Indian Patents
Title of Invention

SUBSTITUTED 4-PHENYLTETRAHYDROISOQUINOLINES, METHOD FOR THE PRODUCTION THEREOF, AND MEDICAMENT CONTAINING THE SAME
Abstract ABSTRACT 1236/CHENP/2004 "SUBSTITUTED 4-PHENYLTETRAHYDROISOQUINOLINES, METHOD FOR THE PRODUCTION THEREOF, THE USE THEREOF AS MEDICAMENTS, IN ADDITION TO A MEDICAMENT CONTAINING SAME" The invention relates to compounds of formula (I), wherein Rl - 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.
Full Text

The invention relates to compounds of the formula I

in which the meanings are: R1fR2,R3andR4
independently of one another H, F, CI, Br, I, CN, NO2, OH, NH2, CaH2a+1.
CqqH2qq.it 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 HorCcH2c+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
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, R3andR4
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, R3andR4
independently of one another CONR11R12 or NR11R12; R11 andR12
independently of one another H, CeH2e+1, CrrH2rM;
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 CeH2e+l and CrrH2rr-l to be replaced by F atoms and for one or more CH2 groups to be replaced by O or NR13; R13 HorCfH2f+i;
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 andR12
together with the N atom to which they are bonded a 5-, 6- or
7-membered ring; or R11 andR12
independently of one another COR14, CSR14 or S02R14;
R14 CgH2g+i;

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
byOorNR13, or R1.R2, R3andR4
independently of one another -On-SOj-R1 5, with
h zero or 1;
j zero, 1 or 2;
R15 CkH2k+1,OH, OC1H21+1 orNR17R18;
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; R17andR18
independently of one another H or CmH2m+1 i
m 1,2,3,4, 5, 6, 7 or 8, it being possible for one or more
H atoms in the group CmH2m+1t0 De replaced by F
atoms and for one or more CH2 groups to be replaced
byO.CO, CSorNR19;
R19 HorCnH2n+i;
n 1,2, 3 or 4;
it being possible for one or more H atoms in CnH2n+i to be replaced by F atoms;
or R17andR18
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+l, CssH2ss-1, COR20 or SO2R2O;
p 1,2,3,4,5, 6, 7or8,
ss 3, 4, 5, 6,7 or 8,
R20 CqH2q+i;
q 1,2,3,4,5f6l7or8i
it being possible for one or more H atoms in the groups CpH2p+i,
CssH2ss-1 ar,d CqH2q+i to be replaced by F atoms and for one or
more CH2 groups to be replaced by O or NR21;
R21 HorCrH2r+i;
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+l orOCOR22; sand 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
Cs^2s+1> CddH2dd-1 an u 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 -CVSOW-R23;
v zero or 1;
w zero, 1 or 2;
R23 CnnH2nn+1. CmmH2mm-1. OH, OCppH2pp+l 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 °CppH2pp+1 to De replaced by F atoms; R25 and R26
independently of one another H, CN or CZH2Z+1, CzzH2zz-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 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 HorCaaH2aa+r.
aa 1,2, 3 or 4;
it being possible for one or more H atoms in CaaH2aa+1t0 De 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 CnH2h+1;
bb 2 or 3;
cc 1,2,3,4, 5,6, 7 or8;
yy 3,4, 5, 6, 7 or 8;

h 1,2,3,4,5,6,7or8,
it being possible for one or more H atoms in CnH2n+1 t0 be replaced by F atoms, and it being possible for one or more H atoms in the groups CccH2cc+1 anQ 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+i;
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 ar|d
COR72;
R72 H, CwH2vv+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 C00H2oo+1 - cuuH2uu+1 or cwH2vv+1 to be replaced by F atoms;

or
R7, R8 and R9
independently of one another H, F, Ci, Br, I, NO2, CN, OH, NH2, CeeH2ee+1 ■
CwwH2ww-1 - OCffH2ff+l, 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>
Cww^2ww-1 ana" OCffH2ff+1 to be replaced by F atoms;
R40 and R41
H,CttH2tt+1orC(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+l to be
replaced by F atoms and for one or more CH2 groups to be replaced
by O or NR44;
R44 HorCggH2gg+1;
gg 1,2,3,4,5, 6, 7 or 8;
it being possible for one or more H atoms in the group
CggH2gg+i 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 HorChhH2hh+i;
hh 1,2, 3, 4, 5, 6, 7 or 8;
it being possible for one or more H atoms in the group CnhH2hh+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, -OvSOwR23, NR32COR30, NR32CSR30
and NR32SODbR30;
and the pharmaceutical^ acceptable salts and trifluoroacetates thereof.
Preference is given to compounds of the formula I in which the meanings are: R1.R2, R3andR4
independently of one another, H, F, CI, Br, I, CN, NO2, OH, NH2, CaH2a+l-cycloalkyl with 3, 4, 5 or 6 C atoms, OCt»H2D+l. 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 HorCcH2c+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, R3andR4
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, R3andR4
independently of one another CONR11R12 or NR11R12; R11 andR12
independently of one another H, CeH2e+1, CrrH2n"-1;
e 1,2,3or4,
rr 3, 4, 5 or 6,
it being possible for one or more H atoms in the groups CeH2e+1 and CrrH2n"-1 to De reP'aced by F atoms

or
R11 andR12
independently of one another hydroxyethyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, pyrrolidinoethyl, N-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl;
or
R11 andR12
together with the N atom to which they are bonded a pyrrolidine, piperidine, N-methylpiperazine, piperazine or morpholine ring;
or
R11 andR12
independently of one another COR14, CSR14, CONHR14, CSNHR14 orS02R14;
R14 CgH2g+i;
g 1, 2, 3 or 4, it being possible for one or more H atoms
to be replaced by F atoms; or R1,R2, R3andR4
independently of one another OSO3H, SO3H, SO2R15, with
R15 CKH2k+1,OC|H2|+i orNR17R18;
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; R17andR18
independently of one another H, CmH2m+1»'n 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 HorCnH2n+i;
n 1,2, 3 or 4;
it being possible for one or more H atoms in CnH2n+l to be replaced by F atoms; . or R17andR18
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+i;
p 1,2,3or4;
it being possible for one or more H atoms in CpH2p+i to be replaced by F atoms; R6 H, CsH2s+1, OCtH2t+i orOCOR22;
s and t
independently of one another 1, 2, 3 or 4;
it being possible for one or more H atoms in CsH2s+1 and OCt^2t+1
to be replaced by F atoms; R22 CuH2u+1;
u 1,2, 3 or 4;
it being possible for one or more H atoms in CuH2u+-| to be replaced
by F atoms; R7, R8 and R9
independently of one another OSO3H, SO3H or S02R23;
R23 CnnH2nn+1. CmmH2mm-i. OCppH2pP+i 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+-|,
CmrnH2mm_i and OCppH2pp+-] to be replaced by F atoms;

R25 and R26
independently of one another H, CN, C2H2z+1. 'n 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, 4,5or6;
it being possible for one or more H atoms in CzH2z+i
to be replaced by F atoms; R27 HorCaaH2aa+i;
aa 1,2, 3 or 4;
it being possible for one or more H atoms in
CaaH2aa+1 *° De 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, 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 CnH2h+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 CnH2n+1 to De replaced by F atoms, and it being possible for one or more H atoms in the groups

CccH2cc+1 anc' ^yyH2yy-1 to De 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+i;
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, COOH2OO+1.NR70R71, R70 and R71
independently of one another H, CuuH2uu+1 or COR72;
R72 H, CwH2vv+1' 00, 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 CWH2W+1 to be replaced by F atoms; or R7, R8 and R9
independently of one another H, F, CI, Br, I, NO2, CN, OH, NH2, CeeH2ee+1. CwwH2ww-1 - OCffH2ff+l • 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>
Cww^2ww-1 ana" OCffH2ff+i to De replaced by F atoms; R40 and R41
H,CttH2tt+iorC(NH)NH2;
tt 1,2,3,4,5,6,7or8;
it being possible for one or more H atoms in the group CftH2tt+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, piperidtne, N-methyl-
piperazine, piperazine and morpholine; R42 HorChhH2hh+i;
hh 1,2,3or4;
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, -OvSOwR23, NR32COR30, NR32CSR30
and NR32SODbR30;
and the pharmaceutical^ acceptable salts and trifluoroacetates thereof.

Particular preference is given to compounds of the formula I in which the meanings
are:
R1,R2,R3andR4
independently of one another H, F, CI, Br, OH, NH2, CaH2a+1. cycloalkyl with
3,4, 5 or 6 C atoms, OCt)H2b+1;
a and b
in the groups CaH2a+1 and OCbH2D+i 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, R3andR4
independently of one another NR11R12; R11 andR12
independently of one another H, CeH2e+1, CrrH2n"-1;
e 1,2,3or4,
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 andR12
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 andR12
independently of one another COR14, CSR14, CONHR14, CSNHR14 orS02R14;
R14 CgH2g+i;

g 1, 2, 3 or 4, it being possible for one or more H atoms
to be replaced by F atoms; or R1.R2, R3andR4
independently of one another OSO3H, S03H, S02R15;
R15 CkH2k+1 orNR17R18;
k 1, 2, 3 or 4, it being possible for one or more H atoms to be
replaced by F atoms; R17andR18
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 t° De replaced by F atoms; or R17andR18
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 ortrifluoromethyl; R6 H; R7, R8 and R9
independently of one another OSO3H, SO3H 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 *° 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 1,2,3,4,5or6;

it being possible for one or more H atoms in C2H2z+1
to be replaced by F atoms;
R27 HorCaaH2aa+i;
aa 1,2, 3 or 4;
it being possible for one or more H atoms in CaaH2aa+1 to De 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 R7f R8 and R9
independently of one another NR32COR30, NR32CSR30 or NR32SO2R30;
R30 H, OH, CccH2cc+1 . Cyy^2yy-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 ar,d
CyyH2yy_i 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, pyrrolyf, 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» OCffH2ff+i, NR40R41, CONR40R41, COOR42 orOCOR42,
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»
Cww^2ww-1 anc* OCffH2ff+i to be replaced by F atoms; R40 and R41
H, CttH2tt+lorC(NH)NH2
tt 1,2,3or4;
it being possible for one or more H atoms in the group CttH2tt+l 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 HorChhH2hh+i;
hh 1,2,3or4;
it being possible for one or more H atoms in the group CnhH2hh+1 *° be replaced by F atoms;

but where two substituents from the group of R7, R8 and R9 may not simultaneously beOHorOCH3
and where at least one of the radicals R7, R8 or R9 must be selected from the group consisting of CONR40R41, -OvSOwR23, NR32COR30, NR32CSR30 and
NR32SObbR30;
and the pharmaceutical^ acceptable salts and trifluoroacetates thereof.
Very particular preference is given to compounds of the formula I in which the meanings are: R1.R2, R3andR4
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, R3andR4
independently of one another NR11R12; R11 andR12
independently of one another H, CeH2e+1, CirH2rr-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 CeH2e+1 and CrrH2rr-1 to De replaced by F atoms; or R11 andR12

