1
CLAIMS
1- Products of the following general formula (I):
H
4
Z3
N
H 5
H
N
H
1
Z6
8 H
H
(I)
5
in which
- Z3 represents a heteroaryl radical constituted of 5 or 6 ring members with 1 to 4
heteroatoms selected from N, S or O bound to the carboline unit either by a C or by
an N belonging to Z3, Z3 optionally being mono- or polysubstituted;
- Z6 is selected from:
10
1. H;
2. halogen
3. -OH
4. alkoxy in which the alkyl moiety is optionally mono-, di- or trisubstituted;
5. -Y-alkyl (Y = S, SO, SO2), linear or branched, optionally mono-, di- or
15
trisubstituted;
6. -X-aryl (X = O, S, SO, SO2) optionally mono-, di- or trisubstituted;
7. -X-heteroaryl (X = O, S, SO, SO2, heteroaryl with 5 or 6 ring members
with 1 to 4 heteroatoms selected from N, S or O bound to X either by a
C or an N) optionally mono-, di- or trisubstituted;
20
8. -NH2,
9. -NH(alkyl), -N(alkyl)2 linear, branched or cyclic in which the alkyl moiety
is optionally mono-, di- or trisubstituted;
10. -NH(aryl) in which the aryl moiety is optionally mono-, di- or
trisubstituted;
25
11. -NH(heteroaryl) in which the heteroaryl moiety (heteroaryl with 5 or 6
ring members with 1 to 4 heteroatoms selected from N, S or O bound to
the nitrogen atom either by a C or by an N) is optionally mono-, di- or
trisubstituted;
2
12. -N(alkyl)(aryl) in which the alkyl (linear, branched or cyclic) and aryl
moieties are optionally mono-, di- or trisubstituted;
13. -N(alkyl)(heteroaryl) in which the alkyl (linear, branched or cyclic) and
heteroaryl (heteroaryl with 5 or 6 ring members with 1 to 4 heteroatoms
5
selected from N, S or O bound to the nitrogen atom either by a C or an
N) moieties are optionally mono-, di- or trisubstituted;
14. -C(O)OH
15. -C(O)Oalkyl, linear, branched or cyclic, optionally mono-, di- or
trisubstituted;
10
16. -C(O)Oaryl optionally mono-, di- or trisubstituted;
17. -C(O)Oheteroaryl (heteroaryl with 5 or 6 ring members with 1 to 4
heteroatoms selected from N, S or O bound to the oxygen by a C atom)
optionally mono-, di- or trisubstituted;
18. -CONH2
15
19. -CO-heterocycloalkyl mono-, di- or trisubstituted
20. -CONH(alkyl),CON(alkyl)2 linear, branched or cyclic in which the alkyl
moiety is optionally mono-, di- or trisubstituted;
21. -CON(alkyl)(aryl), alkyl linear, branched or cyclic in which the alkyl and
aryl moieties are optionally mono-, di- or trisubstituted;
20
22. -CON(alkyl)(heteroaryl), linear, branched or cyclic alkyl and heteroaryl
with 5 or 6 ring members with 1 to 4 heteroatoms selected from N, S or
O bound to the nitrogen atom either by a C or by an N) in which the
alkyl and heteroaryl moieties are optionally mono-, di- or trisubstituted;
23. -C1-C10 alkyl, linear, branched or cyclic, optionally comprising a
25
heteroatom and optionally mono-, di- or trisubstituted
24. aryl optionally mono-, di- or trisubstituted
25. heteroaryl (5 or 6 ring members with 1 to 4 heteroatoms selected from
N, S or O) bound to the carboline unit either by a C or by an N
belonging to Z6, Z6 optionally being mono- or polysubstituted;
30
26. heterocycloalkyl optionally mono- or polysubstituted;
27. -C2-C6 alkenyl optionally mono- or disubstituted;
28. -C2-C6 alkynyl optionally substituted;
3
said products of formula (I) being in all possible isomeric forms, racemic,
enantiomeric and diastereoisomeric, as well as the salts of addition of said products
of formula (I) with mineral and organic acids or with mineral and organic bases.
