamide;
60) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrazole-4-carboxamide;
61) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea;
62) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-methyl-piperazine-1-carboxamide;
63) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-piperidine-1-carboxamide;
64) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-morpholine-4-carboxamide;
65) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrolidine-1-carboxamide;
66) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-diethyl-urea;

67) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-urea;
68) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;
5 69) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-(tetrahyd ro-fu ran-3-yl )-urea;
70) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(tetrahyd ro-pyran-4-yl )-a rea;
71) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methyl-10 1-( 1-methyl-piperidin-4-yl)-urea;
72) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-(3-dimethylamino-propyl)-1-methyl-urea;
73) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-(2-d imethylamino-ethyl)-1-methyl-urea;
15 74) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(3-dimethylamino-propyl)-urea;
75) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-methoxy-ethyl)-urea;
76) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-pyridin-20 3-yl-urea; ~ , 77) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-pyridin-4-yl-a rea;
78) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-methyl-piperazine-1-carboxamide;
25 79) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-a rea;
80) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;
81 ) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-methyl-30 piperazine-1-carboxamide;
82) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-urea;

83) 3-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea;
84) 3-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-diethyl-urea;
85) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;
86) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-morpholine-4-carboxamide;
87) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-formamide;
88) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amine;
89) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-formamide;
90) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amine;
91 ) 1 [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,3,3-trimethyl-urea;

92) 1[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,3-dimethyl-urea;

93) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-morpholine-4-carboxamide;

94) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-4-methyl-piperazine-1-carboxamide;
95) 1[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-1-methyl-urea;
96) 2-dimethylamino-ethyl [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
97) 2-dimethylamino-ethyl [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
98) 2-dimethylamino-ethyl [2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;

99) methyl [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
100) (R or S)-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonamide;
101 ) (R or S)-1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
102) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-hydroxy-ethyl)-urea;
103) ethyl 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoate;
104) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid.
and the pharmaceutically acceptable salts thereof.
If the compounds of the formula I contain one or more centers of asymmetry, these may have both the S and the R configuration. The compounds may be in the form of optical isomers, of diastereomers, of racemates or of mixtures thereof.
The defined alkyl radicals and partly or completely fluorinated alkyl radicals may be both straight-chain and branched. Groups CaH2a_1 and their analogs as far as CyyH2yy_1 mean either the corresponding alkenyls, cycloalkyls, cycloalkylalkyls or alkylcycloalkyls.
Appropriate heteroaryls are, in particular, 2- or 3-thienyl, 2- or 3-furyl, 1-, 2- or 3-pyrrolyl, 1-, 2-, 4- or 5-imic~azolyl, 1-, 3-, 4- or 5-pyrazolyl, 1,2,3-triazol-1-, -4- or 5-yl, 1,2,4-triazol-1-, -3- or -5-yl, 1- or 5-tetrazolyl, 2-, 4- or 5-oxazolyl, 3-, 4- or 5-isoxazolyl, 1,2,3-oxadiazol-4- or 5-yl, 1,2,4-oxadiazol-3-or 5-yl, 1,3,4-oxadiazol-2-yl or -5-yl, 2-, 4-or 5-thiazolyl, 3-, 4- or 5-isothiazolyl, 1,3,4-thiadiazol-2- or -5-yl, 1,2,4-thiadiazol-3- or -5-yl, 1,2,3-thiadiazol-4- or 5-yl, 2-, 3- or 4-pyridyl, 2-, 4-, 5- or 6-pyrimidinyl, 3- or 4-pyridazinyl, pyrazinyl, 1-, 2-, 3-, 4-, 5-, 6- or 7-indolyl, 1-, 2-, 4- or 5-benzimidazolyl, 1-, 3-, 4-, 5-, 6- or 7-indazolyl, 2-, 3-, 4-, 5-, 6-, 7- or 8-quinolyl, 1-, 3-, 4-, 5-, 6-, 7- or 8-isoquinolyl, 2-, 4-, 5-, 6-, 7- or 8-quinazolinyl, 3-, 4-, 5-, 6-, 7- or 8-cinnolinyl, 2-, 3-, 5-, 6-, 7- or 8-quinoxalinyl, 1-, 4-, 5-, 6-, 7- or 8-phthalazinyl. The corresponding N-oxides of these compounds are additionally encompassed, that is to say, for example, 1-oxy-2-, 3- or 4-pyridyl.
Of these, the 5- or 6-membered heterocycles are preferred. The particularly preferred heterocycles are imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thiazolyl and oxazolyl.
The terminal CH3 groups in an alkyl chain are also regarded as CH2 units and are in this connection viewed as CH2 groups.
Methods for preparing the compounds used are also described.
Thus, the substances described herein can be prepared starting from the benzylamine precursors IV. These in turn can, if not obtainable commercially, be synthesized by standard processes from the corresponding benzyl chlorides or bromides III.
R1 R1 .
R2 ~ \ R5-NHZ ~ ~ \
R3 ~ X R3 ~ ~~RS

X = CI, Br III IV
The benzylamines IV obtained in this way are alkylated in a manner known to the skilled worker with the appropriately substituted alpha-bromoacetophenone compounds V.

Rs R8 /

Br O
\ V R2 I \ O
R3 / ~~R5 R3 / N~RS

IV VI
The alpha-bromacetophenone compounds V can be obtained from the corresponding acetophenone precursors by bromination in processes known from the literature.
The desired tetrahydroisoquinolines I can be obtained by known processes by reduction of the carbonyl group in VI and subsequent acid-catalyzed cyclization of the corresponding alcohols VII (cf. Tetrahedron Lett.; 1989, 30, 5837; Org. Prep.
Proced.
Int.; 1995, 27, 513).

R9 ~\ R~ R9 i\
I j I j R1 NaBH4 R1 R2 \ O R2 \ OH ' / i ;, R3 I N~R5 R3 I / N~R5 VI IH+1 VII

When R6 is not equal to H, the desired compounds of the formula I can be prepared for example from the iodides VIII by halogen/metal exchange and subsequent nucleophilic attack of the intermediate organolithium species on the carbonyl group (cf.
Chem. Pharm. Bull.; 1995, 43, 1543).

Rg R7 N~R5 BuLi ~5 R2 ~ 'R4 R4 VIII IX
The tertiary alcohols synthesized in this way can be converted by known methods into 10 other derivatives.
Alkyl-branched analogs (I) are prepared by alkylating the corresponding diphenylacetic esters X in the alpha position by known methods. The desired product XI can be converted by standard processes into the corresponding amides XII, which are 15 converted into the desired tetrahydroisoquinolines I in a Pictet-Spengler-analogous reaction (cf. Tetrahedron; 1987, 43, 439; Chem. Pharm. Bull.; 1985, 33, 340).

R9 /~, /R7 1. LDA

2. R6-X ~ R6 / ~r X XI
1. NaOH
2. SOCIZ
3. R5-NHZ
HCHO/LiAIH, I XII
Compounds of the type I are described in the published specifications WO 01 32 and WO 01 32 625 as norepinephrine, dopamine and serotonin reuptake inhibitors.
However, these patent applications protect exclusively compounds in which R1 and R2 may be exclusively H. It has emerged, however, with the compounds according to the invention that at least for R2 it is necessary that R2 is not equal to H. In addition, it was not possible to detect by means of an exemplary compound of the compounds according to the invention any inhibitory properties on the described receptors, so that the described compounds differ distinctly both in structure and in their pharmacological properties from the compounds described in the patent applications mentioned.
In addition, compounds of type f are described in the patent specification EP

as estrogen agonists and antagonists. It was possible to show that the compounds according to the invention show no activity on said receptors, so that the structural differences of the compounds according to the invention result in distinctly different pharmacological properties in this regard too.

It was possible to show that compounds of the formula I are excellent inhibitors of the sodium-hydrogen exchanger (NHE) - especially of the sodium-hydrogen exchanger of subtype 3 (NHE3).
On the basis of these properties, the compounds are suitable for the treatment of disorders caused by oxygen deficiency. The compounds are, as a result of their pharmacological properties, outstandingly suitable as antiarrhythmic medicaments with a cardioprotective component for prophylaxis of infarction and for treatment of infarction, and for the treatment of angina pectoris, in which connection they also inhibit or greatly reduce in a preventive manner the pathophysiological processes associated with the development of ischemia-induced damage, in particular in the induction of ischemia-induced cardiac arrhythmias. Because of their protective effects against pathological hypoxic and ischemic situations, the compounds of the formula I
which are used according to the invention can, as a result of inhibition of the cellular Na+/H+ exchange mechanism, be used as medicaments for the treatment of all acute or chronic damage induced by ischemia or disorders induced primarily or secondarily thereby. This relates to the use thereof as medicaments for surgical interventions, e.g.
in organ transplantations, in which cases the compounds can be used both to protect the organs in the donor before and during removal, to protect removed organs for example on treatment with or storage thereof in physiological bath fluids, as well as during the transfer into the recipient organism. The compounds are likewise valuable medicaments with a protective action during the performance of angioplastic surgical interventions, for example on the heart as well as peripheral vessels. In accordance with their protective action against ischemia-induced damage, the compounds are also suitable as medicaments for the treatment of ischemias of the nervous system, especially of the CNS, in which connection they are suitable for example for the treatment of stroke or of cerebral edema. In addition, the compounds of the formula I
which are used according to the invention are likewise suitable for the treatment of types of shock, such as, for example, of allergic, cardiogenic, hypovolemic and bacterial shock.

In addition, the compounds induce an improvement in the respiratory drive and are therefore used to treat respiratory conditions associated with the following clinical conditions and diseases: disturbance of central respiratory drive (e.g.
central sleep apnea, sudden infant death, postoperative hypoxia), muscle-related breathing disorders, breathing disorders after long-term ventilation, breathing disorders associated with altitude adaptation, obstructive and mixed type of sleep apnea, acute and chronic pulmonary disorders with hypoxia and hypercapnia.
The compounds additionally increase the tone of the muscles of the upper airways, so that snoring is suppressed.
A combination of an NHE inhibitor with a carbonic anhydrase inhibitor (e.g.
acetazolamide), the latter inducing metabolic acidosis and thus itself increasing respiratory activity, proves to be advantageous due to an enhanced effect and reduced use of active ingredient.

It has emerged that the compounds used according to the invention have a mild laxative effect and accordingly can be used advantageously as laxatives or if there is a risk of constipation, in which case the prevention of the ischemic damage associated with constipation in the intestinal region is particularly advantageous.
It is additionally possible to prevent the formation of gall stones.
The compounds of the formula I used according to the invention are furthermore distinguished by a strong inhibitory effect on the proliferation of cells, for example of fibroblast cell proliferation and the proliferation of smooth muscular muscle cells. The compounds of the formula I are therefore suitable as valuable therapeutic agents for diseases in which cell proliferation represents a primary or secondary cause, and can therefore be used as antiatherosclerotic agents, agents to prevent late complications of diabetes, cancers, fibrotic disorders such as pulmonary fibrosis, hepatic fibrosis or renal fibrosis, organ hypertrophies and hyperplasias, in particular for prostate hyperplasia or prostate hypertrophy.

The compounds used according to the invention are effective inhibitors of the cellular sodium-proton antiporter (Na/H exchanger) which is elevated in numerous disorders (essential hypertension, atherosclerosis, diabetes, etc.), also in those cells which are readily amenable to measurements, such as, for example, in erythrocytes, platelets or leukocytes. The compounds used according to the invention are therefore suitable as excellent and simple scientific tools, for example in their use as diagnostic agents for determining and distinguishing different types of hypertension, but also of atherosclerosis, of diabetes, proliferative disorders etc. The compounds of the formula I are moreover suitable for preventive therapy to prevent the development of high ~ 10 blood pressure, for example of essential hypertension.
It has additionally been found that NHE inhibitors show a beneficial effect on serum lipoproteins. It is generally acknowledged that blood lipid levels which are too high, so-called hyperlipoproteinemias, represent a considerable risk factor for the development of arteriosclerotic vascular lesions, especially coronary heart disease. The reduction of elevated serum lipoproteins therefore has exceptional importance for the prophylaxis and regression of atherosclerotic lesions. The compounds used according to the invention can therefore be used for the prophylaxis and regression of atherosclerotic lesions by eliminating a causal risk factor. With this protection of the vessels against the syndrome of endothelial dysfunction, compounds of the formula I are valuable medicaments for the prevention and treatment of coronary vasospasms, of atherogenesis and of atherosclerosis, of left-ventricular hypertrophy and of dilated cardiomyopathy, and thrombotic disorders.
Said compounds are therefore advantageously used for producing a medicament for the prevention and treatment of sleep apneas and muscle-related respiratory disorders; for producing a medicament for the prevention and treatment of snoring; for producing a medicament for lowering blood pressure; for producing a medicament for the prevention and treatment of disorders induced by ischemia and reperfusion of central and peripheral organs, such as acute renal failure, stroke, endogenous states of shock, intestinal disorders etc.; for producing a medicament for the treatment of late damage from diabetes and chronic renal disorders, in particular of all inflammations of the kidneys (nephritides) which are associated with increased protein/albumin excretion; for producing a medicament for the treatment of infection by ectoparasites in human and veterinary medicine; for producing a medicament for the treatment of said disorders in combinations with hypotensive substances, preferably with angiotensin 5 converting enzyme (ACE) inhibitors, with diuretics and saluretics such as furosemide, hydrochlorothiazide, pseudoaldosterone antagonists and aldosterone antagonists; with adenosine receptor modulators, in particular with adenosine receptor activators (A2 agonists); and with angiotensin receptor antagonists.
10 The administration of sodium-proton exchange inhibitors of the formula I as novel medicaments for lowering elevated blood lipid levels, and the combination of sodium-proton exchange inhibitors with hypotensive medicaments andlor medicaments with hypolipidemic activity is claimed.
15 Medicaments which comprise a compound I can in this connection be administered orally, parenterally, intravenously, rectally, transdermally or by inhalation, the preferred administration being dependent on the particular characteristics of the disorder. The compounds I may moreover be used alone or together with pharmaceutical excipients, both in veterinary medicine and in human medicine.
The excipients suitable for the desired pharmaceutical formulation are familiar to the skilled worker on the basis of his expert knowledge. Besides solvents, gel formers, suppository bases, tablet excipients, and other active ingredient carriers, it is possible to use, for example, antioxidants, dispersants, emulsifiers, antifoams, flavorings, preservatives, solubilizers or colors.
For a form for oral administration, the active compounds are mixed with additives suitable for this purpose, such as carriers, stabilizers or inert diluents, and converted by conventional methods into suitable dosage forms such as tablets, coated tablets, hard gelatin capsules, aqueous, alcoholic or oily solutions. Examples of inert carriers which can be used are gum arabic, magnesia, magnesium carbonate, potassium phosphate, lactose, glucose or starch, especially corn starch. It is moreover possible for the preparation to take place both as dry granules and as wet granules.
Examples of suitable oily carriers or solvents are vegetable or animal oils such as sunflower oil or fish liver oil.
For subcutaneous or intravenous administration, the active compounds used are converted, if desired with the substances customary for this purpose, such as solubilizers, emulsifiers or other excipients, into a solution, suspension or emulsion.
Examples of suitable solvents are: water, physiological saline or alcohols, e.g. ethanol, propanol, glycerol, as well as sugar solutions such as glucose or mannitol solutions, or else a mixture of the various solvents mentioned.
Suitable as pharmaceutical formulation for administration in the form of aerosols or sprays are, for example, solutions, suspensions or emulsions of the active ingredient of the formula I in a pharmaceutically acceptable solvent such as, in particular, ethanol or water, or a mixture of such solvents.
The formulation may, if required, also contain other pharmaceutical excipients such as surfactants, emulsifiers and stabilizers, and a propellant gas. Such a preparation normally contains the active ingredient in a concentration of about 0.1 to 10, in particular of about 0.3 to 3, °io by weight.
The dosage of the active ingredient of the formula I to be administered, and the frequency of administration, depend on the potency and duration of action of the compounds used; additionally also on the nature and severity of the disorder to be treated and on the sex, age, weight and individual responsiveness of the mammal to be treated.
On average, the daily dose of a compound of the formula I for a patient weighing about 75 kg is at least 0.001 mg/kg, preferably 0.01 mg/kg, to a maximum of 10 mg/kg, preferably 1 mg/kg, of body weight. For acute episodes of the disorder, for example immediately after suffering a myocardial infarction, higher and, in particular, more frequent dosages may also be necessary, e.g. up to 4 single doses a day. Up to 200 mg a day may be necessary, in particular on i.v. administration, for example for a patient with infarction in the intensive care unit.
Descriptions of experiments and examples:
List of abbreviations used:
Rt retention time TFA trifluoroacetic acid HPLC high performance liquid chromatography eq equivalent LCMS liquid chromatography mass spectroscopy MS mass spectroscopy CI chemical ionization RT room temperature THF tetrahydrofuran TOTU O-[(ethoxycarbonyl)-cyanomethyleneamino]-N,N,N',N'-tetramethyluronium tetrafluoroborate DMSO dimethyl sulfoxide abs. absolute decomp. decomposition DMF dimethylformamide General:
The retention times (Rt) indicated below relate to LCMS measurements with the following parameters:
Method A:
stationary phase: Merck Purospher 3N2 x 55 mm mobile phase: 95% H20 (0.05% TFA)-~ 95% acetonitrile; 4 min; 95%
acetonitrile; 1.5 min ~ 5% acetonitrile; 1 min; 0.5 ml/min, 30°C.
Method B:
stationary phase: Merck Purospher 3N2 x 55 mm mobile Phase: 0 min 90% H20 (0.05% TFA) 2.5 min-95% acetonitrile;
95% acetonitrile to 3.3 min; 10% acetonitrile 3.4 min;
1 ml/min.
Method B1:
stationary phase: YMC, J'sphere ODS H80 4N 2 x 20 mm mobile phase 0 min 90% H20 (0.05% TFA) 1.9 min-95% acetonitrile;
95% acetonitrile to 2.4 min; 10% acetonitrile 2.45 min;
1 ml/min.
Method C:

stationary phase: Merck LiChroCart 55-2 Purospher STAR RP
18e solvent: solvent A: acetonitrile/water 90:10 +
0.5% HCOOH

solvent B: acetonitrile/water 10:90 +
0.5% HCOOH

flow rate: 0.75 ml/min time[min] solvent B[%]

0.00 95.0 0.50 95.0 1.75 5.0 4.25 5.0 4.50 95.0 5.00 95.0 stop time: 6.20 min temperature: 40C

Method D:
stationary phase: Merck RP18 Purospher STAR, 55 x 2 mm, 3,u particle size.
solvent: solvent A: acetonitrile + 0.08% HCOOH
solvent B: water + 0.1 % HCOOH
flow rate: 0.45 ml/min time[min] solvent B[%]

5 temperature: room temperature Example 1: N-[4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide HN' \
/
CI \
/ NW
CI
Intermediate 1: 2,4-Dichlorobenzyl-(methyl)-amine is prepared by methods known from the literature (J. Med. Chem.; 1984, 27;
1111 ).
Intermediate 2: N-(4-(2-Bromo-acetyl)-phenyl]-acetamide is synthesized in a manner known to the skilled worker by bromination of N-(4-acetyl-phenyl)-acetamide.
The starting compound (0.256 mol) is introduced into 300 ml of acetic acid and, at 60°C, a solution of 39.9 g of bromine (1.0 eq) in 60 ml of acetic acid is added dropwise.
After 1.5 h, the reaction mixture is allowed to cool to room temperature and is added to 1 I of ice-water. The precipitate is filtered off with suction, washed with water and dried, with 60 g of the title compound being isolated (melting point: 192°C).
Intermediate 3: N-{4-[2-(2,4-Dichloro-benzylamino)-acetyl]-phenyl}-acetamide;
37.1 g (0.195 mol) of intermediate 1 are introduced into 400 ml of dioxane, and a solution of 60 g (0.234 mol) of intermediate 2 in 600 ml of dioxane is added.
134 ml of triethylamine are added, and the mixture is stirred at room temperature for 4 h. After standing overnight, the precipitate is filtered off and the filtrate is concentrated in vacuo. The residue is taken up in ethyl acetate, washed with NaHC03 and H20, dried with MgS04 and concentrated. The oily residue resulting thereby is triturated with an ethyl acetate/ether mixture, resulting in 36 g of intermediate 3 in the form of a crystalline solid (melting point: 115-117°C).

Intermediate 4:
N-{4-[2-(2,4-Dichloro-benzylamino)-1-hydroxy-ethyl]-phenyl}-acetamide;
36 g (0.099 mol) of intermediate 3 are dissolved in 500 ml of methanol and, at 0°C, 7.8 g (2 eq) of sodium borohydride are added. The mixture is then stirred at 0°C for 10 30 min and at room temperature for a further hour. For workup, the reaction mixture is concentrated and the residue is partitioned between 1 N HCI and ethyl acetate.
The aqueous phase is separated off, adjusted to pH 9 and extracted twice with ethyl acetate. The combined organic phases are dried with MgS04 and concentrated.
The crude product obtained in this way can be reacted further without further purification.
N-[4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
g (0.054 mol) of intermediate 4 are dissolved in 250 ml of dichlorometharie and, at 0°C, 250 ml of conc. H2S04 are added dropwise. The mixture is stirred at 0°C for 2 h and at room temperature for 1 h. For workup, the reaction mixture is added to ice-20 water, and the precipitate is filtered off with suction. The precipitate is taken up in 300 ml of 1 N NaOH and extracted three times with ethyl acetate. Drying of the organic phases and concentration affords a crude product which is triturated with diisopropyl ether, whereupon 11.7 g of the compound of the example are isolated as a crystalline solid (melting point: 205-206°C).
1a: N-[4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide-hydrochloride;

HN' /
CIH
CI \
/ N~
CI
An analytical sample (100 mg) of the title compound from example 1 is suspended in ml of 2 N HCI, and THF is added until a clear solution is produced. It is concentrated in vacuo, and the residue is triturated with ether and filtered off with 5 suction, whereupon the title compound is obtained as a crystalline solid (Rt =
3.807 min (method A); melting point.: 125°C with decomposition).
Example 2:
2a: (+)-4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzene-10 sulfonamide hydrochloride;
2b: (+)-3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzene-sulfonamide hydrochloride;
2c: (-)-4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzene-sulfonamide acetate; ' 2d: (-)-3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzene-sulfonamide acetate;
O~S~NHz O~ ,O
O
\ I \ ,S~NHz / /
CI HCI/AcOH CI HCI/AcOH
N\ ~ / N\
CI CI
(+ and -) (+ and -) 2a/2c 2b/2d Intermediate 1: 2,4-Dichlorobenzyl-(methyl)-amine is prepared by methods known from the literature (J. Med. Chem.; 1984, 27, 1111 ).

Intermediate 2: 2-[(2,4-Dichloro-benzyl)-methyl-amino]-1-phenyl-ethanone;
Intermediate 1 is reacted with 2-bromo-1-phenyl-ethanone in the manner described in example 1, intermediate 3. Workup in an analogous manner and purification on silica gel affords the desired alkylation product in good yield as a yellowish oil (Rt =
4.188 min (method A); MS(CI+) = 308.2/310.2).
Intermediate 3: 2-[(2,4-Dichloro-benzyl)-methyl-amino]-1-phenyl-ethanol;
Intermediate 2 is reduced with sodium borohydride in the manner described in example 1, intermediate 4. Once monitoring of the reaction indicates complete conversion, the mixture is concentrated and the residue is taken up in ethyl acetate. It is washed twice with H20, dried with MgS04 and freed of solvent. The crude product, which is obtained in quantitative yield, can be reacted further without further purification (Rt = 4.149 min (method A); MS(CI+) = 310.2/312.2).
Intermediate 4: 6,8-Dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
g (64.5 mmol) of intermediate 3 are dissolved in 55 ml of dichloromethane and cooled to 0°C. This solution is added dropwise to 55 ml of precooled conc. H2S04 and then stirred at room temperature for two hours. For workup, the mixture is poured onto ice and made strongly alkaline with 6 N NaOH. Three extractions with dichloromethane 20 are carried out. The combined organic phases are dried with MgS04 and concentrated. The oily crude product is purified on silica gel, resulting in intermediate 4 in a yield of 53% (Rt = 4.444 min (method A); MS(CI+) = 292.2/294.2).
4a: (-)-6,8-Dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline trifluoroacetate;
4b: (+)-6,8-Dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline trifluoroacetate;
Intermediate 4 is separated into the two enantiomers by HPLC on a chiral phase.
chiral column: Chiralpak OD 250 x 4.6 cm;
solvent: n-heptane/isopropanol 7:3 + 0.1 % TFA;
flow rate: 1 ml/min;
Rt((-)-enantiomer/4a) = 9.340 min;
Rt((+)-enantiomer/4b) = 20.327 min.

2a: (+)-4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzene-sulfonamide hydrochloride;
2b: (+)-3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzene-sulfonamide hydrochloride;
A suspension of 500 mg (1.7 mmol) of intermediate 4a in 10 ml of dichloromethane is introduced at 0°C into 1.2 ml of chlorosulfonic acid. The mixture is stirred at 0°C for one hour and at room temperature for a further hour. A further 5 ml of chlorosulfonic acid is added and the mixture is stirred at room temperature for one hour. For workup, it is poured onto ice and adjusted to pH 8 with NaHC03. Three extractions with ethyl acetate are carried out. The combined organic phases are dried with Na2S04 and freed of solvent. The crude product obtained in this way is heated in 20 ml of conc.
NH3 solution at 90°C for three hours. After the conversion is complete, the reaction solution is concentrated and the residue is partitioned between H20 and ethyl acetate.
The organic phase is separated off and the aqueous phase is extracted once more with ethyl acetate. The combined organic phases are dried with Na2S04 and the solvent is removed in vacuo. Subsequent chromatography on silica gel affords 335 mg of a mixture of example 2a and 2b in the form of a yellow amorphous solid.
Further purification on a preparative HPLC affords 212 mg of the para-substituted title compound 2a, plus 58 mg of the meta isomer 2b.
Conditions for the preparative HPLC.
chiral column: Chiralpak AS 250 x 4.6 mm;
solvents: n-heptanelethanol/methanol/acetonitrile 20:1.5:0.5:0.5 flow rate: 1 ml/min;
Rt(main fraction) = 14.145 min (~2a);
Rt(subsidiary fraction) = 11.623 min (-~2b).
Both fractions were dissolved in methanol/2 N HCI mixture and freeze dried, and it was possible to obtain the title compounds 2a and 2b in the form of crystalline solids.

