Cycloalkylamine substituted isoquinoline and isoquinolinone derivatives
View Patent ↗The invention relates to 6-substituted isoquinoline and isoquinolinone 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)
wherein
R 1 is H, OH or NH 2 ;
R 2 is
(C 3 -C 8 )cycloalkyl,
(C 6 -C 10 )aryl,
(C 7 -C 8 )alkyl,
(C 1 -C 6 )alkylene-(C 6 -C 10 )aryl,
(C 2 -C 6 )alkenyl,
(C 2 -C 6 )alkynyl,
(C 1 -C 6 )alkylene-C(O)NH 2 ,
(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)O—(C 1 -C 6 )alkyl,
C(O)(C 1 -C 6 )alkyl,
C(O)—NH—(C 2 -C 6 )alkenyl,
C(O)—NH—(C 2 -C 6 )alkynyl,
C(O)NH—(C 1 -C 6 )alkyl or
C(O)N[(C 1 -C 6 )alkyl] 2 ; or
R 2 is (C 1 -C 6 )alkyl, provided that in said alkyl residue at least one hydrogen is substituted by OH, OCH 3 , COOH, COOCH 3 , NH 2 , NHCH 3 , N(CH 3 ) 2 , CONH 2 , CONHCH 3 or CON(CH 3 ) 2 ;
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 and R 6 ′ are independently of each other
H,
(C 1 -C 8 )alkyl,
(C 1 -C 6 )alkylene-O—(C 1 -C 6 )alkyl,
(C 1 -C 6 )alkylene-C(O)NH 2 ,
(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)O—(C 1 -C 6 )alkyl,
C(O)(C 1 -C 6 )alkyl,
C(O)NH—(C 1 -C 6 )alkyl,
C(O)N[(C 1 -C 6 )alkyl] 2 ,
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—SO 2 H,
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;
m is 3;
r is 0, 1 or 2 and
L is O—(CH 2 )p;
p 0, 1, 2, 3 or 4;
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 or
(C 1 -C 4 )alkylene-N[(C 1 -C 6 )alkyl] 2 ,
wherein in residues R 2 , R 4 , R 5 , R 6 , R 6 ′, R 7 and R 8 as 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 , CONH 2 , CONHCH 3 or CON(CH 3 ) 2 ;
wherein in residues R 2 to R 8 as alkyl or alkylene can optionally be substituted one or more times by halogen;
wherein in residue R2 as (C 6 -C 10 )aryl 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 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 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], or
stereoisomeric form thereof and/or tautomeric form thereof and/or pharmaceutically acceptable salt thereof.
2. The compound according to claim 1 , having the formula (II)
3. The compound according to claim 1 , having the formula (III)
4. The compound according to claim 1 , having the formula (III′)
5. The compound according to claim 1 , wherein R 1 is NH 2 .
6. The compound according to claim 1 , wherein R 3 is H, halogen, O—R″ or NHR″.
7. The compound according to claim 6 , wherein R 3 is H or NHR″.
8. The compound according to claim 7 , wherein R 3 is H.
9. The compound according to claim 1 , wherein R 8 is H, halogen or (C 1 -C 4 )alkyl.
10. The compound according to claim 9 , wherein R 8 is H, Cl, F, methyl or ethyl.
11. The compound according to claim 10 , wherein R 8 is H.
12. The compound according to claim 1 , wherein R 4 is H, halogen or (C 1 -C 6 )alkyl.
13. The compound according to claim 12 , wherein R 4 is H, halogen or (C 1 -C 4 )alkyl.
14. The compound according to claim 13 , wherein R 4 is H.
15. The compound according to one of claim 1 , wherein R 5 is H, halogen, CN, (C 1 -C 6 )alkyl, or (C 2 -C 6 )alkenyl.
16. The compound according to claim 15 , wherein R 5 is H, halogen, (C 1 -C 6 )alkyl, or (C 2 -C 6 )alkenyl.
17. The compound according to claim 16 , wherein R 5 is H, halogen, methyl, ethyl, or vinyl.
18. The compound according to claim 17 , wherein R 5 is H, halogen, methyl, or ethyl.
19. The compound according to claim 18 , wherein R 5 is H.
20. 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.