5
2- Products of general formula (I) as defined in Claim 1 in which the optional
substituents of Z3, i.e. the groups R2a, R2b, R2c, R2d or R2e, are selected
independently of one another from:
1. F;
2. Cl;
10
3. Br;
4. I;
5. -C1-C10 alkyl, linear or branched, optionally mono- or polysubstituted
(R3a,R3b,R3c);
6. -C3-C7 cycloalkyl optionally mono- or polysubstituted (R3a,R3b,R3c),
15
7. -OH;
8. -O-alkyl(C1-C10), linear or branched, optionally mono- or polysubstituted
(R3a,R3b,R3c);
9. -Y-alkyl (Y = S, SO, SO2), linear or branched, optionally mono-, di- or
trisubstituted (R3a,R3b,R3c);
20
10. -O-cycloalkyl
(C3-C7)
optionally
mono-
or
polysubstituted
(R3a,R3b,R3c);
11. -O-aryl optionally mono- or polysubstituted (R3a,R3b,R3c);
12. aryl optionally mono- or polysubstituted (R3a,R3b,R3c);
13. heteroaryl (5 or 6 ring members with 1 to 4 heteroatoms selected from
25
N, S or O) bound either by a C or by an N) optionally mono- or
polysubstituted (R3a,R3b,R3c);
14. heterocycloalkyl optionally mono- or polysubstituted (R3a,R3b,R3c);
15. -NO2;
16. -NH2;
30
17. -NH-(alkyl(C1-C10) or cycloalkyl(C3-C7) or heterocycloalkyl) each group
optionally mono- or polysubstituted (R3a,R3b,R3c);
18. -N(alkyl(C1-C10) or cycloalkyl(C3-C7))2 each group optionally being
mono- or polysubstituted (R3a,R3b,R3c);
19. -NHaryl or NH heteroaryl optionally mono- or polysubstituted
4
20. -NHC(O)substituted (R3a,R3b,R3c);
21. -N(alkyl(C1-C10)C(O)substituted (R3a,R3b,R3c);
22. -NHS(O2)substituted (R3a,R3b,R3c);
23. -N(alkyl(C1-C10)S(O2)substituted (R3a,R3b,R3c);
5
24. -CO2substituted (R3a,R3b,R3c);
25. –S substituted (R3a,R3b,R3c);
26. -S(O2)substituted (R3a,R3b,R3c);
27. -S(O) substituted (R3a,R3b,R3c);
28. oxo (O double bond);
10
29. -C2-C6 alkenyl optionally mono- or disubstituted (R3a,R3b);
30. -C2-C6 alkynyl optionally substituted ((R3a);
the groups R3a, R3b, R3c, or the substituents of the groups R2a, R2b, R2c, R2d or
R2e, are selected independently of one another from:
1. F;
15
2. Cl;
3. Br;
4. I;
5. -C1-C10 alkyl, linear or branched, optionally mono- or polysubstituted with
R4a, R4b, R4c;
20
6. -C3-C7 cycloalkyl optionally mono- or polysubstituted with R4a, R4b, R4c;
7. -OH;
8. -O-alkyl(C1-C10), linear or branched, optionally mono- or polysubstituted
with R4a, R4b, R4c;
9. -Y-alkyl (Y = S, SO, SO2), linear or branched, optionally mono-, di- or
25
trisubstituted with R4a, R4b, R4c;
10. -O-cycloalkyl (C3-C7) optionally mono- or polysubstituted with R4a, R4b,
R4c;
11. -O-aryl optionally mono- or polysubstituted with R4a, R4b, R4c;
12. aryl optionally mono- or polysubstituted with R4a, R4b, R4c;
30
13. heteroaryl optionally mono- or polysubstituted with R4a, R4b, R4c;
14. heterocycloalkyl optionally mono- or polysubstituted with R4a, R4b, R4c;
15. -NO2;
16. -NH2;
5
17. -NH-(alkyl(C1-C10) or cycloalkyl(C3-C7) or heterocycloalkyl) each group
optionally mono- or polysubstituted with R4a, R4b, R4c;
18. -N(alkyl(C1-C10) or cycloalkyl(C3-C7))2 each group optionally being monoor polysubstituted with R4a, R4b, R4c;
5
19. -NHaryl or NH heteroaryl optionally mono- or polysubstituted with R4a,
R4b, R4c;
20. -NHC(O) substituted with R4a, R4b, R4c;
21. -N(alkyl(C1-C10)C(O) substituted with R4a, R4b, R4c;
22. -NHS(O2) substituted with R4a, R4b, R4c;
10
23. -N(alkyl(C1-C10)S(O2) substituted with R4a, R4b, R4c;
24. -CO2 substituted with R4a, R4b, R4c;
25. -CONH2