(Rt(2a) = 3.630 min (method A); MS(2a),(ES+) =371.3/373.3 (M++H)/ 412.3/ 414.3 (M++CH3CN); Rt (2b) = 3.668 min (method A); MS(2b),(ES+) =371.3/373.3 (M++H)/
412.3/ 414.3 (M++CH3CN).
2c: (-)-4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzene-sulfonamide acetate;
2d: (-)-3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzene-sulfonamide acetate;
The title compound is synthesized by the method described under 2a/2b, using intermediate 4b as starting compound. The purification and separation from the meta isomer which is to be expected takes place under the following conditions:
chiral column: Chiralpak AS 250 x 4.6/12 mm;
solvent: acetonitrile flow rate: 1 mllmin;
Rt(main fraction= 4.394 min (-~2c);
Rt(subsidiary fraction) = 4.130 min (-~2d).
The purified products are each taken up in a 10% acetic acid solution and freeze dried, resulting in the desired acetates as slightly yellowish solids (Rt(2c) = 3.656 min (method A); MS(ES+) =371.1/373.1 (M++H)/ 412.1/414.1 (M++CH3CN)); (Rt(2d) _ 1.562 min (method B); MS(ES+) =371.1/373.1 (M++H)/ 412.1/414.1 (M++CH3CN)).
Example 3: 4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N,N-dimethyl-benzenesulfonamide, hydrochloride;
s~Nw o' i CIH
CI
N~
CI

6,8-Dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline (intermediate 4, example 2) was introduced in portions into chlorosulfonic acid (6.6 ml). The mixture was subsequently stirred at 40°C for one hour. The reaction mixture was then cooled to room temperature and an icelwater mixture was added. The precipitate which 5 separated out during this was filtered off with suction and taken up in ethyl acetate which, after washing with saturated brine was dried over magnesium sulfate.
Subsequent concentration afforded 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonyl chloride as a solid crude product, a portion of which (150 mg) was directly introduced in portions into dimethylamine solution (5 ml, approx.
10 40% in water) cooled to 10°C. The resulting suspension was subsequently stirred at this temperature for 1.5 h. Then ice-water was added and, after extraction three times with ethyl acetate, the combined ethyl acetate phases were washed with saturated brine and dried over magnesium sulfate. The residue was taken up with water and, after addition of 2 N HCI, freeze dried. The crude product obtained in this way was 15 then purified by preparative HPLC.
Conditions:
stationary phase: Merck Purospher RP18 (10NM) 250 x 25 mm mobile phase: 90% H20 (0.05% TFA)-~ 90% acetonitrile; 40 min; flow rate:
20 25 ml/min The fractions containing the product were combined, the acetonitrile was stripped off in a rotary evaporator, and the aqueous phase was washed with saturated potassium carbonate solution and then extracted three times with ethyl acetate. The combined ethyl acetate phases were washed with saturated brine, dried over magnesium sulfate 25 and concentrated. The residue was taken up in water and, after addition of 2 N HCI, freeze dried. 80 mg of a pale solid were obtained. This consisted of ~80% of the desired compound, in addition to -20% of a regioisomer (Rt = 4.000 min (method A);
MS(CI+) = 399.1 ).

Example 4:
4a: 4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide, hydrochloride;
O~. ~NHZ
~S
O
CIH
CI \
N\
CI
Intermediate 1: 4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-benzenesulfonyl chloride At 0°C, 1 mmol of 6,8-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline (intermediate 4, example 2) 'is introduced into 1 ml of chlorosulfonic acid and stirred at room temperature for 3 hours. For workup, the reaction mixture is poured onto ice, adjusted to pH 7 to 8 with 1 N NaOH and extracted twice with ethyl acetate.
The combined ethyl acetate phases are dried with Na2S04 and concentrated in a rotary evaporator. The crude product obtained in this way is reacted further without further purification.
Intermediate 2: 4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzene-sulfonamide 319 mg of intermediate 1 are suspended in 6 ml of 25% strength ammonia and heated to 90°C. After 3 h, the mixture is diluted with H20 and extracted with ethyl acetate. The organic phase is separated off and dried with Na2S04, resulting in 165 mg of the title compound.
4-(6,8-Dichloro-2-methyl-1,2"3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide, hydrochloride;
145 mg of intermediate 2 are suspended in 15 ml of diethyl ether, and 1 ml of ethereal HCI is added. After stirring at room temperature for 30 minutes, the precipitate is filtered off with suction and dried, resulting in 136 mg of the hydrochloride in the form of a yellowish solid.
4b: 4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide, acetate;
O~.S~NHz O' AcOH
CI
I / N
CI
255 mg of intermediate 2, example 8, are mixed with 5 ml of glacial acetic acid, and 50 ml of H20 is added. Filtration of sparingly soluble constituents is followed by freeze drying, resulting in 250 mg of the title compound.
Example 5: 4-(4-Bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline, hyd rochloride;
CI cIH
I~ 1 N~
CI
Intermediate 1:
1-(4-Bromo-phenyl)-2-[(2,4-dichloro-benzyl)-methyl-amino]-ethanone;
(2,4-Dichloro-benzyl)-methyl-amine (see example 1, intermediate 1) and 2-bromo-1-(4-bromo-phenyl)-ethanone are reacted in analogy to the method described in example 1, intermediate 3. After analogous workup and chromatography on silica gel, the alkylation product can be isolated in a yield of 69%.

Intermediate 2: 1-(4-Bromo-phenyl)-2-[(2,4-dichloro-benzyl)-methyl-amino]-ethanol;
Intermediate 1 is reduced to the corresponding alcohol with 2 equivalents of NaBH4 in analogy to the manner described for intermediate 4, example 1, and the alcohol can be isolated in a yield of 86%.
Intermediate 3: 4-(4-Bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoline;
5.45 g (14.0 mmol) of 1-(4-bromo-phenyl)-2-[(2,4-dichloro-benzyl)-methyl-amino]-ethanol are introduced into 15 ml of dichloromethane and, at 0°C, 15 ml of conc.
H2S04 are added. After stirring at room temperature for 2 hours, the reaction mixture is poured onto ice and made alkaline with 6 N NaOH. Three extractions with dichloromethane are carried out. The combined organic phases are dried with MgS04 and concentrated. For further purification, the residue is chromatographed on silica gel, resulting in 2.6 g of the title compound as a yellowish oil.
4-(4-Bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline, hydrochloride;
Br CI CIH
/ N~
CI
300 mg of 4-(4-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline are stirred in 2 N HCI at room temperature. The resulting precipitate is filtered off with suction and dried.
Example 6: 4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid;
COOH
CIH
CI
I / Nw CI

4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid;
5.57 g (15 mmol) of 4-(4-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline (example 5, intermediate 3) are dissolved in 150 ml of abs.
DMF/benzene (1:1 ). After the solution has been degassed, under argon 1.18 g (4.5 mmol) of triphenylphosphine and 1.17 g (9 mmol) of Ca(HC02)2 are added.
After renewed flushing with argon, 867 mg (0.75 mmol) of Pd(PPh3)4 are added and carbon monoxide is passed into the solution. The mixture is stirred at 120°C.
After six hours at 120°C and standing overnight under argon, a further 867 mg (0.75 mmol) of Pd(PPh3)4 were added and stirring at 120°C and passing carbon monoxide into the solution were continued for eight hours. After again standing overnight, 135 mg of PdCl2 were added and reaction was allowed to take place under the same conditions.
For workup, the solvent is removed in vacuo and the residue is taken up in ethyl acetate. Three extractions with 2 N NaOH are carried out. The combined aqueous phases are adjusted to pH 6 with 6 N HCI and extracted three times with ethyl acetate.
The organic phases are dried with MgS04 and freed of solvent. The residue is purified on silica gel using a dichloromethane/methanol mixture, resulting in 420 mg of the title compound (Rt = 4.025 min (method A); MS(CI+) = 336.1/338.1 ).
Example 7: 4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-ethyl-benzamide, trifluoroacetate;
o r~ ~
w I/
TFA
CI
I / N
CI
146 mg (0.43 mmol) of 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid (see example 6) are dissolved in 5 ml of DMF, and 1.0 equivalent of triethylamine is added. At 0°C, a solution of 141 mg (0.43 mmol) TOTU
in 3 ml of DMF
is added. The mixture is stirred at 0°C for 30 min and at room temperature for 30 min.
This solution is then added at 0"C to a solution of 0.28 ml of 2 M ethylamine solution and 0.06 ml (0.043 mmol) of triethylamine in 5 ml of DMF, and the reaction mixture is stirred at room temperature for three hours. For workup, the solvent is distilled off in vacuo, and the residue is taken up in ethyl acetate and washed twice with 1 N
KOH
and once with H20. The organic phase is dried with Na2S04 and concentrated.
Chromatography on silica gel (dichloromethane/methanol 95:5) is used for further purification. Further purification on a preparative HPLC
(acetonitrile/H20/trifluoroacetic acid) affords the desired carboxamide as trifluoroacetate (Rt = 4.169 min (method A);
MS(CI+) = 363.3/365.3).
Example 8: 4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-propyl-benzamide, trifluoroacetate;
CI

The title compound can be prepared by the method described in example 7 starting from n-propylamine and 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid (see example 6).
(Rt = 1.881 min (method B); MS(CI+) = 377.3/379.3).
Example 9: 4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N-(2-dimethylamino-ethyl)-benzamide, trifluoroacetate;
C
N~
=A
was prepared in analogy to example 7 starting from example 6 and N1,N1-dimethylethane-1,2-diamine by a TOTU-mediated coupling reaction (Rt = 1.449 min (method B); MS(CI+) = 406.3/408.3).

Example 10: 6,8-Dichloro-2-methyl-4-(4-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline, trifluoroacetate;
C~~
TFA
CI
I / Nw CI
456 mg (1.4 mmol) of Cs2C03, 6.75 mg (0.03 mmol) of palladium acetate and 28 mg (0.045 mmol) of 2,2-bis-(diphenylphosphino)-1,1-binaphthyl are introduced into 5 ml of abs. toluene. Under argon, a solution of 0.104 ml (1.2 mmol) of morpholine in 2.5 ml of abs. DMF, and a solution of 371 mg (1.0 mmol) of 4-(4-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline in 2.5 m! of abs. toluene are added, and the mixture is stirred at 100°C for a total of 9 hours. For workup, the solvent is removed, the residue is taken up in dichloromethane, and insoluble constituents are filtered off.
After concentration of the filtrate, the residue is chromatographed on silica gel (CH2C12 /methanol 95:5), resulting in 350 mg of the desired morpholine derivative.
After a further purification on a preparative HPLC it is possible to isolate 160 mg of the corresponding trifluoroacetate in the form of a colorless solid.
Example 11: [4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-diethyl-amine, trifluoroacetate;
~NJ
I~
TFA
CI
/ Ny CI
The procedure is analogous to the method described in example 10 starting from diethylamine and 4-(4-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoline (example 5, intermediate 3). Reaction time: 2 days at 100°C; three times the amount of Pd catalyst and phosphine ligand. The desired trifluoroacetate can be isolated as a colorless solid after preparative HPLC.
Example 12: 6,8-Dichloro-2-methyl-4-(4-piperidin-1-yl-phenyl)-1,2,3,4-tetrahydro-isoquinoline, trifluoroacetate;
TFA
The desired piperidine derivative can be obtained starting from piperidine and 4-(4-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline (example 5, intermediate 3) in analogy to the method described in example 10.
Example 13: 6,8-Dichloro-2-methyl-4-(4-pyrrolidin-1-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline, hydrochloride;
CIH
CI
N~
CI
The reaction is carried out in analogy to the method described in example 10, starting from pyrrolidine and 4-(4-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline (example 5, intermediate 3). The product obtained after purification by chromatography is taken up in the DMSO/acetonitrile mixture, whereupon a precipitate separates out. This is filtered off, dissolved in 2 N
HCI and freeze dried, resulting in the title compound of a colorless solid.
Example 14: 6,8-Dichloro-2-methyl-4-[4-(4-methyl-piperazin-1-yl)-phenyl]-1,2,3,4-tetrahydro-isoquinoline, trifluoroacetate;

cN~
N
/
TFA
CI \
/ N\
CI
Reaction of N-methyl-piperazine and 4-(4-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline (example 5, intermediate 3) by the method described in example 10 affords the title compound in the form of a colorless solid.
Example 15: 6,8-Dichloro-2-cyclopropyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline, trifluoroacetate;
CI
TFA
Intermediate 1:
Cyclopropyl-(2,4-dichloro-benzyl)-amine;
5.25 g (30 mmol) of 2,4-dichlorobenzaldehyde are introduced into 140 ml of methanol and, at room temperature, a solution of 1.71 g (30 mmol) of cyclopropylamine is added. The mixture is stirred at room temperature for 40 min and then 1.42 g (37.5 mmol) of NaBH4 are added in portions. After standing overnight, the solvent is removed and the residue is taken up in 2 N HCI. Two extractions with ethyl acetate are carried out. The aqueous phase is made alkaline with NaOH and again extracted twice with ethyl acetate. The organic phases are dried with MgS04 and concentrated.
The crude product obtained in this way, in the form of a slightly yellowish oil, can be reacted further without further purification.
Intermediate 2: 2-[Cyclopropyl-(2,4-dichloro-benzyl)-amino]-1-phenyl-ethanone;

Intermediate 1 is reacted with alpha-bromoacetophenone in the presence of triethylamine in dioxane by the method described in example 1, intermediate 3.
For workup, the solvent is distilled off, and the residue is taken up in ethyl acetate. It is washed twice with H20 and twice with 2 N HCI, dried with MgS04 and concentrated.
The crude product obtained in this way can be reacted further without further purification.
Intermediate 3: 2-[Cyclopropyl-(2,4-dichloro-benzyl)-amino]-1-phenyl-ethanol;
Intermediate 2 is reduced with NaBH4 in analogy to the method described in example 1, intermediate 4. For workup, the mixture is concentrated, and the residue is partitioned between 1 N HCI and ethyl acetate. The aqueous phase is separated off and extracted once more with ethyl acetate. The combined organic phases are dried with MgS04 and the solvent is removed in vacuo.
6,8-Dichloro-2-cyclopropyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline, trifluoroacetate;
Intermediate 3 (1.9 g) is dissolved without further purification in 10 ml of dichloromethane and cyclized with conc. H2S04 by the method described in example 1. For workup, the reaction mixture is poured onto ice. The organic phase is separated off, and the aqueous phase is extracted once more with dichloromethane.
The combined organic phases are dried with MgS04 and freed of solvent.
Chromatography on silica gel (n-heptane/ethyl acetate 5:1 -~ 3:1 ) affords 200 mg of a yellowish oil, which is subjected to further purification on a preparative HPLC. This results in 184 mg of the title compound as trifluoroacetate.
Example 16: 16a: (-)-N-[4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
16b: (+)-N-[4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;

(+ and -) 500 mg of the title compound from example 1 are separated on a chiral phase, resulting in about 250 mg of the two enantiomeric acetamides 16a and 16b.
chiral column: Chiralpak OD 250 x 4.6 mm;
solvent: acetonitrile;
flow rate: 1 ml/min;
Rt((-)-enantiomerl16a) = 5.856 min;
Rt((+)-enantiomer/16b) = 8.613 min.
Example 17: 4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine, hydrochloride;
NHz , CI x HCI
/ N~
CI
Intermediate 1:
4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine;
3.0 g (8.6 mmol) of N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide (example 1 ) are dissolved in 100 ml of 20% strength sodium ethanolate solution and heated under reflux for four hours. A further 2.0 g (29.4 mmol) of solid sodium ethanolate are added, and the mixture is heated under reflux for three more hours. For workup, the solvent is removed in vacuo, and the residue is taken up in 200 ml of H20 and extracted twice with dichloromethane. The combined organic phases are dried with MgS04 and concentrated. Further purification by chromatography on silica gel (ethyl acetate/heptane 1:1 ) results in the aniline as a yellowish oil in quantitative yield.
4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine, hydrochloride;
200 mg (0.65 mmol) of 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine are dissolved in 30 ml of ethanolic HCI. The clear solution is concentrated in vacuo. The residue is triturated in ether, filtered off with suction and dried, whereupon it was possible to isolate 208 mg of the desired hydrochloride.
Example 18: N-Ethyl-N'-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonylurea, hydrochloride o\ ~0 0 ,S
HN
I
CI ~ CIH
I / N~
CI
1.0 mmol of 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzene-sulfonamide (example 4, intermediate 2) is mixed with 350 mg (2.5 eq) of K2C03 in 15 ml of dry acetone and stirred at room temperature for 1.5 hours. A solution of 2.5 eq of ethyl isocyanate in acetone is added dropwise at room temperature, and the solution is heated to reflux. For workup, the mixture is concentrated in vacuo, and the residue is taken up in H20 and extracted twice with ethyl acetate. The aqueous phase is acidified with 6 N HCI, and the resulting precipitate is filtered off with suction.
Washing with ethyl acetate and drying in vacuo affords the title compound in good yield.
Example 19: 1-[4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-propylurea;

A solution of 0.17 g (2.0 mmol) of n-propyl isocyanate in toluene is added dropwise to a stirred solution of 500 mg (1.63 mmol) of 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine (see example 17) in 15 ml of toluene. After one hour at 40°C, a further 0.17 g of n-propyl isocyanate is added, and the mixture is stirred at 80°C for one hour. For workup, the solvent is removed and the residue is triturated with H20 and ether. Drying affords 503 mg of the desired n-propylurea.
19a: 1-[4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-propyl-urea, hydrochloride;
450 mg of 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-propyl-urea are dissolved in a mixture of 2 N HCI and THF. The clear solution is concentrated in vacuo, and the residue is triturated with ether and filtered off with suction. Drying affords 473 mg of the desired hydrochloride.
Example 20: 1-[4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl- thiourea;
SII
HN~ N~
CI
/ NW
CI

Proceeding in analogy to the method described in example 19 and starting from 500 mg (1.63 mmol) of 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine (see example 17) and 220 mg (3.0 mmol) of methyl isothiocyanate allows 245 mg of the desired thiourea to be isolated.
Example 21: 1-[4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethylurea;
0I~
HN_ 'N~
I
CI
I / N\
CI
Preparation takes place in analogy to a method described in example 19, starting from 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine (500 mg;
1.63 mmol) and ethyl isocyanate (284 mg/4 mmol).
21 a: 1-[4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-.3-ethyl-urea, hydrochloride;
;IH
Conversion into the corresponding hydrochloride takes place in analogy to the method described in example 19a.
Example 22: N-[4-(6-Methanesulfonyl-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;

H N-I \
O~ ,O /
/S~
I / N\

Intermediate 1: (4-Methanesulfonyl-benzyl)-methyl-amine is synthesized starting from 1-bromomethyl-4-methanesulfonylbenzene and methylamine in a manner known to the skilled worker.
The title compound is prepared in analogy to the synthetic route indicated in example 1, starting from (4-methanesulfonyl-benzyl)-methyl-amine (intermediate 1 ) and N-[4-(2-bromo-acetyl)-phenyl]-acetamide (example 1, intermediate 2).
Example 23~: N-[4-(2,6,8-Trimethyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
0~I
HN- \
I
I
/ N~
The synthetic route detailed in example 1 is followed, starting from (2,4-dimethyl-benzyl)-methyl-amine, which can be prepared from 1-bromomethyl-2,4-dimethyl-benzene and methylamine in a manner known to the skilled worker, and N-[4-(2-bromo-acetyl)-phenyl]-acetamide (example 1, intermediate 2).
Example 24: N-[4-(6-Bromo-8-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;

H N' \
I
Br I / Ny CI
The synthetic route detailed in example 1 is followed, starting from (4-bromo-2-chloro-benzyl)-methyl-amine, which can be prepared from 4-bromo-1-bromomethyl-2-chloro-benzene and methylamine in a manner known to the skilled worker, and N-[4-(2-bromo-acetyl)-phenyl]-acetamide (example 1, intermediate 2).

Example 25: N-[4-(8-Chloro-2-methyl-6-pyrrolidin-1-yl-1,2,3,4-tetrahydro-isoquinolin-4-yl )-phenyl]-acetamide;
1.02 g (3.12 mmol) of Cs2CC73, 8.8 mg (0.04 mmol) of palladium acetate and 36.1 mg (0.06 mmol) of 2,2-bis-diphenylphosphino-1,1-binaphthyl are introduced into 6.5 ml of abs. toluene under argon. At room temperature, a solution of 512 mg (1.3 mmol) of N-[4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide (example 24) in 4 ml of abs. DMF, and a solution of 111 mg (1.56 mmol) of pyrrolidine in 4 ml of DMF are added, and the mixture is heated at 100°C for 7 hours. For workup, the solvent is removed in vacuo, and the residue is taken up in dichloromethane.
Insoluble constituents are filtered off, and the filtrate is concentrated. The residue is chromatographed on silica gel with a dichloromethanelmethanol mixture, and it is possible to isolate 360 mg of the compound of the example.
25a: N-[4-(8-Chloro-2-methyl-6-pyrrolidin-1-yl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide, hydrochloride;
CIH
320 mg of N-[4-(8-chloro-2-methyl-6-pyrrolidin-1-yl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide are dissolved in 20 ml of ethanolic HCI, stirred at room temperature for 30 min and concentrated. The residue is taken up in H20 and freeze dried.
Example 26: N-[4-(8-Chloro-2-methyl-6-morpholin-4-yl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide, trifluoroacetate;

x TFA
Preparation takes place in analogy to the method described in example 25, starting from N-[4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide (example 24) and morpholine. The chromatography on silica gel was followed by a further purification on a preparative HPLC.
Example 27: N-{4-[8-Chloro-2-methyl-6-(4-methyl-piperazin-1-yl)-1,2,3,4-tetrahydro-isoquinolin-4-yl]-phenyl}-acetamide;

HN- \
I \
~N~ /
~N \
N\
CI
Preparation takes place in analogy to the method described in example 25, starting from N-[4-(6-Bromo-8-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide (example 24) and N-methyl-piperazine.
27a: N-{4-[8-Chloro-2-methyl-6-(4-methyl-piperazin-1-yl)-1,2,3,4-tetrahydro-isoquinolin-4-yl]-phenyl}-acetamide, hydrochloride;

HN_ \
\N~ /
N x HCI
/ N~
CI
220 mg of N-{4-[8-Chloro-2-methyl-6-(4-methyl-piperazin-1-yl)-1,2,3,4-tetrahydro-isoquinolin-4-yl]-phenyl}-acetam'ide are dissolved in a little methanol, diluted with 2 N
HCI and freeze dried, resulting in 226 mg of the desired hydrochloride.

Example 28: N-{4-[8-Chloro-6-(cyclopropylmethyl-amino)-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl]-phenyl}-acetamide, hydrochloride;

HN' \
N x HCI
/ N~
CI
Preparation takes place in analogy to the method described in example 25, starting from N-[4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide (example 24) and C-cyclopropyl-methylamine. The chromatography on silica gel was followed by a further purification on a preparative HPLC. The purified compound was dissolved in 1 N HCI, diluted with H20 and freeze dried.
Example 29: 5-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoic acid;
Intermediate 1: Ethyl 5-acetyl-2-hydroxy-benzoate is prepared from 5-acetyl-2-hydroxy-benzoic acid by acid-catalyzed esterification in a manner known to the skilled worker.
Intermediate 2: Ethyl 5-(2-bromo-acetyl)-2-hydroxy-benzoate is prepared from ethyl 5-acetyl-2-hydroxy-benzoate by a known method in analogy to the process described in example 1, intermediate 2.
Intermediate 3: Ethyl 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hyd roxy-benzoate The title compound is synthesized by the synthetic route described in example 1, starting from ethyl 5-(2-bromo-acetyl)-2-hydroxy-benzoate and 2,4-dichlorobenzyl-(methyl)-amine (see example 1, intermediate 1 ).