21. The compound according to claim 20 , wherein R 7 is H, halogen, CN, (C 1 -C 4 )alkyl, O—(C 1 -C 4 )alkyl, or (C 2 -C 4 )alkenyl.
22. The compound according to claim 21 , wherein R 7 is H, fluoro, chloro, bromo, methyl, ethyl, methoxy, nitrile, or vinyl.
23. The compound according to claim 22 , wherein R 7 is H, fluoro, chloro, bromo, methyl or methoxy.
24. The compound according to claim 23 , wherein R 7 is H.
25. The compound according to claim 1 , wherein R 2 is
(C 3 -C 8 )cycloalkyl,
(C 6 -C 10 )aryl,
(C 7 -C 8 )alkyl,
(C 1 -C 6 )alkylene-(C 6 -C 10 )aryl,
(C 2 -C 6 )alkenyl,
(C 1 -C 6 )alkylene-C(O)NH 2 ,
(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)NH—(C 1 -C 6 )alkyl,
C(O)—NH—(C 2 -C 6 )alkenyl,
C(O)—NH—(C 2 -C 6 )alkynyl,
C(O)N[(C 1 -C 6 )alkyl] 2 ,
R 2 is (C 1 -C 6 )alkyl, provided that in said alkyl residue at least one hydrogen is substituted by OH, OCH 3 , COOH, COOCH 3 , NH 2 , NHCH 3 , N(CH 3 ) 2 , CONH 2 , CONHCH 3 or CON(CH 3 ) 2 .
26. The compound according to claim 25 , wherein R 2 is
(C 3 -C 8 )cycloalkyl,
(C 6 -C 10 )aryl,
(C 1 -C 6 )alkylene-(C 6 -C 10 )aryl,
(C 2 -C 6 )alkenyl,
(C 1 -C 6 )alkylene-C(O)NH 2 ,
(C 1 -C 6 )alkylene-C(O)NH—(C 1 -C 6 )alkyl,
C(O)NH—(C 1 -C 6 )alkyl,
C(O)—NH—(C 2 -C 6 )alkynyl,
or
R 2 is (C 1 -C 3 )alkyl, provided that in said alkyl residue at least one hydrogen is substituted by OH, OCH 3 , COOH, COOCH 3 , NH 2 , NHCH 3 , N(CH 3 ) 2 , CONH 2 , CONHCH 3 or CON(CH 3 ) 2 .
27. The compound according to claim 26 , wherein R 2 is
(C 3 -C)cycloalkyl,
(C 6 -C 10 )aryl,
(C 1 -C 6 )alkylene-(C 6 -C 10 )aryl,
(C 2 -C 6 )alkenyl,
(C 1 -C 6 )alkylene-C(O)NH—(C 1 -C 6 )alkyl,
C(O)NH—(C 1 -C 6 )alkyl,
C(O)—NH—(C 2 -C 6 )alkynyl.
