Cycloalkylamine substituted isoquinolone derivatives
View Patent ↗The invention relates to 6-substituted isoquinolone derivatives of the formula (I) useful for the treatment and/or prevention of diseases associated with Rho-kinase and/or Rho-kinase mediated phosphorylation of myosin light chain phosphatase, and compositions containing such compounds.
1. A compound of the formula (I)
or of the formula (I′)
wherein
R 2 is H, halogen or (C 1 -C 6 )alkyl;
R 3 is
H,
halogen,
(C 1 -C 6 )alkyl,
OH,
O—R″,
NH 2 ,
NHR″,
NR″R″ or
NH—C(O)—R″,
R 4 is
H,
halogen,
hydroxy,
CN,
(C 1 -C 6 )alkyl,
R 5 is
H,
halogen,
CN,
NO 2 ,
(C 1 -C 6 )alkyl,
(C 2 -C 6 )alkenyl,
CH(OH)—(C 1 -C 6 )alkyl,
NH 2 ,
NH—SO 2 H,
NH—SO 2 —(C 1 -C 6 )alkyl,
NH—C(O)—(C 1 -C 6 )alkyl,
C(O)N[(C 1 -C 6 )alkyl] 2 ;
C(O)OH, or
C(O)O—(C 1 -C 6 )alkyl;
R 6 is H, (C 1 -C 8 )alkyl, or (C 1 -C 6 )alkylene-phenyl;
is
H,
R′,
(C 1 -C 8 )alkyl,
(C 1 -C 6 )alkylene-R′,
(C 1 -C 6 )alkylene-O—(C 1 -C 6 )alkyl,
(C 1 -C 6 )alkylene-O—R′,
(C 1 -C 6 )alkylene-CH[R′] 2 ,
(C 1 -C 6 )alkylene-C(O)—R′,
(C 1 -C 6 )alkylene-C(O)NH 2 ,
(C 1 -C 6 )alkylene-C(O)NH—R′,
(C 1 -C 6 )alkylene-C(O)NH—(C 1 -C 6 )alkyl,
(C 1 -C 6 )alkylene-C(O)N[(C 1 -C 6 )alkyl] 2 ,
(C 1 -C 6 )alkylene-C(O)N[R′] 2 ;
(C 1 -C 6 )alkylene-C(O)O—(C 1 -C 6 )alkyl,
C(O)OR′
C(O)(C 1 -C 6 )alkyl,
C(O)R′,
C(O)NH—(C 1 -C 6 )alkyl,
C(O)NHR′,
C(O)N[(C 1 -C 6 )alkyl]R′
C(O)N[(C 1 -C 6 )alkyl] 2,
C(O)—(C 1 -C 6 )alkylene-R′,
or
R 6 and R 6 ′, together with the N-atom to which they are attached, form a (C 5 -C 10 ) heterocyclyl group;
R 7 is
H,
halogen,
CN,
NO 2 ,
(C 1 -C 6 )alkyl,
O—(C 1 -C 6 )alkyl,
(C 2 -C 6 )alkenyl,
CH(OH)—(C 1 -C 6 )alkyl,
NH 2 ,
NH—R′,
NH—SO 2 -(C 1 -C 6 )alkyl,
SO 2 —NH 2 ,
NH—C(O)—(C 1 -C 6 )alkyl,
C(O)N[(C 1 -C 6 )alkyl] 2 ,
C(O)OH, or
C(O)O—(C 1 -C 6 )alkyl;
R 8 is H, halogen or (C 1 -C 6 )alkyl;
n is 1, 2, 3 or 4;
m is 1, 3, 4 or 5; and
L is O or -O—(C 1 -C 6 )alkylene;
R′ is
(C 3 -C 8 )cycloalkyl,
(C 5 -C 10 )heterocyclyl,
(C 6 -C 10 )aryl; and
R″ is
(C 1 -C 6 )alkyl,
(C 1 -C 6 )alkylene-O—(C 1 -C 6 )alkyl, or
(C 1 -C 6 )alkylene-NR x R y ; and
R x and R y are independently of each other
(C 1 -C 6 )alkyl,