5-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoic acid;
6.8 g (18 mmol) of ethyl 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoate are hydrolyzed in an ethanol/2 N KOH mixture in a manner known to the skilled worker, resulting in 5.4 g of the free acid.
29a: 5-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoic acid, sodium salt;
352 mg (1 mmol) of the free acid 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoic acid are dissolved in 10 ml of 0.1 M NaOH, diluted with H20 and freeze dried, resulting in 375 mg of the title compound.
Example 30: 5-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-N-methyl-benzamide, trifluoroacetate;
H
i I
/
CI ~ TFA
I / N\
CI
The title compound can be prepared starting from 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoic acid in a TOTU-mediated reaction with methylamine in analogy to the method described in example 7.
Example 31: 5-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N-ethyl-2-hydroxy-benzamide, trifluoroacetate;

TFA
The title compound can be prepared starting from 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoic acid in a TOTU-mediated reaction with ethylamine in analogy to the method described in example 7.
Example 32: 5-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N-(2-dimethylamino-ethyl)- 2-hydroxy-benzamide, trifluoroacetate;
The title compound can be prepared starting from 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoic acid in a TOTU-mediated reaction with N1,N1-dimethyl-ethane-1,2-diamine in analogy to the method described in example 7.
Example 33: N-[5-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoylJ-guanidine;
H O NHz ~ N~NHz CI
/ N~
2.52 g of potassium tert-butoxide are added to a solution of 2.39 g (25 mmol) of guanidine hydrochloride in 15 ml of abs. DMF and stirred at room temperature for 45 min. A solution of 950 mg (2.5 mmol) of ethyl 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoate (example 29, intermediate 3) in 10 ml of abs. DMF is added, and the mixture is stirred at room temperature for four hours.
After no further increase in conversion is detectable, the precipitate is removed by filtration with suction and the solvent is removed in vacuo. The residue is taken up in 2 N HCI and extracted twice with dichloromethane. The aqueous phase is adjusted to a pH of about 10 with KOH, whereupon the desired acylguanidine separates out as a colorless precipitate. Filtration with suction and drying affords 793 mg of the title compound.
Example 34: N-[3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
b~o a I/
a N-[3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
The desired meta-acetanilide is prepared in analogy to the synthetic route indicated for example 1, starting from N-(3-acetyl-phenyl)-acetamide and 2,4-dichlorobenzyl-(methyl)-amine (example 1, intermediate 1) in four analogous stages.
Example 35: 3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine;
NHz I
/ i CI
CI
Acetyl is eliminated from N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide (example 34) by the method described in example 17, intermediate 1, in the presence of sodium ethanolate.
Example 36: 2-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine;
I

CI
I / Nw CI
Intermediate 1: N-[2-(2-Bromo-acetyl)-phenyl]-acetamide;

31 g (0.175 mol) of N-(2-Acetylphenyl)-acetamide (prepared by acylation of 2-aminoacetophenone with acetyl chloride as described by Fuerstner, Alois;
Jumbam, Denis N.; Tetrahedron; 48; 29; 5991-6010, (1992)) are dissolved in 200 ml of glacial acetic acid. 127 ml of 33% strength HBr in glacial acetic acid are added and then, at room temperature, 8.75 ml (CI.175 mol) of bromine are slowly run in. The mixture is stirred at room temperature overnight. The mixture is stirred into 1.5 I of ice-water, and the precipitated product is filtered off with suction, thoroughly washed with ice-water and dried in vacuo. The crude product contains, according to HPLC and NMR, some precursor and dibrominated product, but is pure enough (about 85% strength) for further reaction.
Yield: 43 g Intermediate 2: N-(2-{2-[(2,4-Dichloro-benzyl)-methyl-amino]-acetyl}-phenyl) acetamide;
12.4 g (65.24 mmol) of 2,4-dichloro-N-methylbenzylamine (example 1, intermediate 1 ) are dissolved in 200 ml of dioxane. To this are added 19.96 g of the crude product from the preceding bromination, likewise dissolved in 200 ml of dioxane, and 45 ml of triethylamine. The mixture is stirred at room temperature overnight and then filtered.
The filtrate is evaporated, and the residue is taken up in ethyl acetate and washed with saturated sodium bicarbonate solution and brine, dried over sodium sulfate and concentrated in a rotary evaporator. The crude product (20.4 g) is pure enough according to NMR for further reaction.
Intermediate 3: N-(2-{2-[(2,4-Dichloro-benzyl)-methyl-amino]-1-hydroxy-ethyl}-phenyl)-acetamide;
20 g of the crude product from the preceding stage (about 50 mmol) are dissolved in 200 ml of methanol and cooled to < 5°C in an icebath. To this are added, while stirring vigorously, 4.3 g (109 mmol) of sodium borohydride in portions so that the internal temperature does not exceed 10°C. The mixture is then stirred in the icebath for 30 min and at RT for 1 h. After standing overnight, the mixture is evaporated, and the residue is taken up in ethyl acetate, washed 3x with water and 1 x with brine, dried over sodium sulfate and concentrated in a rotary evaporator. The crude product (19.4 g) is reacted further without purification.
Intermediate 4: 1-(2-Amino-phenyl)-2-[(2,4-dichloro-benzyl)-methyl-amino]-ethanol;
10g of the crude product from the preceding stage are dissolved in 300 ml of methanol.
200 ml of conc. hydrochloric acid are added, and the mixture is stirred at 50°C for 10 h.
The mixture is allowed to cool and is poured into water, and the pH is adjusted to 10-12 with 20% strength NaOH. The product is extracted with ethyl acetate, and the combined extracts are washed with brine, dried over sodium sulfate and evaporated.
The crude product (9.9 g) contains some sodium chloride, but this does not interfere with further reaction.
2-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine;
9.9 g of the crude product from the preceding stage are dissolved in 350 ml of chloroform. While cooling in an icebath, 123 ml of conc. sulfuric acid are added dropwise. The mixture is stirred in the icebath for 2 h and is then allowed slowly to reach RT and is finally heated at 50°C overnight. The cooled mixture is poured onto ice and made alkaline (pH > 10) with sodium hydroxide solution. The organic phase is separated off, the aqueous phase is back-extracted 2x with methylene chloride, and the combined organic phases are washed with water and NaCI, dried over sodium sulfate and evaporated.
General method for preparing the compounds of examples 37 to 77:
154 mg (0.5 mmol) of the title compounds from example 35, example 36 or example 17, intermediate 1, are introduced into 5 ml of dichloromethane, and 0.076 ml (0.55 mmol) of triethylamine is added. At 0°C, a solution of 1.1 equivalents (0.55 mmol) of an acid chloride in 5 ml of dichloromethane is added, and the mixture is stirred overnight while warming up. For workup, it is filtered and freed of solvent.
The residue is dissolved in 20 ml of ethyl acetate and washed once each with 5% strength NaHC03 solution and 5% strength NaCI solution, and dried. Evaporation of the solvent is followed by final purification on a preparative HPLC.

Table 1:
Precursor 1/ Precursor 2/
Example Product aniline acid chloride / I HN
CI \ ~cI \ I

/ \ CI TFA
I o I\ 1 / N\
Ex. 17, Int. 1 NH=
/ I ~ ~
HN
38 cl \ cI \ I
I / N\ CI TFA
\
CI O I / N
Ex. 17, Int. 1 NHz O'I
/I
HN' 39 'I I \ cI \ i / N\ CI TFA
i\ 1 a O / N\
Ex. 17, Int. 1 I
NHz R
/ I HN-I\
/ I
40 cl \ \
I / N\ CI CI \ TFA
CI O I /
Ex. 17, Int. 1 I
NHS
/ I
HN
''\
41 'I \ I
/ N CI CI \\ TFA
CI O I / N
Ex. 17, Int. 1 NHz OII
HN
/I
CI \
42 I cI
/ N\ CI \ TFA
CI O I / N\
Ex. 17, Int. 1 'I
NHz O
I HN V
CI \ \ I
43 I / N\ CI a TFA
CI N
I\
O / \
Ex. 17, Int. 1 I
NHz o / I HN- Y \
1~/\
44 ~I \ \ i I / N\ CI CI TFA
CI I / N
O \
Ex. 17, Int. 1 ~I
NHS -.......
/ ~ 'F
\ I HN~F
CI F / I
I\ F ' \
45 / F~CI CI \ TFA
CI I I I
/ N\
Ex. 17, Int. 1 NHS
/I
\ HN' Y l O ~ l~ IN~
46 * CI I \ ~N \ ~ o / N\ CI \
CI CI I / N~
Ex. 17, Int. 1 ~ I
NHz / HN
\I I
o / I N
CI \ \
47 I / N ~ C~ CI TFA
CI / I / N
N \
Ex. 17, Int. 1 NH7 O~ ,O
~S~
/ HN
\I /
CI \ \
48 I 1 0, , o / N\ '$ ~ CI TFA
CI
Ex. 17, I nt. 1 NH, o,, ,o / I HN~S~
\ /
CI \ \ I
49 I 1 0,, ,o / N\ ~$~ CI \ TFA
CI cl ~ / N
Ex. 17, Int. 1 NH= O~ ,0 / I HN~S~ i /
CI \ p ~ \ I
50 ~ 1 / N\ \N~$\CI CI \ TFA
CI I / N\
Ex. 17, I nt. 1 / NHs \I
/ N' CI ~ '\
51 ~ ~cI \ I
/ N
CI \ TFA
CI ~ I
/ ./N\
Ex. 35 CI
/ NH=
I
N
CI \

/ N~
rFA
a ~ ~ / N\
Ex. 35 ' / NHz I
CI \
53 I /~ci \ ~ o / N\
w TFn CI ~ I ~ N\
Ex. 35 °' / NHz \ I N
CI \ \ I O
54 ~ / Ny CI CI \ TFA
CI I / N~
CI
Ex. 35 / NHz \ I N
CI \ \ I
55 ~ cI
I / N~ c1 \ ~ TFA
CI O I / N~
Ex. 35 cl / NHz \I N
CI \ \ I O
56 I / N\ CI CI \ TFA
CI I / N~
CI
Ex. 35 / NH=
\I / N
CI \ \ I O
57 I / Ny cI CI \ TFA
CI I / N~
CI
Ex. 35 / NHs \ I N if CI \ ~ I O
5H I / N\ CI OI ~ \ TFA
CI / N~ , O cl Ex. 35 / NH= I
\ I ~ F F
/ N II F I I
CI \ F ~ I O
59 ~ F
I / N\ CI O' ~ TFA
cl O cl Ex. 35 / NHz I o N
CI \ ~ N
I W o / N~ N
rFA
C1 C~ I ~ ,,, a Ex. 35 / NHz I /
\ / N \ (N
CI \ O
I / N~ w c~ " ~ TFA
CI
N I
Ex. 35 NHz \ I / N~5/
\ I o' ' o CI \

/ N\ o~ ~o I \
CI ~S C~ / \
CI
Ex. 35 / NHi \ I / N~S/\
O' ~~O
CI \
63 I / N\ o\~ ~ ~ ~ \ TFA
CI ~S~C~
Ex. 35 / NHz -..
\ I / N ~Nw CI \ I O S~~O
64 0, ,o I / N\ \Ni'Syl CI \ TFA
CI I I / N\
Ex. 35 I
/
\ I NH1 / I
CI \ p I \ 1 CI a 65 / N\ I \ TFA
CI / N~

CI
Ex. 36 /I
\ NH2 / I O
CI \
Iw 66 cl N~ I \ TFA
/ N~
CI
Ex. 36 /I
\ NH=
I
CI
I\
67 ~!~~I G ~ TFA
/ N~
/ N~
CI O O
Ex. 36 /I
\ / I o NHz C. \ p I\
68 cl \
/ N\ cl CI I / N\ TFA
CI
Ex. 36 /
\ I NH
z CI \ H
I ~ G
/ N\ cI \
CI I / N\ TFA
CI
Ex. 36 /
\ I NH
z CI
I \

/ N\ cI
C I / N~ TFA

Ex. 36 / ' \ I NH
z G \
I\

/ N\ cI I
/ ~ ~ TFA
CI
I
Ex. 36 /I
\ NH ~ I O
z II
CI \
I\ b 72 / N\
CI ~ / N TFA
CI
G
Ex. 36 /I
NHz \ /I
\ N~ F
CI F 'H I 'F
\ ~ F CI \ F
73 I / N\ ~cI
I / N\ TFA
CI

Ex. 36 /I
\ NHz O i I o CI \
/ \ N

N~ TFA
a CI
i Ex. 36 0 /
\ I NH / I ~
z \ rliS\
CI \
75 ~ / N\ o,, ,o CI \
CI ~S~CI I / N\ TFA
Ex. 36 \ I ~ I o, ,o 'NH=
CI \
I' 1 76 ~ N~ p p C. ' CI ~S\CI I ~ N~ TFA
CI
Ex. 36 ' NHS ~ I 0, ~O
CI \ ~S~N~
77 ~ ~ °,~ ° ~~ ' I
CI N\ \ I'S\CI I ~ ~~ TFA
CI
Ex. 36 *) Product precipitates from the reaction solution and requires no further purification Example 78: 1-[3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea, trifluoroacetate;

CI

cl 0.355 mmol of the compound of example 35 is dissolved in 5 ml of dry acetonitrile, and 0.39 mmol of ethyl isocyanate is added. After standing overnight with exclusion of moisture, the solvent is removed and the crude product is purified on a preparative HPLC, resulting in the title compound as a colorless solid.
Example 79: 1-[3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-thiourea, trifluoroacetate;
\ N~N~
I
I / ~ TFA
\ N' /N' I ~ ~S
CI \
I / N TFA
CI
The title compound is synthesized starting from the compound of example 35 and methyl isothiocyanate by the method described in example 78.

Example 80: 1-[2-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;

/
cl / Nw CI
The process is analogous to example 78, starting from the compound of example and ethyl isocyanate. For workup, the resulting precipitate is filtered off with suction and washed with acetonitrile, resulting in the desired ethylurea as a colorless solid.
Example 81: 1-[2-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-thiourea, trifluoroacetate;
s / pip/
cl I N TFA
CI
The compound of example 36 and methyl isothiocyanate are reacted in analogy to the method described in example 78.
Example 82: N-[3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-ethanesulfonamide, hydrochloride;
b~s~
I / o' °o CI ~ CIH
I / N~
CI
307.1 mg (1 mmol) of the compound of example 35 are dissolved in 10 ml of pyridine and at 0°C, 0.19 g (1.5 mmol) of ethanesulfonyl chloride, and a catalytic amount of DMAP are added. The mixture is stirred at room temperature.
For workup, the solvent is removed in vacuo, the residue is taken up in ethyl acetate and washed with H20. The organic phase is dried with MgS04 and concentrated.
The crude product is chromatographed on silica gel. The sulfonamide obtained in this way is dissolved in a THF/2 N HMI mixture and again concentrated in vacuo, resulting in 208 mg of the desired hydrochloride.
Example 83: N-[3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonamide, hydrochloride;
~~s/
., CIH
The process is analogous to the method described in example 82, starting from the compound of example 35 and methanesulfonyl chloride.
Example 84: N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-ethanesulfonamide, hydrochloride;

CIH
The process is analogous to the method described in example 82, starting from the compound of example 17, intermediate 1, and ethanesulfonyl chloride.
Example 85: N-[4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonamide, hydrochloride;
o, ,o HN~S~
CI ~ CIH
/ N~
CI

The process is analogous to the method described in example 82, starting from the compound of example 17, intermediate 1, and methanesulfonyl chloride.
Example 86: 86a: (-)-N-[3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
86b: (+)-N-[3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
a~
I i o (+ and -) ~~
/ N~
CI
2.0 g of the title compound from example 34 are separated on a chiral phase, resulting in about 1.0 g of the two enantiomeric acetamides 86a and 86b.
chiral column: Chiralpak ADH/31 250 x 4.6 mm;
solvent: acetonitrile;
flow rate: 1 ml/min;
Rt((-)-enantiomer/86a) = 5.541 min;
Rt((+)-enantiomer/86b) = 7.033 min.
General method for preparing the compounds of examples 87 to 98 1.0 mmol of 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine (example 17, intermediate 1 ) or 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine (example 35) is introduced into 10 ml of pyridine and, at 0°C, a solution of 1.2 equivalents of the appropriate sulfonyl chloride (see table 2) in 5 ml of dichloromethane is added dropwise. The mixture is stirred at room temperature.
A
catalytic amount of DMAP is added depending on the progress of the reaction and, where appropriate, the reaction temperature is increased to 50°C until no further increase in conversion can be detected. For workup, the mixture is concentrated and the residue is partitioned between ethyl acetate and saturated NaHC03 solution. The organic phase is separated off and washed once more with saturated NaHC03 solution and H20, dried with Na2S04 and concentrated. For further purification, the crude product obtained in this way is chromatographed on silica gel. The products obtained in this way are converted into the corresponding hydrochlorides by dissolving the substances in 2 N HCI or ethanolic HCI and freeing off solvent, resulting in the desired HCI salts.
Purification in a preparative HPLC system results in the corresponding products as trifluoroacetates.
Table 2:
Precursor 1/ Precursor 2/
Example Product aniline acid chloride ""= o,, , o HN~S~F
F
\ F
87 'I I \ F o. S ~ \
/ "\ ~ \CI CI \ TFA
cl F I I
F / "\
Ex. 17, Int. 1 NH2 O~, .o i/F
HN~S~F
88 cl I \ F F o. , o \ I
/ N\ ~ ' a cl F SCI \
I / N\
Ex. 17, Int. 1 NHz O'..o i/F
HN S F
a \ F \ I
88a I / N\ F\l o,. ,C cl cIH
cl F~S~CI \
I / N\
Ex. 17, Int. 1 NH= O~ ,O
/ HN'S i \I S~
CI / \ ~ / I Br 89 \ \
I / "\ Br S s=o cl CI I I
/ N\
Ex. 17, Int. 1 NH= 0~ ,O
/ HN~S i \ I / S ~
CI \ / \ ~ \ I Br 89a I / ~\ Br S S=o CI
' CIH
CI C~'~ I / N
Ex. 17, Int. 1 NH= O
~~O
/ I HN'S
\ IS~N
O ,O
90 cl I ' -~ ~~~_ \ I NN
/ N\ N S S ~ CI

cl CI I / N\
Ex. 17, Int. 1 HN'S
N
/ S
O ~ O
90a cl I ' ~~\° \ i N
N\ ~N S S-O CI \
CIH
CI CI I / N
Ex. 17, Int. 1 NHz O O
HN'SYN
I I~ \
' / N
I
I o,so N\ \
91 cl ' / N\ CI; ~Y CI .
N ' cl \ I / ~ \
Ex. 17, Int. 1 I' NHz O O
/ I HN'S~N
\ / N
CI \
91 a I o,sP N\ \
/ N\ CI/ CI \ CIH
CI \ I / N\
Ex. 17, I nt. 1 NH, o, ,o a ,s' / I HN ~ N-\
/ N
CI I \ ~~~5 \ I
92 1 cl / N\ ~ \ CI
I ' CI N N CI
I / N\
Ex. 17, int. 1 NH= O O. CI
~5~
/ ( HN ~ N-~i O / N
cl O,~ H_ I
92a I
/ N\
CI ~ CIH
CI NON CI I
/ N~
Ex. 17, Int. 1 / NHS
I F
F
CI \ I O%S°O F
°~~ i°
93 I / N\ F s'cI ~' ~ ~FA
a F~ I / ~ w F
Ex. 35 \ I / ~',S~ F
\ I o. ~'p F'F
CI
94 I / N\ F F °. . ° cl cl F~S'y Ex. 35 / NH=
I / I~,S F
\ I ~' ''~ F
CI
94a I / N\ F F °,, ,,° ~' ~ ~IH
a F~S~C~ I /
Ex. 35 / NHZ Br / S
b.
95 cl ~ /
I / N\ Br S S=° cl cl C~ I
/ N\
Ex. 35 / NHz O
~N

96 ~ \ ~ ~~~ ~ I o S~'O
N\ N S S-O
CI CI C~ \
I / N\
Ex. 35 / NHz O
CI O / p ' N
96a I ~ N\ ~N~~°=o \
s a CI ~~ \ cIH
Ex. 35 I / N\

/ NHi I N
\ , ,C o-CI \ o I ~ o S.~c N
97 ~ / N~ o CI CI' ~~ G \
y I / N, Ex. 35 / NH=
. I N
\ ~ ,~
CI N S N
\ ~ I / O ~ ~~O
97a I / N
CI CI N I \ CIH
/ N~
Ex. 35 / NHS \y N
I H ' I \N-CI I \ \ O~\ O CI \ ~ O S 0\CI
9H / Nw N/ N \ CI ~I \
CI I I
Ex. 35 c General method for synthesizing the compounds of examples 99 to 110 Preparation of the amine component 4.0 mmol of the aromatic aldehyde (see table 3) are stirred with 8.0 mmol of the aliphatic amine (see table 3) in methanol at room temperature for 2 hours and then, depending on the progress of the reaction, 0.67 to 2.0 eq of NaBH4 are added in portions. After standing at room temperature overnight, the solvent is removed and the residue is taken up in 1 N HCI. It is extracted with dichloromethane. The aqueous phase is adjusted to a pH of 11 to 12 with NaOH and again extracted with dichloromethane. The organic phases are dried with MgS04 and concentrated in a rotary evaporator. Further purification takes place by chromatography on silica gel or on a preparative HPLC.
Preparation of the bromo ketone component The bromo ketone building blocks are synthesized by methods known from the literature, starting from commercial acetophenones by treatment with bromine in glacial acetic acid in analogy to example 1, intermediate 2.

The compounds of examples 100 to 111 can be prepared starting from the amine and bromo ketone components shown in table 3 in analogy to the synthetic route shown in example 1 (alkylation of the amine component by the bromo ketone component, subsequent reduction with NaBH4 and final H2S04-mediated cyclization).
The resulting tetrahydroisoquinolines can be converted into the corresponding salts in a manner known to the skilled worker.
Table 3:
Bromo Example Aromatic Aliphatic Amine Compound of ketone No. aldehyde amine component example component I
o 0 CI CI ~ \ ~NHZ ~ ~ S~NH=
\ ~ /
b gg cHO -NH ~ Br /
a 2 cl o * ) cl w cl \ a ~ \ I /
CI / CIH

~cHO -NHZ cl o er a I
t cl \ a ~
101 I ~ cHO p~ I ~ cl / cIH
CI -NHz G er cl cl \ cl ~ \ I /
102 I ~ ~ i b I ~ cl cIH
cHO NHZ ~ / I
cl cl o er - F
F F w F F \ \ li F \ F F C
103 ~ ~ ~ ~~ ~ ~ F ~ , cHO -NH I
2 F 8r . _ F F F
F

CI \ G \ \ I i o o I ~ cHO -NHZ I ~ b ~ G
CI CI O Br \ I N' /
C ~i CI I \
\ I\ I

105 t b cHO --NHz \ I
CI O Br \
cl G
__ F
CI \
\ CI \ I
106 I ~ cHO I ~ p\ I
--NHZ G ~ an cl Br \ I
cl G
a \
\ \ \ I~
107 I ~ cHO I ~ a\ I ~ c cl ~NHz G Br \ I

G
I CI \ \ ( \
I
108 cl \ b I
-_NHZ \ a ~ GH
CHO CI O Br \ I Nw CI \ CI I \ I \ I /
109 ~ p\ ~
ci ~ cHO -NHZ G ~ c~H
CI o Br \ I N\ I , G
\
I \ cl I \ \
110 ~ ~ b\ I
cHO --NH ~ I
CI Br \ NW
Br p Br *) Synthesis described in: Lang et al., DE-A 24 ~Ei zb3 General method for preparing the compounds of examples 111 to 124 0.358 mmol of the acids indicated in table 4 are dissolved in 1 ml of DMF, and 0.221 ml (1.30 mmol) of diisopropylethylamine is added. At 0°C, a solution of 128 mg (0.390 mmol) of TOTU in 1 ml of DMF is added dropwise. After addition of a solution of 100 mg (0.325 mmol) of the amine component indicated in table 4, in 2 ml of DMF, the mixture is stirred at room temperature overnight. For workup, insoluble constituents are filtered off and washed with 20 ml of ethyl acetate. The filtrate is washed twice with saturated NaHC03 solution and once with 5% strength NaCI solution, dried and concentrated.
The crude products which still contain Boc protective groups are deprotected without further purification (see below: general method for eliminating the Boc protective groups). Workup of building blocks without Boc protection is followed by purification by preparative HPLC, with the desired compounds of the examples being obtained as trifluoroacetates.
General method for preparing the compounds of examples 124 to 147 0.358 mmol of the acids indicated in table 4 are dissolved in 1 ml of DMF, and 0.221 ml (1.30 mmol) of diisopropylethylamine is added. At 0°C, 151 mg (0.975 mmol) of diethylcarbodiimide, a solution of 132 mg (0.975 mmol) of HOBt in 1 ml of DMF, and 20 mg (0.162 mmol) of DMAP are added. After addition of a solution of the amine component indicated in table 4, in 2 ml of DMF, the mixture is stirred at room temperature overnight. For workup, insoluble constituents are filtered off and washed with 20 ml of ethyl acetate. The filtrate is washed twice with saturated NaHC03 solution and once with 5% strength NaCI solution, dried and concentrated.
The crude products which still contain Boc protective groups are deprotected without further purification (see below: general method for eliminating the Boc protective groups). Workup of building blocks without Boc protection is followed by purification by preparative HPLC, with the desired compounds of the examples being obtained as trifluoroacetates.
General method for eliminating Boc protective groups The resulting crude products are stirred in 5 ml of a 10% strength solution of trifluoroacetic acid in dichloromethane at room temperature for one hour. The residue from evaporation in vacuo is purified on a preparative HPLC, with the desired compounds of the examples being obtained as trifluoroacetates.
Table 4:

Example Acid componentAmine component Compound of example.
No.