28. The compound according to claim 1 , wherein r is 0 or 1.
29. The compound according to claim 1 , wherein
R 6 and R 6 ′ are independently of each other
H,
(C 1 -C 6 )alkyl,
(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)O—(C 1 -C 6 )alkyl,
C(O)(C 1 -C 6 )alkyl,
C(O)NH—(C 1 -C 6 )alkyl,
C(O)N[(C 1 -C 6 )alkyl] 2 ,
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 and R 6 ′ are independently of each other
H,
(C 1 -C 6 )alkyl,
(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)O—(C 1 -C 6 )alkyl,
C(O)(C 1 -C 6 )alkyl,
C(O)NH—(C 1 -C 6 )alkyl,
C(O)N[(C 1 -C 6 )alkyl] 2 ,
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, (C 1 -C 6 )alkyl, and R 6 ′ is H,
(C 1 -C 6 )alkyl,
(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)O—(C 1 -C 6 )alkyl,
C(O)(C 1 -C 6 )alkyl,
C(O)NH—(C 1 -C 6 )alkyl,
C(O)N[(C 1 -C 6 )alkyl] 2 ,
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 or (C 1 -C 6 )alkyl and
R 6 ′ is H,
(C 1 -C 6 )alkyl,
(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,
or
R 6 and R 6 ′, together with the N-atom to which they are attached, form a (C 5 -C 10 )heterocyclyl group.
33. The compound according to claim 32 , wherein
R 6 is H or (C 1 -C 6 )alkyl and
R 6 ′ is
H,
(C 1 -C 6 )alkyl;
(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(O)(C 1 -C 4 )alkyl;
or R 6 and R 6 ′, together with the N-atom to which they are attached, form a (C 5 -C 6 )heterocyclyl group.
34. The compound according to claim 33 , wherein R 6 is H or (C 1 -C 6 )alkyl and R 6 ′ is H or (C 1 -C 6 )alkyl.
35. The compound according to claim 34 , wherein R 6 is H and R 6 ′ is H or (C 1 -C 6 )alkyl.
36. The compound according to claim 35 , wherein R 6 and R 6 ′ are H.
37. 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.
38. The compound according to claim 1 , wherein m is 3 and L is attached to the 4-position of the amino cyclohexane ring.
39. The compound according to claim 1 , wherein p is 0.
40. The compound according to claim 1 , wherein
R 1 is H or OH
R 2 is (C 7 -C 8 )alkyl, (C 3 -C 8 )cycloalkyl, (C 6 -C 10 )aryl, (C 1 -C 6 )alkylene-(C 6 -C 10 )aryl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkylene-C(O)NH 2 , (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)NH—(C 1 -C 6 )alkyl, C(O)—NH—(C 2 -C 6 )alkenyl, C(O)—NH—(C 2 -C 6 )alkynyl, C(O)N[(C 1 -C 6 )alkyl] 2 ; or
R 2 is (C 1 -C 6 )alkyl, provided that in said alkyl residue at least one hydrogen is substituted by OH, OCH 3 , COOH, COOCH 3 , NH 2 , NHCH 3 , N(CH 3 ) 2 , CONH 2 , CONHCH 3 or CON(CH 3 ) 2 ;
R 3 is H, halogen, 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 )alkenyl;
R 6 and R 6 ′ are independently of each other H, (C 1 -C 8 )alkyl, (C 1 -C 6 )alkylene-O—(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylene—C(O)NH 2 , (C 1 -C 6 )alkylene-C(O)N[(C 1 -C 4 )alkyl] 2 , C(O)O—(C 1 -C 6 )alkyl, C(O)(C 1 -C 6 )alkyl, C(O)NH—(C 1 -C 6 )alkyl, C(O)N[(C 1 -C 6 )alkyl] 2 ,
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,
r is 0, 1 or 2
L is O—(CH 2 )p; and
p is 0, 1 or 2.
41. The compound according to claim 1 , wherein
R 1 is H or OH;
R 2 is, C 3 -C 8 )cycloalkyl, (C 6 -C 10 )aryl, (C 1 -C 6 )alkylene-(C 6 -C 10 )aryl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkylene-C(O)NH 2 , (C 1 -C 6 )alkylene-C(O)NH—(C 1 -C 6 )alkyl, C(O)NH—(C 1 -C 6 )alkyl, C(O)—NH—(C 2 -C 6 )alkynyl, or
R 2 is (C 1 -C 3 )alkyl, provided that in said alkyl residue at least one hydrogen is substituted by OH, OCH 3 , COOH, COOCH 3 , NH 2 , NHCH 3 , N(CH 3 ) 2 , CONH 2 , CONHCH 3 or CON(CH 3 ) 2 ;
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 and R 6 ′ are independently of each other H, (C 1 -C 8 )alkyl, (C 1 -C 6 )alkylene-O—(C 1 -C 6 )alkyl, C(O)(C 1 -C 6 )alkyl;
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;
r is 0 or 1;
L is O—(CH 2 )p; and
p is 0 or 1.