(C 1 -C 4 )alkylene-NH(C 1 -C 6 )alkyl,
(C 1 -C 4 )alkylene-N[(C 1 -C 6 )alkyl] 2 ,
wherein in residues R 4 , R 5 , R 6 , R 6 ′, R 7 and R 8 alkyl, alkylene or cycloalkyl can optionally be substituted one or more times by OH, OCH 3 , COOH, COOCH 3 , NH 2 , NHCH 3 , N(CH 3 ) 2 , CONHCH 3 or CON(CH 3 ) 2 ;
wherein in residues R 2 to R 8 alkyl or alkylene can optionally be substituted one or more times by halogen;
wherein in residues R 3 and R 6 ′ (C 6 -C 10 )aryl and (C 5 -C 10 )heterocyclyl are unsubstituted or substituted one or more times by a group independently selected from halogen, OH, NO 2 , N 3 , CN, C(O)—(C 1 -C 6 )alkyl, COOH, COO(C 1 -C 6 )alkyl, CONH 2 , CONH(C 1 -C 6 )alkyl, CON[(C 1 -C 6 )alkyl] 2 , (C 3 -C 8 )cycloalkyl, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkylene-OH, (C 1 -C 6 )alkylene-NH 2 , (C 1 -C 6 )alkylene-NH(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylene-N[(C 1 -C 6 )alkyl] 2 , (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, O—(C 1 -C 6 )alkyl, O—C(O)—(C 1 -C 6 )alkyl, PO 3 H 2 , SO 3 H, SO 2 —NH 2 , SO 2 NH(C 1 -C 6 )alkyl, SO 2 N[(C 1 -C 6 )alkyl] 2 , S—(C 1 -C 6 )alkyl; SO—(C 1 -C 6 )alkyl, SO 2 —(C 1 -C 6 )alkyl, SO 2 —N═CH—N[(C 1 -C 6 )alkyl] 2 , C(NH)(NH 2 ), NH—(C 1 -C 6 )alkyl, N[(C 1 C 6 )alkyl] 2 , NH—C(O)—(C 1 -C 6 )alkyl, NH—C(O)O—(C 1 -C 6 )alkyl, NH—SO 2 —(C 1 -C 6 )alkyl, N(C 1 -C 6 )alkyl-C(O)—(C 1 -C 6 )alkyl, N(C 1 -C 6 )alkyl-C(O)O—(C 1 -C 6 )alkyl, N(C 1 -C 6 )alkyl-C(O)—NH—(C 1 -C 6 )alkyl]; and
wherein, if m is 3, R 6 is not H; and
wherein, if m is 3 and R 6 ′ is a residue selected from
(C 1 -C 8 )alkyl,
(C 3 -C 8 )cycloalkyl,
(C 1 -C 6 )alkylene-R′,
(C 1 -C 6 )alkylene-O—(C 1 -C 6 )alkyl,
(C 1 -C 6 )alkylene-O—R′,
(C 1 -C 6 )alkylene-CH[R′] 2 ,
(C 1 -C 6 )alkylene-C(O)—R′,
(C 1 -C 6 )alkylene-C(O)NH 2 ,
(C 1 -C 6 )alkylene-C(O)NH—R′, or
(C 1 -C 6 )alkylene-C(O)N[R′] 2 ;
alkyl, alkylene or cycloalkyl in said residue is substituted one or more times by OH, OCH 3 , COOH, COOCH 3 , NH 2 , NHCH 3 , N(CH 3 ) 2 , CONHCH 3 or CON(CH 3 ) 2 ; or
stereoisomeric form thereof and/or tautomeric form thereof and/or pharmaceutically acceptable salt thereof.