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 andR12
independently of one another COR14, CSR14, CONHR14, CSNHR14
orS02R14;
R14 CgH2g+i;
g 1, 2, 3 or 4, it being possible for one or more H atoms
to be replaced by F atoms; or R1,R2, R3andR4
independently of one another OSO3H, S03H, S02R15;
R15 CkH2k+1 orNR17R18;
k 1, 2, 3 or 4, it being possible for one or more H atoms to be
replaced by F atoms;
R17andR18
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+1t0 De replaced by F
atoms; or R17andR18
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 ortrifluoromethyl; R6 H; R7, R8 and R9
independently of one another OSO3H, SO3H 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+1to 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 HorCaaH2aa+i;
aa 1,2,3or4;
it being possible for one or more H atoms in CaaH2aa+1 t0 De 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, CccH2cc+1 > ^yy^2yy-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 CccH2cc+1 and
CyyH2yy-i 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, imidazoiyl, pyrazolyl, pyrroly!, 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-OCffH2ff+l, 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»
cwwH2ww-1 and ocffH2ff+1 *° De replaced by F atoms; R40 and R41
H, CftH2tt+1 orC(NH)NH2;
tt 1,2,3or4;
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 HorChhH2hh+i;
hh 1,2, 3 or 4;
it being possible for one or more H atoms in the group CnnH2hh+1 to be replaced by F atoms; but where two substituents from the group of R7, R8 and R9 may not simultaneously beOHorOCH3
and where at least one of the radicals R7, R8 or R9 must be selected from the group consisting of -OvSOwR23, NR32COR30, NR32CSR30 and NR32SODbR30;
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-pipendin-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) e.S-dichloro^-methyl^-^^-methyl-piperazin-l-ylJ-phenyll-I^.S^-tetrahydro-isoquinoline;
15) 6,8-dichloro-2-cyclopropyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline;
16) 4-(6,8-dichloro-2-methyJ-1 ,2 A4-tetrahydro-isoquinolin^-yl)-phenylamine;
17) 1-[4-(6,8-dichloro-2-methyl-1t2,3,4-tetrahydro-isoquinolin-4-yl)-phenyf]-3-propylurea;
18) l-^^e^-dichloro^-methyl-l^^^-tetrahydro-isoquinolin^-yO-phenyll-S-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)-pheny!]-acetamide;
21) N-[4-(2,6^4nmethyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetanriide;
22) N-[4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydro-isoquino!in-4-yl)-phenyl]-acetamide;
23) N-[4-(8-chloro-2-methyl-6-pyrrolidin-1-yl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylj-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) S^e^-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yl^-hydroxy-benzoic acid;
28) 5-(63-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-N-nnethyl-benzamide;
I 29) S^e^-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yO-N-ethyl^-hydroxy-benzamide;

30) 5-(63-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-tS-Ce^-dichloro^-methyl-l^^^-tetrahydro-isoquinolin^-yO-phenyl]-acetamide;
33) 3-(63-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoiin-4-yl)-phenylarriine;
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)-phenyI]-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-1f2,3,4-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-^B.B-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yO-phenyl]-cyclopentanecarboxamide;
43) N-^e.S-dichloro^-methyl-l^^^-tetrahydro-isoquinolin^-yO-phenyl]^^^-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-1f2,3,4-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-rnethyl-1,2J3t4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide;
49) N-[3-(6,8-dichloro-2-methyl-1r2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;
50) N-[3-(6,8-dichloro-2-methyl-1,2f3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;
51) N-[3-(6,8-dichloro-2-methyl-1 f2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pentanamide;
52) N-[3-(6,8-dichloro-2-methyl-1,2f3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-isobutyramide;
53) N-P-Ce.S-dichloro^-methyl-l^^^-tetrahydro-isoquinolin^-ylVphenyl]^^-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-1t2,3(4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2,2-trifluoro-acetamide;
58) N-fS-fe.S-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yO-phenylJ-l-acetylpiperidine-4-carboxamide;
59) N-[3-(6T8-dichloro-2-methyl-1f2,3,4-tetrahydro-isoquinotin-4-yl)-phenyl]-nicotinamide;
60) N-p-je.S-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yO-phenyll-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-(6f8-dichloro-2-methyl-1(2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide;

63) N-[2-(6,8-dichloro-2-methyl-1,2,3t4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;
64) N-^-Ce.S-dichloro-a-methyl-I^.S^-tetrahydro-isoquinolin^-yO-phenyl]-butyramide;
65) N-[2-(6,8-dichloro-2-methy{-1,2,3,4-tetrahydro-isoquinoIin-4-yI)-phenyl]-pentanamide;
66) N-[2-(6,8-dichloro-2-methyl-1(2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-isobutyramide;
67) N-P^e.S-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yO-phenyl]^^-dimethyl-propionamide;
68) N-[2-(6,8-dichloro-2-methyl-1T2,3,4-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]-2t2(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-P^e^Klichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yO-phenyll-rnethane-sulfon amide;
74) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydn>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-1f2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
77) 1-[3-(6,8-dichloro-2-methyl-1t2,3,4-tetrahydroMsoquinolin^-yl)-phenyl]-3-methyl-thiourea;
78) 1-[2-(63-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;

79) 1-[2-(6,8-dichloro-2-methyl-1,2,3Atetrahydro-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-thia2ol-2-yl}-acetamide;
81) N-fS-P-je^-dichloro^-methyl-I^.S.A-tetrahydro-isoquinolin^-yl)-phenylsulfamoyl]-4-methyl-thiazol-2-yl}-acetamide;
82) N-I^e^-dichloro^-methyl-l^^^-tetrahydro-isoquinolin^-yO-phenyll-l^-dimethyl-1H-imidazole-4-sulfonamide;
83) N-[3-(6f8-dichloro-2-iriethyl-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]-CfC,C-trifluoro-methanesulfonamide;
89) N-[3-(6,8-dichloro-2-methyl-1T2,3,4-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]-2,2l2-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'^e.S-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-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-methyi-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
96) N-[4-(6,8-dichioro-^-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-isoquino(in-4-yl)-phenyl]-2-dimethylamino-acetamide;
98) 2-amino-N-[4-(6,8-dichloro-2-methyl-1t2,3,4-tetrahydro-isoquino!in-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-isoquinoiin-4-yl)-phenylj-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]-1H-pyrrole-3-carboxamide;
104) N-[4-(6,8-dichloro-2-methyl-1 ,2,3,4-tetrahydro-isoquinolin^-yl)-phenyI]-1H-pyrrole-2-carboxamide;
105) N-[4-(63-dichloro-2-methyl-1,2f3,4-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-1H-pyrrole-3-carboxamide;
109) N-[4-(6,8-dichloro-2-methyl-1 t2,3f4-tetrahydro-isoquinolin-4-yl)-phenyl]-1 H-imidazole-4-carboxamide;
110) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-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-^-Ce^-dichloro^-methyi-I^.S^-tetrahydro-isoquinolin^-ylJ-phenylJ-IH-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-p^.S-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yO-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-p^e.S-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yO-phenyll-IH-pyrrole-3-carboxamide;
122) N-[3-(6,8-dichloro-2-methyl-1 ^.S^-tetrahydro-isoquinolin^-yO-phenylJ-l H-pyrrole-2-carboxamide;
123) N-[3-(6^-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-1H-pyrrole-3-carboxamide;

127) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1H-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-p-Ce.a-dichloro^-methyl-l^^^-tetrahydro-isoquinoiin^-ylJ-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]-1H-pyrazole-4-ca rboxa mide;
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-1,2,3,44etrahydro-isoquinolin^-yl)-phenyl]^-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;
HOJS-p-Ce.S-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yO-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)-phenyI]-3-(tetra hyd ro-fu ra n-3-yl )-u rea;
144) 1-[3-(63-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-1,2,3P4-tetrahydro-isoquinolin^-yl)-phenyl]-1-methy!-1-(1-methyl-piperidfn-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) l-P-Ce^-dichloro^-rnethyl-I^.S^-tetrahydro-isoquinolin^-yO-phenyll-S-(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) l-p^e^-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-ylJ-phenyll-S-pyridin-3-yl-urea;
151) l-p-Ce^-dichloro^-methyl-l^^^-tetrahydro-isoquinolin^-yO-phenyll-S-pyridin-4-yl-urea;
152) N-[2-(6,8-dichloro-2-methyl-1,2^ piperazine-1 -carboxamide;
153) 1 -[2-(6,8-dichloro-2-methyl-1 ^.S^-tetrahydro-isoquinolin^-yO-phenyll-S-methyl-urea;
154) 3-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea;
155) S-P-fe.S-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-ylJ-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-ietrahydro-isoquinolin-4-yl)-phenyi]-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-yi)-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-yI)-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^-yl)-phenyl]-piperidine-1-carboxamide;
167) N-^-Ce^-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yO-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-1,2t3,4-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-1t2,3,4-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-isoqurnolin-4-yl)-phenyl]-metriyl-morpholine-4-carboxamide;

175) N-[4-(6,8-dichloro-2-methyl-1 f2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-pyrrolidine-1-carboxamide;
176) 144-(6t8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquino[in-4-yl)-pheny[]-3-(2-dimethylamino-ethyl)-1-methyl-urea;
177) l-[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)-phenyi]-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-1t2,3r4-tetrahydroHsoquinolin-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^-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-dichioro-2-methyl-1,2,3,4-tetrahydro-isoquinolin^-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)-pheny!]-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-1,2,3t4-tetrahydro-isoquino!in-4-yl)-phenyl]-carbamate;
194) 2,2-dimethyl-propyl [3-(6,8-dichloro-2-methyl-1f2,3,4-tetrahydro-isoqu!nolin-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-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 pharmaceutical^ 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;
2) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesu)fonamide;
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-P-Ce.S-dichloro^-methyl-l^^^-tetrahydro-isoquinolin^-ylJ-phenyt]-acetamide;
8) N-[4-(6,8-dichioro-2-methyl-1,2,3t4-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'^'-dimethylamino-N-^e.S-dichloro^-methyl-I^.S^-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-1f2f3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2,2-trifluoro-acetamide;
19) N-p^.S-dichloro^-methyl-l^^^-tetrahydro-isoquinolin^-ylJ-phenyll-l-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,KJimethylamino-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^-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-acetyl-piperidine-4-carboxarnide;
26) 1-[3-(6t8-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-(6f8-dichloro-2-methyl-1,23,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
29) 1-[2-(6,8-dichloro-2-methyl-1,23t44etrahydro-isoquinolin^-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-p^e^-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yO-phenyl]-1,2-dimethyl-1 H-imidazole-4-sulfonamide;
32) N-[4-(6T8-dichloro-2-rnethyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-C,CrC-trifluoro-methanesulfonamide;

33) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-CrC,C-trifluoro-methanesulfonamide;
34) N-ethyl-NM-Ce.S-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-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-1,2,3J4-tetrahydro-isoquinolin-4-yl)-phenyl]-hexanamide;
37) N-[4-(6,8-dichloro-2-methyl-1(2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1H-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]-1H-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-1f2,3,4-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-1l2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;
45) 2,6-diamino-N-[3-(6J8-dichloro-2-methyl-1,2t3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-hexanamide;
46) N-[3-(63-dichloro-2-methyl-1,2,3,4-tetrahydro-tsoquinolin-4-yl)-phenyl]-1-methyl-piperidine-4-carboxamide;
47) N-[3-(63-dichloro-2-methyl-1,2,3(4-tetrahydro-isoquinolin-4-yl)-phenyl]-1H-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-p^e.S-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-ylJ-phenyll-S.S-dimethyl-1H-pyrazole-4-carboxarnide;
50) N-[3-(6,8-dichloro-2-methyl-1,2t3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1H-pyrazole-carboxamide;
51) 3-[3-(63-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-IS-Ce.S-dichloro^-methyl-l^^^-tetrahydro-isoquinolin^-yO-phenyll-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) l-p-Ce^-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-ylJ-phenyll-S-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-1f2,3,4-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 -rnethyl-piperidin-4-yl)-urea;
62) S-P^.S-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-ylJ-phenyll-I^S-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) l-ia^.S-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yO-phenylJ-S^-methoxy-ethyl)-urea;
66) l-^-Ce^-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yO-phenyll-S-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-(6t8-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-1f2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-urea;
70) 1-[2-(6,8-dichloro-2-methyi-1,2)3,4-tetrahydro-isoquino!in-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;
71) N-[4-(63-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-1,23,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-urea;
73) 3-[4-(6,8-dichlora-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^-(6^-dichloro-2-methyl-1,2t3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-forrnamide;
78) N-[3-(6,8-dichloro-2-methyi-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-formamide;
79) 1 -t3-(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-p-Ce.S-dichloro^-methyl-l^^^-tetrahydro-isoquinolin^-ylJ-phenyO-methyW-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-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-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-hyd roxy-ethy I )-u rea;
and the pharmaceutical^ 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
inhibition of the sodium-proton exchanger of subtype III (NHE3), in which the meanings
are:
R1.R2, R3andR4
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 OCbH2D+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 HorCcH2c+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
cdH2d+i:
d 1, 2, 3 or 4, it being possible for one or more H atoms
to be replaced by F atoms, or R1.R2, R3andR4
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, R3andR4
independently of one another CONR11R12 or NR11R12; R11 andR12
independently of one another H, CeH2e+1, CrrH2ir-1;
e 1,2, 3,4,5, 6,7 or8,
rr 3,4, 5,6,7, or 8,
it being possible for one or more H atoms in the groups CeH2e+1 and CrrH2rr-1to De replaced by F atoms and for one or more CH2 groups to be replaced by O or NR13;

R13 HorCfH2f+i;
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 andR12
together with the N atom to which they are bonded a 5-, 6- or
7-membered ring; or R11 andR12
independently of one another COR14, CSR14 or S02R14;
R14 CgH2g+i;
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
byOorNR13, or R1.R2, R3andR4
independently of one another -On-SOj-R15, with
h zero or 1;
j zero, 1 or 2;
R15 Cj 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; R17andR18
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
byO, CO, CSorNR19;
R19 HorCnH2n+i;
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 R17andR18
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+l, CssH2ss-1, COR20 orSO2R20;
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+i
and CssH2ss-1 *° be replaced by F atoms R20 CqH2q+i;
q 1,2,3,4,5,6,7or8f
it being possible for one or more H atoms in CqH2q+i to be replaced
by F atoms and for one or more CH2 groups to be replaced by O or
NR21;
R21 HorCrH2r+i;
r 1,2, 3 or 4;
it being possible for one or more H atoms in CrH2r+l to be
replaced by F atoms; R6 H, F, CI, Br, I, CsH2s+1. CddH2dd-1. OH, OCtH2t+l orOCOR22; sand 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 u 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 CnnH2nn+1. CmmH2mm-1' °H' 0CPPH2pp+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» CmrnH2mm-1 ar,d OCppH2pp+i to be replaced by F atoms; R25 and R26
independently of one another H, CN or CzH2z+i, Czz^zz-I I
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
orNR27;
R27 HorCaaH2aa+i:
aa 1,2, 3 or 4;
it being possible for one or more H atoms in Caa^2aa+1to ^e 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 CnH2n+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 CnH2n+1 to De replaced by F
atoms, and it being possible for one or more H atoms in the groups
CccH2cc+1 anc* CyyH2yy-i to De 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 1,2, 3, or 4;
it being possible for one or more H atoms to be replaced by F atoms, R65 H, CxxH2xx+i;
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;

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 anc*
COR72;
R72 H, CwH2w+i;
oo, 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 C00H2oo+1 - cuuH2uu+1 or cwH2w+1 to De replaced by F atoms; or R7, R8 and R9
independently of one another H, F, CI, Br, I, N02, CN, OH, NH2, CeeH2ee+1 -CwwH2ww-1. OCffH2ff+l, 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»
cwwH2ww-1 and 0CffH2ff+1 to De replaced by F atoms; R40 and R41
H,CttH2tt+lorC(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+lto be
replaced by F atoms and for one or more CH2 groups to be replaced
by O or NR44;

R44 HorCggH2gg+1;
gg 1,2, 3,4, 5, 6, 7 or 8;
it being possible for one or more H atoms in the group
CggH2gg+i 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 HorChhH2hh+i;
hh 1,2,3,4,5,6t7or8;
it being possible for one or more H atoms in the group CnhH2hh+1t0
be replaced by F atoms;
and the pharmaceutical^ acceptable salts thereof.
Preference is given to the use of compounds of the formula I, in which the meanings
are:
R1,R2, R3andR4
independently of one another, H, F, CI, Br, I, CN, NO2, OH, NH2, CaH2a+1.
cycloalkyl with 3,4,5 or 6 C atoms, OCt>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 HorCcH2c+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, R3andR4
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, R3andR4
independently of one another CONR11R12 or NR11R12; R11 andR12
independently of one another H, CeH2e+1, CrrH2n"-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 CeH2e+1 and CrrH2rr-1 to be replaced by F atoms
or
R11 andR12
independently of one another hydroxyethyl, N,N-dimethylarninoethyl, N,N-diethyiaminoethyl, pyrrolidinoethyl, N-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl orpiperidinoethyl;
or
R11 andR12
together with the N atom to which they are bonded a pyrrolidine, piperidine, N-methylpiperazine, piperazine or morpholine ring;
or
R11 andR12
independently of one another COR14, CSR14, CONHR14, CSNHR14 orS02R14;
R14 CgH2g+i;
g 1, 2, 3 or 4, it being possible for one or more H atoms
to be replaced by F atoms; or R1,R2, R3andR4
independently of one another OSO3H, SO3H, SO2R15, or
R15 CkH2k+1,00^21+1 orNR17R18;
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; R17andR18
independently of one another H, CmH2m+1 > 'n 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 De replaced by F
atoms; R19 HorCnH2n+i;
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 R17andR18
together with the N atom to which they are bonded a 5- or
6-membered ring;
R5 H,CpH2p+l,CssH2ss-i;
p 1,2, 3 or 4;
ss 3,4, 5 or 6, it being possible for one or more H atoms in CpH2p+i and
CssH2ss-1 to be replaced by F atoms; R6 H, CsH2s+1. OCtH2t+l or OCOR22; s and t
independently of one another 1, 2, 3 or 4;
it being possible for one or more H atoms in CsH2s+1 ar|d OCtH2t+i to be replaced by F atoms; R22 CuH2u+i;
u 1,2,3or4;
it being possible for one or more H atoms in CUH2U+1 to be replaced
by F atoms;

R7, R8 and Rg
independently of one another OSO3H, SO3H or SO2R23;
R23 CnnH2nn+1. CmmH2mm.1. OCppH2pp+i 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 0CppH2pp+1 to De 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 HorCaaH2aa+i; aa 1,2, 3 or 4;
it being possible for one or more H atoms in CaaH2aa+1 to De 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; Dr R7, R8 and R9
independently of one another NR32COR30, NR32CSR30 or NR32SO2R30;

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 CnH2h+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 CnH2n+1 to be replaced by F
atoms, and it being possible for one or more H atoms in the groups
CccH2cc+1 and CyyH2yy-i to De 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 SO2R65;
kk 1,2, 3, or 4;
it being possible for one or more H atoms to be replaced by F atoms,
R65 H, CxxH2xx+i;
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, CI, Br, I, CooH2oo+1.NR70R71, R70 and R71
independently of one another H, CuuH2uu+1 or
COR72;
R72 H, CwH2vv+i;

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 cwH2w+1 to be replaced by F atoms; or R7, R8 and R9
independently of one another H, F, CI, Br, I, NO2.CN, OH, NH2, CeeH2ee+1» CwwH2ww-1- 0CffH2ff+i, 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 ■ cwwH2ww-1 and 0CffH2ff+1 t0 be replaced by F atoms; R40 and R41
H,CttH2tt+torC(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, pyrrofidinoethyl,
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 HorChhH2hh+i;

hh 1,2,3or4;
it being possible for one or more H atoms in the group CnnH2hh+1 *°
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, R3andR3
independently of one another H, F, CI, Br, OH, NH2, CaH2a+1 > cycloalkyi with
3, 4, 5 or 6 C atoms, OCfcH2b+1; a and b
in the groups CaH2a+1 and OCkH2D+i 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, R3andR4
independently of one another NR11R12; R11 andR12
independently of one another H, CeH2e+1 CrrH2rr-1'
e 1,2,3or4,
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 andR12
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 andR12
independently of one another COR14, CSR14, CONHR14, CSNHR14 orS02R14;
R14 CgH2g+i;
g 1, 2, 3 or 4, it being possible for one or more H atoms
to be replaced by F atoms; or R1,R2, R3andR4
independently of one another OSO3H, SO3H, S02R15;
R15 CkH2k+1 orNR17R18;
k 1, 2, 3 or 4, it being possible for one or more H atoms to be
replaced by F atoms;
R17andR18
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+*i to be replaced by F
atoms; or R17andR18
together with the N atom to which they are bonded a 5- or
6-membered ring;
R5 H, CpH2p+l, 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+i and
CssH2ss-1 *° be replaced by F atoms; R6 H, CH3;
R7, R8 and R9
independently of one another OSO3H, SO3H or S02R23;
R23 CnnH2nn+1 or NR25R26;
nn 1,2, 3, 4 or 5,

it being possibfe for one or more H atoms in CnnH2nn+1to 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+i
to be replaced by F atoms;
R27 HorCaaH2aa+i;
aa 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 NR32SO2R30;
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, CH3 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 ar|d
CyyH2yy-i 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 > OCffH2ff+l, 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 >
cwwH2ww-1 and 0CffH2ff+1 to be replaced by F atoms; R40 and R41
H, CttH2tt+1 orC(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 orpiperidinoethyl;
R40
and R41
together with the N atom to which they are bonded a pyrrolidine,
piperidine, N-methylpiperazine, piperazine or morpholine ring;
R42
HorCnnH2hh+i;
hh 1,2,3or4;
it being possible for one or more H atoms in the group CnnH2hh+1 to
be replaced by F atoms;
and the pharmaceutical^ 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-1,2f3,4-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)-benzoicacid;
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) e^-dichloro^-methyM^-morpholin^-yl-phenyO-I^.S^-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) e.S-dichloro^-methyM-^^-methyl-piperazin-l-yO-phenyll-I^.S^-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-isoquino!in-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-1,2,3t4-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) S^.S-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-ylJ^-hydroxy-benzoic acid;
28) 5-(63-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-(63-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-isoquinoiin-4-yl)-2-hydroxy-benzoylj-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-isoquinoiin-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)-phenyljpentanamide;
38) N-[4-(6t8-dichloro-2-methyM,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-isobutyramide;
39) N-^-te^-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-ylJ-phenyl]^^-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-1t2,3,4-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-1T2,3,4-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;