42. The compound according to claim 1 , wherein
R 1 is H or OH;
R 2 is C 3 -C 8 )cycloalkyl, (C 6 -C 10 )aryl, (C 1 -C 6 )alkylene-(C 6 -C 10 )aryl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkylene-C(O)NH—(C 1 -C 6 )alkyl, C(O)NH—(C 1 -C 6 )alkyl or C(O)—NH—(C 2 -C 6 )alkynyl;
R 3 is H;
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 H or (C 1 -C 4 )alkyl;
R 6 ′ is H, (C 1 -C 8 )alkyl, C(O)O—(C 1 -C 6 )alkyl,
C(O)(C 1 -C 6 )alkyl;
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;
r is 0 or 1 and
L is 0; or
stereoisomeric form thereof and/or tautomeric form thereof and/or pharmaceutically acceptable salt thereof.
43. A compound selected from the group consisting of
6-(4-Allyl-4-amino-cyclohexyloxy)-7-chloro-2H-isoquinolin-1-one,
6-(4-Allyl-4-amino-cyclohexyloxy)-2H-isoquinolin-1-one,
6-(4-amino-4-benzyl-cyclohexyloxy)-7-chloro-2H-isoquinolin-1-one,
6-(4-Amino-4-phenyl-cyclohexyloxy)-7-chloro-2H-isoquinolin-1-one,
6-(4-Aminomethyl-4-phenyl-cyclohexyloxy)-7-chloro-2H-isoquinolin-1-one,
6-[4-Aminomethyl-4-(4-chloro-phenyl)-cyclohexyloxy]-7-chloro-2H-isoquinolin-1-one,
6-[4-Aminomethyl-4-(3-chloro-phenyl)-cyclohexyloxy]-7-chloro-2H-isoquinolin-1-one,
6-[4-Aminomethyl-4-(3-methyl-phenyl)-cyclohexyloxy]-7-chloro-2H-isoquinolin-1-one,
6-[4-Aminomethyl-4-(3,4-dimethoxy-phenyl)-cyclohexyloxy]-7-chloro-2H-isoquinolin-1-one,
6-[4-Aminomethyl-4-(4-fluoro-phenyl)-cyclohexyloxy]-7-chloro-2H-isoquinolin-1-one,
6-[4-Aminomethyl-4-(4-methoxy-phenyl)-cyclohexyloxy]-7-chloro-2H-isoquinolin-1-one,
6-[4-Aminomethyl-4-(4-methyl-phenyl)-cyclohexyloxy]-7-chloro-2H-isoquinolin-1-one,
6-[4-Aminomethyl-4-(3,4-chloro-phenyl)-cyclohexyloxy]-7-chloro-2H-isoquinolin-1-one, and
C—[4-(7-Chloro-isoquinolin-6-yloxy)-1-phenyl-cyclohexyl]-methylamine), and
stereoisomeric form thereof and/or tautomeric form thereof and/or pharmaceutically acceptable salt thereof.