2. The compound according to claim 1 , wherein R 3 is H, halogen, O—R″ or NHR″.
3. The compound according to claim 2 , wherein R 3 is H or NHR″.
4. The compound according to claim 3 , wherein R 3 is H; NH—(C 5 -C 6 )heterocyclyl, or NH-phenyl.
5. The compound according to claim 4 , wherein R 3 is H.
6. The compound according to claim 1 , wherein R 8 is H, halogen or (C 1 -C 4 )alkyl.
7. The compound according to claim 6 , wherein R 8 is H, Cl, F, methyl or ethyl.
8. The compound according to claim 7 , wherein R 8 is H.
9. The compound according to claim 1 , wherein R 4 is H, halogen or (C 1 -C 6 )alkyl.
10. The compound according to claim 9 , wherein R 4 is H, halogen or (C 1 -C 4 )alkyl.
11. The compound according to claim 10 , wherein R 4 is H.
12. The compound according to claim 1 , wherein R 5 is H, halogen, CN, or (C 1 -C 6 )alkyl.
13. The compound according to claim 12 , wherein R 5 is H, halogen, (C 1 -C 6 )alkyl, or (C 2 -C 6 )alkenyl.
14. The compound according to claim 13 , wherein R 5 is H, halogen, methyl, ethyl, or vinyl.
15. The compound according to claim 14 , wherein R 5 is H, halogen, methyl, or ethyl.
16. The compound according to claim 15 , wherein R 5 is H.
17. The compound according to claim 1 , wherein R 7 is H, halogen, CN, (C 1 -C 6 )alkyl, O—(C 1 -C 6 )alkyl, or (C 2 -C 6 )alkenyl.
18. The compound according to claim 17 , wherein R 7 is H, halogen, CN, (C 1 -C 4 )alkyl, O—(C 1 -C 4 )alkyl, or (C 2 -C 4 )alkenyl.
19. The compound according to claim 18 , wherein R 7 is H, fluoro, chloro, bromo, methyl, ethyl, methoxy, or vinyl.
20. The compound according to claim 19 , wherein R 7 is H, fluoro, chloro, bromo, methyl or methoxy.
21. The compound according to claim 20 , wherein R 7 is H.
22. The compound according to claim 1 , wherein R 2 is H, halogen or (C 1 -C 4 )alkyl.
23. The compound according to claim 22 , wherein R 2 is H or (C 1 - C 2 )alkyl.
24. The compound according to claim 23 , wherein R 2 is H, methyl or ethyl.
25. The compound according to claim 1 , wherein n is 1, 2 or 3.
26. The compound according to claim 25 , wherein n is 1 or 2.
27. The compound according to claim 26 , wherein n is 1.
28. The compound according to claim 1 , wherein R 6 is H, (C 1 -C 6 )alkyl, or (C 1 -C 6 )alkylene-phenyl;
is
H,
(C 1 -C 6 )alkyl,
R′,
(C 1 -C 4 )alkylene-(C 3 -C 8 )cycloalkyl,
(C 1 -C 4 )alkylene-(C 5 -C 10 )heterocyclyl,
C 1 -C 4 )alkylene-(C 6 -C 10 )aryl,
(C 1 -C 6 )alkylene-O—(C 1 -C 6 )alkyl,
(C 1 -C 4 )alkylene-C(O)—(C 5 -C 10 )heterocyclyl,
(C 1 -C 4 )alkylene-C(O)—(C 6 -C 10 )aryl,
(C 1 -C 6 )alkylene-C(O)N[(C 1 -C 6 )alkyl] 2 ,
(C 1 -C 6 )alkylene-C(O)NH—(C 1 -C 6 )alkyl,
(C 1 -C 6 )alkylene-C(O)O—(C 1 -C 6 )alkyl,
C(O)(C 1 -C 6 )alkyl,
C(O)R′
C(O)NH—(C 1 -C 6 )alkyl,
C(O)N[(C 1 - 6 )alkyl] 2 , or
C(O)(C 1 -C 6 )alkylene-R′,
or R 6 and R 6 ′, together with the N-atom to which they are attached, form a (C 5 -C 10 )heterocyclyl group.