26. -CONH(alkyl), CON(alkyl)2 linear, branched or cyclic in which the alkyl
moiety is optionally mono-, di- or trisubstituted with R4a, R4b, R4c;
15
27. -C(O)heterocycloalkyl optionally mono-, di- or trisubstituted with R4a, R4b,
R4c;
28. -S substituted with R4a, R4b, R4c;
29. -S(O2) substituted with R4a, R4b, R4c;
30. -S(O) substituted with R4a, R4b, R4c;
20
31. oxo (O double bond);
32. -C2-C6 alkenyl optionally mono- or polysubstituted with R4a, R4b, R4c;
33. -C2-C6 alkynyl optionally mono- or polysubstituted with R4a, R4b, R4c;
the groups R4a, R4b, R4c, or the substituents of the groups R3a, R3b and R3c, are
selected independently of one another from:
25
1. F;
2. Cl;
3. Br;
4. I;
5. -CF3; -CHF2
30
6. -C1-C10 alkyl linear or branched;
7. -C3-C7 cycloalkyl;
8. -OH;
9. -O-alkyl(C1-C10) linear or branched;
10. -Y-alkyl (Y = S, SO, SO2) linear or branched;
6
11. -O-cycloalkyl (C3-C7);
12. -O-aryl;
13. aryl;
14. heteroaryl;
5
15. heterocycloalkyl;
16. -NO2;
17. -NH2;
18. -NH-(alkyl(C1-C10) or cycloalkyl(C3-C7) or heterocycloalkyl);
19. -N(alkyl(C1-C10) or cycloalkyl(C3-C7))2;
10
20. -NHaryl or NH heteroaryl;
21. -NHS(O2)alkyl;
22. -N(alkyl(C1-C10)S(O2)alkyl;
23. -CO2alkyl;
24. -CONH2
15
25. -CONH(alkyl), CON(alkyl)2 linear, branched or cyclic;
26. -C(O)heterocycloalkyl;
27. –S-alkyl;
28. -S(O2)alkyl;
29. -S(O)alkyl;
20
30. oxo (O double bond);
31. -C2-C6 alkenyl linear or branched;
32. -C2-C6 alkynyl linear or branched;
said products of formula (I) being in all possible isomeric forms, racemic,
enantiomeric and diastereoisomeric, as well as the salts of addition of said products
25
of formula (I) with mineral and organic acids or with mineral and organic bases.
3 - Products of general formula (I) as defined in Claim 1 in which the optional
substituents of Z6, i.e. the groups R2a, R2b, R2c, R2d or R2e, are selected
30
independently of one another from:
1. F;
2. Cl;
3. Br;
4. I;
7
5. -C1-C10 alkyl, linear or branched, optionally mono- or polysubstituted
(R3a,R3b,R3c);
6. -C3-C7 cycloalkyl optionally mono- or polysubstituted (R3a,R3b,R3c),
7. -OH;
5
8. -O-alkyl(C1-C10), linear or branched, optionally mono- or polysubstituted
(R3a,R3b,R3c);
9. -Y-alkyl (Y = S, SO, SO2), linear or branched, optionally mono-, di- or
trisubstituted (R3a,R3b,R3c);
10. -O-cycloalkyl
10
(C3-C7)
optionally
mono-
or
polysubstituted
(R3a,R3b,R3c);
11. -O-aryl optionally mono- or polysubstituted (R3a,R3b,R3c);
12. aryl optionally mono- or polysubstituted (R3a,R3b,R3c);
13. heteroaryl (5 or 6 ring members with 1 to 4 heteroatoms selected from
N, S or O) bound either by a C or by an N) optionally mono- or
15
polysubstituted (R3a,R3b,R3c);
14. heterocycloalkyl optionally mono- or polysubstituted (R3a,R3b,R3c);
15. -NO2;
16. -NH2;
17. -NH-(alkyl(C1-C10) or cycloalkyl(C3-C7) or heterocycloalkyl) each group
20
optionally mono- or polysubstituted (R3a,R3b,R3c);
18. -N(alkyl(C1-C10) or cycloalkyl(C3-C7))2 each group optionally being
mono- or polysubstituted (R3a,R3b,R3c);
19. -NHaryl or NH heteroaryl optionally mono- or polysubstituted
20. -NHC(O)substituted (R3a,R3b,R3c);
25
21. -N(alkyl(C1-C10)C(O)substituted (R3a,R3b,R3c);
22. -NHS(O2)substituted (R3a,R3b,R3c);
23. -N(alkyl(C1-C10)S(O2)substituted (R3a,R3b,R3c);
24. -CO2substituted (R3a,R3b,R3c);
25. –S substituted (R3a,R3b,R3c);
30
26. -S(O2)substituted (R3a,R3b,R3c);
27. -S(O) substituted (R3a,R3b,R3c);