111 H N~ ~NH
~N HN
O

~ ~ \
~
H j,'( I _O

0 / y /
a ~ 1 a /

\ N\ \ I N\ TFA

CI a Ex.17, int. 1 112 ~ ( NHz ~N

hi0 N \ HN
/ ~
I \

a / ., a \ N\ \ I N\ TFA

CI G

113 - o I NHZ
~ ~~N
~N \

HO \
\

j \
I

i CI / I a I /

N\ \ ( N\ TFA

CI a i'+J

114 HO -fl O I Nhiz H I NH
i/
I
G ~ I a \ N~ \ I N~. TFA
I
CI CI
0'I
115 Q n - O NH, HN~NH7 f-10 /\\
~ ~ I ~ I
/
G / I a \ N~ \ i N~ TFA
CI G

116 p r"a o- ~ ~ NH' HO \
1~ '~ I , I , /
G / I G / NH:

NHz \ N\ \ I N~ TFA
G a 117 p O p NH HN
HO~ I / \ , I /
G / I a .TFA
\ N\ \ I N~
G , . a ' ~ 7 p NH2 0 1 1 8 Hp HN
\ \
iN
I N / I
ct / I V G
TFA
\ N\ ~ I N\
t CI U
p N f.tx O
_119 HN i NH
HO~NH , I I
/ I\
/
CI / I CI / ~ TFA
\ N\ ~ I Nw G a 12~ ~ H NH, 0 HO ~ / , ~ \
N HH~O
i CI /
C. / TrA
\ N\ \ I N\
. a a 121 °, N~ o H0~ I \ HN
lvN' \
N\ / I \
CI /
a / TFA
\ N\ \ I Nw G a 122 ° ~ N"~ ~° ~I
N HN' YN
\
I / NHS
Nlii a / ~ a \ N\ \ I N\
G a 123 ° ~H "H2 H
HO. N \ HN
I / NO~
N0~
a ~
a / TFA
\ Nw \ I N\
I
CI '~ a 124 ° N"~ °
H° ~ NH ~ \ ~ ~ NH
/ I \
/
CI /
..r~ 1 a / TFA
\ N~ ~ I N\
CI G
125 ° . N~ _ °
~ _ N
HO~N~ ~ \ HN
H / I\
CI /
a / TFA
\ N\ \ I N\
a a 12fi ~ H= p HO \

~N' ~O \ N.
~~..// j I S.
/ O
~ C1 /
TFA
\ N\ \ I N\
i i CI G
127 N"-HO I ~N I \ ~ , ~N
H / I \' N
CI
G~ TFA
\ N\ \ I N~
CI a 128 -- H p HO ~ ~N I \ HN I ~N
/ I\
/
CI
G / TFA
\ N~ \ ( N\
G a 129 O F F N~ p F F F .
HO ~N / HN I ~N
i \ N
N I H
. H CI / /
\ I N\ G / I - TFA
G . \ Nw G
0 \ NH=
N
130 Ho~N~O I / I / 1>~H
O ~ G / G
\ \ I N~ TFA
G
CI
Ex. 35 131 ~ I \ N"=
\ N
Ho~Nw I / I / 1~ I
G y G /
\ I N \ I N~ TFA
W I
a G

132 " \ N"=
i \ NFL, HO N~O
° ~ / 0 CI / I a /
\ N\ \ II N~ TFA
G ' G
133 o N o I \
H
HO~ ~ / I \ N~Nr~

/
G /
\ N\ \ I N\ TFA
G
a 134 O N"~ NH>
HO ~~O I ~
O
CI / \
I ~NH7 / O
CI a /
\ I N~ TFA
a 135 ° o \
° ~- ~ I ~ \
HO~ . I / O
G
a / TFA
\ I N \ I N
w G a ..
136 ° \ ;"_ ~N
H I
HO I \ > I / I ~ N /
,N
/
G /
I a / TFA
\ N\ I ~ , \ Nw CI G
137 I \ N"- _ ~
~~NH
\\
HO N" / I / O
G /
I G / TFA
\ N\ \ I N\
CI a 138 ~ I \ N~, - N ~ v HO I / \ H
/ I i o G / G
TFA
CI
139 _ ( O \ NHz Ni H
HO I / \
N\ I / O
I a i TFA
\ \ I N\
G
G
14O ~ N I j NHz NH, H I
I I \ N N
G / I i O
NH= ~ .
\ ~ N\ G / TFA
CI \ I N\
G
NO;
141 o H ~ N H i HO N ~~
H
. I / / I '~ N if / O
NO= CI /
G / TFA
N\ \ I N\
Ct ° .
~. 142 ~ ' \ NHz HO i NH / \ N ~ NH
Ct I / 0 N~ \ I N
w Cl G
143 ~0 HO- 1j N\\ / \ N N
' ~/ o CI / TFA
wt Nw \ ( N\
CI' CI

144 0 \ N~= v /~ ,'s' H0~1 ~I / I IN o , N~ ,,0 I
CI ~ I / 0 I ' Ii N ~ i I TFA
w N~
CI ci 145 ° w N~ , I
H
HO ~N I ~ N I ~N
' N I / O
H CI
'11 G / TFA
w N\ w I \/Nw CI
146 . I ~ N"= _ HO I ~N / \ N I ~N

CI / ( TFA
~ I N\
\ N~
CI
CI

N I ~_N
HO ~ N / ~ ~I
CI / / O F F F
H ~ l a TFA
\ N\ f CI I
cl Example 148: 1-[2-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-thiourea, hydrochlorides;
ci ~N~
~S
2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine (95 mg, compound of example 36) is introduced into 4 ml of acetonitrile and, while stirring, 27 mg of ethyl isothiocyanate are added. After standing at room temperature for 15 hours, the solvent is removed in vacuo, and the residue is purified on a preparative HPLC. The trifluoroacetate obtained in this way is taken up in water and made alkaline with K2C03. The aqueous phase is extracted with ethyl acetate. The organic phase is separated off, dried with MgS04 and concentrated. The residue is taken up in dilute HCI and freeze dried, resulting in 36 mg of the title compound.
Example 149: 1-[4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-thiourea, hydrochlorides;
S
4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine (50 mg, compound of example 17, intermediate 1 ) are introduced into 4 ml of THF, and ethyl isothiocyanate (14 mg) is added. After heating to reflux for 2 hours, the reacfion solution is concentrated and heated at 85°C to 2 hours. The crude product obtained in this way is purified on a preparative HPLC. Further treatment of the trifluoroacetate obtained in this way as described in example 148 affords 33 mg of the desired hydrochloride after freeze drying.
Example 150: 1-[3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-thiourea, trifluoroacetate;

w ~ ,. ~ SII
CI N~N~
NJ TFA

3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine (50 mg, compound of example 35) are dissolved in 3 ml of THF and, while stirring, 14 mg of ethyl isothiocyanate are added. After heating to reflux for 2 hours, the reaction solution is concentrated and heated at 85°C for 2 hours. The crude product obtained in this way is purified on a preparative HPLC, becoming 66 mg of the title compound.
Example 151: 3-[3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea, hydrochloride;
N~ N~ I
O

C!
CI
Intermediate 1: 4-nitrophenyl [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]carbamate, hydrochlorides;
3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine (350 mg, compound of example 35) are dissolved in 17.5 ml of dichloromethane and, while stirring, 230 mg of 4-ntirophenyl chloroformate are added. After 4.5 hours, a further 0.1 I
equivalent (23 mg) of 4-nitrophenyl chloroformate were added, and the solution was stirred overnight. For workup, the resulting precipitate is filtered off and washed with dichloromethane. The title compound obtained in this way can be reacted further without further purification.
3-[3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea, hydrochloride;
35 mg of 4-nitrophenyl [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]carbamate hydrochlorides (intermediate 1 ) are suspended in 3.5 ml of dichloromethane and, while stirring, a solution of 3.7 mg of dimethylamine in 1 ml of dichloromethane is added dropwise. After 1 hours, the mixture is diluted with dichloromethane and washed with aqueous K2COg solution. The organic phase is separated and washed twice with saturated K2COg solution, dried with MgS04 and concentrated. The residue is taken up in dilute HCI and freeze dried, resulting in 29 mg of the title compound.
The following examples are prepared in analogy to the method described in example 151, starting from intermediate 1 and the appropriate amine components:

Table 5:
Example No.: Structure 152 ~n' N NJ
' i 0 CI
CI~ ' I i N.~ CI

N1f J
I i o CI ~ CI
I I I
i N~
Ct 154 ~ ~'o i w. N~NJ

cy ~ cl \ NON
i ~ o CI ~ CI

i N~
cl 156 '.
w N~N,./
( i O
CI ~ C1 I I
~N~
CI
157 I ,. N N w I / O
CI ~
I CI
/ N~

CI

~ 58~ I
o CI ~ Cs \~W CI
Gi The following examples were prepared in analogy to the method described in example 151. THF was used as solvent, and the reactions were carried out in a closed reaction vessel. Reaction temperatures of 85°C were necessary for examples 159 to 166. Compound of example 167 was purified by preparative HPLC.

Table 6:
Example No.: Structure 159 . I \ N~O Chiral N
G ~~O
W G
cl 160 I ~ r,~o / N
G - ~ 1 ~O d ~I~ CI ' 9 61 ~ ~ ~O
/
G ~ CI ~N~ ., / N~ CI

162 1. ~ N~o i /N .
G ~ CI
i Nw CI /Nw CI
~~iN~~/~
r N._ Ch ,~ '~~ CI
N
~ ,~ ~~~N,,~ CI ~
I
Cl .. , ~~ N~~... .. _ ___.___....._.._ ~- I N-, cl c' I
cl i N~ rNo CI
165 -_ ~ ~! ~~o ,r' N
ct ~, 166 - _ ~ ~ \ N~o _ ~1 i I , Ci I ~ CI N~
1J~ CI
I
CI
167 I \ N~o , ~ N
' CI ~ CI ~ ; N
N~ C1.
CI
Example 168: N-[2-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-methylpiperazine-1-carboxamide, hydrochloride;

N~N
CI
CI
C1 Cl Intermediate 1: 4-Nitrophenyl [2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]carbamate, hydrochlorides;
[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine (200 mg, comparative example 36) are dissolved in 10 ml of dichloromethane and, while stirring, 131 mg of 4-nitrophenyl chloroformate are added. After 3.5 hours, the resulting precipitate is filtered off with suction and washed with dichloromethane. The crude product obtained in this way is recrystallized from dichloromethane, resulting in 159 mg of the title compound.
N-[2-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-methylpiperazine-1-carboxamide, hydrochloride;
15 mg of 4-nitrophenyl [2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]carbamate hydrochlorides are suspended in 2 ml of dichloromethane, and a ' solution of 3.2 mg of 1-methylpiperazine in 1 ml of dichloromethane is added.
After 1 hours, the mixture is diluted with dichloromethane and washed with aqueous solution. The organic phase is separated and washed twice with saturated K2C03 solution, dried with MgS04 and concentrated. The residue is taken up in dilute HCI
and freeze dried, resulting in 13 mg of the title compound.
The following examples are prepared in analogy to the method described for example 168.
Table 7:
Example No.: Structure 769 ~ ~ o i N~N~ .

CI ~
CI

i N~

CI

170 I ~ o _ i N~N~

CI ~ I

i N~

CI

171 I .~
N~N~i, CI
N CI
CI
t 172 \ _ ._ N~N
Ch CI
173 I \ o NJ~N~
Ct CI ~O
i N~
CI

N~N
CI~
il N~ CI
CI
175 ~ ~ O
'1 I
N~N~Nw CI
CI
I N~
CI
CI
Example 176: N-(4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-methyl-piperazine-1-carboxamide, hydrochlorides;
O
N~N
i ~ ~N..
Cl. ~ CI
N~ CI
CI
Intermediate 1: 4-Nitrophenyl [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]carbamate, hydrochlorides;
4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine (200 mg, compound of example 17, intermediate 1 ) are dissolved in 10 ml of dichloromethane and, while stirring, 131 mg of 4-nitrophenyl chloroformate are added. After 4.5 hours, the resulting precipitate is filtered off with suction and washed with dichloromethane.
The crude product obtained in this way is recrystallized twice from dichloromethane, resulting in 254 mg of the title compound.
N-[4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-methyl- ' , piperazine-1-carboxamide, hydrochlorides;
15 mg of 4-nitrophenyl [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]carbamate hydrochloride are suspended in 2 ml of dichloromethane, and a solution of 3.2 mg of 1-methylpiperazine in 1 ml of dichloromethane is added.
After stirring for 5 hours and standing overnight, the mixture is diluted with dichloromethane and washed with aqueous K2CO3 solution. The organic phase is separated and washed twice with saturated K2C03 solution, dried with MgS04 and concentrated.
The residue is taken up in dilute HCI and freeze dried, resulting in 13 mg of the title compound.
The following examples are prepared in analogy to the method described for example 176.
Table 8:
Example No.: Structure 777 °
~ N~N
I ~ ~/
CI ~ ~ G
I ~ N' CI "
178 -o NON
I
Ci CI ~ .~
f 179 -__ _ o N~N~
I

r C!
I .-- N
I CI

N~N~
cl I ~ ~
CI ~
I r N
CI
181 o I
NJLN~Nw I r CI
C! ~
N CI
C!
182 °
N~N
I
/
G i G
I / N\
G
1$3 ~ ' °
w ~o I
r CI
I
/ N~ ..
a Example 184: N-[4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]formamide, hydrochloride;
N"O
i C!

Ci 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine (200 mg, compound of example 17, intermediate 1 ) is dissolved in 1 ml of formic acid and heated to reflux for 15 min. After standing overnight, the mixture is added to an ice/water mixture and extracted twice with ethyl acetate. The combined organic phases are dried with MgS04 and concentrated. The residue is taken up in dichloromethane and washed with saturated NaHC03 solution. The phases are separated and the aqueous are extracted three times more with dichloromethane. Drying of the organic phases (MgS04) and removal of the solvent by distillation afford 167 mg of crude product. 10 mg are dissolved in dilute HCI and freeze dried, resulting in 11 riig of the title compound.
Example 185: [4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylJmethyl-amine, hydrochloride N~
3~
GI
N-[4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]formamide (150 mg, compound of example 184) are dissolved in 2.5 ml of THF and, at 50°C
under argon, added dropwise to a solution of 0.45 ml of a 1 M solution of lithium aluminum hydride/THF in 2.5 ml of THF. The mixture is heated to reflux for 1 hour.
After standing overnight, a further 0.22 ml of a 1 M lithium aluminum hydride solution are added at 50°C, and the mixture is heated to reflux for a further hour. For workup, the solvent is removed and the residue is partitioned between dichloromethane and aqueous HCI. The phases are separated and the aqueous are extracted three times with dichloromethane, The combined organic phases are dried with with MgS04 and concentrated. Further purification takes place on a preparative HPLC. The product obtained in this way is taken up in an NaHC03 solution and extracted with dichloromethane. Drying of the organic phase with MgS04 affords 80 mg of the free base. 10 mg are taken up in diluted HCI and freeze dried, resulting in 10 mg of the title compound.
Example 186: 1-[4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,3-dimethyl-urea, hydrochlorides;

m c~
The title compound is prepared by the method described for example 151, starting from [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]methyl-amine (example 185), 4-nitrophenyl chloroformate and methylamine (20,u1, 2 M in THF) resulting in 9 mg of the desired hydrochloride.
The following compounds are prepared in analogy to example 186 starting from [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]methyl-amine (example 185), 4-nitrophenyl chloroformate and the appropriate amine components:
Table 9:
Example No.: Structure 187 ______ .~ ~"~N..
I
CI ~ CI
I ~ N CI

CI

~N~N~
. ! I
' i CI
CI
I ' i N1 , C!
189 ~
~'N N~ ' CI
Cl [I ' i N~ , CI
'190 N
CI
CI~
' ~ N., CI

. \N~N~
I ~
Cl \ CI
I i ~N~
T ~~ ~j r~ N
CiH
CIH
. N
CI~
! ~ N-CI

N N
CIH
Cf ., ~:, ~ ~ N~
,.....
CI
Example 194: N-[3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl)formamide w CI
3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine (600 mg, compound of example 35) is dissolved in 2.4 ml of formic acid and heated to reflux for min. After standing overnight, the mixture is added to a mixture of ice/water and saturated NaHC03 solution and extracted three times with dichloromethane. The combined organic phases are dried with MgS04 and concentrated, resulting in 588 mg of the title compound.
Example 195: [3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amine, hydrochloride;
CI '', N'', j GI
GI~,~~~
N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]formamide (588 mg, compound of example 194) is dissolved in 10 ml of THF and, at 50°C under argon, added to a solution of 1.8 ml of a 1 M solution of lithium aluminum hydride in THF. The mixture is heated to reflux for 1 hour. After standing overnight, a further 2 ml of a 1 M lithium aluminum hydride solution are added at 50°C, and heated to reflux for a further 30 min. For workup, ice is added and the aqueous phase is extracted four times with ethyl acetate. The combined organic phases are dried with MgS04 and concentrated. Further purification takes place on a preparative HPLC. The product obtained in this way is taken up in NaHC03 solution and extracted with ethyl acetate.
Drying of the organic phase with MgS04 affords 270 mg of the free base. 45 mg are taken up in diluted HCI and freeze dried, resulting in 45 mg of the title compound.
The compounds of the following examples can be prepared starting from [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]methylamine (example 195), 4-nitrochloroformate and the appropriate amine components by the method described for example 151:
Table 10: .
Example No.: Structure \ N N
CI
/ N~
CI
r~ N
I
/ o cl I cl / ~Ny CI

N"N\
/ OO
Cl C( / \/N\
CI

N\ 'N\
OO

CI
/ ~N\
I
CI
209 I o ' \ N NJ
~l CI J
~N\
CI
2~1 ~ N N/
~J
C/ O
CI
I ~ N cl CI
202 I ~N~
I
.- o cv ,~
c! c!
/ N~, C!
203 .
N~N~
/ OO
C!
c!
/ N~
c1 Example 204: 2-Dimethylaminoethyl [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate, hydrochloride;
~p~/'.Ni O CI
c~
a 15 mg of 4-nitrophenyl [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]carbamate hydrochloride (see example 151, intermediate 1) are suspended in 1.5 ml of dichloromethane while stirring under an argon atmosphere, and a solution of 3 mg of 2-dimethylaminoethanol in 0.5 ml of dichloromethane is added, and the mixture is stirred for 6 hours. After standing overnight, water, dichloromethane and saturated NaHC03 solution are added, and the organic phase is separated. The dichloromethane phase is washed three times with saturated NaHC03 and dried with MgS04, and the solvent is removed in vacuo. The crude product obtained in this way is purified on a preparative HPL.C. The product fractions are concentrated and partitioned between ethyl acetate and saturated NaHC03 solution. The organic phase is separated off, dried with MgS04 and concentrated. The residue is taken up in dilute HCI and freeze dried, resulting in 5 mg of the title compound.
In an analogous manner, the corresponding isomers 2-dimethylaminoethyl [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]carbamate hydrochloride and 2-dimethylaminoethyl [2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate hydrochloride are prepared starting from 4-nitrophenyl [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate hydrochloride and 4-nitrophenyl [2-(6,8-dichlor-o-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate hydrochloride.
Table 11:
Example No.: ~ Structure 205 ~

N o'~''~~

I

cy ~ ci I i ~t~ cc 206 ~ ' ~ r / N~p~./NW

cs ~ ci N~ Ci ' C1 Example 207: Methyl [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate, hydrochloride;
c~ :-~ cl N, c~
15 mg of 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine (example 35) are introduced under an argon atmosphere into 1.5 ml of dichloromethane while stirring, and a solution of 4.6 mg of methyl chloroformate in 0.5 ml of dichloromethane is added. After stirring for 6 hours and standing overnight, a further 2.3 mg of methyl chloroformate are added, and the mixture is stirred for 5 hours. For workup, the solvent is removed, and the residue is taken up in dilute HCl and freeze dried, resulting in 20 mg of the title compound.
The following carbamates can be prepared in an analogous manner starting from the appropriate anilines 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine and 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine.
Table 12:
Example No.: Structure 208 ~ N~~
( ~ o G i .I

w N~

. G

209 I ~ N o~ .

i G , CI ' w I N., :

.
c1 ~ a . \
~

a ~ ci w I N~
21~
i N a!
' , C f -.
i ~ ~ .
W

CI
1~
cr ~ N1 c~

N o I
cl .~ ci ci N~O
GI
I
C!
f i N~
Ci Example 215a: (+)-N-[3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonamide, hydrochloride;
215b: : (-)-N-[3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonamide, hydrochloride;
N. / N~ i S ~ ,~S ~
o' o ~ ~ o 0 of cl ~ cl r N~
C1 GI .
96 mg of racemic N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]methanesuffonamide (see example 83) are separated into the enantiomers on a chiraf preparative HPLC.
chiral column: Chiralpak AD 250 x 50 mm; 20 N;
solvent: heptane:ethanol:methanoi: 10:1:1;
flow rate: 50 ml/min;
the resulting enantiomers are dissolved in dilute HCI and freeze dried, resulting in 37 mg of each of the title compounds 215a and 215b. The enantiomeric purity is determined on a chiral HPLC.
chiral column: Chirafpak AD-H/31 250 X 4.6 mm;
solvent: heptane:ethanol:methanol: 10:1:1;
flow rate: 1 ml/min;
Rt (enantiomer eluting first) = 6.84 min; 100°I° ee;
Rt (enantiomer eluting second) = 8.02 min, 100% ee.
Example 216x: (+)-1-[2-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethylurea, hydrochloride;
216b: (-)-1-[2-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethylurea, hydrochloride;
M
0 ~ . ~ \ O
~N / N"N
CI ,~ C. ~ J
Ci ~ N~
C( CI C( 316 mg of racemic 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethylurea (compound of example 80) are separated into the enantiomers on a chiral preparative HPLC.
chiral column: Chiralpak OD 250 x 50 mm, 20 N;
solvent: heptane:ethanol:isopropanol: 50:2:1; 0.3% diethylamin flow rate: 50 ml/min;
The enantiomers are subjected separately to further purification on a preparative HPLC. The resulting products are partitioned between saturated NaHC03 solution and ethyl acetate, and the organic phase is separated off, dried with MgS04 and freed of solvent. Dissolving the residue in dilute HCI and freeze drying affords 37 mg of the enantiomer eluting first and 58 mg of that eluting second. The enantiomeric purity is determined by analytical HPLC.
chiral column: Chiralpak OD 250 X 4.6 mm;
solvent: heptane:ethanol:isopropanol: 50:2:1; (0.3% diethylamine);
flow rate: 10 ml/min;
Rt (enantiomer eluting first) = 9.22 min; 100% ee;
Rt (enantiomer eluting second) = 9.96 min, 98% ee.
Example 217: N-(3-(6,8-Difluoro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide, hydrochloride;

F
N
O
CI
Intermediate 1: 2,4-Difluorobenzylmethylamine 2,4-Difluorobenzylmethylamine can be prepared in a manner known to the skilled worker starting from 2,4-difluorobenzaldehyde (cf. example 1, intermediate 1 ).
N-[3-(6,8-Difluoro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]acetamide, hydrochloride;
The title compound can be prepared by the synthetic route described in example starting from N-(3-acetylphenyl)acetamide and 2,4-difluorobenzylmethylamine (intermediate 1 ).
Example 218: 4-(3-Bromophenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydro isoquinoline, hydrochloride;
Br The title compound can be prepared by the synthetic route described in example starting from 2,4-dichlorobenzylmethylamine (see example 1 ) and 2-bromo-1-(3-bromophenyl)ethanone as alkylating agent.
Example 219: 1-[3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl-3-(2-hydroxyethyl)urea H H
~~N~OH
O
509 mg (1 mmol) of 4-nitrophenyl [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroiso-quinolin-4-yl)-phenyl]carbamate hydrochlorides (compound of example 151, intermediate 1 ) are dissolved in 15 ml of absolute DMF and, at 0°C, a solution of 67.2 mg (1.1 mmol) of 2-aminoethanol in 10 ml of DMF is added. The mixture is stirred at room temperature for three hours and then the solvent is removed in vacuo.
The residue is partitioned between ethyl acetate and saturated NaHC03 solution.
The organic phase is separated off and the aqueous is extracted trace more with ethyl acetate. The combined organic phases are washed with saturated NaCI solution, dried with MgS04 and concentrated. Chromatography on silica gel (dichloromethane/methanol) affords 265 mg of the title compound.
Example 220: Ethyl 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoate Intermediate 1: 3-Acetylbenzoic acid is prepared in a manner known to the skilled worker from 3-acetylbenzonitrile by hydrolysis of the nitrite group.
Intermediate 2: Ethyl 3-acetylbenzoate is prepared from intermediate 1 in a manner known to the skilled worker.
Intermediate 3: Ethyl 3-(2-bromoacetyl)benzoate is synthesized in analogy to the method described in example 1, intermediate 2, from ethyl 3-acetylbenzoate (intermediate 2).
Ethyl 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoate, Starting from ethyl 3-(2-bromoacetyl)benzoate (intermediate 3) and 2,4-dichlorobenzyl-methylamine (example 1, intermediate 1 ) it is possible to proceed further in analogy to the synthetic route described in example 1, resulting in ethyl 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzoate after alkylation reaction, reduction and ring-closure reaction.
Example 221: 3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzoic acid;
O
OH
~1 C~
500 mg of ethyl 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoate (compound of example 220) are dissolved in 15 ml of methanol, and 10 m1 of 2 N
of KOH are added. After one hour at 50°C, the mixture is concentrated in vacuo and the residue is partitioned between water and ether. The aqueous phase is adjusted to a pH
of about 6 with 2 N HCI, and the resulting precipitate is filtered off with suction. Drying affords 304 mg of the title compound as a colorless solid.
Analytical data for the compounds of examples 1 to 221:
Table 13:
MS_ MS, jM+H~ Remarks Ex. Structure [min]Method, Method I

1 349,11350,1 m,p.:
!

a 1,60B ESI

I ~ 351,0 205-206 C

a __ .

I
1 "" 1,60B 349,21351,2ES m'p"
a f (decomp.) O

t ~ 371,31373,3 2a ~ 63 A ESI
c~H 3 \ , enantiomer ~ ~ N\ 412,3/414,3 "o \ ~S'NHz 371,31373,3 2b c, aH (+) ;' , enantiomer 412,3!414,3 _ O
O

1 ~ . 371,11373,1 , (_) 2C AcOH 3,66A ESI
\ enantiomer "~ 412,11414,1 G
- -._..

371,1 !373,1(-) 2d G I ~ ~~ 1,56B ESI enantiomer ~N ~

a 412,1/414,1 O N
O

3 ~ aH
4,00A 399,1/401,1CI

~ NW

a p' ~N~
D' I / 371,21373,2 4a a"

G ~ 3,59A ESI
I

' N' 412,21414,2 G

per' ~N~

4b ~" 371,01372,01 1,58B ESI

i i N 373,0/373,9 G

r J

GH 369,9371,9/

4,57A CI

I / N~ 373,9 o~

I/
6 aN

a ~ 4,03A 336,1/338,1CI
I

/ N

G ' o~'p.~

i ~1 G ~ 4,17A 363,3/365,3CI
I

~N~

I

1,88B 377,3/379,3CI

/ N~ _ CI
-~

~ , N

I

G 1,45B 406,3/408,3CI
~

I
/ N~

G

a ~ - ~A 4,37A 377.11379,1CI

d J

~NJ

~\

G ~ ~A 4,05A 363,21365,2ESI

I / N~ _ G

~~' 3,79A 375,2/377,2ESI

YI

~N~
~~'' '''' G
_ N

13 / 4,92A 361,2!363,2ESI
a ~ ~' I / N~

a JN

14 t /
r~A 4,08A 390,2/392,2ESl a \

I /
N\

.
a /
15 rF~
a ~

I 4,80A 318,2/320,2CI
~

~
y7 o N-16a ~ 349,11350,11 a 1,61B ESI enantiomer 351,1 \

a , N' \
I

16b / 349,11350,11 ~

c, 1,61B ESI enantiomer \ 351,1 a NHZ

I / .
17 G x Ha 0,91B 307,1/309,0ESI

/ N~

G
~N N~ _...__.
O~ \

I /
18 G \ G" 1,63B 442,01444,0ESI
' N\

CI

~I
HN~N~

I/
19 4,00A 392,21394,2ESI
G \

I / Nw G .