29. The compound according to claim 28 , wherein R 6 is H, (C 1 -C 6 )alkyl, or (C 1 -C 6 )alkylene-phenyl;
is
H,
(C 1 -C 6 )alkyl,
(C 5 -C 10 )heterocyclyl,
(C 3 -C 8 )cycloalkyl,
(C 6 -C 10 )aryl,
(C 1 -C 4 )alkylene-(C 3 -C 8 )cycloalkyl,
(C 1 -C 4 )alkylene-(C 5 -C 10 )heterocyclyl,
(C 1 -C 4 )alkylene-(C 6 -C 10 )aryl,
(C 1 -C 6 )alkylene-O—(C 1 -C 6 )alkyl,
(C 1 -C 6 )alkylene-C(O)N[(C 1 -C 6 )alkyl] 2 ,
(C 1 -C 6 )alkylene-C(O)NH—(C 1 -C 6 )alkyl,
(C 1 -C 6 )alkylene-C(O)O—(C 1 -C 6 )alkyl,
C(O)(C 1 -C 6 )alkyl,
C(O)(C 3 -C 8 )cycloalkyl,
C(O)NH—(C 1 -C 6 )alkyl,
C(O)N[(C 1 -C 6 )alkyn] 2 ,
C(O)(C 1 -C 6 )alkylene-(C 3 -C 8 )cycloalkyl,
C(O)(C 1 -C 6 )alkylene- (C 5 -C 10 )heterocyclyl,
C(O)(C 1 -C 6 )alkylene-(C 6 -C 10 )aryl,
or R 6 and R 6 ′, together with the N-atom to which they are attached form a (C 5 -C 10 )heterocyclyl group.
30. The compound according to claim 29 , wherein
R 6 is H, (C 1 -C 6 )alkyl, and R 6 ′ is H,
(C 1 -C 6 )alkyl,
(C 3 -C 8 )cycloalkyl,
(C 5 -C 10 )heterocyclyl,
(C 6 -C 10 )aryl,
(C 1 -C 4 )alkylene-(C 3 -C 8 )cycloalkyl,
(C 1 -C 4 )alkylene-(C 5 -C 10 )heterocyclyl,
(C 1 -C 4 )alkylene-(C 6 -C 10 )aryl,
(C 1 -C 6 )alkylene-O—(C 1 -C 6 )alkyl,
(C 1 -C 6 )alkylene-C(O)NH—(C 1 -C 6 )alkyl,
(C 1 -C 6 )alkylene-C(O)N[(C 1 -C 6 )alkyl] 2 ,
(C 1 -C 6 )alkylene-C(O)O—(C 1 -C 6 )alkyl,
C(O)(C 1 -C 6 )alkyl,
C(O)(C 3 -C 8 )cycloalkyl,
C(O)NH—(C 1 -C 6 )alkyl,
C(O)N[(C 1 -C 6 )alkyl] 2 ,
C(O)(C 1 -C 6 )alkylene-(C 3 -C 8 )cycloalkyl,
C(O)(C 1 -C 6 )alkylene-(C 5 -C 10 )heterocyclyl,
C(O)(C 1 -C 6 )alkylene-(C 6 -C 10 )aryl, or
R 6 and R 6 ′, together with the N-atom to which they are attached, form a (C 5 -C 10 )heterocyclyl group.
31. The compound according to claim 30 , wherein
R 6 is H or (C 1 -C 6 )alkyl and
R 6 ′ is H,
(C 1 -C 6 )alkyl,
(C 3 -C 8 )cycloalkyl,
(C 6 -C 10 )aryl,
(C 5 -C 10 )heterocyclyl,
(C 1 -C 4 )alkylene-(C 3 -C 8 )cycloalkyl,
(C 1 -C 4 )alkylene-(C 5 -C 10 )heterocyclyl,
(C 1 -C 6 )alkylene-(C 6 -C 10 )aryl,
(C 1 -C 4 )alkylene-O—(C 1 -C 4 )alkyl,
(C 1 -C 4 )alkylene-C (O)N[(C 1 -C 4 )alkyl] 2 ,
(C 1 -C 6 )alkylene-C(O)NH—(C 1 -C 6 )alkyl,
C(O)(C 1 -C 6 )alkyl,
C(O)(C 1 -C 6 )alkylene-(C 5 -C 10 )heterocyclyl, or
R 6 and R 6 ′, together with the N-atom to which they are attached, form a (C 5 -C 10 )heterocyclyl group.