28. oxo (O double bond);
29. -C2-C6 alkenyl optionally mono- or disubstituted (R3a,R3b);
30. -C2-C6 alkynyl optionally substituted ((R3a);
8
the groups R3a, R3b, R3c, or the substituents of the groups R2a, R2b, R2c, R2d or
R2e, are selected independently of one another from:
1. F;
2. Cl;
5
3. Br;
4. I;
5. -C1-C10 alkyl, linear or branched, optionally mono- or polysubstituted with
R4a, R4b, R4c;
6. -C3-C7 cycloalkyl optionally mono- or polysubstituted with R4a, R4b, R4c;
10
7. -OH;
8. -O-alkyl(C1-C10), linear or branched, optionally mono- or polysubstituted
with R4a, R4b, R4c;
9. -Y-alkyl (Y = S, SO, SO2), linear or branched, optionally mono-, di- or
trisubstituted with R4a, R4b, R4c;
15
10. -O-cycloalkyl (C3-C7) optionally mono- or polysubstituted with R4a, R4b,
R4c;
11. -O-aryl optionally mono- or polysubstituted with R4a, R4b, R4c;
12. aryl optionally mono- or polysubstituted with R4a, R4b, R4c;
13. heteroaryl optionally mono- or polysubstituted with R4a, R4b, R4c;
20
14. heterocycloalkyl optionally mono- or polysubstituted with R4a, R4b, R4c;
15. -NO2;
16. -NH2;
17. -NH-(alkyl(C1-C10) or cycloalkyl(C3-C7) or heterocycloalkyl) each group
optionally mono- or polysubstituted with R4a, R4b, R4c;
25
18. -N(alkyl(C1-C10) or cycloalkyl(C3-C7))2 each group optionally being monoor polysubstituted with R4a, R4b, R4c;
19. -NHaryl or NH heteroaryl optionally mono- or polysubstituted with R4a,
R4b, R4c;
20. -NHC(O) substituted with R4a, R4b, R4c;
30
21. -N(alkyl(C1-C10)C(O) substituted with R4a, R4b, R4c;
22. -NHS(O2) substituted with R4a, R4b, R4c;
23. -N(alkyl(C1-C10)S(O2) substituted with R4a, R4b, R4c;
24. -CO2 substituted with R4a, R4b, R4c;
25. -CONH2
9
26. -CONH(alkyl), CON(alkyl)2 linear, branched or cyclic in which the alkyl
moiety is optionally mono-, di- or trisubstituted with R4a, R4b, R4c;
27. -C(O)heterocycloalkyl optionally mono-, di- or trisubstituted with R4a, R4b,
R4c;
5
28. -S substituted with R4a, R4b, R4c;
29. -S(O2) substituted with R4a, R4b, R4c;
30. -S(O) substituted with R4a, R4b, R4c;
31. oxo (O double bond);
32. -C2-C6 alkenyl optionally mono- or polysubstituted with R4a, R4b, R4c;
10
33. -C2-C6 alkynyl optionally mono- or polysubstituted with R4a, R4b, R4c;
the groups R4a, R4b, R4c, or the substituents of the groups R3a, R3b and R3c, are
selected independently of one another from:
1. F;
2. Cl;
15
3. Br;
4. I;
5. -CF3; -CHF2
6. -C1-C10 alkyl linear or branched;
7. -C3-C7 cycloalkyl;
20
8. -OH;
9. -O-alkyl(C1-C10) linear or branched;
10. -Y-alkyl (Y = S, SO, SO2) linear or branched;
11. -O-cycloalkyl (C3-C7);
12. -O-aryl;
25
13. aryl;
14. heteroaryl;
15. heterocycloalkyl;
16. -NO2;
17. -NH2;
30
18. -NH-(alkyl(C1-C10) or cycloalkyl(C3-C7) or heterocycloalkyl);
19. -N(alkyl(C1-C10) or cycloalkyl(C3-C7))2;
20. -NHaryl or NH heteroaryl;
21. -NHS(O2)alkyl;
22. -N(alkyl(C1-C10)S(O2)alkyl;
10
23. -CO2alkyl;
24. -CONH2
25. -CONH(alkyl), CON(alkyl)2 linear, branched or cyclic;
26. -C(O)heterocycloalkyl;
27. –S-alkyl;
5
28. -S(O2)alkyl;
29. -S(O)alkyl;
30. oxo (O double bond);
31. -C2-C6 alkenyl linear or branched;
10
32. -C2-C6 alkynyl linear or branched;
said products of formula (I) being in all possible isomeric forms, racemic,
enantiomeric and diastereoisomeric, as well as the salts of addition of said products
of formula (I) with mineral and organic acids or with mineral and organic bases.