l)-phenyl]-
l)-phenyl]-
l)-phenyl]-
l)-phenyl]-
l)-phenyl]-2,2-
l)-phenyl]-
l)-phenyl]-
l)-phenyl]-
l)-phenyl]-2,2,2-
l)-phenyl]-1-
l)-phenyl]-
l)-phenyl]-methane-
I)- phenyl]-
48) N\N,-dirnethylamino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide;
49) N-tS^e.S-dichloro^-methyl-l^^^-tetrahydro-isoquinolin^-yi; propionamide;
50) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yi; butyramide;
51) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yr pentanamide;
52) N-[3-(6,8-dichloro-2-m9thyl-1,2,3,4-tetrahydro-isoquinolin-4-yi; isobutyramide;
53) N-[3-(6r8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yi; dimethyl-propionamide;
54) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yi; cyclopropanecarboxamide;
55) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yi; cyclobutanecarboxamide;
56) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yi; cyclopentanecarboxamide;
57) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yi; trifluoro-acetamide;
58) N-[3-(6,8-dichloro-2-methyl-1t2,3,4-tetrahydro-isoquinolin-4-yi; acetyipiperidine-4-carboxamide;
59) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yi; nicotinamide;
60) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yi; sulfonamide;
61) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yi; ethanesulfonamide;
62) N'.N'-dimethylamino-N-p-je.S-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yl)-phenyl]-sulfamide;
63) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;

64) N-P-fe.S-dichloro^-methyl-l^^^-tetrahydro-isoquinolin^-yO-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-p^e.S-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yO-phenyl]^^-dimethyi-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-1,2t3,4-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-(63-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin^-yl)-phenyl]-3-ethyl-urea;
77) l-P-je^-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yO-phenyll-S-methyl^ thiourea;
78) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin^-yl)-phenyl]-3-ethyl-urea;
79) 1-[2-(63-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin^-yl)-phenyl]-3-methyl-thiourea;

80) N-{5-[4-(6t8-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-^e.S-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-ylJ-phenylJ-l^-dimethyl-1H-imidazole-4-sulfonamide;
83) N-[3-(6,8-dichloro-2-m9thyl-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-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-(6t8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-5-bromo-thiophene-2-sulfonamide;
88) N-t4-(6f8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-C,C,C-trifluoro-methanesulfonamide;
89) N-tS^e.S-dichloro^-methyl-l^^^-tetrahydro-isoquinolin^-yO-phenylJ-CCC-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]-2r2,2-trifluoro-ethanesulfonamide;
92) N-ethyl-NM-(6,8-dichloro-2-methyl-1l2,3,4-tetrahydro-isoquinolin-4-yi)-benzenesulfonylurea;
93) 2-chloro-5-(6,8-dichloro-2~methyl-1l2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide;
94) 2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinolin-8-ylamine;
95) 6t8-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) S-CS-amino^-methyl-I^.S^-tetrahydro-isoquinolin^-yl^-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-yI)-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-1,2t3,4-tetrahydro-isoquinolin-8-ylamine; 106)4-(2f4-dichloro-phenyl)-2-methyl-1,2T3,4-tetrahydro-isoquinolin-8-ylamine;

107) 4-(3-chloro-phenyl)-2-methyl-1r2,3,4-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]-2-methylamino-acetamide;
132) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2-dimethylamino-acetamide;
133) 2-amino-N-[4-(6,8-dichioro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;
134) 2-amino-N-[4-(6J8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;
135) 2,6-diamino-N-[4-(6,8-dichloro-2-methyl-1,2,3F4-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-1T2,3,4-tetrahydro-isoquinolin-4-yl)-phenyi]-isonicotinamide;
138) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1H-pyrrole-3-carboxamide;
139) N-t4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1 H-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-^e.S-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yiVphenyll-l^-dimethyl-1H-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-^-Ce.S-dichloro^-methyl-l^^^-tetrahydro-isoquinolin^-yO-phenylJ^.S-dimethyl-1H-pyrrole-3-carboxamide;
144) N-^e.S-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yO-phenyO-IH-imidazole-4-carboxamide;
145) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methanesulfonyl-piperidine-4-carboxamide;

146) N-[4-(6f8-dichloro-2-methyl-1,2f3,4-tetrahydro-isoquinoiin-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]-1H-pyrazole-4-carboxamide;
148) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-trifluoromethyl-1H-pyrazole-4-carboxamide;
149) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2-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-(6t8-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)-phenylj-hexanamide;
154) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrolidine-2-carboxamide;
155) N-p^.S-dichioro^-methyl-I^.S^-tetrahydro-isoquinolin^-ylJ-phenyl]-isonicotinamide;
156) N-[3-(6,8-dichloro-2-methyl-1,2,3t4-tetrahydro-isoquinolin-4-yl)-phenyl]-1 H-pyrrole-3-carboxamide;
157) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1 H-pyrrole-2-carboxamide;
158) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1 -methyl-pipe rid ine-4-carboxa mid e;
159) N-[3-(6,8-dichloro-2-methyl-1 ,2,3/44etrahydro-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-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-1H-pyrra!e-3-carboxamide;

162) N-[3-(6,8-dichloro-2-methyl-1,2,3t4-tetrahydrO'isoquinolin-4-yl)-phenyl]-1H-imidazole-4-carboxamide;
163) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroHSoquinolin-4-yl)-phenyl]-1 -methanesulfonyl-piperidine-4-carboxamide;
164) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroHSoquinolin-4-yl)-phenyl]-3,5-dimethyl-1H-pyrazole-4-carboxamide;
165) N-p-te^-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yO-phenyll-IH-pyrazole-4-carboxamide;
166) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroHSoquinolin-4-yl)-phenyl]-3-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) l-^e.S-dichlora^-methyl-l^^^-tetrahydro-isoquinolin^-yO-phenyll-S-ethyl-thiourea;
169) 1 -[3-(6,8-dichloro-2-methyl-1,2,3f4-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-P-Ce^-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yO-phenylH-methyl-piperazine-1-carboxamide;
172) N-[3-(6,8-dichloro-2-methyl-1,2,3f4-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) S-IS^e.S-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yO-phenylJ-l.l-diethyl-urea;
176) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-urea;
177) l-IS-fe^-dichloro^-methyl-l^^^-tetrahydro-isoquinolin^-yO-phenylJ-S^-dimethylamino-ethyl)-urea;

178) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yI)-phenyl]-3-(tetrahydro-furan-3-yl)-urea;
179) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(tetrahydro-pyran-4-yl)-urea;
180) 3-[3-(6,8-dichloro-2-methyl-1f2,3,4-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-1t2,3,4-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) l-p^.S-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-ylJ-phenyll-S-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^-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-(6f8-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-p^.S-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yO-phenyll-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-methyi-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-^e.S-dichloro^-methyl-l^^^-tetrahydro-isoquinolin^-ylJ-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) l-^^e^-dichloro^-methyl-l^^^-tetrahydro-isoqutnolin^-yO-phenyll-S^-dimethylamino-ethyl)-urea;
201) N-^e.S-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yO-phenyll-piperidine-1-carboxamide;
202) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-morpholine-4-carboxarnide;
203) N-[4-(6I8-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-1,23,4-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-tri methyl-urea;
208) N-^e.S-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yO-phenyll-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-y!)-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-P-je^-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yO-phenyll-methyl-piperidine-1 -carboxamide;
217) 1-[3-(6,8-dichloro-2-methyl-1,2,3f4-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-dich!oro-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-isoquinoiin-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-yI)-phenyl]-carbamate;
229) 2,2-dimethyl-propyl [3-(6,8-dichloro-2-methyl-1 ,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylj-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-yi)-phenyl]-methanesulfonamide;
235) (S)-N-[3-(6f8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonamide;
236)(R)-1-[2-(6f8-dichloro-2-methyl-1,2,3t4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
237) (SJ-l-p-te^-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yO-phenyll-S-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)-6r8-dichloro-methyl-1!2(3,4-tetrahydro-isoquinoline;
240) 1-[3-(6t8-dichloro-2-methyl-1F2,3,4-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)-ben2oic acid.

and the pharmaceutical^ 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)-phenyl]-acetamide;
2) 4-(6,8-dichloro-2-methyl-1,213,4-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)-benzoicacid;
5) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-ethyl-benzamide;
6) 4-(6t8-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)-1t2,3,4-tetrahydroisoquinoline;
9) 4-(6,8-dichloro-2-methyl-1t2,3r4-tetrahydro-isoquinolin-4-yl)-phenylamine;
10) 1-[4-(6,8-dfchloro-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-tS^e^-dichloro^-methyl-l^^^-tetrahydro-isoquinolin^-ylJ-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-1,2t3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;
19) N-[4-(6,8-dichloro-2-methyl-1r2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-acetyl-piperidine-4'Carboxamide;
20) N--2e.S-dichloro-2-methyl-I-2.S-2-tetrahydro-isoquinolin-2-yO-phenyll-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-1,2r3,4-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-p-2.S-dichloro-2-methyl-l-2-2-2-tetrahydro-isoquinolin-2-yO-phenyll-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-(6l8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquino!in-4-yl)-phenyl]-1-acetyl-piperidine-4-carboxamide;
36) 1-[3-(6,8-dichloro-2-methyl-1,2,3t4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
37) 1-[3-(6,8-dichloro-2-methyl-1,2T3,4-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) l-p-Ce-2-dichloro-2-methyl-l-2-2-2-tetrahydro-isoquinolin-2-yO-phenyll-S-methyl-thiourea;
40) N-{5-[3-(6,8-dichloro-2-methyl-1,2t3,4-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--2e.S-dichloro-2-methyl-l-2-2-2-tetrahydro-isoquinolin-2-yO-phenylJ-CCC-trifluoro-methanesulfonamide;
43) N-p-Ce-2-dichloro-2-methyl-I-2.S-2-tetrahydro-isoquinolin-2-yO-phenylJ-C.CC-trifluoro-methanesulfonamide;
44) N-ethyl-N'-4-(6,8-dichloro-2-methyl-1f2,3,4-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]-1H-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]-1H-pyazole-4-carboxamide;

51) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2-methylamino-acetamide;
52) N-p-2.S-dichloro-2-methyl-l-2-2-2-tetrahydro-isoquinolin-2-yO-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-(63-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-hexanamide;
56) N-p-te.S-dichloro-2-methyl-I-2.S-2-tetrahydro-isoquinolin-2-yO-phenyll-l-methyl-piperidine-4-carboxamide;
57) N-[3-(6,8-dichloro-2-methyl-1,2t3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1H-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]-1H-pyrazole-4-carboxamide;
61) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1f1-dimethyl-urea;
62) N-[3-(6F8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-methyl-piperazine-1-carboxamide;
63) N-P-fe-2-dichloro-2-methyl-I-2.S-2-tetrahydro-isoquinolin-2-ylJ-phenylJ-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-rnethyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-urea;
68) 1-[3-(6t8-dichloro-2-methyl-1I2,3,4-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)-pheny!]-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-nriethyl-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-(63-dichIoro-2-methyl-1f2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-methoxy-ethy I )-u rea;
76) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-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-(6t8-dichloro-2-methyl-1,23,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-me% piperazine-1-carboxamide;
79) 1-[2-(6,8-dichloro-2-methyl-1(2,3,4-2 urea;
80) 1-[2-(6,8-dichloro-2-methyl-1t2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;
81) N-[4-(6,8-dichloro-2-methyl-1,23,44etrahydro-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-mem urea;

83) 3-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yf)-phenyi]-1 ,1-dimethyl-urea;
84) 3-[4-(6,8-dichloro-2-methyt-1,2,3,4-tetrahydro-isoquinolin-4-yl)-pheny!]-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-isoquinoiin-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]-methyi-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-nriethyl-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)-pheny[]-morpholine-4-carboxamide;
94) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-4-methyI-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-dimethyiamino-ethyl -2-(e.S-dichloro-2-methyl-I-2.S-2-tetrahydro-isoquinolin-2-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) (RorS)-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_i 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-imidazolyl, 1-, 3-, 4- or 5-pyrazolyl, 1,2,3-triazoM-, -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-thiadiazo!-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- or4-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.