32. The compound according to claim 31 , wherein
R 6 is H, (C 1 -C 6 )alkyl and
R 6 ′ is H;
(C 1 -C 6 )alkyl;
(C 3 -C 8 )cycloalkyl;
(C 1 -C 4 )alkylene-(C 3 -C 8 )cycloalkyl;
(C 1 -C 4 )alkylene-O—(C 1 -C 4 )alkyl;
C(O)(C 1 -C 4 )alkyl;
(C 1 -C 4 )alkylene-(C(O)N[(C 1 -C 4 )alkyl] 2 ;
(C 1 -C 4 )alkylene-(C 5 -C 10 )heterocyclyl wherein heterocyclyl is unsubstituted or substituted one or more times by a group indepedently selected from (C 1 -C 4 )alkyl, O—(C 1 -C 4 )alkyl, halogen, or phenyl or is substituted once by (C 5 -C 6 )heterocyclyl, wherein phenyl or (C 5 -C 6 )heterocyclyl is unsubstituted or substituted one to three times by a group independently selected from halogen, (C 1 -C 4 )alkyl or O—(C 1 -C 4 )alkyl;
(C 1 -C 4 )alkylene-(C 6 -C 10 )aryl wherein aryl is unsubstituted or substituted one or more times by a group independently selected from halogen, (C 1 -C 4 )alkyl, O—(C 1 -C 4 )alkyl, CN, SO 2 —NH 2 ,
SO 2 —(C 1 -C 4 )alkyl, SO 2 —N═CH—N[(C 1 -C 4 )alkyl] 2 , NH—CO—(C 1 -C 4 )alkyl, CO—O—(C 1 -C 4 )alkyl, or is substituted once by unsubstituted phenyl, unsubstituted O-phenyl or unsubstituted (C 5 -C 6 )heterocyclyl;
C(O)(C 1 -C 6 )alkyl;
C(O)(C 1 -C 6 )alkylene-(C 5 -C 10 )heterocyclyl;
or R 6 and R 6 ′, together with the N-atom to which they are attached, form a (C 5 -C 6 )heterocyclyl group, which is unsubstituted or substituted one to three times by (C 1 -C 4 )alkyl or C(O)O(C 1 -C 4 )alkyl;
wherein a (C 1 -C 6 )alkyl or (C 1 -C 4 ) alkyl residue is unsubstituted or substituted one to three times by halogen.
33. The compound according to claim 32 , wherein R 6 is H, (C 1 -C 6 )alkyl and R 6 ′ is H, (C 1 -C 6 )alkyl or (C 3 -C 8 )cycloalkyl.
34. The compound according to claim 33 , wherein R 6 is H and R 6 ′ is H, (C 1 -C 6 )alkyl or (C 3 -C 8 )cycloalkyl.
35. The compound according to claim 34 , wherein R 6 and R 6 ′ are H.
36. The compound according to claim 1 , wherein m is 3 and L is attached to the 3-position or to the 4-position of the amino cyclohexane ring.
37. The compound according to claim 1 , wherein m is 3 and L is attached to the 4-position of the amino cyclohexane ring.
38. The compound according to claim 1 , wherein L is O-methylene, O-ethylene or O.
39. The compound according to claim 1 , wherein L is O.
40. The compound according to claim 1 , wherein
R 3 is H, halogen, (C 1 -C 4 )alkylene-R′, O—R″ or NHR″;
R 4 is H, halogen or (C 1 -C 6 )alkyl;
R 5 is H, (C 1 -C 6 )alkyl, halogen, CN, or (C 2 -C 6 )alkeny;
R 6 is H, (C 1 -C 8 )alkyl, or (C 1 -C 6 )alkylene-phenyl;
is H, R′, (C 1 -C 8 )alkyl, (C 1 -C 6 )alkylene-R′, (C 1 -C 6 )alkylene-O—(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylene-O—R′, (C 1 -C 6 )alkylene-CH[R′] 2 , (C 1 -C 6 )alkylene-C(O)NH 2 , (C 1 -C 6 )alkylene-C(O)NH—R′, (C 1 -C 6 )alkylene-C(O)N[(C 1 -C 4 )alkyl] 2 , (C 1 -C 6 )alkylene-C(O)N[R′] 2 , C(O)(C 1 -C 6 )alkyl, C(O)(C 3 -C 8 )cycloalkyl, C(O)(C 5 -C 10 )heterocyclyl, C(O)NH—(C 1 -C 6 )alkyl, C(O)N[(C 1 -C 6 )alkyl] 2 , C(O)(C 1 -C 6 )alkylene-C 3 -C 8 )cycloalkyl, C(O)(C 1 -C 6 )alkylene-(C 5 -C 10 )heterocyclyl, C(O)(C 1 -C 6 )alkylene-(C 6 -C 10 )aryl,
or R 6 and R 6 ′, together with the N-atom to which they are attached, form a (C 5 -C 6 )heterocyclyl group;
R 7 is H, halogen, CN, (C 1 -C 6 )alkyl, O—(C 1 -C 6 )alkyl, or (C 2 -C 6 )alkenyl;
m is 3
n is 1, 2 or 3, and
L is O, O-methylene or O-ethylene.