.
HHXN~
\

19a ( 1,80B 392,1/394,1ESI
a ~ cH

I/

a HN- _N/

I /
20 67 B 380,1/382,2ESI

\ , I / N\

G J

OI, a HN~N~

I.

21 / m.p.:
1,68B 378,3!380,2ESI
G

C

I / N

HN"N~ , I /
21 378,1!379,11 a a 1,68B ESI
~I

~ 380,1 / N
I
I I
_ "" 359,1 o,, ,,0 0,32 B ESI
717,31718,3/
719,3 l 1,60 B 309,2!310,1 ESI
N
24 I ~ ~ 393,0/394,0/3 e. ~ 1,67 B ESI
I ~ N 96,0!397,0 a 1,85 B 384,1/386,1 ESI , i 25a I ~ c", 384,11385,1/
1,78 B ESI
I ~ N 386,2 a o H
26 ~~ ~ 1,46 B 400,1/401,21 ESI
x TFA.
401,2 ~ i N
a n r~
_ HN

27 'N'~ ~ 413,2J414,21 ~ 0 B ESI

N \ . 415,2 I

/ N' G

HN- ' 27a / 0,25B 413,2/414,2!ESI
'~
xHd N 415,2 ' 1 . I / N\

a _ o HN' ' /
2g 384,21385,2 . 1,65B ESI
xHa \ 386,2 ~
~

/

G

H
2g I \ OOH 352,0/353,0/

a 1,67B ESi \

N' 354,0 ci V

H O
I \ 'O~ , 29a 352,OJ353,01 a 1,68B ESI
\

I / N\ 354,0 ci H O_ \ /

30 365,1/366,1/

G 1;68B ES1 \ TFA

N\ 367,0/368,0 a H
I

I
/

31 I c, 379,11380,11 I \~ ~ TFA 1,79 B ESI

N\ 381,1 a OH
I \ y~N.w 32 ~, 422,1/423,1/

\ xTFA 1,47 g ESI
I
"

/ 424,11425,1 \

OH O NHS
I \ N~N~..,~ ~~i 33 393,11394,1 I

1',46B ESI

I \ 395,1 CJ

\ p~o I, 34 a \ 349,0/350,11 1,63 B ESI
I

/ 351,0 \

cl N1i I
I

J
' 35 cl w , B 307,01308,1/ESI
1,17 , 3091 a I ,1 .
NHZ

36 cl 307,0/308,01 ~

I 1,66 B ESI
N

~ 309,1 cl _. HN
I

a ~ 1 TFA 2,35 C 363,31365,3 ESl N~
I
a HN
/I

a ~ TFA 2,43 C 377,31379,3 ESI
i / 1\
a / I

a ~ TFA 2,49 C 391,31393,3 ESI
.
a HN' Y
40 \ 2,43 C 377,3!379,3 ESI
OI ~ TFA
I / N~ J
r CI
O i H' G ~ -~q 2,48 C 391,31393,3 ESI
G
O
/ I

G ~ TFA 2,40 C 375,31377,3 ESI
I
/ ~
a i i HN , /

I
43 \

TFA 2,45 C 389,31391,3ESI

IT _H\

G

I
44 \

a \ rF" 2,52 C 403,4/405,4ESI

I/ \

G

O'' X 'F
HN' F

/ F

\I

G ~. rFA 2,49 C 403,2/404,2ESI

I / N\

G

0I~
HN
I

N ~
I

46 ~

a \ 2,36 C 460,4/462,4ESI

I/

a ' i-.
I \
/
N

\

G ~ rfA 2,35 C 412,2/414,3ESI

I / N\

G

'S\
O, O

HN
/

I

TFA 2,29 C 385,3/387,3ESI

I / N\

G
IOJ
SW/

I

CI ~ TFA 2,37C 399,31401,3ESI

N

CI

~S~N~ I

HN
I
/

G ~ TFA 2,42C 414,41416,4ESI

I~N

N' ' I ~

\
O

CI

I ~ 2,37C 363,31365,3ES1 TFA

N

G

~ N
~f ~' ~ ?~

O
\

52 c' I \ TFA . 2,44C 377,3/379,3ESI

N\

G

N

a O

53 G I j 2,51C 391,3/393,3ESI
TFA

N
\w G

/ N

2,44C 377,3!379,3ESI
\ ~ TFA
G

I / N~

CI ' / N
I

\
O

55 CI 2,49C 391,3J393,3ESl TFA

CI

/.

O

'FA 2,41C 375,31377,3ESI

/ N\
G

/ N
l 1~ ~f \
O

57 ~
Y TFA 2,47C 389,3J391,3ESI

~N~

CI

/ N

G I \ TFA 2,52C 403,4/405,4ESI

N~

CI

F
N iF J
/ ~F
I

o \

59 2,48C 403,21404,2ESI
\ TFA
~I

/ N\

G

N
~ I

60 \

a I ~ rA 2,,34C 460,4/462,4ESI
/ N

~
a 'i I

\

\ TFA 2,36C 412,2/414,3ESI
c' I

G

N S
~

O
\ ~ O ~ ~

62 cl '~ ~A 2,32C 385,3/387,3ESI
I / N_\

CI

/ N'S~

( O O

63 CI \ TFA
1 2,38C 399,31401,3ESI
I

/ N

CI

I
/ N ~N~
S

O
~~O

64 CI \ TFA 2,41C 414,4/416,4ESI

I / N~

CI

/ .I O

>.
65 G \ TFA C 363,31365,3ESI
I N 2;30 cl i I o 66 0' \ Ti=A
2,41C 377,31379,3ESl G

' I o 67 c' ~ ~ 2,52C 391,3/393,3ESI
TrA

N

G
/ I o \ p .

68 G \
I / N TFA 2,41 C 377,3/379,3ESI
w G

r I o G
69 \ 2,45 C 391,31393,3ESI
( / N\ rFA

I
G

/ I o .
b a 70 I % N ~A 2,36 C 375,31377,3ESI

G

. . ~ I o \ b G
71 i / N TFA 2,44 C 389,31391,3ESI
\

G

rI

72 a \
2,51 C X403,41405,4ESI
I

/ tJ\ TFA

CI

F
F

a F
73 I / N TFA 2,70 C~ 403,21404,2ESI

a ~I o \ b Q

74 \
I ~ 1 ~A ~ 2,30 C 460,41462,4ESI

G
2,41C 385,3/387,3ESI

N\ TFA

a ~ i o, o 76 G w.
2,49C 399,3/401,3ESI

N\ rFA

G

~ I o, :o :

p:S
N~
I

77 ~' i w 2,55C 414,41416,4ESI

TFA

G

\ N~N~

78 a ~ % 1,72B 378,3/380,3ESI

N

a \ N"N\
i / sg 79 a w I - 74 B J380,3/382,3ESI

~A , ' N\ r I \ o i p~~~

so ~~
1,75B 378,3/380,3ESI

, \

G

I w s i p~

81 C~ ~ TFA 1,68B 380,31382,3ESI
i ~

G
\ p S'~
~

/
o, .
I
o / 399,0/4D0,0/-82 a ~ cw 1,718 401,0/402,01ESI
I

/ N\

a 403,0 b /

.s \
~

I / o' ' o 83 cl 385,0/386,0/
clrl ~ 1,66B ESI
~
N

/ 387,0 \

cl o, ,o I
84 ~ 399,0/400,0/

a 1,69B ESI

/
401,01402,0 a o, ,o ~S\

_ HN
\

I
85 / 385,01386,01 a 1,64B ESI
~ c"., , 387,0/388,0 / N\

CI

\ N ~

I

86a a 1,648 349,31351,3ESI Enantiomer I

/ N\ .

C I

86b a 1,fi3B 349,31351,3ESI Enantiomer I

/ N\

CI
~S
F

N
~
~F

F
I

/
87 1 l 439 ESI
rFA g7 8 0/441 \ , I / N\ , CI.

S F

I /

c, 1,83B 453,0/455,0ESI

\
I~ N

CI

O F - _ S

N
F .
\

/
88a CIH 1,83B 453,0/455,0ESI

S

N
\ S /

Br 89 / 531,01533,01 cI \ 2,01B " ESI

534,9 / N\ i O
, . 0 .
S, N
/
\ S
~

r 89a / 531,01533,0!

ci ~ GH 2,02B ESI

~ 534,9 ~

/
\

ci . .
o, ,o HN,S, S

\ N
I

c, \ 1,78B 525,11527,1ESI

I
/ N~

CI

O~ ,O
HN S' S
N

N

I
90a 1,79B 525,1/527,1ESI
~ ~ CIH

I
i N~

a ,o ~S~ N

N

I

a \ 1,63B 465,11467,1ESI

I ~ N

a ,O
,,S, N

N
\ ~..