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.



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).

The tertiary alcohols synthesized in this way can be converted by known methods into 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 converted into the desired tetrahydroisoquinolines I in a Pictet-Spengler-analogous reaction (cf. Tetrahedron; 1987,43,439; Chem. Pharm. Bull.; 1985, 33, 340).


Compounds of the type I are described in the published specifications WO 01 32 624 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 I are described in the patent specification EP 11 13 007 as estrogen agonists and antagonists. It was possible to show that the compounds i 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 formu\a 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 antiatherosderotic 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 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 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.
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 and/or medicaments with hypolipidemic activity is claimed.
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 arable, 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, % 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 0-[(ethoxycarbonyl)-cyanomethyleneamino]-NXN\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:
mobile phase:
Method B: stationary phase:

Merck Purospher 3/;2 x 55 mm
95% H2O (0.05% TFA)-» 95% acetonitrile; 4 min; 95%
acetonitrile; 1.5 min --2 5% acetonitrile; 1 min; 0.5 ml/min, 30°C.
Merck Purospher 3//2 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: mobile phase

YMC, J'sphere ODS H80 4// 2 x 20 mm
0 min 90% H2O (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: solvent:
flow rate:
stop time: temperature:


0.00
0.50
1.75
4.25
4.50
5.00
6.20 min
40°C
Merck LiChroCart 55-2 Purospher STAR RP 18e solvent A: acetonitrile/water 90:10 + 0.5% HCOOH solvent B: acetonitrile/water 10:90 + 0.5% HCOOH 0.75 ml/min time[min] solvent B[%]
95.0
95.0
5.0
5.0
95.0
95.0



Method D: stationary phase: solvent:
flow rate:

Merck RP18 Purospher STAR, 55 x 2 mm, 3 // particle size.
solvent A: acetonitrile + 0.08% HCOOH
solvent B: water + 0.1% HCOOH
0.45 ml/min
time[min] solvent B[%]
0 95

5 5
7 5
8 95
9 5 temperature: room temperature
Example 1: N-[4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide

Intermediate 1: 2J4-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 NaHCC>3 and H2O, 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 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; 20 g (0.054 mol) of intermediate 4 are dissolved in 250 ml of dichloromethane and, at 0°C, 250 ml of cone. H2SO4 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-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;


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 H2O, 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; 20 g (64.5 mmo!) 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 cone. H2SO4 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 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(2I3,4-tetrahydro-isoquinolin-4-yl)-benzene-sulfonamide hydrochloride;
2b:(+)-3-(6f8-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 NaHCC>3. Three extractions with ethyl
acetate are carried out. The combined organic phases are dried with Na2SC>4 and
freed of solvent. The crude product obtained in this way is heated in 20 ml of cone. NH3 solution at 90°C for three hours. After the conversion is complete, the reaction
solution is concentrated and the residue is partitioned between H2O 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-heptane/ethanol/methanol/acetonitrile 20:1.5:0.5:0.5
flow rate: 1 ml/min;
Remain 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-1,2f3,4-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 ml/min;
Remain fraction)= 4.394 min (--22c);
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;


6,8-Dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoltne (intermediate 4, example 2) was introduced in portions into chiorosulfonic 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 ice/water mixture was added. The precipitate which 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. 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 then purified by preparative HPLC.
Conditions:
stationary phase: Merck Purospher RP18 (10//M) 250 x 25 mm
mobile phase: 90% H2O (0.05% TFA)-» 90% acetonitrile; 40 min; flow rate:
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 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-(6J8-Dichloro-2-methyl-1,23t4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide, hydrochloride;
Intermediate 1: 4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-benzenesulfonyl chloride
AtO°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 Na2SC>4 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 H2O 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-Dtchloro-2-methyl-1I2,3,4-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.

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]-ethanoi; 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 cone.
H2SO4 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.


-2(e-2-Dichloro-2-methyl-I-2.S-2-tetrahydro-isoquinolin-2-yO-benzoicacid; 5.57 g (15 mmol) of 4-(4-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3r4-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 mmoi) 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 (F?t = 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;
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 0QC 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 H2O. The organic phase is dried with Na2SC>4 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 (Rj = 4.169 min (method A);
MS(CI+) = 363.3/365.3).


Example 10: 6,8-Dichloro-2-methyl-4-(4-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline, trifluoroacetate;

456 mg (1.4 mmol) of CS2CO3, 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 ml 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 (CH2CI2
/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;

The procedure is analogous to the method described in example 10 starting from diethylamide 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.

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;


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 MgSC>4 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 H2O 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.
Intermediates: 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 cone. H2SO4 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 MgSC>4 and freed of solvent.
Chromatography on silica gel (n-heptane/ethyl acetate 5:1 --2 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)-
phenylj-acetamide;
16b: (+)-N-[4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-
acetamide;


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 H2O and extracted twice with dichloromethane. The combined organic
phases are dried with MgS04 and concentrated. Further purification by





















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 (0.175 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.
Intermediates: 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 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 3* with water and 1* 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 cone, 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 cone, 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 2* 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 triethyiamine is added. At0°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 NaHCC>3 solution and 5% strength NaCI solution, and dried. Evaporation of the solvent
is followed by final purification on a preparative HPLC.

































saturated NaHCC>3 solution and once with 5% strength NaCI solution, dried and concentrated.
The crude products which still contain Boc protective groups are deprotected without i 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 NaHCC>3
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:



















dichloromethane and washed with aqueous K2CO3 solution. The organic phase is
separated and washed twice with saturated K2CO3 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;













Example 176: N-[4-(6,8-Dichloro-2-rnethyl-1 T2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-4-methyl-piperazine-1 -carboxamide, hydrochlorides;

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 K2CO3 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.























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 NaHCC>3 and dried with
MgS04? and the solvent is removed in vacuo. The crude product obtained in this way
is purified on a preparative HPLC. The product fractions are concentrated and partitioned between ethyl acetate and saturated NaHC03 solution. The organic phase
is separated off, dried with Mg$04 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-methyM ,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)-phenyi]-carbamate hydrochloride and 4-nitrophenyl [2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate hydrochloride.



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 HCI 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.




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;

96 mg of racemic N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-
phenyl]methanesulfonamide (see example 83) are separated into the enantiomers on
a chiral preparative HPLC.
chiral column: Chiralpak AD 250 x 50 mm; 20//;
solvent: heptane:ethanol:methanol: 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: Chiralpak 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% ee;
Rt (enantiomer eluting second) = 8.02 min, 100% ee.
Example
216a: (+)-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;


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 chira! preparative HPLC.
chiral column: Chiralpak OD 250 x 50 mm, 20//;
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 MgSC>4 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;

























































































The intracellular acidification was induced by adding 975 pi of an NH4CI-free buffer (see below) to 25 //I aliquots of the cells incubated in NH4CI buffer. The subsequent
rate of pH recovery was recorded for two minutes with NHE1, five minutes with NHE2 and three minutes with NHE3. To calculate the inhibitory potency of the tested substances, the cells were initially investigated in buffers with which a complete or absolutely no pH recovery took place. For complete pH recovery (100%), the cells were incubated in Na+-containing buffer (133.8 mM NaCI, 4.7 mM KCI, 1.25 mM CaCl2» 1.25 mM MgCl2, 0.97 mM Na2HPC>4, 0.23 mM NaH2PC>4, 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 Na+-free buffer (133.8 mM choline chloride, 4.7 mM KCI, 1.25 mM CaCl2, 1.25 mM MgCl2, 0.97 mM K2HPO4, 0.23 mM KH2P04, 5 mM Hepes, 5 mM glucose, a pH of 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 substance was expressed as a percentage of the maximum recovery. The IC50 value for the particular substance for the individual NHE subtypes was calculated from the pH recovery percentages using the Sigma-Plot
program.





WE CLAIM :
1. A 4-phenyitetrahydroisoquinoline of the formula I

in which the meanings are: R1,R2,R3andR4
independently of one another H, F, CI, Br, I, CN, NO2, OH, NH2, CaH2a+i,
cqqH2qq-1> OCbH2b+1- COOR10, OCOR10, COR10orOx-(CH2)y-phenyl; aandb
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 HorCcH2c+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
CdH2d+i:
d , 1, 2, 3 or 4, it being possible for one or more H atoms to be replaced by F atoms, or