41. The compound according to claim 1 , wherein
R 2 is H or (C 1 -C 4 )alkyl;
R 3 is H, halogen or NHR″;
R 4 is H, halogen or (C 1 -C 4 )alkyl;
R 5 is H, (C 1 -C 6 )alkyl, halogen, or (C 2 -C 4 )alkenyl;
R 6 is H, (C 1 -C 8 )alkyl, or (C 1 -C 6 )alkylene-phenyl;
is H, (C 3 -C 8 )cycloalkyl, (C 1 -C 8 )alkyl, (C 1 -C 6 )alkylene-O—(C 1 -C 6 )alkyl, (C 1 -C 3 )alkylene-R′ , C(O)(C 1 -C 6 )alkyl, C(O)(C 3 -C 8 )cycloalkyl, C(O)(C 5 -C 6 )heterocyclyl, C(O)(C 1 -C 6 )alkylene-(C 3 -C 8 )cycloalkyl, C(O)(C 1 -C 6 )alkylene-(C 5 -C 6 )heterocyclyl or C(O)(C 1 -C 6 )alkylene-(C 6 -C 10 )aryl;
R 7 is H, halogen, CN, (C 1 -C 6 )alkyl, O—(C 1 -C 6 )alkyl, or (C 2 -C 6 )alkenyl;
R 8 is H, halogen or (C 1 -C 6 )alkyl;
m is 3
n is 1, 2 or 3; and
L is O.
42. The compound according to claim 1 , wherein
R 2 is H or (C 1 -C 4 )alkyl;
R 3 is H, NH—(C 5 -C 6 )heteroaryl or NH-phenyl;
R 4 is H, halogen or (C 1 -C 4 )alkyl;
R 5 is H, (C 1 -C 4 )alkyl, halogen, or (C 2 -C 4 )alkenyl;
R 6 is (C 1 -C 4 )alkyl;
R 6 ′ is H, (C 3 -C 8 )cycloalkyl, (C 1 -C 8 )alkyl, (C 1 -C 3 )alkylene-R′; C(O)(C 1 -C 6 )alkyl, C(O)(C 3 -C 6 )cycloalkyl, C(O)(C 5 -C 6 )heterocyclyl, C(O)(C 1 -C 3 )alkylene-(C 3 -C 6 )cycloalkyl, C(O)(C 1 -C 3 )alkylene-(C 5 -C 6 )heterocyclyl, or C(O)(C 1 -C 3 )alkylene-phenyl;
R 7 is H, halogen, CN, (C 1 -C 4 )alkyl, O—(C 1 -C 4 )alkyl, or (C 2 -C 4 )alkenyl;
R 8 is H, halogen or (C 1 -C 4 )alkyl;
m is 3
n is 1; and
L is O.