15
4 - Products of general formula (I) as defined in any one of the preceding claims in
which
- Z3 represents a heteroaryl radical with 5 or 6 ring members with 1 to 4 heteroatoms
selected from N, S or O bound to the carboline unit either by a C or by an N
belonging to Z3, Z3 optionally being mono- or polysubstituted with R2a, R2b, R2c,
20
R2d, R2e, which may be identical or different;
- Z6 is selected from:
1. H;
2. halogen;
3. -OH
25
4. alkoxy in which the alkyl moiety is optionally mono-, di- or trisubstituted
with R2a, R2b, R2c, which may be identical or different;
5. -Y-alkyl (Y = S, SO, SO2), linear or branched, optionally mono-, di- or
trisubstituted with R2a, R2b, R2c, which may be identical or different;
6. -X-aryl (X = O, S, SO, SO2) optionally mono-, di- or trisubstituted with
30
R2a, R2b, R2c, which may be identical or different;
7. -X-heteroaryl (X = O, S, SO, SO2, heteroaryl with 5 or 6 ring members
with 1 to 4 heteroatoms selected from N, S or O bound to X either by a
C or an N) optionally mono-, di- or trisubstituted with R2a, R2b, R2c,
which may be identical or different;
11
8. -NH2,
9. -NH(alkyl), -N(alkyl)2 linear, branched or cyclic in which the alkyl moiety
is optionally mono-, di- or trisubstituted with R2a, R2b, R2c, which may
be identical or different;
5
10. -NH(aryl) in which the aryl moiety is optionally mono-, di- or
trisubstituted with R2a, R2b, R2c, which may be identical or different;
11. -NH(heteroaryl) in which the heteroaryl moiety (heteroaryl with 5 or 6
ring members with 1 to 4 heteroatoms selected from N, S or O bound to
the nitrogen atom either by a C or by an N) is optionally mono-, di- or
10
trisubstituted with R2a, R2b, R2c, which may be identical or different;
12. -N(alkyl)(aryl) in which the alkyl (linear, branched or cyclic) and aryl
moieties are optionally mono-, di- or trisubstituted with R2a, R2b, R2c,
which may be identical or different;
13. -N(alkyl)(heteroaryl) in which the alkyl (linear, branched or cyclic) and
15
heteroaryl (heteroaryl with 5 or 6 ring members with 1 to 4 heteroatoms
selected from N, S or O bound to the nitrogen atom either by a C or an
N) moieties are optionally mono-, di- or trisubstituted with R2a, R2b,
R2c, which may be identical or different;
14. -C(O)OH
20
15. -C(O)Oalkyl, linear, branched or cyclic, optionally mono-, di- or
trisubstituted with R2a, R2b, R2c, which may be identical or different;
16. -C(O)Oaryl optionally mono-, di- or trisubstituted with R2a, R2b, R2c,
which may be identical or different;
17. -C(O)Oheteroaryl (heteroaryl with 5 or 6 ring members with 1 to 4
25
heteroatoms selected from N, S or O bound to the oxygen by a C atom)
optionally mono-, di- or trisubstituted with R2a, R2b, R2c, which may be
identical or different;
18. -CONH2
19. -CO-heterocycloalkyl mono-, di- or trisubstituted
30
20. -CONH(alkyl),CON(alkyl)2 linear, branched or cyclic in which the alkyl
moiety is optionally mono-, di- or trisubstituted with R2a, R2b, R2c,
which may be identical or different;
12
21. -CON(alkyl)(aryl), alkyl linear, branched or cyclic in which the alkyl and
aryl moieties are optionally mono-, di- or trisubstituted with R2a, R2b,
R2c, which may be identical or different;
22. -CON(alkyl)(heteroaryl), alkyl linear, branched or cyclic and heteroaryl
5
with 5 or 6 ring members with 1 to 4 heteroatoms selected from N, S or
O bound to the nitrogen atom either by a C or by an N) in which the
alkyl and heteroaryl moieties are optionally mono-, di- or trisubstituted
with R2a, R2b, R2c, which may be identical or different;
23. -C1-C10 alkyl, linear, branched or cyclic, optionally comprising a
10
heteroatom and optionally mono-, di- or trisubstituted with R2a, R2b,
R2c, which may be identical or different;
24. aryl optionally mono-, di- or trisubstituted with R2a, R2b, R2c, which
may be identical or different;
25. heteroaryl (5 or 6 ring members with 1 to 4 heteroatoms selected from
15
N, S or O) bound to the carboline unit either by a C or by an N
belonging to Z6, Z6 optionally being mono- or polysubstituted with R2a,