R1.R2, R3andR4
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, R3and.R4
independently of one another CONR11R12 or NR11R12; R11 andR12
independently of one another H, CeH2e+l, crrH2rr-1;
e 1,2,3,4,5,6,7 0^,
rr 3,4, 5,6,7, or 8,
it being possible for one or more H atoms in the groups CeH2e+1 and Cn*H2rr-1t0 De replaced by F atoms and for one or more CH2 groups to be replaced by O or NR13; R13 HorCfH2f+i;
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 R11andR12
together with the N atom to which they are bonded a 5-, 6- or
7-membered ring; or R11andR12
independently of one another C0R14, CSR14 or S02R14;
R14 CgH2g+i;
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
byOorNR13, or R1.R2, R3andR4
independently of one another -On-SOj-R15, with
h zero or 1;
j zero, 1 or 2;
R15 CkH2k+1f 0H- oclH2l+1 or NR17R18;
k 1 f 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; R17andR18
independently of one another H or CmH2m+i;
m 1,2,3,4, 5, 6, 7 or 8, it being possible for one or more
H atoms in the group CmH2m+1t0 De replaced by F
atoms and for one or more CH2 groups to be replaced
byO,CO,CSorNR19;
R19 HorCnH2n+i;
n 1,2, 3or4;
it being possible for one or more H atoms in CnH2n+1 to be replaced by F atoms; or R17andR18
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+l, CssH2ss-1, COR20 or SO2R20;
p 1,2,3(4,5,6,7or8,
ss 3,4,5, 6, 7 or 8,
R20 CqH2q+l;
q 1,2, 3, 4, 5, 6, 7 or 8,
it being possible for one or more H atoms in the groups CpH2p+i,
Css^2ss-1 apd ^q^2q+1 *° De replaced by F atoms and for one or more CH2 groups to be replaced by O or NR21;
R21 HorCrH2r+i;
r 1,2, 3 or 4;
it being possible for one or more H atoms in CrH2r+i to be
replaced by F atoms; R6 H, F, CI, Br, I, CsH2s+i, CddH2dd-1» OH, OCtH2t+i orOCOR22; sand 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 °CtH2t+1 to be replaced by F atoms; R22 CuH2u+i;
u 1,2, 3 or 4;
it being possible for one or more H atoms in CuH2u+i 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+1to De replaced by F atoms; R25 and R26
independently of one another H, CN or CZH2Z+1 . czzH2zz-1:
2 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+i, 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 HorCaaH2aa+i; aa 1,2,3 or 4;
it being possible for one or more H atoms in CaaH2aa+1 *° De 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 NR32SODbR30;
R30 H, CccH2cc+1» CyyH2yy-1» pyrrolidinyl or piperidinyl, in which rings a
CH2 group may be replaced by 0 or NR33; R32 and R33 independently of one another H or CnH2h+11
bb 2 or 3;
cc 1,2, 3, 4, 5, 6, 7 or 8;
yy 3,4,5,6,7or8;

h 1,2,3,4,5,6,7or8,
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 De 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, Ck| it being possible for one or more H atoms to be replaced by F atoms, R65 H, CxxH2xx+i;
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, Cvyh^vv+I'
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 C00H2oo+1*cuuH2uu+1 orCwH2w+1 to b© replaced by F atoms; or

R7, R8 and R9
independently of one another H, F, CI, Br, I, NO2, CN, OH, NH2, CeeH2ee+1 • CwwH2ww-1- OCffH2ff+l, 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 • cwwH2ww-1 and ocffH2ff+1 to be replaced by F atoms; R40 and R41
H,CttH2tt+lorC(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 t° be
replaced by F atoms and for one or more CH2 groups to be replaced
by O or NR44;
R44 HorCggH2gg+i;
gg 1,2,3,4, 5, 6, 7 or 8;
it being possible for one or more H atoms in the group
CggH2gg+i 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 HorChhH2hh+i;
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, -OvSOwR23, NR32COR30, NR32CSR30 and NR32$OfcbR30;and tne pharmaceuticaliy acceptable salts and trifluoroacetates thereof.
2. The compound of the formula I as claimed in claim 1, in which the meanings are; R1.R2, R3andR4
independently of one another, H, F, CI, Br, I, CN, NO2, 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 HorCcH2c+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,R3andR4
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, R3andR4
independently of one another CONR11R12 or NR11R12; R11andR12
independently of one another H, CeH2e+l, crrH2rr-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 ceH2e+1 and crrH2rr-1 to be replaced by F atoms or

R11 andR12
independently of one another hydroxyethyl, N,N-dimethylaminoethyl, N.N-diethylaminoethyl, pyrrolidinoethyl, N-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl;
or
R11ahdR12
together with the N atom to which they are bonded a pyrrolidine, piperidine, N-methylpiperazine, piperazine or morpholine ring;
or
R11andR12
independently of one another COR14, CSR14, CONHR14, CSNHR14 orS02R14;
R14 CgH2g+i;
g 1, 2, 3 or 4, it being possible for one or more H atoms
to be replaced by F atoms; or R1.R2, R3andR4
independently of one another OS03H, SO3H, SO2R15, with R15 CkH2k+1, OC|H2|+i orNR17R18;
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; R17andR18
independently of one another H, CmH2m+1,in wnjch 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 HorCnH2n+i:

n 1,2, 3 or 4;
it being possible for one or more H atoms in CnH2n+1t0 De 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, CpH2p+i;
p 1,2,3or4;
it being possible for one or more H atoms in CpH2p+i 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+i
to be replaced by F atoms; R22 CuH2U+i;
u 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 OSO3H, SO3H or S02R23;
R23 CnnH2nn+1. CmmH2mm-1. OCppH2pp+i orNR25R26; nn and pp
independently of one another 1,2,3,4 or 5, mm 3,4, 5 or 6f
it being possible for one or more H atoms in CnnH2nn+1« cmmH2mm-1 and 0CppH2pp+1 to De replaced by F atoms;

R25 and R26
independently of one another H, CN or CzH2z+1. ^zz^2zz-1 >
z 1,2,3,4,5,6,7or8;
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* '* 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 orNR27; R27 HorCaaH2aa+i: aa 1,2, 3 or 4;
it being possible for one or more H atoms in CaaH2aa+1t0 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 NR32SODbR30;
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 CnH2h+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 CnH2h+1 to be replaced by F
atoms, and it being possible for one or more H atoms in the groups

CccH2cc+1 ana" ^yy^2yy-1t0 De 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 SO2R65;
kk 1,2, 3, or 4;
it being possible for one or more H atoms to be replaced by F atoms,
R65 H, CxxH2xx+V>
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, COoH2oo+1.NR70R71,
R70 and R71
independently of one another H, CuuH2Uu+1 or
COR72;
R72 H, CwH2w+1I 00, 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 CwH2w+ito be reP,aced by F atoms; or R7, R8 and R9
independently of one another H, F, CI, Br, I, NO2, CN, OH, NH2, CeeH2ee+1. CwwH2ww-1. OCffH2ff+i, 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> CwwH2ww-1 and OCffH2ff+1 to be replaced by F atoms; R40andR41
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-diethylaminoethylp 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-methyi-
piperazine, piperazine and morpholine; R42 HorChhH2hh+1!
hh 1,2,3or4;
it being possible for one or more H atoms in the group ChnH2hh+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, -OvSOwR23, NR32COR30, NR32CSR30 and
NR32SObbR30;
and the pharmaceutical^ acceptable salts and trifluoroacetates thereof.

3., The compound of the formula I as claimed in claims 1 or 2, in which the meanings are: R1.R2, R3andR4
independently of one another H, F, CI, Br, OH, NH2, CaH2a+1. cycloalkyl with
3,4, 5 or 6 C atoms, OCbH2b+i; a and b
in the groups CaH2a+l and OCfcH2b+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,R3andR4
independently of one another NR11R12; R11 andR12
independently of one another H, CeH2e+1, CrrH2rr-1;
e 1,2, 3 or 4,
IT 3,4, 5 or 6,
it being possible for one or more H atoms in the groups CeH2e+l and CrrH2rr-1 to ^e replaced by F atoms; or R11andR12
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 R11andR12
independently of one another COR14, CSR14, CONHR14, CSNHR14 or S02R14;
R14 CgH2g+i;
g 1 f 2, 3 or 4, it being possible for one or more H atoms
to be reolaced bv F atnmc

or R1,R2,R3andR4
independently of one another OS03H, SO3H, S02R15;
R15 CkH2k+lorNR17R18;
k 1, 2, 3 or 4, it being possible for one or more H atoms to be
replaced by F atoms;
R17andR18
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 tc> be replaced by F
atoms; or R17andR18
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 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 HorCaaH2aa+i;
aa 1,2, 3 or 4;
it being possible for one or more H atoms in CaaH2aa+1to De 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, 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 ar,d
CyyH2yy-i 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, pyrazolyt, pyrrolyl, triazotyl, tetrazolyl, thiazotyl 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 ■ OCffH2ff+l, 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»
CwwH2ww-1 and 0CffH2ff+1to De replaced by F atoms; R40 and R41
H,CttH2tt+1orC(NH)NH2;
tt 1,2, 3 or 4;
it being possible for one or more H atoms in the group CttH2tt+l to be
replaced by F atoms; or R40 and R41
independently of one another hydroxyethyi, N,N-dimethylaminoethyl,
N,N-diethylaminoethy1, pyrrolidinoethyl, N-methylpiperazinoethyi,
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 HorCnhH2hh+i;
hh 1,2, 3 or 4;
it being possible for one or more H atoms in the group CnhH2hh+1 to
be replaced by F atoms; but where two substituents from the group of R7, R8 and R9 may not simultaneously be OH orOCH3,

and where at least one of the radicals R7, R8 or R9 must be selected from the group consisting of CONR40R41, -OvSOwR23, NR32COR30, NR32CSR30 and
NR32SObt)R30; and the pharmaceutical^ acceptable salts and trifluoroacetates
thereof.
4. The compound of the formula I as claimed in claims 1-3 in which the meanings are: R1.R2, R3andR4
independently of one another H, Ff CI, Br, OH, NH2, CaH2a+l. cycloalkyl with
3,4, 5 or 6 C atoms, OCt>H2b+l; 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, R3andR4
independently of one another NR11R12; R11 andR12
independently of one another H, CeH2e+1, CrrH2rr-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 CeH2e+1 and Cn-h^rM to be replaced by F atoms; or R11 andR12
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 andR12

independently of one another COR14, CSR14, CONHR14, CSNHR14 orS02R14;
R14 CgH2g+i;
g 1, 2, 3 or 4, it being possible for one or more H atoms
to be replaced by F atoms;
or
R1.R2, R3andR4
independently of one another OS03H, S03H, S02R15;
R15 CkH2k+1 orNR17R18;
k 1, 2,3 or 4, it being possible for one or more H atoms to be
replaced by F atoms; R17andR18
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 R17andR18
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 trifluoromethyi; R6 H; R7, R8 and R9
independently of one another OSO3H, SO3H 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+1to be
replaced by F atoms; R25 and R26

independently of one another H, CN or CzH2z+1»in wn'Ch the
first CH2 group bonded to the nitrogen is replaced by CO or
CS and the second CH2 is replaced by NR27;
z 1,2,3,4,5or6;
it being possible for one or more H atoms in CZH2Z+1
to be replaced by F atoms; R27 HorCaaH2aa+i: aa 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 NR32SO2R30;
R30 H, OH, CccH2cc+1» CyyH2yy-i, pyrrolidine 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 or8;
yy 3,4,5or6;
it being possible for one or more H atoms in the groups CccH2cc+1 and
CyyH2yy-i 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, tetrazoiyl, 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» OCffH2ff+i, 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 R40 and R41
H,CttH2tt+i,orC(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+V.
hh 1,2,3or4;
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 beOHorOCH3,
and where at least one of the radicals R7, R8 or R9 must be selected from the group consisting of-OvSOwR23, NR32COR30, NR32CSR30 and NR32SObbR30;
and the pharmaceutical^ acceptable salts and trifluoroacetates thereof.
5. The 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-isoquino!in-4-yi)-phenyQ-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-methyI-1,2,3,4-tetrahydro-isoquinolin-4-yl)-NtN-dimethyI-benzenesulfonamide;
5) 4-(4-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline;
6) 4-(6,8-dichioro-2-methyl-1f2,3,4-tetrahydro-isoquinoiin-4-yl)-benzoicacid;
7) 4-(6I8-dichloro-2-methyl-1t2,3,4-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) 6f8-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) 6r8-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-(63^ichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-propylurea;
18) 1-[4-(63-dichloro-2-methyl-1,2,3,44etrahydro-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-methanesulfony!-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]-acetanriide;
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)-phenylj-acetamide;
24) N-[4-(8-chloro-2-methyl-6-morpholin-4-yl-1,2p3,4-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-1t2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoic acid;
28) 5-(6,8-dichloro-2-methyl-1p2,3l4-tetrahydro-isoquinolin^-ylV2-hydroxy-N-methyl-benzamide;
29) 5-(63-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N-ethyl-2-hydroxy-benzamide;
30) 5-(63-dichloro-2-methyl-1,2,3,44etrahydro-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-1,2,3t4-tetrahydro-isoquinolin^-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-1,2,3I4-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-K^CS-dichioro^-methyl-l^^^tetrahydro-isoquinolin^-yl)-phenyl]pentanamide;
38) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyI]-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£4-tetrahydro4soquinolin-4-y\)-pheny!]-cyclobutanecarboxamide;
42) N-[4-(6,8-dfchloro-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>2l2-trifluoro-acetamide;
44) N-[4-(63-dichloro-2-methyl-1,2,3t4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-acetylpiperidine-4-carboxamide;
45) N-[4-(6l8-dichloro-2-methyl-1,2)3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-nicotinamide;
46) N-t4-(6,8-dichloro-2-methyl-1,2t3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methane-sulfonamide;
47) N-^e^-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-ylJ-phenyl]-ethanesutfonamide;
48) N\N'-dimethylamino-N-t4-(6(8-dichloro-2-rnethyl-1,2l3,4-tetrahydro-isoquinolin-4 yl)-phenyl]-sulfamide;
49) N-p-Ce.S-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yO-phenyl]-propionamide;