44. A compound selected from the group consisting of
6-(4-Allyl-4-amino-cyclohexyloxy)-4,7-dimethyl-2H-isoquinolin-1-one,
6-(cis-4-Allyl-4-amino-cyclohexyloxy)-7-methyl-2H-isoquinolin-1-one,
6-(cis-4-Amino-4-cyclopropyl-cyclohexyloxy)-7-chloro-2H-isoquinolin-1-one,
6-(trans-4-amino-4-cyclopropyl-cyclohexyloxy)-7-chloro-2H-isoquinolin-1-one,
6-(trans-4-amino-4-cyclopropyl-cyclohexyloxy)-7-methyl-2H-isoquinolin-1-one,
6-(cis-1-amino-bicyclohexyl-4-yloxy)-7-chloro-2H-isoquinolin-1-one,
6-(trans-1-amino-bicyclohexyl-4-yloxy)-7-chloro-2H-isoquinolin-1-one,
6-[cis-4-amino-4-(3-methoxy-propyl)-cyclohexyloxy]-7-chloro-2H-isoquinolin-1-one,
6-[trans-4-amino-4-(3-methoxy-propyl)-cyclohexyloxy]-7-chloro-2H-isoquinolin-1-one,
6-(trans-4-Benzylamino-4-cyclopropyl-cyclohexyloxy)-7-chloro-2H-isoquinolin-1-one,
7-chloro-6-(trans-4-cyclopropyl-4-isopropylamino-cyclohexyloxy)-2H-isoquinolin-1-one,
7-chloro-6-(4-cyclopropyl-4-ethylamino-cyclohexyloxy)-2H-isoquinolin-1-one,
6-[cis-4-Amino-4-(3-hydroxy-propyl)-cyclohexyloxy]-7-chloro-2H-isoquinolin-1-one,
6-[trans-4-amino-4-(3-hydroxy-propyl)-cyclohexyloxy]-7-chloro-2H-isoquinolin-1-one,
6-[4-amino-4-(2,3-dihydroxy-propyl)-cyclohexyloxy]-7-chloro-2H-isoquinolin-1-one,
6-[cis-4-Amino-4-(4-fluoro-phenyl)-cyclohexyloxy]-7-chloro-2H-isoquinolin-1-one,
6-(cis-4-Amino-4-phenyl-cyclohexyloxy)-7-chloro-2H-isoquinolin-1-one,
6-(trans-4-Amino-4-phenyl-cyclohexyloxy)-7-chloro-2H-isoquinolin-1-one,
6-[cis-4-Amino-4-(4-trifluoromethyl-phenyl)-cyclohexyloxy]-7-chloro-2H-isoquinolin-1-one,
6-[cis-4-Amino-4-(3,5-dimethyl-phenyl)-cyclohexyloxy]-7-chloro-2H-isoquinolin-1-one,
6-[cis-4-Amino-4-(3,5-dimethyl-phenyl)-cyclohexyloxy]-7-methyl-2H-isoquinolin-1-one,
6-[cis-4-Amino-difluoro-phenyl)-cyclohexyloxy]-7-chloro-2H-isoquinolin-1-one,
6-[cis-4-Amino-4-(2,6-difluoro-phenyl)-cyclohexyloxy]-7-chloro-2H-isoquinolin-1-one,
6-[cis-4-Amino-4-(2,6-difluoro-phenyl)-cyclohexyloxy]-7-methyl-2H-isoquinolin-1-one,
6-[cis-4-Amino-4-(4-fluoro-phenyl)-cyclohexyloxy]-7-methyl-2H-isoquinolin-1-one,
6-[cis-4-Amino-4-(2,4-difluoro-phenyl)-cyclohexyloxy]-7-methyl-2H-isoquinolin-1-one,
6-[cis-4-Amino-4-(2-fluoro-phenyl)-cyclohexyloxy]-7-chloro-2H-isoquinolin-1-one,
6-[cis-4-Amino-4-(2-fluoro-phenyl)-cyclohexyloxy]-7-methyl-2H-isoquinolin-1-one,
6-[cis-4-Amino-4-(3,5-dimethyl-phenyl)-cyclohexyloxy]-7-chloro-2H-isoquinolin-1-one, and
stereoisomeric form thereof and/or tautomeric 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 compounds.
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 compounds.
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 one or more other active compounds.