R2b, R2c, R2d, R2e which may be identical or different;
26. heterocycloalkyl optionally mono- or polysubstituted with R2a, R2b, R2c,
which may be identical or different;
20
27. -C2-C6 alkenyl optionally mono- or disubstituted with R2a, R2b, which
may be identical or different;
28. -C2-C6 alkynyl optionally substituted with R2a;
the groups R2a, R2b, R2c, R2d or R2e are selected independently of one another
from:
25
1. F;
2. Cl;
3. Br;
4. I;
5. -C1-C10 alkyl, linear or branched, optionally mono- or polysubstituted
30
with R3a, R3b, R3c, which may be identical or different
6. -C3-C7 cycloalkyl optionally mono- or polysubstituted with R3a, R3b,
R3c, which may be identical or different,
7. -OH;
13
8. -O-alkyl(C1-C10), linear or branched, optionally mono- or polysubstituted
with R3a, R3b, R3c, which may be identical or different;
9. -Y-alkyl (Y = S, SO, SO2), linear or branched, optionally mono-, di- or
trisubstituted with R3a, R3b, R3c, which may be identical or different;
5
10. -O-cycloalkyl (C3-C7) optionally mono- or polysubstituted with R3a, R3b,
R3c, which may be identical or different;
11. -O-aryl optionally mono- or polysubstituted with R3a, R3b, R3c, which
may be identical or different;
12. aryl optionally mono- or polysubstituted with R3a, R3b, R3c, which may
10
be identical or different;
13. heteroaryl constituted of 5 or 6 ring members with 1 to 4 heteroatoms
selected from N, S or O bound either by a C or by an N) optionally
mono- or polysubstituted with R3a, R3b, R3c, which may be identical or
different;
15
14. heterocycloalkyl optionally mono- or polysubstituted with R3a, R3b, R3c,
which may be identical or different;
15. -NO2;
16. -NH2;
17. -NH-(alkyl(C1-C10) or cycloalkyl(C3-C7) or heterocycloalkyl) each group
20
optionally mono- or polysubstituted with R3a, R3b, R3c, which may be
identical or different;
18. -N(alkyl(C1-C10) or cycloalkyl(C3-C7))2 each group optionally being
mono- or polysubstituted with R3a, R3b, R3c, which may be identical or
different;
25
19. -NHaryl or NH heteroaryl optionally mono- or polysubstituted with R3a,
R3b, R3c, which may be identical or different
20. -NHC(O) substituted with R3a, R3b, R3c, which may be identical or
different;
21. -N(alkyl(C1-C10)C(O) substituted with R3a, R3b, R3c, which may be
30
identical or different;
22. -NHS(O2) substituted with R3a, R3b, R3c, which may be identical or
different;
23. -N(alkyl(C1-C10)S(O2) substituted with R3a, R3b, R3c, which may be
identical or different;
14
24. -CO2 substituted with R3a, R3b, R3c, which may be identical or
different;
25. –S substituted with R3a, R3b, R3c, which may be identical or different;
26. -S(O2) substituted with R3a, R3b, R3c, which may be identical or
5
different;
27. -S(O) substituted with R3a, R3b, R3c, which may be identical or
different;
28. oxo (O double bond);
29. -C2-C6 alkenyl optionally mono- or disubstituted with R3a, R3b which
10
may be identical or different;
30. -C2-C6 alkynyl optionally substituted with R3a;
the groups R3a, R3b, R3c, or the substituents of the groups R2a, R2b, R2c, R2d or
R2e, are selected independently of one another from:
1. F;
15
2. Cl;
3. Br;
4. I;
5. -C1-C10 alkyl, linear or branched, optionally mono- or polysubstituted with
R4a, R4b, R4c;
20
6. -C3-C7 cycloalkyl optionally mono- or polysubstituted with R4a, R4b, R4c;
7. -OH;
8. -O-alkyl(C1-C10), linear or branched, optionally mono- or polysubstituted
with R4a, R4b, R4c;
9. -Y-alkyl (Y = S, SO, SO2), linear or branched, optionally mono-, di- or
25
trisubstituted with R4a, R4b, R4c;
10. -O-cycloalkyl (C3-C7) optionally mono- or polysubstituted with R4a, R4b,
R4c;
11. -O-aryl optionally mono- or polysubstituted with R4a, R4b, R4c;
12. aryl optionally mono- or polysubstituted with R4a, R4b, R4c;
30
13. heteroaryl optionally mono- or polysubstituted with R4a, R4b, R4c;
14. heterocycloalkyl optionally mono- or polysubstituted with R4a, R4b, R4c;
15. -NO2;
16. -NH2;
15
17. -NH-(alkyl(C1-C10) or cycloalkyl(C3-C7) or heterocycloalkyl) each group