43. A compound selected from the group consisting of
1-[4-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yloxy)-cyclohexyl]-piperidine-4-carboxylic acid amide,
7-Chloro-6-(4-piperidin-1-yl-cyclohexyloxy)-2H-isoquinolin-1-one,
7-Chloro-6-(4-morpholin-4-yl-cyclohexyloxy)-2H-soquinolin-1-one,
7-Chloro-6-(4-pyrrolidin-1-yl-cyclohexyloxy)-2H-isoquinolin-1-one,
7-Chloro-6-[4-(4-methyl-piperazin-1-yl)-cyclohexyloxy]-2H-isoquinolin-1-one,
[4-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yloxy)-cis-cyclohexylamino]-acetic acid ethyl ester,
[4-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yloxy)-cis-cyclohexylamino]-acetic acid,
7-Methyl-6-(4-pyrrolidin-1-yl-cyclohexyloxy)-2H-isoquinolin-1-one,
N-[4-(7-Methyl-1-oxo-1,2-dihydro-isoquinolin-6-yloxy)-trans-cyclohexyl]-3-piperidin-4-yl-propionamide,
N-[4-(7-Methyl-1-oxo-1,2-dihydro-isoquinolin-6-yloxy)-trans-cyclohexyl]-2-piperidin-4-yl-acetamide,
N-[4-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yloxy)-cis-cyclohexyl]-3-piperidin-4-yl-propionamide,
N-[4-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yloxy)-cis-cyclohexyl]-2-piperidin-4-yl-acetamide,
6-((1S,3S)-3-Amino-cyclopentyloxy)-2H-isoquinolin-1-one,
6-((1S,3S)-3-Amino-cyclopentyloxy)-7-chloro-2H-isoquinolin- 1-one,
6-((1S,3R)-3-Amino-cyclopentyloxy)-2H-isoquinolin- 1-one,
6-((1S,3R)-3-Amino-cyclopentyloxy)-7-chloro-2H-isoquinolin-1-one,
6-((cis-4-Amino-cycloheptyloxy)-7-methyl-2H-isoquinolin-1-one, and
7-Chloro-6-(cis-4-Amino-cycloheptyloxy)-2H-isoquinolin-1-one, or stereoisomeric form thereof and/or pharmaceutically acceptable salt thereof.
44. A compound selected from the group consisting of
6-(cis-4-Amino-cycloheptyloxy)-2H-isoquinolin-1-one,
6-(3-Amino-cyclobutoxy)-7-chloro-2H-isoquinolin-1-one,
cis-6-(3-Amino-cyclobutylmethoxy)-7-chloro-2H-isoquinolin-1-one,
trans-6-(3-Amino-cyclobutylmethoxy)-7-chloro-2H-isoquinolin-1-one,
6-(5-Amino-cyclooctyloxy)-7-chloro-2H-isoquinolin-1-one,
5-(1-Benzyloxy-7-chloro-isoquinolin-6-yloxy)-1-propyl-cyclooctylamine,
6-(5-Amino-5-propyl-cyclooctyloxy)-7-chloro-2H-isoquinolin-1-one,
6-(5-Benzyl-amino-5-propyl-cyclo-octyloxy)-7-chloro-2H-isoquinolin-1-one,
7-Chloro-6-(5-ethylamino-5-propyl-cyclooctyloxy)-2H-isoquinolin-1-one,
7-Chloro-6-(cis-3-isopropylamino-cyclobutoxy)-2H-isoquinolin-1-one,
6-(3-cis-Benzylamino-cyclobutoxy)-7-chloro-2H-isoquinolin-1-one,
6-(3-trans-Benzylamino-cyclobutoxy)-7-chloro-2H-isoquinolin-1-one,
7-Chloro-6-(3-cis-dibenzylamino-cyclobutoxy)-2H-isoquinolin-1-one,
7-Chloro-6-(3-trans-dibenzylamino-cyclobutoxy)-2H-isoquinolin-1-one and
7-Chloro-6-(3-trans-diethylamino-cyclobutoxy)-2H-isoquinolin-1-one, or stereoisomeric form thereof and/or pharmaceutically acceptable salt thereof.
45. A pharmaceutical composition comprising a pharmaceutically effective amount of at least one compound according to claim 1 and/or a pharmacologically acceptable salt thereof, and physiologically tolerated excipient or carriers, and optionally one or more additives and/or one or more other active ingredients.
46. A pharmaceutical composition comprising a pharmaceutically effective amount of at least one compound according to claim 43 and/or a pharmacologically acceptable salt thereof, and physiologically tolerated excipient or carriers, and optionally one or more additives and/or one or more other active ingredients.
47. A pharmaceutical composition comprising a pharmaceutically effective amount of at least one compound according to claim 44 and/or a pharmacologically acceptable salt thereof, and physiologically tolerated excipient or carriers, and optionally one or more additives and/or or more other active ingredients.