50) N-[3-(63-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-y^)-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-1l2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-isobutyramide;
53) N-[3-(6,8-dichloro-2-methyl-1,2P3,4-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-methyi-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-1P2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2l2,2-trifluoro-acetamide;
58) N-[3-(63-dichloro-2-methyl-1t2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-acetylpiperidine-4-carboxamide;
59) N-P-Ce.S-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-ylJ-phenyl]-nicotinamide;
60) N-[3^6,8Klichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-y»)-phenyl]-methane-sulfonamide;
61) N-[3-(6,8-dichloro-2-methy!-1,2,3,4-tetrahydro-isoquinolin-4-yl)- phenyl]-ethanesulfonamide;
62) N\N,^imethylamino-N 63) N42-(6l8^ichloro-2-methyl-1,23,4-tetrahydro-isoquinolin^-yl)-phenyl]-propionamide;
64) N^SKe^-dichlor^-methyl-I^.S^-tetrahydro-isoquinolin^-yO-phenyl]-butyramide;
65) N-p^e^^iichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yii-phenyl]-pentanamide;

66) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-isobutyramide;
67) N-[2-(63-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)-phenyi]-cyclopropanecarboxamide;
69) N-p-Ce.S-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-ylVphenyl]-cyclobutanecarboxamide;
70) N-[2-(63-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclopentanecarboxamide;
71) N-[2-(6,8-dtchloro-2-methy!-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-2,2,2-trifiuoro-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]-ethanesulfbnamide;
75) N\N,^imethylamino-N-[2-(63^ichloro-2-methyl-1,2,3,4-tetrahydro-iscKiuinolin^ yl)-phenyl]-sulfamide;
76) 1-[3-(6,8 77) 1-[3-(6,8^ichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin^-yl)-phenyl]-3-methyi-thiourea;
78) 1-[2-(6,8
79) 1-[2-(6,8 80) N-{5-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinofin-4-yl)-phenylsulfamoyl]-4-methyl-thiazoI-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-dimethyI-1H-imidazole-4-sulfonamide;
83) N-[3-(6,8-dichloro-2-methyl-1,2P3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1F2-dimethyl-1H-imidazole-4-suifonamtde;
84) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-5-chioro-1,3-dimethyl-1 H-pyrazole-4-sulfonamide;
85) N-[3-(63^ichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-5-chioro-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^ichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-5-bromo-thiophene-2-suIfonamide;
88) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-C,CpC-trlfluoro-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]-2,2t2-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'^-Ce.S-Dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yl}-benzenesulfonylurea;
93) 2-chloro-5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide;
94) 2-methyl-4-phenyI-6,8-bis-trifluoromethyl-1,2,3,4-tetrahydro-isoquinoIine;
95) 2-amino-N-[4-(6,8-dich)oro-2-methyl-1,2)3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;
96) N-[4K6,8HJichloro-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-dtchloro-2-methyi-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^iamino-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-1t2,3,4-tetrahydro-isoqufnolin-4-yi)-phenyl]-pyrrolidine-2-carboxamide;
102) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-isonfcotinamide;
103) N-[4-(6,8-dichloro-2-methyM,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1 H-pyrrole-3-carboxamide;
104) N-[4-(6,8-d»chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1 H-pyrroIe-2-carboxamide;
105) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yi)-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;
lOgjN-^^e.S-dichloro^-methyl-l^^^-tetrahydro-isoquinolin^-ylJ-phenyq-IH-imidazole-4-carboxamide;
110) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoiin-4-yl)-phenyl]-1 -methanesulfonyl-piperidfne-4-carboxamide;
111) N-[4-(6,8-dichloro-2-methyl-1 ,2,3,4-tetrahydro-isoquinolin^-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]-1 H-pyrazole-4-carboxamide;
113) N-[4-(6,8-dichloro-2-methyI-1 ^^^-tetrahydro-isoquinolin^-yO-phenyl]-3-trifluoromethyl-1H-pyrazole-4-carboxamide;

114) N-[3-(6,8-dichloro-2-methyM,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]-2-dimethylamino-acetamide;
116) 2-amtno-N-[3-(6,8-dichIoro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yf)-phenyl]-propionarnide;
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-dich!oro-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-isoquinotin-4-yl)-phenyl]-isonicotinamide;
121) N-p-Ce.S-dichloro^-methyl-l^^^-tetrahydro-isoquinotin^-ylVphenyll-IH-pyrrole-3-carboxamide;
122) N-[3-(6,8-dichloro-2-methy1-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1 H-pyrrole-2-carboxamide;
123) N-[3-(6)8-dichloro-2-methyi-1,2l3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methyl-piperidine-4-carboxamide;
124) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoiin-4-yl)-phenyl]-1,4-dimethyM 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-yt)-phenyl]-2,5-dimethyl-1H-pyrrole-3-carboxamide;
127) N-[3-(6,8-dichloro-2-methyi-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1 H-imidazote-4-carboxamide;
128) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-y!)-phenyl]-1-methanesulfonyl-piperidine-4-carboxamide;
129) N-P-Ce.S-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-ylJ-phenyl]-3,5-dimethyl-1H-pyrazole-4-carboxamide;

130)N-[3 131) N-[3-(6^^ichloro-2-methyl-1,2,3.4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-trifluoromethyl-1H-pyrazole-4-carboxamide;
132) 1 -[2-(6,8-dichloro-2-rnethyl-1,2t3,4-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) N43-(6,8-dichIoix>-2-methyi-112t3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-piperidine-1-carboxamide;
138) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyi]-morpholine-4-carboxamide;
139) N-[3-(6,8-dichloro-2-methyl-1 ,2,3,4-tetrahydro-isoquinolin-4-yi)-phenyl]-pyrrolidine-1-carboxamide;
140) S-p^e.S-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yO-phenyl]-1,1-diethyl-urea;
141) 1-[3-(63^ichloro-2-methyl-1,2,3,44etrahydro-isoquinolin^-yl)-phenyl]-3-methyU urea;
142) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquino!in-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;
143) 1-[3-(6,8-dichloro-2-methyl-1t2,3l4-tetrahydro-isoquinolin-4-yi)-phenyl]-3-(tetrahyd ro-fu ran-3-yl )-u rea;
144) 1-[3-(6,8^iichloro-2-methyl-1t2l3t4-tetrahydro-isoquinolin-4-yl)-prienyl]-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-methyI-urea; 147)3-[3-(6,8-dichloro-2-methy!-1I2t3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-
1-(2-dimethylamino-ethyl)-1-methyl-urea;
148) 1-[3-(6,8-dichloro-2-methyl-1l2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(3-dimethylamino-propyl)-urea;
149) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-methoxy-ethyI)-urea;
150) 1-[3-(6,8-dichIoro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-pyridin-3-yl-urea;
151) 1-[3-(6,8-dichloro-2-methyl-1,2A^ 4-yl-urea;
152) N-[2-(6,8-dichloro-2-methyl-1,2,3P4-tetrahydro-isoquinolin-4-yO-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) S-p-fe.S-dichloro^-methyl-l^^^-tetrahydro-isoquinolin^-yO-phenyl]-1,1-dimethyl-urea;
155)3-[2-(63^ichloro-2-methyl-1,2,3,4-tetrahydron'soquinolin-4-yl)-phenyl]-1,1-diethyl-urea;
156) N-[2-(6,8-dichloro-2-methy1-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-piperidine-1-carboxamide;
157) N-[2-(6,8-dichloro-2-methyi-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-morpholine-4-carboxamide;
158) N-[2-(6,8-dichloro-2-methyM,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)-phenyi]-4-methyl-piperazine-1-carboxamide;
161) N-[4-(6,8-dichioro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-pyrrolidine-1 -carboxamide;

162) 1-[4-(6,8-dichloro-2-methyl-1f2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-
urea; 163)3-[4-(6,8-dichloro-2-methyl-1,2,3P4-tetrahydro-isoquinolin-4-yl)-phenyll-
1,1-dimethyl-urea;
164) 3-[4-(6,8-dich1oro-2-methyM ,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-diethyl-urea;
165) 1-[4-(63*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-rnethyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-fonmamide;
169) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amine;
170) 1-[4-(6,8-dichioro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,3-dimethyl-urea;
171) N-t4-(6,8^ichioro-2-methyl-1,2,3t4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-4-methyl-ptperazine-1-carboxamide;
172) 1 -[4-(6,8-dichloro-2-methy!-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-fsoquinolin-4-yI)-phenyl>methyi-piperidine-1-carboxamide;
174) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yi)-phenyl]-methyl-morprioline-4-carboxamide;
175) N-[4-(6,8-dichloro-2-rriethyl-1,2t3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-pyrrolidine-1-carboxamide;
176) 1-[4-(6,8-dichloro-2-rnethyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-1-methyl-urea;
177) 1-[4-(6,8^ichloro-2-rnethyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3,3-diethyi-1-methyl-urea;

178) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoIin-4-yl)-phenyl]-formamide;
179) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-pheny(]-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-methy!-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-isoquinonn-4-yl)-phenyl3-methyl-morpholine-4-carboxamide;
185) N-[3-(6,8-dichloro-2-methyl-1 ^.S^-tetrahydro-isoquinolin^-ylVphenyll-methyW methyl-piperazine-1-carboxamide;
186) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrabydro-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)-phenyI3-3,3-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-ethyi [4-(6,8-dichIoro-2-methyl-1 ,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyi]-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-isoqurnolin-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-yI)-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-1,2l3l4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
199) (R)-N-[3-(6,8-dichloro-2-methyl-1,213(4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonamide;
200)(S)-N-l3-(6,8-dichloro-2-methyl-1,2,3t4-tetrahydro-isoquinolin-4-yi)-phenyl]-methanesulfonamide;
201) (R)-1-[2-(6,8-dichloro-2-methyl-1f2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;
202) (SJ-1-t2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoNn-4-yl)-phenyl]-3-ethyl-urea;
203)N-[3-(6,8-dichloro-2-methyl-1,2l3,4-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-1t2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-hydroxy-ethyl )-u rea;
206) ethyl 3-(6,8-dich!oro-2-methyl-1 ,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoate;
207) 3-(6,8-dichloro-2-methy1-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid,
and the pharmaceutical^ acceptable salts thereof.
and from the pharmaceuticaiiy acceptable salts thereof.
6. The 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-memyl-1,23t4-tetrahydro-isoquinolin^-yl)-ben2enesu!fonamide;
3) 3-(6^-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yt)-ben2enesutfonamide;
4) 1-[4-(6,8 5) 1-[4-(63^ichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-
urea;
6) N-[4-(6-bromo-8-chloro-2-rnethyl-1,2,3,4-tetrahydro-isoquinolin-4-y()-phenyl]-acetamide;
7) N-P-fe.S-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yO-phenyl]-acetamide;
8) N-[4-(6,8-dichioro-2-methyl-1,2,3,4-tetrahydro-isoquinoiin-4-yl)-phenyl]-propionamide;
9) N-[4-(63-dichloro-2-methyI-1,2,3,4-tetrahydro-isoquinoIin-4-yl)-phenyl]-1-acetyl-piperidine-4-carboxamide;
10) N-^-fe^Hdichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-ylJ-phenylJ-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-t4-(63-dichloro-2-methyl--1t2,3,4-tetrahydro-isoqumolin-4-yl>-phenyl]-sulfamid8;
13) N-[3-(6,8-dichloro-2-methyM,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;
14) N-[3-(6,8-dichloro-2-methy!-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;
15) N-P^.S-dichloro^-methyM^.S^-tetrahydro-isoquinolin^-ylJ-phenyl]-isobutyramide;
16) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-cycJopropanecarboxamide;
17) N-[3-(6,8-dichloro-2-methyM ,2,3t4-tetrahydro-isoquinolin-4-yl)-phenyl]-cyclobutanecarboxamide;
18) N-fS-Ce^-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-ylJ-phenyll-a^^-trifluoro-acetamide;

19) N-IS^e^-dichloro^-methyl-l^^^-tetrahydro-isoquinoIin^-yO-phenylJ-l-acetyl-piperidine-4-carboxamide;
20) N-[3-(6,8-dichloro-2-methyl-1t2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-nicotinamide;
21) N-[3-(6,8-dichloro-2-methyl-1 ^.S^-tetrahydro-isoquinolin^-ylJ-phenyll-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«1,2,3l4-tetrahydra-isoquinolin-4-yl)-phenyl]-sulfamide;
24) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoIin-4-yl)-phenyl]-cyclopropanecarboxamide;
25) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-acety[-piperidine-4-carboxamide;
26) l-IS-fe.S-dichloro^-methyl-l^^^-tetrahydro-isoquinolin^-yO-phenyll-S-ethyl-urea;
27) 1-[3-(6,8^ichloro-2-methyl-1,2,3,4-tetrahydro-isoq thiourea;
28) 1-[2-(63^ichloro-2-methyl-1,2t3,44etrahydro-fsoquinolin-4-yl)-phenyl]-3-ethyl-urea;
29) 1-[2-(63-dichlorcH2-methyl-1,2,3,4-tetrahydro-isoquinolin^-yl)-phenyl]-3-meth thiourea;
30) N-{5-[3-(6,8-dichloro-2-methyl-1,2,3t4-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-yi)-pheny!]-1,2-dimethyl-1H-imidazo!e-4-sulfonamide;
32) N-[4-(6,8-dichloro-2-methyl-1f2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-C,C,C-trifluoro-methanesulfonamide;
33) N-[3-(6?8-dichloro-2-methyl-1,2,3l4-tetrahydro-isoquinolin-4-yl)-phenyl]-ClC,C-trifluoro-methanesulfonamide;
34) N^thyl-NM-(6,8^ich)oro-2-methvl-1.2.3.44etrahvrimJcnniiinrtiin^-wi\_
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]-1H-pyrrole-3-carboxamide;
38) N-[4-(6,8^ichloro-2-rnethyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-methyl-piperidine-4-carboxamide;
39) N-[4-(6,8-dichloro-2-methyl-1,2,3f4-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)-pheny(]-1H-pyrazole-carboxamide;
41) N-[3-(6,8-dichloro-2-methyM f2(3,4-tetrahydro-isoquinoiin-4-yl)-phenyl]-2-methylamino-acetamide;
42) N-p^.e-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-yO-phenyl]^-dimethylamino-acetamide;
43) 2-amino-N-[3-(6,8KJichloro-2-methyl-1,213,4-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) 2r6-diamino-N-[3-(6,8-dichloro-2-methyl--1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-hexanamide;
46) N-I3-(6,8-dich1oro-2-methyl-1,2,3(4-tetrahydro-isoquinolin-4-y1)-phenyl]-1 -methyl-pipe ridine-4-carboxamide;
47) N-[3-(6t8-dichloro-2-methyl-1,2F3,4-tetrahydro-isoquinolin-4-yl)-phenyi]-1H-imidazole-4-carboxamide;
48) N-p-fe.S-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-ylJ-phenylJ-l-methanesulfonyl-piperidine-4-carboxamide;
49) N-[3-(6,8Klichloro-2-.methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3t5-dimethyl-1 H-pyrazole-4-carboxamide;
50) N-[3-(6,8-dichloro-2-methyM ,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1 H-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-(6f8-dichloro-1,2P3,4-tetrahydro-isoquinolin-4-yl)-phenyI]-4-methyl-piperazine-1 -carboxamide;
53) N-p-fe^-dichlor^-methyl-l^^^-tetrahydro-isoquinolin^-ylJ-phenylJ-piperidine-1-carboxamide;
54) N-[3-(6,8-dichloro-2-methyM12,3l4-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- 57) 1-[3-(6,8-dichloro-2-methyl-1,2f3,4-tetrahydro-isoquinolin^-yl)-phenyl]-3-methyl-urea;
58) 1 -[3-(6,8-dichloro-2-methyl-1,2,3t4-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-(63-dichioro-2-methyi-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(tetrahydro-pyran-4-yl)-urea;
61) 3-[3-(6f8-dichIoro-2-methyl-1,2,3,4-tetrahydro-isoquinolin^-y!)-phenyl]-1-methyl--1-(1 -methyl-piperidin-4-yl)-urea;
62) 3-[3-(63-dichloro-2-methyl-1l2f3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1'(3-dimethylamino-propyl)-1-methyl-urea;
63) 3-[3-(6,8-dichloro-2-methyl-1,2>3l4-tetrahydro-isoquinolin-4-yl)-phenyl]-1-(2-dimethylamino-ethyl)-1-methyl-urea;
64) ^^-(e.S-dichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-ylJ-phenyll-S^S-diethylamino-propyi)-urea;
65) 1-[3-(6l8-dichloro-2-methyl-1p2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-methoxy-ethyl)-urea;
66) 1-[3-(6,8-dichloro-2-methyl-1f2,3,4-tetrahydro-isoquinolin-4-yl)-phenyt]-3-pyridin-3-yl)-urea;

67) l-p-Ce^S-dichloro^-methyl-l^^^-tetrahydro-isoquinolin-A-ylJ-phenylJ-S-pyridin-4-yl-urea;
68) N-[2-(6,8-dichloro-2-methyl-1,2(3,4-tetrahydro-isoqutnolin-4-yl)-phenyl]-4-methyl-piperazine-1 -carboxamide;
69) l-p-fe^-dichloro-a-rnethyl-l^^^-tetrahydro-isoquinolin^-ylJ-phenyll-S-methyl-urea;
70) 1-[2-{6t8-dichloro-2-methyl-1l2,3,4-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) l-^e.SHdichloro^-methyl-I^.S^-tetrahydroHSoquinolin^-yl^phenylJ-S-methyl-urea;
73) 3-[4-(6p8-dichloro-2-methyl-1,2p3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea;
74) 3-[4-(6,8-dichloro-2-methyl-1,2,3p4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-diethyl-urea;
75) 1-[4-(6,8-dichloro-2-methyl-1,2l3t4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyI)-urea;
76) N-t4-(6f8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoIin-4-yl)-phenyl]-morpholine-4-carboxamide;
77) N^^e^Klichloro^-methyl-I^.S^-tetrahydro-isoquinolin^-ylVphenyll-foiTnamide^
78) N-[3-(6,8-dichloro-2-methyl-1I2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-formamide;
79) 1 -[3-(6,8-dichioro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,3,3-trimethyl-urea;
80) 1 -P-(6,8-dichloro-2-methyl-1 ,2,3,4-tetrahydro-isoquinolin^-yl^phenyl]-! ,3-dimethyl-urea;
81) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoIin-4-yl)-phenyl]-methyl-morpholine-4-carboxamide;
82) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydrD-isoquinolin-4-yl)-phenyl]-methyl-4-methyl-piperazine-1 -carboxamide;

83) 1-[3-(6r8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-
dimethylamino-ethyl)-1-methyl-urea;
84) 2-dimethylamine-ethyl[3-(63-dichloro-2-methyl-1,2,3A-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamate;
85) 2-dimethylamino-ethyl t4-(6l8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoiin-4-yl)-phenyl]-carbamate;
86) 2-dimethy!amino-ethyl[2-(6,8-dichloro-2-methyl-1,2,3p4-tetrahydro-isoquinolin-4-
yi)-phenyl]-carbamate;
87) methyl [3-(6,8-dichloro-2-methy1-1,2,3,4-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-clichloro-2-methy!-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-
ethyl-urea;
90) 1-t3-(6,8-dichloro-2-methyl-1)2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-(2-
hydroxy-ethyl)-urea;
and from the pharmaceutical^ acceptable salts thereof.

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Patent Number 227152
Indian Patent Application Number 1236/CHENP/2004
PG Journal Number 07/2009
Publication Date 13-Feb-2009
Grant Date 05-Jan-2009
Date of Filing 04-Jun-2004
Name of Patentee SANOFI-AVENTIS DEUTSCHLAND GmbH
Applicant Address BRUNINGSTRASSE 50, D-65929 FRANKURT AM MAIN,
Inventors:
# Inventor's Name Inventor's Address
1 HEINELT, UWE MOSBACHER STRASSE 54, 65187 WIESBADEN,
2 BLEICH, MARKUS EUFINGER STRASSE 73, 65597 HUNFELDEN-DAUBORN,
3 LANG, HANS-JOCHEN RUDESHEIMER STRASSE 7, 65719 HOFHEIM,
4 WIRTH, KLAUS ROBERT-SCHUMANN-RING 104, 65830 KRIFTER,
5 GEKLE, MICHAEL SCHIESSHAUSSTRASSE 11, 97072 WURZBURG,
6 HOFMEISTER, ARMIN PFAUGASSE 16, 55276 OPPENHEIM,
PCT International Classification Number CO7D217/22
PCT International Application Number PCT/EP02/12990
PCT International Filing date 2002-11-20
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 101 59 714 2001-12-05 Germany