optionally mono- or polysubstituted with R4a, R4b, R4c;
18. -N(alkyl(C1-C10) or cycloalkyl(C3-C7))2 each group optionally being monoor polysubstituted with R4a, R4b, R4c;
5
19. -NHaryl or NH heteroaryl optionally mono- or polysubstituted with R4a,
R4b, R4c;
20. -NHC(O) substituted with R4a, R4b, R4c;
21. -N(alkyl(C1-C10)C(O) substituted with R4a, R4b, R4c;
22. -NHS(O2) substituted with R4a, R4b, R4c;
10
23. -N(alkyl(C1-C10)S(O2) substituted with R4a, R4b, R4c;
24. -CO2 substituted with R4a, R4b, R4c;
25. -CONH2
26. -CONH(alkyl), CON(alkyl)2 linear, branched or cyclic in which the alkyl
moiety is optionally mono-, di- or trisubstituted with R4a, R4b, R4c;
15
27. -C(O)heterocycloalkyl optionally mono-, di- or trisubstituted with R4a, R4b,
R4c;
28. -S substituted with R4a, R4b, R4c;
29. -S(O2) substituted with R4a, R4b, R4c;
30. -S(O) substituted with R4a, R4b, R4c;
20
31. oxo (O double bond);
32. -C2-C6 alkenyl optionally mono- or polysubstituted with R4a, R4b, R4c;
33. -C2-C6 alkynyl optionally mono- or polysubstituted with R4a, R4b, R4c;
the groups R4a, R4b, R4c, or the substituents of the groups R3a, R3b and R3c, are
selected independently of one another from:
25
1. F;
2. Cl;
3. Br;
4. I;
5. -CF3; -CHF2
30
6. -C1-C10 alkyl linear or branched;
7. -C3-C7 cycloalkyl;
8. -OH;
9. -O-alkyl(C1-C10) linear or branched;
10. -Y-alkyl (Y = S, SO, SO2) linear or branched;
16
11. -O-cycloalkyl (C3-C7);
12. -O-aryl;
13. aryl;
14. heteroaryl;
5
15. heterocycloalkyl;
16. -NO2;
17. -NH2;
18. -NH-(alkyl(C1-C10) or cycloalkyl(C3-C7) or heterocycloalkyl);
19. -N(alkyl(C1-C10) or cycloalkyl(C3-C7))2;
10
20. -NHaryl or NH heteroaryl;
21. -NHS(O2)alkyl;
22. -N(alkyl(C1-C10)S(O2)alkyl;
23. -CO2alkyl;
24. -CONH2
15
25. -CONH(alkyl), CON(alkyl)2 linear, branched or cyclic;
26. -C(O)heterocycloalkyl;
27. –S-alkyl;
28. -S(O2)alkyl;
29. -S(O)alkyl;
20
30. oxo (O double bond);
31. -C2-C6 alkenyl linear or branched;
32. -C2-C6 alkynyl linear or branched;
said products of formula (I) being in all possible isomeric forms, racemic,
enantiomeric and diastereoisomeric, as well as the salts of addition of said products
25
of formula (I) with mineral and organic acids or with mineral and organic bases.
5 - Products of formula (I) as defined in any one of the preceding claims with the
following names:
- 6-methoxy-3-(pyridin-3-yl)-9H-beta-carboline
30
- 3-(pyridin-3-yl)-9H-beta-carboline
- 6-bromo-3-(pyridin-3-yl)-9H-beta-carboline
- methyl 3-(pyridin-3-yl)-9H-beta-carboline-6-carboxylate
- 6-methoxy-3-(5-methoxypyridin-3-yl)-9H-beta-carboline
- 5-(6-methoxy-9H-beta-carbolin-3-yl)pyridin-2-amine
17
- 3-(pyrimidin-5-yl)-9H-beta-carboline
- 6-methoxy-3-(6-methoxypyridin-3-yl)-9H-beta-carboline
- 6-methoxy-3-[6-(methylsulphanyl)pyridin-3-yl]-9H-beta-carboline
- 3-(pyridin-3-yl)-6-(trifluoromethyl)-9H-beta-carboline
5
- 3-(pyridin-3-yl)-6-(trifluoromethoxy)-9H-beta-carboline
- 6-fluoro-3-(pyridin-3-yl)-9H-beta-carboline
-N,N-diethyl-2-{4-[3-(pyridin-3-yl)-9H-beta-carbolin-6-yl]-1H-pyrazol-1yl}ethanamine
- N,N-diethyl-2-{4-[3-(1-methyl-1H-pyrazol-4-yl)-9H-beta-carbolin-6-yl]-1H-pyrazol1-yl}ethanamine
10
- 6-{4-[3-(piperidin-1-yl)propoxy]phenyl}-3-(pyridin-3-yl)-9H-beta-carboline
3-(1-methyl-1H-pyrazol-4-yl)-6-{4-[3-(piperidin-1-yl)propoxy]phenyl}-9H-betacarboline
- 6-(difluoromethoxy)-3-(pyridin-3-yl)-9H-beta-carboline
15
- 6-(difluoromethoxy)-3-(1-methyl-1H-pyrazol-4-yl)-9H-beta-carboline
- 6-methoxy-3-(1-methyl-1H-pyrazol-4-yl)-9H-beta-carboline
6 - Method for preparing the products of formula (I) as defined in the preceding
claims, characterized by the following general scheme:
NH2
Sn
Cl
+
N
Z3
(XIII)
(XII)
Z6
Hal
Z6
N
H
H
Z3
Z6
"Pd0"
Cl
"Pd0" or "Cu0,1,2"
(XIV)
Hal: Cl, Br, I
Z3
N
N
N
H
(I)
LDA / Cl-SnMe3
Cl
Pd(PPh3)3
Cl
(X)
N
H
Z3
O
(XI)
20
O
B
Z3
ou
H
O
O
B
N
Hal
Hal: Cl, Br, I
Z3
in which the substituents Z3 and Z6 have the meanings given for the products of
formula (I) in any one of the preceding claims, the optionally reactive functions of Z3
and Z6 being optionally protected by known protecting groups.