I

91 '~ _ '~ a ci ~ aH 1,6dB 465,11467,1ESI

I ~
\

o, , ~S _ N
~N-i \ N

I
92 ' 499,1/501,11 c, 1,81B ESI

\ .
I 503,1 ~ , \
p, ,p ' ,s ' ~N- i "
~~~----N

i 92a ~ 499,11501,11 c'" 1,82B ESI

503,1 ~N\

CI

F
~F I
s ' F

I ~ o ' p 93 a TFA. 1,99B 439,0/411,1ESI

N
a N F' I
' S''~F

p 94 G ~

1 1,87B 453,0/455,0ESI

N~

G

N F
~S
O, '.~F

94a a w cIH 1,g7B 453,0/455,0ESI
I

~ N\

CI

8 l "\

\
I S
' '' o p g5 c~ 2 B 531,01533,01ESI

N , 535, 0 ci \ p\S~~
Iv o. ', o \ 1;75B 525,0/527,0ESI
I

/ N~

CI
b. ~ r"

\ .S. S
~ ~

O

96a a , ~ aH 1,75B 525,0/527,0ESI

i / Nw CI
i N

N.Si\N
/ . O~ ~0 1,66B 465,01467,0ESI

N\
G

rN
N.
~

\
N
S

/ 0~ ~0 97a a ~ 1,66B 465,0/467,0ESI

GH

/ N\

a N\
N_ \ N

.5 ' S

.

gg 499,11501,11 a 1,81B ESi ~

i 503;1 N\

CI

i 0\X0 \ S~NHx g c' \ 405,11407,1ESI m~P~~

a see Ex.
2;

100 cl ~ intermediate cIH 4;44A 292,21294,2CI 4 a \I
/
see Ex. 2;
100a ~_~ c' ., I intermediate TFA
\ 4a ci / i I
_, see Ex. 2;
100b a .. ~ intermediate ~+~ I ; TFA
\ 4b a /I
101 a ~ 4,43 A 326,0/328,0 ESI
I ~ aH
G
/ I
GH
102 a I i ~ N~ 4,23 A 306,1/308,0 ESI
a w p F F
103 \
2,g4 C ~' 360,0 ESI
F
\
Ov O
104 ~~ \ " . _ I / ~ Y 2,79 C~ 320,01322,0 ESI
G
105 ~ j N 2,64 C 291,91293,9 ESI
c.
t t 106 I w GH 4,26A 310,0/312,0ESI

/ N~

a i i I
107 / 4,43A 306,1/308,1ESI
G I ~ co-, ' / N~

I
i G
I ~ GH 4,11A 292,01294,0ESl N~

I w i i 109 c, I ~ cw 4,28A 292,01294,0ESI I

/ N' G

I
i i i 110 I w c~H 4,05A J 302,01304ESl I

I

/ N~

~r II

111 ~NH II
HN

I/
1,37D 364,4/366,4ESI

G /

I N~ TFA

G
112-_ HN

I

1,44D 378,4/380,4ESI
G

\ I N~ TFA

CI

113 ~N

HN

I /
1,51D 392,41394,4ESI

a /

N\ ~
a II

x 'NH7 HN

1,51D 378,31380,3ESI

G

N~ TFA

CI

115 . - II
- ~~NH=

I/
1,58D 392,41394,4ESI

a \ I N~ TFA

CI

NH ' =
HN

/
7 D 435,51437,5ESI
,04 G / NHi N~ TFA

CI . ' 117 xfI
HHN

-HN

I
/ 1,67D 404,4!406,4ESI

CI ~.
TFA

I
\ N~

G
HN I
\ iN

/
2,08D 412,31414,3ESI

G /
TcA

I
\ N\

G

HN / NH
\

2,27D 400,4/402,4ESI

G /
TFA

I .
\ N\ . _ a , HN I

I/
2,37D 400,4!402,4ESI

G / .r>:A

\ I N\

G

121 ~

~
HN- 'i' 1 ~ I

\
Ny ~ / 1,54D 432,5/434,5ESI

G / TFA

\ I N\

G

HN

/ _ 1,70D 428,51430,5ESI

1FA , G /

I
N\

G

HN I

1 ~ No, 2,55D 445,414-47,4ESI

G / j~ TFA

\~N\
'~
' '' C
I
124 ~ ~
HN ~ NH
I\
2,43 D 428,51430,5 ESI
cl i TFn W I NW
CI
125 ~0 HN~N
H
1,88 D 401,41403,4 ESI
G / TFA
\ ~ N\
G p 126 yII~ ~
HN
IN~ ~0 \ OS\
2,31 D 496,5/498,5 ~ ESI
G i I TFA
\ N\
a 127 °
HN , ~ N .
'~ 2,14 D 429,4J431,4 ESI
a i I TFA .
N\ .
G J ' 128 °
HN ~ ~r I \ H
2,07 D 401,4/403,4 ESI
G / TFA
\ I~ N\
G
129 p F F F
HN ~ ~ N , 2,44 D 469,41471,4 ESI
G / ~A
I N\
CI
130 I i N~~

G ~ 1,55D 378,41380,4ESI

\ I ~ ~ TFA
' a 131 "
N~

a / 1.52D 392,41394,4ESI

\ I N~ TFA

p / o a 1,63D 378,31380,3ESI

I N\ TFA

a 133 i "
\ N~ ~
I ~NH=
~~

O
1,64D 392,41394,4ESI

a ' 1 \ I N\ TFA

G

134 j "~

H
I ~ N~N'i' 1,14D '435,51437,5ESI

G

I N\ TFA
G

135 "
' II N

O
1,62D 404,41406,4ESI

a i TFA

\ I N\

a 136 --_-H - I 1N
,1 N
I

2,16D 412,31414,3ESI

G. / TFA

\ I N

CI
I.

137 ~ NH

\
I

/ o 2,31D 400,4/402,4ESI

G
/
~ , TFA

I
\ n\

a 138 \ N IN
I H

/ O

2,41D 400,41402,4ESI

G
/ TFA

~ I N\

a 139 N f ,N/
N ~~~J\//
I

/ , a 1,62D 432,5/434,5ESI

Q
TFA

\ N\

CI

N 1\
\ N N ~
I
~

/ o 1,75D 428,51430,5ESI

G / TrA
I , \ I N\

G

141 N' N

I \
H

0 2,54D 445,4/447,4ESI

G / TFA

\ I N\

a ' 142_.
H ~\
N \ NH
I \v / ° 2,50 D 428,51430,5 ESI
G / TFA
\ I N\
G

I \ ~ N
/ ° 1,95 D 401,41403,4 ESI
G / TFA
\ I N\
a 144 °, ~\ ~s/
H ' iI N v0 N
I / ° 2,34 D 496,51498,5 ESI
a / hA
\ I N\
G

N , /N
I\
/ ° 2,31 D 429,4/431,4 ESI
/ TFA
\ I N\_ G
-146 . "
H I /N >
I i ~
2,11 D 401,4!403,4 ESI

\ I N\
G
H
N

\ /
147 I / ° F F F 2,48 D 469,4/471,4 ESI
G / I TFA
N\
G
G

N~

CI

148 ~ v 2,36 B 394,2 ESl N~N~

SS

I
CI

N~N~

2,35 B 394,2 ESI

N
I G i .

y l w I ~ ' I .
N N~ ' 150 ~' 2,35 B 394,2 ESI

N TFA
I I

I w N~Nw ~~
I

i O
151 G ~ 2,15 B 378,2 ESI

I
G

/ Nw a N~ , w N~NJ
I

152 ~ ~ a 1,64 B ~ 433,3 ESI

G

I i N~ G ~
i G

N
N

\
O

~

153 ~ 2,56 B' 418,3 ESI
~i w 1 a I
i N~

CI

w N~N~ , I

154 ~ ~ ' 2,16 B 420,2 ESI

G
~ G

I
i N~ I
___ __. N~N

I

/ O
155 G cl 2,34B 404,2 ESt I ~ Nw CI

i i N~N.~
I

/ O

156 cl ~ ~I 2,43g 406,2 ESI

I / N~

CI

-_ N
_ t 157 a ~ 2,12B 364,2 ESI

G
I / Nw G

I w N~N~.N/
~
I

O

158 G ' G 1,65B 421,2 ESI

w N~ C1 CI

I ~ N"'0 Chiral / NN~
I O
c 159 I ~ cl 2,23B 420,3 ESI

N~

CI

I ~ N

~ 2 434 ESI

160 ~ , B , I G

G

I w ~0 iN
~

161 ~ G 1,72B 461,4 ESI
N.

I
/ N~ CI

CI
\ N~0 I ~

i ,N
162 cl ~ cl ~ 1,6$B 449,4 ESI

I
/ N\ C! /N' C!

1 N~ i ~N1 163 cl ~ cl ~N~ 1,62B 435,3 ESI

i / Nw cl I

CI

~ N'l0 ~' I

~
164 N 1,71B 435,3 ESI
c w G ~
I

I
G
N~ ~N~

CI

N ~
.

I /
165 N 2,21B 408,3 ESI
cl ~

~
I ~ Nw CI

N C

I / . N ~
166 1,88B .~ 427,3 ESI
I
cl. w cl I N G > 1 CI

N O
N

~ 1 By 427 ESI

cl 167 w cl , , ' 0 N~ CI

CI

I ,1 If N~N
~ ~
G

168 N. 1,59B 433,3 ESI
I

N~ G

G CI
N~Nr 169 ~I ~ CI 2,128 364,2 ESI
I

i N~

CI

I ~

i_ r N

170 I 2,12B 378,2 ESI
cl ~

N' CI

CI

I w N ! 34 B 406 ESI
a 2 3 171 \ , , ~

N a a I
r N~N~

172 a I ~ ~~ 2,44B 418,3 ESI

a a I ~~ o 173 G 11 B 420 ESl \N 2 3 ~

~ , , G
I I

i N.~

G

I ~ O

~ N

974 G ~ 2,25B 404,3 ESI
~) ~

I i Nw CI

G

I ~ O
I' I
N~N~Nw 175 G 0,90B' 421,5 ESI

~
I G
N~

G
CI

O
N~N~ .

~N~

176 I ~ 1,52B 433,3 ESI

CI ~ CI

N ~ CI

CI
-_ ~

N
N

177 I ~ 2,34B 404,3 ESI

CI
GI

I i N

Ct . N~N

I

178 cl I ~ 2,17B 364,2 ESI

CI

N\
k:>

CI

N~N~

179 G I ~ ~ 2,17B 378,3 ESI

CI

I i N

GI

N~N~

' 180 cl ~ 2,51B 406,3 ESI

cl I i N

CI

I
N~N~

w ~

181 ~ ~ cl 1,59B 421,2 ESI

CI
CI

\ N\
CI

N~N

I

~
\

182 ~ I ~ 2,47B 418,2 ESI

G
G \

N~

CI
o , _ N

183 ~ / 2,16B 420,2 ESI

a G

I / N\

a N 0 ~

w 184 2,02B 335,2 ESI

cl I / N, a cl N
CI I ~

185 CI ~ 1,92B 321,2 ESI

CI

~ N\

CI

O
~N~N

I

186 cl ~ 1,05C 378,4 ESI

CI

i N

CI

. ~N~L

N\

187 I ~ 0,92C 447,5 ESI

~

c~ ~ ci _ I ~ Nw O
N~N

.
' 1gg I ~ 1 C 392,5 ESI
,10 cl ci I i N

CI
~M~N

ss ~~ ~ c 4s2,5 ssl z~

.i Nr, 1N~N~

~O
~

1a0 a '1,10C 434,5 ESI

a .~ . .

ci c ~N~'N~

~

191 I ~ 1.75C 418,4 ~Sl ' N.

a 1N~'N . "

CIH

19z~ ~ I ~ -'N'~ o,s~C 435.4 ESI
~'H

r Y

C1 - ' are -193 1,22C 420,5 ESl a N~

Cl Nv 0 194 G ~ 2,04C 335,4 ESI

I f N~

CI

\ N~

CI ' ' CI

195 G 0,90C ~ 321,3 ESl ~

i / N\

G

\ N~N

O

196 2,488 418,3 ESI

cl \

I G
/ N~

CI

N N

I

197 2,62B 432,3 ESI

G ~ .

/ ~ G ' G ~

\ N N

O

8 , , cl \

~ ..
/ ' N~

CI

I
\ N Ny / O

199 cl 2,19B 378,2 ESI

' ~ / 1 G , G
I

~ N
a ~
200 I2,16B 434,3 ESI

cl ' I

G
N\

i N~
~

I
\ N~
I ~

/ O

201 a ~ 1,61B 447,4 ESI
' as N\

G

WN~

\ N~ NCI
I

/ OO

202 G ' 1,59B 435,3 ES!

I I G CI
/ N\

G

I

N~N~/
I

y o 203 2,57B ' 420,3 ESI

cl \ >

N\

Ct I

o a 204 a ~ 9,71B 422,2 ESI

i \ N, a a o I ~
N O~N~' /
205 1,70B 422,3 ESI

G ~ G

N~ G

CI

o i /
~N~

N O

G ~ G 1,68B 422,3 ESI

I

/ N~ CI

G

N
C~

w ~

~

207 CI ~ 2,34B 365,1 ESI
I l CI

N

CI

~ N~O~
II

O

208 a / 1,18C 379,4 ESI

I 1 ct w N~

a _ J

209 a / a 1,24C 393,4 ESI

I
w N~ , i a . o ~ N

l~

o ' 210 1,38C 421,5 ESI

G ~ G

I I
w N~

CI
N~O

CI

211 I ~ , 1,13C 365,4 ESI

' ~j a 212 i 1,26C . 393.4 ESI

a .

N.

ct ~ 42 ESI

2~3 . 1_,40C 1, ~

ci d ~ ~ ' k cr 214 .~ 1,20C 379,'4 BSI

N

a o ~=~e 215aP 385,2 ESI

215b ' 2lfia J~$,1 ES1 216b .

i .
217 F 1,86B 317.2 ESI

. 1 a I .
N~

i -I

218 G 1,27C 370,2 ESI
G
p / N\

CI

H H
N N~\

1i ""

y 219 a .. 0,99B1 394,1/396,2ESI
I

/ N\

O

I \ D/\

220 1,24B1 364,1/366;1ESI

G \
I
N

\
/
CI

O
\ ~

I
221 OH 1,02B1 336,11338,1ESI

a \
I
N

/ ' CI

Pharmacological data:
Description of test:
In this test, the recovery in the intracellular pH (pHi) after an acidification is ascertained, which is initiated if the NHE is capable of functioning, even under bicarbonate-free conditions. For this purpose, the pHi was determined using the pH-sensitive fluorescent dye BCECF (Calbiochem, the precursor BCECF-AM is employed). The cells were initially loaded with BCECF. The BCECF fluorescence was determined in a "Ratio Fluorescence Spectrometer" (Photon Technology International, South Brunswick, N.J., USA) at excitation wavelengths of 505 and 440 nm and an emission wavelength of 535 nm and converted into the pHi using calibration curves.
The cells were incubated in NH4C1 buffer (pH 7.4) (NH4C1 buffer: 115 mM NaCI, mM NH4C1, 5 mM KCI, 1 mM CaCl2, 1 mM MgS04, 20 mM Hepes, 5 mM glucose, 15 1 mg/ml BSA; a pH of 7.4 is adjusted with 1 M NaOH) even during the BCECF
loading.
The intracellular acidification was induced by adding 975 pl of an NH4C1-free buffer (see below) to 25 ~tI aliquots of the cells incubated in NH4C) buffer. The subsequent rate of pH recovery was recorded for two minutes with NHE1, five minutes with and three minutes with NHE3. To calculate the inhibitory potency of the tested substances, the cells were initially investigated irt buffers with which a complete or absolutely no pH recovery took place. For complete pH recovery (100%), the cells were incubated in Nay'-containing buffer (133.8 mM NaCi, 4,7 mM KCI, 1.25 mM
CaCl2, 1.25 mM MgCl2, 0.97 mM Na2H1'04, 0,23 mM NaH2P04, 5 mM Hepes, 5 mM
glucose, a pH of 7.0 is adjusted with 1 M NaOH). To determine the 0% value, the cells were incubated in an Nay'-free buffer (133.8 mM choline chloride, 4.7 mM KCI, 1.25 mM GaCl2, 1 _25 mM MgCl2, 0.97 mM K2HPO4, 0.23 mM KH2P04, 5 mM Hepes, 5 mM glucose, a pH ofi 7.0 is adjusted with 1 M NaOH). The substances to be tested were made up in the Na+-containing buffer. The recovery of the intracellular pH at each test concentration of a subshance was expressed as a percentage of the maximum recovery, The ICSp value for the particular substance for the individual NHE
subtypes was calculated from the pH recovery percentages using the Sigma-Plot program.
Results:
Table 14:
IC50 ~M~, IC50 ~M~~
Example Example (rNHE3) (rNHE3) 1 a 0.075 119 0.0682 2a 0.082 144 0.695 2b 0.026 146 0.024 6 0.670 153 0.602 7 0.250 183 0.597 1.000 199 0.252 17 0.049 207 0.186 21 0.814 23 1.507 24 0.340 29 0.318 36 0.274 -48 0.349 51 0.215 60 0.202 64 0.507 81 0.730 g7 0.418 g7 0.308 113 0.279

Claims

claims 1. A 4-phenyltetrahydroisoquinoline of the formula I
in which the meanings are:
R1, R2, R3 and R4 independently of one another H, F, CI, Br, I, CN, NO2, OH, NH2, CaH2a+1 CqqH2qq-1, OCbH2b+1, COOR10, OCOR10, COR10 or Ox-(CH2)y-phenyl;
a and b in the groups CaH2a+1 and OCbH2b+1 independently of one another 1, 2, 3, 4, 5, 6, 7 or 8, it being possible for one or more H atoms to be replaced by F atoms;
qq 3, 4, 5, 6, 7 or 8, it being possible for one or more H atoms to be replaced by F atoms;
R10 H or CcH2c+1;
c 1, 2, 3, 4, 5, 6, 7 or 8, it being possible for one or more H
atoms to be replaced by F atoms, x zero or 1;
y zero, 1, 2, 3 or 4;
where the phenyl ring in the group Ox-(CH2)y-phenyl is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, CI, Br, CN, NO2, OH, NH2 or C d H2d+1;
d 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms, or R1, R2, R3 and R4 independently of one another heteroaryl, it being possible for zero, 1, 2, 3 or 4 N atoms, zero or 1 oxygen atom or zero or 1 S atom to be present as ring atoms;
or R1, R2, R3 and R4 independently of one another CONR11R12 or NR17 R12;
R11 and R12 independently of one another H, CeH2e+1, CrrH2rr-1;
a 1, 2, 3, 4, 5, 6, 7 or 8, rr 3, 4, 5, 6, 7, or 8, it being possible for one or more H atoms in the groups CeH2e+1 and CrrH2rr-1 to be replaced by F atoms and for one or more CH2 groups to be replaced by O or NR13;
R13 H or CfH2f+1;
f 1, 2, 3 or 4, it being possible for one or more H
atoms to be replaced by F atoms;
or R13 and a CH2 group of R11 or R12 together with the N atom to which they are bonded a 5- or 6-membered ring;
or R11 and R12 together with the N atom to which they are bonded a 5-, 6- or 7-membered ring;
or R11 and R12 independently of one another COR14, CSR14 or S02R14;
R14 CgH2g+1;
g 1, 2, 3, 4, 5, 6, 7 or 8, it being possible for one or more H atoms to be replaced by F atoms, and it being possible for one or more CH2 groups to be replaced by O or NR13, or R 1, R2, R3 and R4 independently of one another -Oh-SOj-R15, with h zero or 1;
j zero, 1 or 2;
R15 CkH2k+1, OH, OCIH21+1 or NR17R18;
k 1, 2, 3, 4, 5, 6, 7 or 8, it being possible for one or more H
atoms to be replaced by F atoms;
I 1, 2, 3, 4, 5, 6, 7 or 8, it being possible for one or more H
atoms to be replaced by F atoms;
R17 and R18 independently of one another H or CmH2m+1;
m 1, 2, 3, 4, 5, 6, 7 or 8, it being possible for one or more H atoms in the group CmH2m+1 to be replaced by F
atoms and for one or more CH2 groups to be replaced by O, CO, CS or NR19;
R19 H or CnH2n+1 n 1, 2, 3 or 4;
it being possible for one or more H atoms in CnH2n+1 to be replaced by F atoms;
or R17 and R18 together with the N atom to which they are bonded a 5-, 6- or 7-membered ring;
or R19 and a CH2 group with R17 or R18 together with the N
atom to which they are bonded a 5- or 6-membered ring but where R2 must always not be equal to H, R5 H, CpH2p+1, CssH2ss-1, COR20 or SO2R20;
p 1,2,3,4,5,6,7or8, ss 3, 4, 5, 6, 7 or 8, R20 CaH2q+1;
q 1, 2, 3, 4, 5, 6, 7 or 8, it being possible far one or more H atoms in the groups CpH2p+l, CssH2ss-1 and CqH2q+1 to be replaced by F atoms and for one or more CH2 groups to be replaced by O or NR21;
R21 H or CrH2r+1;
r 1, 2, 3 or 4;
it being possible for one or more H atoms in CrH2r+1 to be replaced by F atoms;
R6 H, F, GI, Br, I, GSH2s+1, CddH2dd-1, OH, OCtH2t+1 or OCOR22;
s and t independently of one another 1, 2, 3, 4, 5, B, 7 or 8;
dd 3, 4, 5, 6, 7 or 8, it being possible for one or more H atoms in CsH2s+1. CddH2dd-1 and OGtH2t+1 to be replaced by F atoms;
R22 CuH2u+1;
a 1,2,3or4;
it being possible for one or more H atoms in CuH2u+1 to be replaced by F atoms;
R7, R8 and R9 independently of one another -Ov-SOwR23;
v zero or 1;
w zero, 1 or 2:
R23 CnnH2nn+1. CmmH2mm-1,OH, OCppH2pp+1 or NR25R26;
nn and pp independently of one another 1 , 2, 3, 4, 5, 6, 7 or 8, mm 3, 4, 5, 6, 7 or 8, it being possible for one or more H atoms in C nn H2nn+1, C mm H2mm-1 and OC pp H2pp+1 to be replaced by F atoms;
R25 and R26 independently of one another H,CN or C z H2z+1,C zz H2zz-1;
z 1,2,3,4,5,6,7 or 8;
zz 3,4,5,6,7 or 8,it being possible for one or more H
atoms to be replaced by F atoms and, in C z H2z+1,it being possible for one or more H atoms to be replaced by F atoms and it being possible for one or more CH2 groups to be replaced by O,CO,CS
or NR27;
R27 H or C aa H2aa+1 aa 1,2,3 or 4;
it being possible for one or more H atoms in C aa H2aa+1 to be replaced by F atoms;
or R25 and R26 together with the N atom to which they are bonded a 5-,6- or 7-membered ring, or R27 and a CH2 group of R25 or R26 together with the N atom to which they are bonded a 5- or 6-membered ring;
or R7,R8 and R9 independently of one another NR32COR30,NR32CSR30 or NR32SO bb R30;
R30 H,C cc H2cc+1,C yy H2yy-1,pyrrolidinyl or piperidinyl,in which rings a CH2 group may be replaced by O or NR33;
R32 and R33 independently of one another H or C h H2h+1;
bb 2 or 3;
cc 1,2,3,4,5,6,7 or 8;
yy 3,4,5,6,7 or 8;

h 1, 2, 3, 4, 5, 6, 7 or 8, it being possible for one or more H atoms in C h H2h+1 to be replaced by F
atoms, and it being possible for one or more H atoms in the groups C cc H2cc+1 and C yy H2yy-1 to be replaced by F atoms and for one or more CH2 groups to be replaced by NR31 and for a CH2 group to be replaced by O
R31 H, C kk H2kk+1, COR65 or SO2R65 kk 1, 2, 3, or 4;
it being possible for one or more H atoms to be replaced by F
atoms, R65 H, C xx H2xx+1;
xx 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
or R31 forms together with a CH2 group of R30 a 5-, 6- or 7-membered ring;
or R30 a 5- or 6-membered heteroaryl with 1, 2, 3 or 4 N atoms, zero or 1 S
atoms and zero or 1 O atoms, which is unsubstituted or substituted by up to three substituents selected from the group consisting of F, Cl, Br, I, C oo H2oo+1, NR70R71;
R70 and R71 independently of one another H, C uu H2uu+1 and COR72;
R72 H, C vv H2vv+1 oo, uu and vv independently of one another 1, 2, 3, 4, 5, 6, 7 or 8;
it being possible for one or more H atoms in the groups C oo H2oo+1, C uu H2uu+1 or C vv H2vv+1 to be replaced by F atoms;
or R7, R8 and R9 independently of one another H, F, Cl, Br, I, NO2, CN, OH, NH2, C ee H2ee+1 C ww H2ww-1, OC ff H2ff+1, NR40R41, CONR40R41, COOR42, COR42 or OCOR42, ee and ff independently of one another 1, 2, 3, 4, 5, 6, 7 or 8;
ww 3, 4, 5, 6, 7 or 8;
it being possible for one or more H atoms in the groups C ee H2ee+1, C ww H2ww-1 and OC ff H2ff+1 to be replaced by F atoms;
R40 and R41 H, C tt H2tt+1 or C(NH)NH2;
tt 1, 2, 3, 4, 5, 6, 7or 8;
it being possible for one or more H atoms in the group C tt H2tt+1 to be replaced by F atoms and for one or more CH2 groups to be replaced by O or NR44;
R44 H or C gg H2gg+1;
gg 1, 2, 3, 4, 5, 6, 7 or 8;
it being possible for one or more H atoms in the group C gg H2gg+1 to be replaced by F atoms, and it being possible for R44 together with a (CH2) group of R40 or R41 and the N
atom to which they are jointly bonded to form a 5- or 6-membered ring;
or R40 and R41 with the N atom to which they are bonded a 5- or 6-membered ring;
R42 H or C hh H2hh+1 hh 1, 2, 3, 4, 5, 6, 7 or 8;
it being possible for one or more H atoms in the group C hh H2hh+1 to be replaced by F atoms;
but where two substituents from the group of R7, R8 and R9 may not simultaneously be OH or OCH3 and where at least one of the radicals R7, R8 or R9 must be selected from the group consisting of CONR40R41, -O v SO w R23, NR32COR30, NR32CSR30 and NR32SO bb R30; and the pharmaceutically acceptable salts and trifluoroacetates thereof.

2. A compound of the formula I as claimed in claim 1, in which the meanings are:
R1, R2, R3 and R4 independently of one another, H, F, Cl, Br, I, CN, NO2, OH, NH2, C a H2a+1, cycloalkyl with 3, 4, 5 or 6 C atoms, OC b H2b+1, COOR10;
a and b independently of one another 1, 2, 3 or 4, it being possible far one or more H atoms to be replaced by F atoms;
R10 H or C c H2c+1;
c 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
or R1, R2, R3 and R4 independently of one another 5- or 6-membered heteroaryl selected from the group consisting of pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thiazolyl and oxazolyl;
or R1, R2, R3 and R4 independently of one another CONR11R12 or NR11R12;
R11 and R12 independently of one another H, C e H2e+1, C rr H2rr-1;
e 1, 2, 3 or 4, rr 3, 4, 5 or 6, it being possible for one or more H atoms in the groups C e H2e+1 and C rr H2rr-1 to be replaced by F atoms or R11 and R12 independently of one another hydroxyethyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, pyrrolidinoethyl, N-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl;
or R11 and R12 together with the N atom to which they are bonded a pyrrolidine, piperidine, N-methylpiperazine, piperazine or morpholine ring;
or R11 and R12 independently of one another COR14, CSR14, CONHR14, CSNHR14 or SO2R14;
R14 C g H2g+1;
g 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
or R1, R2, R3 and R4 independently of one another OSO3H, SO3H, SO2R15, with R15 C k H2k+1, OC l H2l+1 or NR17R18;
k 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
l 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
R17 and R18 independently of one another H, C m H2m+1, in which the first CH2 group bonded to the nitrogen is replaced by CO and the second CH2 group is replaced by NR19;
m 1, 2, 3, 4 or 5, it being possible for one or more H
atoms in the group C m H2m+1 to be replaced by F
atoms;
R19 H or C n H2n+1 n 1, 2, 3 or 4;
it being possible for one or more H atoms in C n H2n+1 to be replaced by F atoms;
or R17 and R18 together with the N atom to which they are bonded a 5- or 6-membered ring;
but where R2 must always not be equal to H, R5 H, C p H2p+1;
p 1, 2, 3 or 4;
it being possible for one or more H atoms in C p H2p+1 to be replaced by F atoms;
R6 H, C s H2s+1, OC t H2t+1 or OCOR22;
s and t independently of one another 1, 2, 3 or 4;
it being possible for one or more H atoms in C s H2s+1 and OC t H2t+1 to be replaced by F atoms;
R22 C u H2u+1;
u 1, 2, 3 or 4;
it being possible for one or more H atoms in C u H2u+1 to be replaced by F atoms;
R7, R8 and R9 independently of one another OSO3H, SO3H or SO2R23;
R23 C nn H2nn+1, C mm H2mm-1, OC pp H2pp+1 or NR25R26;
nn and pp independently of one another 1, 2, 3, 4 or 5, mm 3, 4, 5 or 6, it being possible for one or more H atoms in C nn H2nn+1 C mm H2mm-1 and OC pp H2pp+1 to be replaced by F atoms;

R25 and R26 independently of one another H, CN or C z H2z+1, in which the first CH2 group bonded to the nitrogen is replaced by CO or CS and the second CH2 is replaced by NR27;
z 1, 2, 3, 4, 5 or 6;
it being possible for one or more H atoms in C z H2z+1 to be replaced by F atoms;
R27 H or C aa H2aa+1 aa 1, 2, 3 or 4;
it being possible for one or more H atoms in C aa H2aa+1 to be replaced by F atoms;
or R25 and R26 together with the N atom to which they are bonded a 5- or 6-membered ring;
or R27 and a CH2 group of R25 or R26 together with the N atom to which they are bonded a 5- or 6-membered ring;
or R7, R8 and R9 independently of one another NR32COR30, NR32CSR30 or NR32SO2R30;
R30 H, OH, C cc H2cc+1, C yy H2yy-1, pyrrolidinyl or piperidinyl, in which rings a CH2 group may be replaced by O or NR33;
R32 and R33 independently of one another H or C h H2h+1 cc 1, 2, 3, 4, 5, 6, 7 or 8;
yy 3, 4, 5, 6;
h 1, 2, 3 or 4;
it being possible for one or more H atoms in C h H2h+1 to be replaced by F
atoms, and it being possible for one or more H atoms in the groups C cc H2cc+1 and C yy H2yy-1 to be replaced by F atoms and for one or more CH2 groups to be replaced by NR31 and for a CH2 group to be replaced by O;
R31 H, C kk H2kk+1, COR65 or SO2R65;
kk 1, 2, 3, or 4;
it being possible for one or more H atoms to be replaced by F atoms, R65 H, C xx H2xx+1;
xx 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
or R31 together with a CH2 group of R30 and the N atom to which they are jointly bonded form a 5- or 6-membered ring;
or R30 a 5- or 6-membered heteroaromatic system selected from the group consisting of pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thienyl, thiazolyl and oxazolyl, which are unsubstituted or substituted by up to three substituents selected from the group consisting of F, Cl, Br, I, C oo H2oo+1, NR70R71, R70 and R71 independently of one another H, C uu H2uu+1 or COR72;
R72 H, C vv H2vv+1 oo, uu and vv independently of one another 1, 2, 3 or 4;
it being possible for one or more H atoms in the groups C oo H2oo+1, C uu H2uu+1 or C vv H2vv+1 to be replaced by F
atoms;
or R7, R8 and R9 independently of one another H, F, Cl, Br, I, NO2, CN, OH, NH2, C ee H2ee+1 C ww H2ww-1, OC ff H2ff+1, NR40R41, CONR40R41, COOR42, COR42 or OCOR42;

ee and ff independently of one another 1, 2, 3 or 4;
ww 3, 4, 5 or 6, it being possible for one or more H atoms in the groups C ee H2ee+1 C ww H2ww-1 and OC ff H2ff+1 to be replaced by F atoms;
R40 and R41 H, C tt H2tt+1 or C(NH)NH2;
tt 1, 2, 3, 4, 5, 6, 7 or 8;
it being possible for one or more H atoms in the group C tt H2tt+1 to be replaced by F atoms;
or R40 and R41 to be selected independently of one another hydroxyethyl, , N,N-dimethylaminoethyl, N,N-diethylaminoethyl, pyrrolidinoethyl, N-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl;
or R40 and R41 together with the N atom to which they are bonded form a ring selected from the group consisting of pyrrolidine, piperidine, N-methyl-piperazine, piperazine and morpholine;
R42 H or C hh H2hh+1 hh 1, 2, 3 or 4;
it being possible for one or more H atoms in the group C hh H2hh+1 to be replaced by F atoms;
but where two substituents from the group of R7, R8 and R9 may not simultaneously be OH or OCH3 and where at least one of the radicals R7, R8 or R9 must be selected from the group consisting of CONR40R41, -O v SO w R23, NR32COR30, NR32CSR30 and NR32SO bb R30;
and the pharmaceutically acceptable salts and trifluoroacetates thereof.

3. A compound of the formula I as claimed in claims 1 or 2, in which the meanings are:
R1, R2, R3 and R4 independently of one another H, F, Cl, Br, OH, NH2, C a H2a+1, cycloalkyl with 3, 4, 5 or 6 C atoms, OC b H2b+1;
a and b in the groups C a H2a+1 and OC b H2b+1 independently of one another 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
or R1, R2, R3 and R4 independently of one another NR11R12;
R11 and R12 independently of one another H, C e H2e+1, C rr H2rr-1;
e 1,2,3 or 4, rr 3, 4, 5 or 6, it being possible for one or more H atoms in the groups C e H2e+1 and C rr H2rr-1 to be replaced by F
atoms;
or R11 and R12 together with the N atom to which they are bonded form a ring selected from the group consisting of pyrrolidine, piperidine, N
methylpiperazine, piperazine and morpholine;
or R11 and R12 independently of one another COR14, CSR14, CONHR14, CSNHR14 or SO2R14;
R14 C g M2g+1:
g 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;

or R1, R2, R3 and R4 independently of one another OSO3H, SO3H, SO2R15;
R15 C k H2k+1 or NR17R18;
k 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
R17 and R18 independently of one another H or C m H2m+1;
m 1, 2, 3, 4 or 5, it being possible for one or more H
atoms in the group C m H2m+1 to be replaced by F
atoms;
or R17 and R18 together with the N atom to which they are bonded a 5- or 6-membered ring;
but where R2 must always not be equal to H;
R5 methyl or trifluoromethyl;
R6 H;
R7, R8 and R9 independently of one another OSO3H, SO3H or SO2R23;
R23 C nn H2nn+1 or NR25R26;
nn 1, 2, 3, 4 or 5, it being possible for one or more H atoms in C nn H2nn+1 to be replaced by F atoms;
R25 and R26 independently of one another H, CN or C z H2z+1, in which the first CH2 group bonded to the nitrogen is replaced by CO or CS and the second CH2 is replaced by NR27;
z 1, 2, 3, 4, 5 or 6;
it being possible for one or more H atoms in C z H2z+1 to be replaced by F atoms;

R27 H or C aa H2aa+1 as 1, 2, 3 or 4;
it being possible for one or more H atoms in C aa H2aa+1 to be replaced by F atoms;
or R25 and R26 together with the N atom to which they are bonded a 5- or 6-membered ring, or R27 and a CH2 group of R25 or R26 together with the N atom to which they are bonded a 5- or 6-membered ring;
or R7, R8 and R9 independently of one another NR32COR30, NR32CSR30 or NR32SO2R30;
R30 H, OH, C cc H2cc+1, C yy H2yy-1, pyrrolidinyl or piperidinyl, in which rings a CH2 group may be replaced by O or NR33;
R32 and R33 H, methyl or CF3;
cc 1,2,3,4,5,6,7or8;
yy 3, 4, 5, 6;
it being possible for one or more H atoms in the groups C cc H2cc+1 and C yy H2yy-1 to be replaced by F atoms and for one or more CH2 groups to be replaced by NR31 and for a CH2 group to be replaced by O;
R31 H, methyl, ethyl, CF3, CH2CF3, acetyl, propionyl, methanesulfonyl or ethanesulfonyl;
or R31 together with a CH2 group of R30 and the N atom to which they are jointly bonded form a 5- or 6-membered ring;
or R30 pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thiazolyl or oxazolyl, which are unsubstituted or substituted by a maximum of 3 substituents selected from the group consisting of F, Cl, methyl, ethyl, trifluoromethyl, NH2, NHacetyl;
or R7, R8 and R9 independently of one another H, F, Cl, OH, NH2, C ee H2ee+1, C ww H2ww-1, OC ff H2ff+1, NR40R41, CONR40R41, COOR42 or OCOR42, ee and ff independently of one another 1, 2, 3 or 4;
ww 3, 4, 5 or 6, it being possible for one or more H atoms in the groups C ee H2ee+1, C ww H2ww-1 and OC ff H2ff+1 to be replaced by F atoms;
R40 and R41 H, C tt H2tt+1 or C(NH)NH2;
tt 1, 2, 3 or 4;
it being possible for one or more H atoms in the group C tt H2tt+1 to be replaced by F atoms;
or R40 and R41 independently of one another hydroxyethyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, pyrrolidinoethyl, N-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl;
or R40 and R41 together with the N atom to which they are bonded a pyrrolidine, piperidine, N-methylpiperazine, piperazine or morpholine ring;
R42 H or C hh H2hh+1:
hh 1, 2, 3 or 4;
it being possible for one or mote H atoms in the group C hh H2hh+1 to be replaced by F atoms;
but where two substituents from the group of R7, R8 and R9 may not simultaneously be OH or OCH3, and where at least one of the radicals R7, R8 or R9 must be selected from the group consisting of CONR40R41, -O v SO w R23, NR32COR30, NR32CSR30 and NR32SO bb R30; and the pharmaceutically acceptable salts and trifluoroacetates thereof.

4. A compound of the formula I as claimed in claims 1-3 in which the meanings are:
R1, R2, R3 and R4 independently of one another H, F, Cl, Br, OH, NH2, C a H2a+1, cycloalkyl with 3, 4, 5 or 6 C atoms, OC b H2b+1 a and b in the groups C a H2a+1 and OC b H2b+1 independently of one another 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
or R1, R2, R3 and R4 independently of one another NR11R12;
R11 and R12 independently of one another H, C e H2e+1, C rr H2rr-1;
e 1, 2, 3 or 4, rr 3, 4, 5 or 6, it being possible for one or more H atoms in the groups C e H2e+1 and C rr H2rr-1 to be replaced by F
atoms;
or R11 and R12 together with the N atom to which they are bonded form a ring selected from the group consisting of pyrrolidine, piperidine, N-methylpiperazine, piperazine and morpholine;
or R11 and R12 independently of one another COR14, CSR14, CONHR14, CSNHR14 or SO2R14;
R14 C g H2g+1:
g 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
or R1, R2, R3 and R4 independently of one another OSO3H, SO3H, SO2R15;
R15 C k H2k+1 or NR17R18;
k 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
R17 and R18 independently of one another H or C m H2m+1 m 1, 2, 3, 4 or 5, it being possible for one or more H
atoms in the group C m H2m+1 to be replaced by F
atoms;
or R17 and R18 together with the N atom to which they are bonded a 5- or 6-membered ring;
but where R2 must always not be equal to H;
R5 methyl or trifluoromethyl;
R6 H;
R7, R8 and R9 independently of one another OSO3H, SO3H or SO2R23;
R23 C nn H2nn+1 or NR25R26;
nn 1,2,3,4 or 5, it being possible for one or more H atoms in C nn H2nn+1 to be replaced by F atoms;
R25 and R26 independently of one another H, CN or C z H2z+1, in which the first CH2 group bonded to the nitrogen is replaced by CO or CS and the second CH2 is replaced by NR27;
z 1, 2, 3, 4, 5 or 6;
it being possible for one or more H atoms in C z H2z+1 to be replaced by F atoms;
R27 H or C aa H2aa+1 aa 1, 2, 3 or 4;
it being possible for one or more H atoms in C aa H2aa+1 to be replaced by F atoms;
or R25 and R26 together with the N atom to which they are bonded a 5- or 6-membered ring, or R27 and a CH2 group of R25 or R26 together with the N atom to which they are bonded a 5- or 6-membered ring;
or R7, R8 and R9 independently of one another NR32COR30, NR32CSR30 or NR32SO2R30;
R30 H, OH, C cc H2cc+1, C yy H2yy-1. pyrrolidinyl or piperidinyl, in which rings a CH2 group may be replaced by O or NR33;
R32 and R33 H, methyl or CF3;
cc 1, 2, 3, 4, 5, 6, 7 or 8;
yy 3, 4, 5 or 6;
it being possible for one or more H atoms in the groups C cc H2cc+1 and C yy H2yy-1 to be replaced by F atoms and for one or more CH2 groups to be replaced by NR31 and for a CH2 group to be replaced by O;
R31 H, methyl, ethyl, CF3, CH2CF3, acetyl, propionyl, methanesulfonyl or ethanesulfonyl;

or R31 together with a CH2 group of R30 and the N atom to which they are jointly bonded form a 5- or 6-membered ring;
or R30 pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thiazolyl or oxazolyl, which are unsubstituted or substituted by a maximum of 3 substituents selected from the group consisting of F, Cl, methyl, ethyl, trifluoromethyl, NH2, NHacetyl;
or R7, R8 and R9 independently of one another H, F, Cl, OH, NH2, C ee H2ee+1. C ww H2ww-1 OC ff H2ff+1, NR40R41, CONR40R41, COOR42 or OCOR42, ee and ff independently of one another 1, 2, 3 or 4;
ww 3, 4, 5 or 6, it being possible for one or more H atoms in the groups C ee H2ee+1 C ww H2 ww-1 and OC ff H2ff+1 to be replaced by F atoms;
R40 and R41 H, C tt H2tt+1, or C(NH)NH2;
tt 1, 2, 3 or 4;
it being possible for one or more H atoms in the group C tt H2tt+1 to be replaced by F atoms;
or R40 and R41 independently of one another hydroxyethyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, pyrrolidinoethyl, N-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl;
or R40 and R41 together with the N atom to which they are bonded a pyrrolidine, piperidine, N-methylpiperazine, piperazine or morpholine ring;

R42 H or C hh H2hh+1 hh 1, 2, 3 or 4;
it being possible for one or more H atoms in the group C hh H2hh+1 to be replaced by F atoms;
but where two substituents from the group of R7, R8 and R9 may not simultaneously be OH or OCH3, and where at least one of the radicals R7, R8 or R9 must be selected from the group consisting of -O v SO w R23, NR32COR30, NR32CSR30 and NR32SO bb R30;
and the pharmaceutically acceptable salts and trifluoroacetates thereof.

5. A compound of the formula I characterized in that it is selected from the group consisting of:
1) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
2) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide;
3) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide;
4) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N,N-dimethyl-benzenesulfonamide;
5) 4-(4-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline;
6) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid;
7) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-ethyl-benzamide;
8) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-propyl-benzamide;
9) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N-(2-dimethylamino-ethyl)-benzamide;
10) 6,8-dichloro-2-methyl-4-(4-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline;
11) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-diethyl-amine 12) 6,8-dichloro-2-methyl-4-(4-piperidin-1-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline;
13) 6,8-dichloro-2-methyl-4-(4-pyrrolidin-1-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline;
14) 6,8-dichloro-2-methyl-4-[4-(4-methyl-piperazin-1-yl)-phenyl]-1,2,3,4-tetrahydro-isoquinoline;
15) 6,8-dichloro-2-cyclopropyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline;
16) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine;

17) 1-[4-{6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-propylurea;
18) 1-[4-(6,8-dichloro-2-methyl-1,2.3,4-tetrahydro-isoquinolin-4-yl)-phenyl)-3-methyl-thiourea;
19) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
24) N-[4-(6-methanesulfonyl-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
21) N-[4-(2,6,8-trimethyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
22) N-[4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
23) N-[4-(8-chloro-2-methyl-6-pyrrolidin-1-yl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl)-acetamide;
24) N-[4-(8-chloro-2-methyl-6-morpholin-4-yl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
25) N-{4-[8-chloro-2-methyl-6-(4-methyl-piperazin-1-yl)-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl)-acetamide;
26) N-{4-[8-chloro-6-(cyclopropylmethyl-amino)-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl]-phenyl}-acetamide;
27) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoic acid;
28) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-N-methyl-benzamide;
29) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N-ethyl-2-hydroxy-benzamide;
30) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N-(2-dimethylamino-ethyl)-2-hydroxy-benzamide;
31) N-[5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoyl]-guanidine;
32) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
33) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine;

34) 2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine;
35) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;
36) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;
37) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl)pentanamide;
38) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-isobutyramide;
39) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2.2-dimethyl-propionamide;
40) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclopropanecarboxamide;
41) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclobutanecarboxamide;
42) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro,isoquinolin-4-yl)-phenyl]-cyclopentanecarboxamide;
43) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl)-2,2,2-trifluoro-acetamide;
44) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl)-1-acetylpiperidine-4-carboxamide;
45) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-nicotinamide;
46) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methane-sulfonamide;
47) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)- phenyl]-ethanesulfonamide;
48) N',N'-dimethylamino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide;
49) N-[3-(6.8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;

50) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;
51) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pentanamide;
52) N-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-isobutyramide;
53) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2-dimethyl-propionamide;
54) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclopropanecarboxamide;
55) N-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclobutanecarboxamide;
56) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclopentanecarboxamide;
57) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2,2-trifluoro-acetamide;
58) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-acetylpiperidine-4-carboxamide;
59) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-nicotinamide;
60) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methane-sulfonamide;
61) N-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)- phenyl]-ethanesulfonamide;
62) N',N'-dimethylamino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide;
63) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;
64) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;
65) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pentanamide;

66) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-isobutyramide;
67) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2-dimethyl-propionamide;
68) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]cyclopropanecarbox-amide;
69) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)- phenyl]-cyclobutanecarboxamide;
70) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclopentanecarboxamide;
71) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2,2-trifluoro-acetamide;
72) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-acetylpiperidine-4-carboxamide;
73) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methane-sulfonamide;
74) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)- phenyl]-ethanesulfonamide;
75) N',N'-dimethylamino-N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide;
76) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
77) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-thiourea;
78) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
79) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-thiourea;
80) N-{5-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylsulfamoyl]-4-methyl-thiazol-2-yl}-acetamide;
81) N-{5-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylsulfamoyl]-4-methyl-thiazol-2-yl}-acetamide;

82) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,2-dimethyl-1H-imidazole-4-sulfonamide;
83) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,2-dimethyl-1H-imidazole-4-sulfonamide;
84) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonamide;
85) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonamide;
86) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-5-bromo-thiophene-2-sulfonamide;
87) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-5-bromo-thiophene-2-sulfonamide;
88) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-C,C,C-trifluoro-methanesulfonamide;
89) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl)-C,C,C-trifluoro-methanesulfonamide;
90) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2,2-trifluoroethanesulfonamide;
91) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2,2-trifluoro-ethanesulfonamide;
92) N-ethyl-N'-4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonylurea;
93) 2-chloro-5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide;
94) 2-methyl-4-phenyl-6,8-bis-trifluoromethyl-1,2,3,4-tetrahydro-isoquinoline;
95) 2-amino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
96) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2-methylamino-acetamide;
97) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2-dimethylamino-acetamide;

98) 2-amino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;
99) 2-amino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;
100) 2,6-diamino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-hexanamide;
101) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrolidine-2-carboxamide;
102) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-isonicotinamide;
103) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrole-3-carboxamide;
104) N-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrole-2-carboxamide;
105) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methyl-piperidine-4-carboxamide;
106) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,4-dimethyl-1H-pyrrole-2-carboxamide;
107) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-nitro-1H-pyrrole-2-carboxamide;
108) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,5-dimethyl-1H-pyrrole-3-carboxamide;
109) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-imidazole-4-carboxamide;
110) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonyl-piperidine-4-carboxamide;
111) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3,5-dimethyl-1H-pyrazole-4-carboxamide;
112) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrazole-4-carboxamide;
113) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-trifluoromethyl-1H-pyrazole-4-carboxamide;

114) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2-methylamino-acetamide;
115) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-dimethylamino-acetamide;
116) 2-amino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;
117) 2-amino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;
118) 2,6-diamino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-hexanamide;
119) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrolidine-2-carboxamide;
120) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-isonicotinamide;
121) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrole-3-carboxamide;
122) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrole-2-carboxamide;
123) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methyl-piperidine-4-carboxamide;
124) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,4-dimethyl-1H-pyrrole-2-carboxamide;
125) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-nitro-1H-pyrrole-2-carboxamide;
126) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,5-dimethyl-1H-pyrrole-3-carboxamide;
127) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-imidazole-4-carboxamide;
128) N-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methanesulfonyl-piperidine-4-carboxamide;
129) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3,5-dimethyl-1H-pyrazole-4-carboxamide;

130) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrazole-4-carboxamide;
131) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-trifluoromethyl-1H-pyrazole-4-carboxamide;
132) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-thiourea;
133) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-thiourea;
134) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-thiourea;
135) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea;
136) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-methyl-piperazine-1-carboxamide;
137) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-piperidine-1-carboxamide;
138) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-morpholine-4-carboxamide;
139) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrolidine-1-carboxamide;
140) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-diethyl-urea;
141) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-urea;
142) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;
143) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(tetrahydro-furan-3-yl)-urea;
144) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(tetrahydro-pyran-4-yl)-urea;
145) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methyl-1-(1-methyl-piperidin-4-yl)-urea;

146) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-(3-dimethylamino-propyl)-1-methyl-urea;
147) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-(2-dimethylamino-ethyl)-1-methyl-urea;
148) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-(3-dimethylamino-propyl)-urea;
149) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-methoxy-ethyl)-urea;
150) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-pyridin-3-yl-urea;
151) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl)-3-pyridin-4-yl-urea;
152) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-methyl-piperazine-1-carboxamide;
153) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-urea;
154) 3-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea;
155) 3-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-diethyl-urea;
156) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-piperidine-1-carboxamide;
157) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-morpholine-4-carboxamide;
158) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrolidine-1-carboxamide;
159) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;
160) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-methyl-piperazine-1-carboxamide;
161 ) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrolidine-1-carboxamide;

162) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-urea;
163) 3-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea;
164) 3-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-diethyl-a rea;
165) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;
166) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-piperidine-1-carboxamide;
167) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-morpholine-4-carboxamide;
168) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-formamide;
169) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amine;
170) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,3-dimethyl-urea;
171) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-4-methyl-piperazine-1-carboxamide;
172) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,3,3-trimethyl-urea;
173) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-piperidine-1-carboxamide;
174) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-morpholine-4-carboxamide;
175) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-pyrrolidine-1-carboxamide;
176) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-1-methyl-urea;
177) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3,3-diethyl-1-methyl-urea;

178) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-formamide;
179) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amine;
180) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-pyrrolidine-1-carboxamide;
181) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-piperidine-1-carboxamide;
182) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,3,3-trimethyl-urea;
183) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,3-dimethyl-urea;
184) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-morpholine-4-carboxamide;
185) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-4-methyl-piperazine-1-carboxamide;
186) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-1-methyl-urea;
187) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3,3-diethyl-1-methyl-urea;
188) 2-dimethylamino-ethyl [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
189) 2-dimethylamino-ethyl [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
190) 2-dimethylamino-ethyl [2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
191) methyl [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
192) ethyl [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
193) isopropyl [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;

194) 2,2-dimethyl-propyl [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
195) methyl [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
196) isopropyl [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
197) 2,2-dimethyl-propyl [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
198) ethyl [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
199) (R)-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonamide;
200) (S)-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonamide;
201) (R)-1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
202) (S)-1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
203) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
204) 4-(3-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoline;
205) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-hydroxy-ethyl)-urea;
206) ethyl 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoate;
207) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid.
and the pharmaceutically acceptable salts thereof.
and from the pharmaceutically acceptable salts thereof.
6. A compound of the formula I as claimed in claim 1, selected from the group consisting of:
1) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;

2) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide;
3) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide;
4) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-thiourea;
5) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
6) N-[4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
7) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
8) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;
9) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-acetyl-piperidine-4-carboxamide;
10) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methane-sulfonamide;
11) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-.
ethanesulfonamide;
12) N',N'-dimethylamino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide;
13) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;
14) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;
15) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-isobutyramide;
16) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclopropanecarboxamide;
17) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclobutanecarboxamide;
18) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2,2-trifluoro-acetamide;

19) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-acetyl-piperidine-4-carboxamide;
20) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-nicotinamide;
21 ) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methane-sulfonamide;
22) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-ethanesulfonamide;
23) N',N'-dimethylamino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide;
24) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclopropanecarboxamide;
25) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-acetyl-piperidine-4-carboxamide;
26) 1-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
27) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-thiourea;
28) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
29) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-thiourea;
30) N-{5-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylsulfamoyl]-4-methyl-thiazol-2-yl}-acetamide;
31 ) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,2-dimethyl-1 H-imidazole-4-sulfonamide;
32) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-C,C,C-trifluoro-methanesulfonamide;
33) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-C,C,C-trifluoro-methanesulfonamide;
34) N-ethyl-N'-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonylurea;

35) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2-dimethylamino-acetamide;
36) 2,6-diamino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-hexanamide;
37) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrole-3-carboxamide;
38) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methyl-piperidine-4-carboxamide;
39) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methanesulfonyl-piperidine-4-carboxamide;
40) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrazole-carboxamide;
41) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2-methylamino-acetamide;
42) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2-dimethylamino-acetamide;
43) 2-amino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;
44) 2-amino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;
45) 2,6-diamino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-hexanamide;
46) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methyl-piperidine-4-carboxamide;
47) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-imidazole-4-carboxamide;
48) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methanesulfonyl-piperidine-4-carboxamide;
49) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3,5-dimethyl-1H-pyrazole-4-carboxamide;
50) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrazole-carboxamide;

51) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea;
52) N-[3-(6,8-dichloro-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-methyl-piperazine-1-carboxamide;
53) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-piperidine-1-carboxamide;
54) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-morpholine-4-carboxamide;
55) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrolidine-1-carboxamide;
56) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-diethyl-urea;
57) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-urea;
58) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;
59) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(tetrahydro-furan-3-yl)-urea;
60) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(tetrahydro-pyran-4-yl)-urea;
61) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methyl-1-(1-methyl-piperidin-4-yl)-urea;
62) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-(3-dimethylamino-propyl)-1-methyl-urea;
63) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-(2-dimethylamino-ethyl)-1-methyl-urea;
64) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(3-diethylamino-propyl)-urea;
65) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-methoxy-ethyl)-urea;
66) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-pyridin-3-yl)-urea;

67) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-pyridin-4-yl-urea;
68) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-methyl-piperazine-1-carboxamide;
69) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-urea;
70) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;
71) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-methyl-piperazine-1-carboxamide;
72) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-urea;
73) 3-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea;
74) 3-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-diethyl-urea;
75) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;
76) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-morpholine-4-carboxamide;
77) N-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-formamide;
78) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-formamide;
79) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,3,3-trimethyl-urea;
80) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,3-dimethyl-urea;
81) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-morpholine-4-carboxamide;
82) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-4-methyl-piperazine-1-carboxamide;

83) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-1-methyl-urea;
84) 2-dimethylamine-ethyl [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
85) 2-dimethylamino-ethyl [4-(5,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
86) 2-dimethylamino-ethyl [2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
87) methyl [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
88) (R or S)-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonamide;
89) (R or S)-1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
90) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-hydroxy-ethyl)-urea;
and from the pharmaceutically acceptable salts thereof.
7. The use of a compound of the formula I and of the pharmaceutically acceptable salts thereof for producing a medicament for the treatment of disorders which can be influenced by inhibition of the sodium-proton exchanger of subtype III (NHE3), in which the meanings are:
R1, R2, R3 and R4 independently of one another H, F, Cl, Br, I, CN, NO2, OH, NH2, C a H2a+1, C qq H2qq-1, OC b H2b+1, COOR10, OCOR10, COR10 or O x-(CH2)y-phenyl;
a and b in the groups C a H2a+1 and OC b H2b+1 independently of one another 1, 2, 3, 4, 5, 6, 7 or 8, it being possible for one or more H atoms to be replaced by F atoms;
qq 3, 4, 5, 6, 7 or 8, it being possible for one or more H atoms to be replaced by F atoms;
R10 H or C c H2c+1;

c 1, 2, 3, 4, 5, 6, 7 or 8, it being possible for one or more H
atoms to be replaced by F atoms, x zero or 1;
y zero, 1, 2, 3 or 4;
where the phenyl ring in the group O x-(CH2)y-phenyl is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, Br, CN, NO2, OH, NH2 or C d H2d+1;
d 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms, or R1, R2, R3 and R4 independently of one another heteroaryl, it being possible for zero, 1, 2, 3 or 4 N atoms, zero or 1 oxygen atom or zero or 1 S atom to be present as ring atoms;
or R1, R2, R3 and R4 independently of one another CONR11R12 or NR11R12;
R11 and R12 independently of one another H, C e H2e+1, C rr H2rr-1;
e 1, 2, 3, 4, 5, 6, 7 or 8, rr 3, 4, 5, 6, 7, or 8, it being possible for one or more H atoms in the groups C e H2e+1 and C rr H2rr-1 to be replaced by F atoms and for one or more CH2 groups to be replaced by O or NR13;
R13 H or C f H2f+1;
f 1, 2, 3 or 4, it being possible for one or more H
atoms to be replaced by F atoms;
or R13 and a CH2 group of R11 or R12 together with the N atom to which they are bonded a 5- or 6-membered ring;

or R11 and R12 together with the N atom to which they are bonded a 5-, 6- or 7-membered ring;
or R11 and R12 independently of one another COR14, CSR14 or SO2R14;
R14 C g H2g+1;
g 1, 2, 3, 4, 5, 6, 7 or 8, it being possible for one or more H atoms to be replaced by F atoms, and it being possible for one or more CH2 groups to be replaced by O or NR13, or R1, R2, R3 and R4 independently of one another -O h-SO j-R15, with h zero or 1;
j zero, 1 or 2;
R15 C k H2k+1, OH, OC l H2l+1 or NR17R18;
k 1, 2, 3, 4, 5, 6, 7 or 8, it being possible for one or more H
atoms to be replaced by F atoms;
l 1, 2, 3, 4, 5, 6, 7 or 8, it being possible for one or more H
atoms to be replaced by F atoms;
R17 and R18 independently of one another H or C m H2m+1;
m 1, 2, 3, 4, 5, 6, 7 or 8, it being possible for one or more H atoms in the group C m H2m+1 to be replaced by F
atoms and for one or more CH2 groups to be replaced by O, CO, CS or NR19;
R19 H or C n H2n+1;
n 1, 2, 3 or 4;

it being possible for one or more H atoms in C n H2n+1 to be replaced by F atoms;
or R17 and R18 together with the N atom to which they are bonded a 5-, 6- or 7-membered ring;
or R19 and a CH2 group of R17 or R18 together with the N atom to which they are bonded a 5- or 6-membered ring;
R5 H, C p H2p+1, C ss H2ss-1, COR20 or SO2R20;
p 1, 2, 3, 4, 5, 6, 7 or 8, ss 3, 4, 5, 6, 7 or 8, is being possible for one or more H atoms in C p H2p+1 and C ss H2ss-1 to be replaced by F atoms, R20 C q H2q+1;
q 1, 2, 3, 4, 5, 6, 7 or 8, it being possible for one or more H atoms in C q H2q+1 to be replaced by F atoms and for one or more CH2 groups to be replaced by O or NR21;
R21 H or C r H2r+1;
r 1, 2, 3 or 4;
it being possible for one or more H atoms in C r H2r+1 to be replaced by F atoms;
R6 H, F, Cl, Br, I, C s H2s+1, C dd H2dd-1, OH, OC t H2t+1 or OCOR22;
s and t independently of one another 1, 2, 3, 4, 5, 6, 7 or 8;
dd 3, 4, 5, 6, 7 or 8, it being possible for one or more H atoms in C s H2s+1, C dd H2dd-1 and OC t H2t+1 to be replaced by F atoms;
R22 C u H2u+1;
u 1, 2, 3 or 4;

it being possible for one or more H atoms in C u H2u+1 to be replaced by F atoms;
R7, R8 and R9 independently of one another -O v-SO w-R23;
v zero or 1;
w zero, 1 or 2;
R23 C nn H2nn+1, C mm H2mm-1, OH, OC pp H2pp+1 or NR25R26;
nn and pp independently of one another 1, 2, 3, 4, 5, 6, 7 or 8, mm 3, 4, 5, 6, 7 or 8, it being possible for one or more H atoms in C nn H2nn+1, C mm H2mm-1 and OC pp H2pp+1 to be replaced by F atoms;
R25 and R26 independently of one another H, CN or C z H2z+1, C zz H2zz-1;
z 1, 2, 3, 4, 5, 6, 7 or 8;
zz 3, 4, 5, 6, 7 or 8, it being possible for one or more H
atoms to be replaced by F atoms and, in C z H2z+1, it being possible for one or more H atoms to be replaced by F atoms and it being possible for one or more CH2 groups to be replaced by O, CO, CS
or NR27;
R27 H or C aa H2aa+1;
aa 1, 2, 3 or 4;
it being possible for one or more H atoms in C aa H2aa+1 to be replaced by F atoms;
or R25 and R26 together with the N atom to which they are bonded a 5-, 6- or 7-membered ring, or R27 and a CH2 group of R25 or R26 together with the N atom to which they are bonded a 5- or 6-membered ring;
or R7, R8 and R9 independently of one another NR32COR30, NR32CSR30 or NR32SO bb R30;
R30 H, C cc H2cc+1, C yy H2yy-1, pyrrolidinyl or piperidinyl, in which rings a CH2 group may be replaced by O or NR33;
R32 and R33 independently of one another H or C h H2h+1;
bb 2 or 3;
cc 1, 2, 3, 4, 5, 6, 7 or 8;
yy 3, 4, 5, 6, 7 or 8;
h 1, 2, 3, 4, 5, 6, 7 or 8, it being possible for one or more H atoms in C h H2h+1 to be replaced by F
atoms, and it being possible for one or more H atoms in the groups C cc H2cc+1 and C yy H2yy-1 to be replaced by F atoms and for one or more CH2 groups to be replaced by NR31 and for a (CH2) group to be replaced by O;
R31 H, C kk H2kk+1, COR65 or SO2R65;
kk 1, 2, 3, or 4;
it being possible for one or more H atoms to be replaced by F
atoms, R65 H, C xx H2xx+1;
xx 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
or R31 forms together with a CH2 group of R30 a 5-, 6- or 7-membered ring;
or R30 a 5- or 6-membered heteroaryl with 1, 2, 3 or 4 N atoms, zero or 1 S
atoms and zero or 1 O atoms, which is unsubstituted or substituted by up to three substituents selected from the group consisting of F, Cl, Br, I, C oo H2oo+1, NR70R71;
R70 and R71 independently of one another H, C uu H2uu+1 and COR72;
R72 H, C vv H2vv+1;
oo, uu and vv independently of one another 1, 2, 3, 4, 5, 6, 7 or 8;
it being possible for one or more H atoms in the groups C oo H2oo+1, C uu H2uu+1 or C vv H2vv+1 to be replaced by F atoms;
or R7, R8 and R9 independently of one another H, F, Cl, Br, I, NO2, CN, OH, NH2, C ee H2ee+1, C ww H2ww-1, OC ff H2ff+1, NR40R41, CONR40R41, COOR42, COR42 or OCOR42, ee and ff independently of one another 1, 2, 3, 4, 5, 6, 7 or 8;
ww 3, 4, 5, 6, 7 or 8;
it being possible for one or more H atoms in the groups C ee H2ee+1, C ww H2ww-1 and OC ff H2ff+1 to be replaced by F atoms;
R40 and R41 H, C tt H2tt+1 or C(NH)NH2;
tt 1, 2, 3, 4, 5, 6, 7 or 8;
it being possible for one or more H atoms in the group C tt H2tt+1 to be replaced by F atoms and for one or more CH2 groups to be replaced by O or NR44;
R44 H or C gg H2gg+1;
gg 1, 2, 3, 4, 5, 6, 7 or 8;

it being possible for one or more H atoms in the group C gg H2gg+1 to be replaced by F atoms, and it being possible for R44 together with a (CH2) group of R40 or R41 and the N
atom to which they are jointly bonded to form a 5- or 6-membered ring, or R40 and R41 with the N atom to which they are bonded a 5- or 6-membered ring;
R42 H or C hh H2hh+1;
hh 1, 2, 3, 4, 5, 6, 7 or 8;
it being possible for one or more H atoms in the group C hh H2hh+1 to be replaced by F atoms.
8. The use as claimed in claim 7, characterized in that compounds of the formula I are used, in which the meanings are:
R1, R2, R3 and R4 independently of one another, H, F, Cl, Br, I, CN, NO2, OH, NH2, C a H2a+1, cycloalkyl with 3, 4, 5 or 6 C atoms, OC b H2b+1, COOR10;
a and b independently of one another 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
R10 H or C c H2c+1;
c 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
or R1, R2, R3 and R4 independently of one another 5- or 6-membered heteroaryl selected from the group consisting of pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thiazolyl and oxazolyl;
or R1, R2, R3 and R4 independently of one another CONR11R12 or NR11R12;
R11 and R12 independently of one another H, C e H2e+1, C rr H2rr-1;
e 1, 2, 3 or 4, rr 3, 4, 5 or 6, it being possible for one or more H atoms in the groups C e H2e+1 and C rr H2rr-1 to be replaced by F atoms or R11 and R12 independently of one another hydroxyethyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, pyrrolidinoethyl, N-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl;
or R11 and R12 together with the N atom to which they are bonded a pyrrolidine, piperidine, N-methylpiperazine, piperazine or morpholine ring;
or R11 and R12 independently of one another COR14, CSR14, CONHR14, CSNHR14 or SO2R14;
R14 C g H2g+1;
g 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
or R1, R2, R3 and R4 independently of one another OSO3H, SO3H, SO2R15, or R15 C k H2k+1, OC l H2l+1 or NR17R18;
k 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
l 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;

R17 and R18 independently of one another H, C m H2m+1, in which the first CH2 group bonded to the nitrogen is replaced by CO and the second CH2 group is replaced by NR19;
m 1, 2, 3, 4 or 5, it being possible for one or more H
atoms in the group C m H2m+1 to be replaced by F
atoms;
R19 H or C n H2n+1;
n 1, 2, 3 or 4;
it being possible for one or more H atoms in C n H2n+1 to be replaced by F atoms;
or R17 and R18 together with the N atom to which they are bonded a 5- or 6-membered ring;
R5 H, C p H2p+1; C ss H2ss-1;
p 1, 2, 3 or 4;
ss 3, 4, 5 or 6, it being possible for one or more H atoms in C p H2p+1 and C ss H2ss-1 to be replaced by F atoms;
R6 H, C s H2s+1, OC t H2t+1 or OCOR22;
s and t independently of one another 1, 2, 3 or 4;
it being possible for one or more H atoms in C s H2s+1 and OC t H2t+1 to be replaced by F atoms;
R22 C u H2u+1;
u 1, 2, 3 or 4;
it being possible for one or more H atoms in C u H2u+1 to be replaced by F atoms;
R7, R8 and R9 independently of one another OSO3H, SO3H or SO2R23;

R23 C nn H2nn+1, C mm H2mm-1, OC pp H2pp+1 or NR25R26;
nn and pp independently of one another 1, 2, 3, 4 or 5, mm 3, 4, 5 or 6, it being possible for one or more H atoms in C nn H2nn+1, C mm H2mm-1 and OC pp H2pp+1 to be replaced by F atoms;
R25 and R26 independently of one another H, CN or C z H2z+1, in which the first CH2 group bonded to the nitrogen is replaced by CO or CS and the second CH2 is replaced by NR27;
z 1, 2, 3, 4, 5 or 6;
it being possible for one or more H atoms in C z H2z+1 to be replaced by F atoms;
R27 H or C aa H2aa+1;
aa 1, 2, 3 or 4;
it being possible for one or more H atoms in C aa H2aa+1 to be replaced by F atoms;
or R25 and R26 together with the N atom to which they are bonded a 5- or 6-membered ring;
or R27 and a CH2 group of R25 or R26 together with the N atom to which they are bonded a 5- or 6-membered ring;
or R7, R8 and R9 independently of one another NR32COR30, NR32CSR30 or NR32SO2R30;
R30 H, OH, C cc H2cc+1, C yy H2yy-1, pyrrolidinyl or piperidinyl, in which rings a CH2 group may be replaced by O or NR33;
R32 and R33 independently of one another H or C h H2h+1;

cc 1, 2, 3, 4, 5, 6, 7 or 8;
yy 3, 4, 5 or 6;
h 1, 2, 3 or 4;
it being possible for one or more H atoms in C h H2h+1 to be replaced by F
atoms, and it being possible for one or more H atoms in the groups C cc H2cc+1 and C yy H2yy-1 to be replaced by F atoms and for one or more (CH2) groups to be replaced by NR31 and for a (CH2) group to be replaced by Q;
R31 H, C kk H2kk+1,COR65 or SO2R65;
kk 1, 2, 3, or 4;
it being possible for one or more H atoms to be replaced by F atoms, R65 H, C xx H2x+1;
xx 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
or R31 together with a CH2 group or R30 and the N atom to which they are jointly bonded form a 5- or 6-membered ring;
or R30 a 5- or 6-membered heteroaromatic system selected from the group consisting of pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thienyl, thiazolyl and oxazolyl, which are unsubstituted or substituted by up to three substituents selected from the group consisting of F, Cl, Br, I, C oo H2oo+1, NR70R71, R70 and R71 independently of one another H, C uu H2uu+1 or COR72;
R72 H, C vv H2vv+1;
oo, uu and vv independently of one another 1, 2, 3 or 4;

it being possible for one or more H atoms in the groups C oo H2oo+1, C uu H2uu+1 or C vv H2vv+1 to be replaced by F
atoms;
or R7, R8 and R9 independently of one another H, F, Cl, Br, I, NO2, CN, OH, NH2, C ee H2ee+1, C ww H2ww-1, OC ff H2ff+1, NR40R41, CONR40R41, COOR42, COR42 or OCOR42;
ee and ff independently of one another 1, 2, 3 or 4;
ww 3, 4, 5 or 6, it being possible for one or more H atoms in the groups C ee H2ee+1, C ww H2ww-1 and OC ff H2ff+1 to be replaced by F atoms;
R40 and R41 H, C tt H2tt+1 or C(NH)NH2 ;
tt 1, 2, 3, 4, 5, 6, 7 or 8;
it being possible for one or more H atoms in the group C tt H2tt+1 to be replaced by F atoms;
or R40 and R41 to be selected independently of one another hydroxyethyl, , N,N-dimethylaminoethyl, N,N-diethylaminoethyl, pyrrolidinoethyl, N-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl;
or R40 and R41 together with the N atom to which they are bonded form a ring selected from the group consisting of pyrrolidine, piperidine, N-methyl-piperazine, piperazine and morpholine;
R42 H or C hh H2hh+1;
hh 1, 2, 3 or 4;

it being possible for one or more H atoms in the group C hh H2hh+1 to be replaced by F atoms.
9. The use as claimed in claim 7, characterized in that the meanings in formula I are:
R1, R2, R3 and R4 independently of one another H, F, Cl, Br, OH, NH2, C a H2a+1, cycloalkyl with 3, 4, 5 or 6 C atoms, OC b H2b+1 a and b in the groups C a H2a+1 and OC b H2b+1 independently of one another 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
or R1, R2, R3 and R4 independently of one another NR11R12;
R11 and R12 independently of one another H, C e H2e+1, C rr H2rr-1;
e 1, 2, 3 or 4, rr 3, 4, 5 or 6, it being possible for one or more H atoms in the groups C e H2e+1 and C rr H2rr-1 to be replaced by F
atoms;
or R11 and R12 together with the N atom to which they are bonded form a ring selected from the group consisting of pyrrolidine, piperidine, N-methylpiperazine, piperazine and morpholine;
or R11 and R12 independently of one another COR14, CSR14, CONHR14, CSNHR14 or SO2R14;
R14 C g H2g+1;

g 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
or R1, R2, R3 and R4 independently of one another OSO3H, SO3H, SO2R15;
R15 C k H2k+1 or NR17R18;
k 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms;
R17 and R18 independently of one another H or C m H2m+1;
m 1, 2, 3, 4 or 5, it being possible for one or more H
atoms in the group C m H2m+1 to be replaced by F
atoms;
or R17 and R18 together with the N atom to which they are bonded a 5- or 6-membered ring;
R5 H, C p H2p+1, C ss H2ss-1;
p 1, 2, 3 or 4;
ss 3, 4, 5 or 6, it being possible for one or more H atoms in C p H2p+1 and C ss H2ss-1 to be replaced by F atoms;
R6 H, CH3;
R7, R8 and R9 independently of one another OSO3H, SO3H or SO2R23;
R23 C nn H2nn+1 or NR25R26;
nn 1, 2, 3, 4 or 5, it being possible for one or more H atoms in C nn H2nn+1 to be replaced by F atoms;
R25 and R26 independently of one another H, CN or C z H2z+1, in which the first CH2 group bonded to the nitrogen is replaced by CO or CS and the second CH2 is replaced by NR27;
z 1, 2, 3, 4, 5 or 6;
it being possible for one or more H atoms in C z H2z+1 to be replaced by F atoms;
R27 H or C aa H2aa+1;
aa 1, 2, 3 or 4;
it being possible for one or more H atoms in C aa H2aa+1 to be replaced by F atoms;
of R25 and R26 together with the N atom to which they are bonded a 5- or 6-membered ring, or R27 and a CH2 group of R25 or R26 together with the N atom to which they are bonded a 5- or 6-membered ring;
or R7, R8 and R9 independently of one another NR32COR30, NR32CSR30 or NR32SO2R30;
R30 H, OH, C cc H2cc+1, C yy H2yy-1, pyrrolidinyl or piperidinyl, in which rings a CH2 group may be replaced by O or NR33;
R32 and R33 H, CH3 or CF3;
cc 1, 2, 3, 4, 5 or 6;
yy 3, 4, 5, 6, 7 or 8;
it being possible for one or more H atoms in the groups C cc H2cc+1 and C yy H2yy-1 to be replaced by F atoms and for one or more (CH2) groups to be replaced by NR31 and for a (CH2) group to be replaced by O;
R31 H, methyl, ethyl, CF3, CH2CF3, acetyl, propionyl, methanesulfonyl or ethanesulfonyl;

or R31 together with a CH2 group of R30 and the N atom to which they are jointly bonded form a 5- or 6-membered ring;
or R30 pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thiazolyl or oxazolyl, which are unsubstituted or substituted by a maximum of 3 substituents selected from the group consisting of F, Cl, methyl, ethyl, trifluoromethyl, NH2, NHacetyl;
or R7, R8 and R9 independently of one another H, F, Cl, OH, NH2, C ee H2ee+1, C ww H2ww-1, OC ff H2ff+1, NR40R41, CONR40R41, COOR42 or OCOR42, ee and ff independently of one another 1, 2, 3 or 4;
ww 3, 4, 5 or 6, it being possible for one or more H atoms in the groups C ee H2ee+1, C ww H2ww-1 and OC ff H2ff+1 to be replaced by F atoms;
R40 and R41 H, C tt H2tt+1 or C(NH)NH2 ;
tt 1, 2, 3 or 4;
it being possible for one or more H atoms in the group C tt H2tt+1 to be replaced by F atoms;
or R40 and R41 independently of one another hydroxyethyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, pyrrolidinoethyl, N-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl;
or R40 and R41 together with the N atom to which they are bonded a pyrrolidine, piperidine, N-methylpiperazine, piperazine or morpholine ring;

R42 H or C hh H2hh+1 hh 1, 2, 3 or 4;
it being possible for one or more H atoms in the group C hh H2hh+1 to be replaced by F atoms.

10. The use as claimed in claim 7, characterized in that the compounds of the formula I
are selected from the group consisting of:
1) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
2) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide;
3) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide;
4) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N,N-dimethyl-benzenesulfonamide;
5) 4-(4-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline;
6) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid;
7) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-ethyl-benzamide;
8) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-propyl-benzamide;
9) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl}-N-(2-dimethylamino-ethyl)-benzamide;
10) 6,8-dichloro-2-methyl-4-(4-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline;
11) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-diethyl-amine 12) 6,8-dichloro-2-methyl-4-(4-piperidin-1-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline;
13) 6,8-dichloro-2-methyl-4-(4-pyrrolidin-1-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline;
14) 6,8-dichloro-2-methyl-4-[4-(4-methyl-piperazin-1-yl)-phenyl]-1,2,3,4-tetrahydro-isoquinoline;
15) 6,8-dichloro-2-cyclopropyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline;
16) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine;
17) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-propylurea;
18) 1-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-thiourea;

19) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
20) N-[4-(6-methanesulfonyl-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
21) N-[4-(2,6,8-trimethyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
22) N-[4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
23) N-[4-(8-chloro-2-methyl-6-pyrrolidin-1-yl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
24) N-[4-(8-chloro-2-methyl-6-morpholin-4-yl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
25) N-{4-[8-chloro-2-methyl-6-(4-methyl-piperazin-1-yl)-1,2,3,4-tetrahydro-isoquinolin-4-yl]-phenyl}-acetamide;
26) N-{4-[8-chloro-6-(cyclopropylmethyl-amino)-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl]-phenyl}-acetamide;
27) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoic acid;
28) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-N-methyl-benzamide;
29) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N-ethyl-2-hydroxy-benzamide;
30) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N-(2-dimethylamino-ethyl)-2-hydroxy-benzamide;
31) N-[5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoyl]-guanidine;
32) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
33) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine;
34) 2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine;
35) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;

36) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;
37) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]pentanamide;
38) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-isobutyramide;
39) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2-dimethyl-propionamide;
40) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclopropanecarboxamide;
41) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclobutanecarboxamide;
42) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclopentanecarboxamide;
43) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2,2-trifluoro-acetamide;
44) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-acetylpiperidine-4-carboxamide;
45) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-nicotinamide;
46) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methane-sulfonamide;
47) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-ethanesulfonamide;
48) N',N'-dimethylamino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide;
49) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;
50) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;
51) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pentanamide;

52) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-isobutyramide;
53) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2-dimethyl-propionamide;
54) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclopropanecarboxamide;
55) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclobutanecarboxamide;
56) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclopentanecarboxamide;
57) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2,2-trifluoro-acetamide;
58) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-acetylpiperidine-4-carboxamide;
59) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-nicotinamide;
60) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methane-sulfonamide;
61) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)- phenyl]-ethanesulfonamide;
62) N',N'-dimethylamino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide;
63) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;
64) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;
65) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pentanamide;
66) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-isobutyramide;
67) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2-dimethyl-propionamide;

68) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclopropanecarboxamide;
69) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)- phenyl]-cyclobutanecarboxamide;
70) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclopentanecarboxamide;
71) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2,2-trifluoro-acetamide;
72) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-acetylpiperidine-4-carboxamide;
73) N-[2-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methane-sulfonamide;
74) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)- phenyl]-ethanesulfonamide;
75) N',N'-dimethylamino-N-[2-(6,8-dichloro-2-methyl-1.2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide;
76) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
77) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-thiourea;
78) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
79) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-thiourea;
80) N-{5-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylsulfamoyl]-4-methyl-thiazol-2-yl}-acetamide;
81) N-{5-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl-phenylsulfamoyl]-4-methyl-thiazol-2-yl}-acetamide;
82) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,2-dimethyl-1H-imidazole-4-sulfonamide;
83) N-[3-{6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,2-dimethyl-1H-imidazole-4.-sulfonamide;

84) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonamide;
85) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonamide;
86) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-5-bromo-thiophene-2-sulfonamide;
87) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-5-bromo-thiophene-2-sulfonamide;
88) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-C,C,C-trifluoro-methanesulfonamide;
89) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-C,C,C-trifluoro-methanesulfonamide;
90) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2,2-trifluoroethanesulfonamide;
91) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2,2-trifluoro-ethanesulfonamide;
92) N-ethyl-N'-4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonylurea;
93) 2-chloro-5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide;
94) 2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinolin-8-ylamine;
95) 6,8-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
96) 4-(8-amino-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenol;
97) 8-methoxy-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
98) 2-(8-amino-2-ethyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenol;
99) 2-(8-amino-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenol;
100) 5-(8-amino-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-methoxy-phenol;
101) 2-methyl-8-nitro-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
102) 4-(8-amino-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzene-1,2-diol;
103) 2,8-dimethyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
104) 4-(3,4-dichloro-phenyl)-2-methyl-1,2,3,4-tetrahydro-isoquinoline;
105) 4-(3,4-dichloro-phenyl)-2-methyl-1,2,3,4-tetrahydro-isoquinolin-8-ylamine;

106) 4-(2,4-dichloro-phenyl)-2-methyl-1,2,3,4-tetrahydro-isoquinolin-8-ylamine;
107) 4-(3-chloro-phenyl)-2-methyl-1,2,3,4-tetrahydro-isoquinolin-8-ylamine;
108) 2,4-dimethyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
109) 2-butyl-4-phenyl-1,2,3,4-tetrahydro-isoquinolin-8-ylamine;
110) N-(2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinolin-8-yl)-acetamide;
111) 7-chloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
112) 8-chloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
113) 2,6-dimethyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
114) 6-chloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
115) 6-methoxy-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
116) 2-ethyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
117) 2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
118) 6,8-dichloro-2-ethyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
119) 4-(4-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoline;
120) 2-methyl-4-phenyl-6,8-bis-trifluoromethyl-1,2,3,4-tetrahydro-isoquinoline;
121) 6,8-dichloro-2-isopropyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
122) 5,8-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
123) 6,8-dichloro-4-(4-fluoro-phenyl)-2-methyl-1,2,3,4-tetrahydro-isoquinoline;
124) 6,8-dichloro-2-methyl-4-p-tolyl-1,2,3,4-tetrahydro-isoquinoline;
125) 5,6-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
126) 6,7-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
127) 8-bromo-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
128) 6,8-dichloro-4-(4-chloro-phenyl)-2-methyl-1,2,3,4-tetrahydro-isoquinoline;
129) 6,8-dichloro-2-cyclopropyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;
130) 2-amino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
131) N-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methylamino-acetamide;
132) N-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-dimethylamino-acetamide;
133) 2-amino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;

134) 2-amino-N-[6-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;
135) 2,6-diamino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-hexanamide;
136) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrolidine-2-carboxamide;
137) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-isonicotinamide;
138) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrole-3-carboxamide;
139) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrole-2-carboxamide;
140) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methyl-piperidine-4-carboxamide;
141) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,4-dimethyl-1H-pyrrole-2-carboxamide;
142) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-nitro-1H-pyrrole-2-carboxamide;
143) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,5-dimethyl-1H-pyrrole-3-carboxamide;
144) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-imidazole-4-carboxamide;
145) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonyl-piperidine-4-carboxamide;
146) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3,5-dimethyl-1H-pyrazole-4-carboxamide;
147) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrazole-4-carboxamide;
148) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-trifluoromethyl-1H-pyrazole-4-carboxamide;
149) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methylamino-acetamide;

150) N[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2-dimethylamino-acetamide;
151) 2-amino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;
152) 2-amino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;
153) 2,6-diamino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-hexanamide;
154) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrolidine-2-carboxamide;
155) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-isonicotinamide;
156) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrole-3-carboxamide;
157) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrole-2-carboxamide;
158) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methyl-piperidine-4-carboxamide;
159) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,4-dimethyl-1H-pyrrole-2-carboxamide;
160) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-nitro-1H-pyrrole-2-carboxamide;
161) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,5-dimethyl-1H-pyrrole-3-carboxamide;
162) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-imidazole-4-carboxamide;
163) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonyl-piperidine-4-carboxamide;
164) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3,5-dimethyl-1H-pyrazole-4-carboxamide;
165) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrazole-4-carboxamide;

166) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-trifluoromethyl-1H-pyrazole-4-carboxamide;
167) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-thiourea;
168) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-thiourea;
169) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-thiourea;
170) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea;
171) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-methyl-piperazine-1-carboxamide;
172) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-piperidine-1-carboxamide;
173) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-morpholine-4-carboxamide;
174) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrolidine-1-carboxamide;
175) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-diethyl-urea;
176) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-urea;
177) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;
178) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-(tetrahydro-furan-3-yl)-urea;
179) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-(tetrahydro-pyran-4-yl)-urea;
180) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methyl-1-(1-methyl-piperidin-4-yl)-urea;
181) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-(3-dimethylamino-propyl)-1-methyl-urea;

182) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-(2-dimethylamino-ethyl)-1-methyl-urea;
183) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(3-dimethylamino-propyl)-urea;
184) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-methoxy-ethyl)-urea;
185) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-pyridin-3-yl-urea;
186) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-pyridin-4-yl-urea;
187) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-methyl-piperazine-1-carboxamide;
188) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-urea;
189) 3-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea;
190) 3-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-diethyl-urea;
191) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-piperidine-1-carboxamide;
192) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-morpholine-4-carboxamide;
193) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrolidine-1-carboxamide;
194) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;
195) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-methyl-piperazine-1-carboxamide;
196) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrolidine-1-carboxamide;
197) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-urea;

198) 3-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea;
199) 3-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-diethyl-urea;
200) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;
201) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-piperidine-1-carboxamide;
202) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-morpholine-4-carboxamide;
203) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-formamide;
204) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amine;
205) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,3-dimethyl-urea;
206) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-4-methyl-piperazine-1-carboxamide;
207) 1-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,3,3-trimethyl-urea;
208) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-piperidine-1-carboxamide;
209) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-morpholine-4-carboxamide;
210) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-pyrrolidine-1-carboxamide;
211) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-1-methyl-urea;
212) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3,3-diethyl-1-methyl-urea;
213) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-formamide;

214) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amine;
215) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-pyrrolidine-1-carboxamide;
216) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-piperidine-1-carboxamide;
217) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,3,3-trimethyl-urea;
218) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,3-dimethyl-urea;
219) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-morpholine-4-carboxamide;
220) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-4-methyl-piperazine-1-carboxamide;
221) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-1-methyl-urea;
222) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3,3-diethyl-1-methyl-urea;
223) 2-dimethylamino-ethyl[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
224) 2-dimethylamino-ethyl[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
225) 2-dimethylamino-ethyl[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
226) methyl[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
227) ethyl[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
228) isopropyl[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
229) 2,2-dimethyl-propyl[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;

230) methyl[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
231) isopropyl[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
232) 2,2-dimethyl-propyl[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
233) ethyl[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
234) (R)-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonamide;
235) (S)-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonamide;
236) (R)-1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
237) (S)-1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
238) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
239) 4-(3-bromo-phenyl)-6,8-dichloro-methyl-1,2,3,4-tetrahydro-isoquinoline;
240) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-hydroxy-ethyl)-urea;
241) ethyl 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoate;
242) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid.
and from the pharmaceutically acceptable salts thereof.

11. The use as claimed in claim 7, characterized in that the compounds of the formula I
are selected from the group consisting of:
1) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
2) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide;
3) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide;

4) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid;
5) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-ethyl-benzamide;
6) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-propyl-benzamide;
7) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N-(2-dimethylamino-ethyl)-benzamide;
8) 6,8-dichloro-2-methyl-4-(4-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline;
9) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine;
10) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-thiourea;
11) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
12) N-[4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
13) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoic acid;
14) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N-(2-dimethylamino-ethyl)-2-hydroxy-benzamide;
15) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
16) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine;
17) 2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine;
18) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;
19) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-acetyl-piperidine-4-carboxamide;
20) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methane-sulfonamide;
21) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-ethanesulfonamide;
22) N',N'-dimethylamino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide;

23) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;
24) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;
25) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-isobutyramide;
26) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclopropanecarboxamide;
27) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclobutanecarboxamide;
28) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2,2-trifluoro-acetamide;
29) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-acetyl-piperidine-4-carboxamide;
30) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-nicotinamide;
31) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methane-sulfonamide;
32) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-ethanesulfonamide;
33) N',N'-dimethylamino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide;
34) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclopropanecarboxamide;
35) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-acetyl-piperidine-4-carboxamide;
36) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
37) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-thiourea;
38) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;

39) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-thiourea;
40) N-{5-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylsulfamoyl]-4-methyl-thiazol-2-yl}-acetamide;
41) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,2-dimethyl-1H-imidazole-4-sulfonamide;
42) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-C,C,C-trifluoro-methanesulfonamide;
43) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-C,C,C-trifluoro-methanesulfonamide;
44) N-ethyl-N'-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonylurea;
45) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2-dimethylamino-acetamide;
46) 2,6-diamino N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-hexanamide;
47) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrole-3-carboxamide;
48) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methyl-piperidine-4-carboxamide;
49) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methanesulfonyl-piperidine-4-carboxamide;
50) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrazole-4-carboxamide;
51) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2-methylamino-acetamide;
52) N-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2-dimethylamino-acetamide;
53) 2-amino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;
54) 2-amino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;

55) 2,6-diamino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-hexanamide;
56) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methyl-piperidine-4-carboxamide;
57) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-imidazole-4-carboxamide;
58) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methanesulfonyl-piperidine-4-carboxamide;
59) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3,5-dimethyl-1H-pyrazole-4-carboxamide;
60) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrazole-4-carboxamide;
61) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea;
62) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-methyl-piperazine-1-carboxamide;
63) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-piperidine-1-carboxamide;
64) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-morpholine-4-carboxamide;
65) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrolidine-1-carboxamide;
66) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-diethyl-urea;
67) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-urea;
68) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;
69) 1-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(tetrahydro-furan-3-yl)-urea;
70) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(tetrahydro-pyran-4-yl)-urea;

71) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methyl-1-(1-methyl-piperidin-4-yl)-urea;
72) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-(3-dimethylamino-propyl)-1-methyl-urea;
73) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-(2-dimethylamino-ethyl)-1-methyl-urea;
74) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(3-dimethylamino-propyl)-urea;
75) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-methoxy-ethyl)-urea;
76) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-y1)-phenyl]-3-pyridin-3-yl-urea;
77) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-pyridin-4-yl-urea;
78) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-methyl-piperazine-1-carboxamide;
79) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-urea;
80) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;
81) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-methyl-piperazine-1-carboxamide;
82) 1-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-urea;
83) 3-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea;
84) 3-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-diethyl-urea;
85) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;
86) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-morpholine-4-carboxamide;

87) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-formamide;
88) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amine;
89) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-formamide;
90) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amine;
91) 1[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,3,3-trimethyl-urea;
92) 1[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,3-dimethyl-urea;
93) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-morpholine-4-carboxamide;
94) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-4-methyl-piperazine-1-carboxamide;
95) 1[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-1-methyl-urea;
96) 2-dimethylamino-ethyl [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
97) 2-dimethylamino-ethyl [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
98) 2-dimethylamino-ethyl [2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
99) methyl [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
100) (R or S)-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonamide;
101) (R or S)-1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
102) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-hydroxy-ethyl)-urea;

103) ethyl 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoate;
104) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid.
and from the pharmaceutically acceptable salts thereof.
12. The use of a compound I as claimed in claim 7 for producing a medicament for the treatment or prophylaxis of disorders of respiratory drive.
13. The use of a compound I as claimed in claim 7 for producing a medicament for the treatment or prophylaxis of respiratory disorders, in particular sleep-related respiratory disorders such as sleep apneas.
14. The use of a compound I as claimed in claim 7 for producing a medicament for the treatment or prophylaxis of snoring.
15. The use of a compound I as claimed in claim 7 for producing a medicament for the treatment or prophylaxis of acute and chronic renal disorders, particularly of acute renal failure and of chronic renal failure.
16. The use of a compound I as claimed in claim 7 for producing a medicament for the treatment or prophylaxis of disorders of intestinal function.
17. The use of a compound I as claimed in claim 7 for producing a medicament for the treatment or prophylaxis of disorders of biliary function.
18. The use of a compound I as claimed in claim 7 for producing a medicament for the treatment or prophylaxis of ischemic states of the peripheral and central nervous system and of stroke.
19. The use of a compound I as claimed in claim 7 for producing a medicament for the treatment or prophylaxis of ischemic states of peripheral organs and limbs.

20. The use of a compound I as claimed in claim 7 for producing a medicament for the treatment of states of shock.
21. The use of a compound I as claimed in claim 7 for producing a medicament for use in surgical operations and organ transplantations.
22. The use of a compound I as claimed in claim 7 for producing a medicament for the preservation and storage of transplants for surgical procedures.
23. The use of a compound I as claimed in claim 7 for producing a medicament for the treatment of disorders in which cell proliferation represents a primary or secondary cause.
24. The use of a compound I as claimed in claim 7 for producing a medicament for the treatment or prophylaxis of disorders of lipid metabolism.
25. The use of a compound I as claimed in claim 7 for producing a medicament for the treatment or prophylaxis of infestation by ectoparasites.
26. A medicine comprising an effective amount of a compound I as claimed in
claim 1.
CA002469385A 2001-12-05 2002-11-20 Substituted 4-phenyltetrahydroisoquinolines, process for their preparation, their use as medicament, and medicament containing them Abandoned CA2469385A1 (en)

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TW200526626A (en) 2003-09-13 2005-08-16 Astrazeneca Ab Chemical compounds
DE102004046492A1 (en) * 2004-09-23 2006-03-30 Sanofi-Aventis Deutschland Gmbh Substituted 4-phenyltetrahydroisoquinolines, process for their preparation, their use as medicament, and medicament containing them
US20060111393A1 (en) * 2004-11-22 2006-05-25 Molino Bruce F 4-Phenyl substituted tetrahydroisoquinolines and use thereof to block reuptake of norepinephrine, dopamine and serotonin
DE102005001411A1 (en) 2005-01-12 2006-07-27 Sanofi-Aventis Deutschland Gmbh Substituted 4-phenyltetrahydroisoquinolines, process for their preparation, their use as medicament, and medicament containing them
BRPI0607756A2 (en) 2005-02-18 2010-05-18 Astrazeneca Ab compound or a pharmaceutically acceptable salt thereof, pharmaceutical composition, method for inhibiting bacterial DNA gyrase and / or topoisomerase iv in a warm-blooded animal, use of a compound or a pharmaceutically acceptable salt thereof, and process for preparing compounds or pharmaceutically acceptable salts thereof
EP1861393A2 (en) * 2005-03-04 2007-12-05 AstraZeneca AB Pyrrole derivatives as dna gyrase and topoisomerase inhibitors
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