7- As medicinal products, the products of formula (I) as defined in Claims 1 to 4 as
25
well as their prodrugs, said products of formula (I) being in all possible isomeric
18
forms, racemic, enantiomeric and diastereoisomeric, as well as the salts of addition
of said products of formula (I) with pharmaceutically acceptable mineral and organic
acids or mineral and organic bases.
5
8- As medicinal products, the products of formula (I) as defined in Claims 1 to 4 with
the following names:
- 6-methoxy-3-(pyridin-3-yl)-9H-beta-carboline
- 3-(pyridin-3-yl)-9H-beta-carboline
- 6-bromo-3-(pyridin-3-yl)-9H-beta-carboline
10
- methyl 3-(pyridin-3-yl)-9H-beta-carboline-6-carboxylate
- 6-methoxy-3-(5-methoxypyridin-3-yl)-9H-beta-carboline
- 5-(6-methoxy-9H-beta-carbolin-3-yl)pyridin-2-amine
- 3-(pyrimidin-5-yl)-9H-beta-carboline
- 6-methoxy-3-(6-methoxypyridin-3-yl)-9H-beta-carboline
15
- 6-methoxy-3-[6-(methylsulphanyl)pyridin-3-yl]-9H-beta-carboline
- 3-(pyridin-3-yl)-6-(trifluoromethyl)-9H-beta-carboline
- 3-(pyridin-3-yl)-6-(trifluoromethoxy)-9H-beta-carboline
- 6-fluoro-3-(pyridin-3-yl)-9H-beta-carboline
20
N,N-diethyl-2-{4-[3-(pyridin-3-yl)-9H-beta-carbolin-6-yl]-1H-pyrazol-1yl}ethanamine
- N,N-diethyl-2-{4-[3-(1-methyl-1H-pyrazol-4-yl)-9H-beta-carbolin-6-yl]-1H-pyrazol1-yl}ethanamine
- 6-{4-[3-(piperidin-1-yl)propoxy]phenyl}-3-(pyridin-3-yl)-9H-beta-carboline
25
3-(1-methyl-1H-pyrazol-4-yl)-6-{4-[3-(piperidin-1-yl)propoxy]phenyl}-9H-betacarboline
- 6-(difluoromethoxy)-3-(pyridin-3-yl)-9H-beta-carboline
- 6-(difluoromethoxy)-3-(1-methyl-1H-pyrazol-4-yl)-9H-beta-carboline
- 6-methoxy-3-(1-methyl-1H-pyrazol-4-yl)-9H-beta-carboline
30
9 - Pharmaceutical compositions containing, as active principle, a compound
according to any one of the preceding claims as well as at least one
pharmaceutically compatible excipient.
10 - Pharmaceutical compositions according to the preceding claim used for the
35
treatment of cancer.
19
11- As novel industrial products, the synthesis intermediates of formula (XIV) as
defined in the general scheme of Claim 6 and hereunder:
NH2
Z3
Z6
N
Cl
(XIV)
5
in which the substituents Z3 and Z6 have the meanings given for the products of
formula (I) in any one of the preceding claims, the optionally reactive functions of Z3
and Z6 being optionally protected by known protecting groups.
20
PATENT
DISUBSTITUTED 9H-PYRIDINO[3,4-b]INDOLE DERIVATIVES, PREPARATION
THEREOF AND THERAPEUTIC USE THEREOF
5
SANOFI-AVENTIS
Abstract
10
Products of formula (I):
H
4
Z3
N
H 5
H
N
H
1
Z6
8 H
H
(I)
15
in which Z3 represents heteroaryl with 5 or 6 ring members with 1 to 4 heteroatoms
selected from N, S or O, optionally substituted;
Z6 notably represents H; Hal; OH; alkoxy; -Y-alkyl (Y = S, SO, SO2); -X-aryl or -Xheteroaryl (X = O, S, SO, SO2); -NH2, -NH(alkyl), -N(alkyl)2; -NH(aryl); NH(heteroaryl); -N(alkyl)(aryl); -N(alkyl)(heteroaryl); -C(O)OH; linear -C(O)Oalkyl; -
20
C(O)Oaryl;
-C(O)Oheteroaryl;
-CONH2;
-CONH(alkyl),
CON(alkyl)2;
-CO-
heterocycloalkyl; -CON(alkyl)(aryl); -CON(alkyl)(heteroaryl); -C1-C10 alkyl linear,
branched or cyclic; aryl; heteroaryl; heterocycloalkyl; -C2-C6 alkenyl; -C2-C6 alkynyl;
all optionally mono- or polysubstituted;
as well as the isomers and the salts of said products of formula (I) and their
25
30
application in therapeutics for the treatment of cancer.