# US 8,772,492 B2 · Substituted isoquinoline and isoquinolinone derivatives

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- Number: US 8,772,492 B2
- Document ID: US8772492B2
- Status: Granted
- Kind: B2
- Application number: 12/487,409
- Filed: 2009-06-18
- Published: 2010-03-04
- Granted: 2014-07-08
- Earliest claimed: 2006-12-27
- Assignees: Sanofi
- Applicants: Oliver Plettenburg; Katrin Lorenz; Jochen Goerlitzer; Matthias Lohn
- Inventors: Oliver Plettenburg; Katrin Lorenz; Jochen Goerlitzer; Matthias Lohn
- Web page: https://patentgrep.com/patent/US8772492B2

## CPC

- C07D 401/12: linked by a chain containing hetero atoms as chain links
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 5/00: Drugs for disorders of the endocrine system
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 9/12: Antihypertensives
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/06: Antiasthmatics
- A61P 13/08: of the prostate
- A61P 13/12: of the kidneys
- A61P 15/06: Antiabortive agents; Labour repressants
- A61P 15/10: for impotence
- A61P 19/08: for bone diseases, e.g. rachitism, Paget's disease
- A61P 19/10: for osteoporosis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 27/02: Ophthalmic agents
- A61P 27/06: Antiglaucoma agents or miotics
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/04: Antibacterial agents
- A61P 31/18: for HIV
- A61P 35/00: Antineoplastic agents
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 401/14: containing three or more hetero rings
- C07D 405/14: containing three or more hetero rings
- C07D 451/06: Oxygen atoms
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The invention relates to 6-substituted isoquinoline and isoquinoline 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.

## Claims

### Claim 1

A compound of the formula (I)
wherein
R1 is H, OH or NH2
R2 is
(C6-C10)aryl,
(C7-C8)alkyl,
(C2-C6)alkenyl,
(C2-C6)alkynyl,
(C1-C6)alkylene-C(O)NH2,
(C1-C6)alkylene-C(O)NH—(C1-C6)alkyl,
(C1-C6)alkylene-C(O)N[(C1-C6)alkyl]2,
(C1-C6)alkylene-C(O)O—(C1-C6)alkyl,
C(O)O—(C1-C6)alkyl,
C(O)(C1-C6)alkyl,
C(O)NH—(C1-C6)alkyl,
C(O)NHR′,
C(O)—NH(C2-C6)alkenyl,
C(O)—NH(C2-C6)alkynyl,
C(O)—NH(C1-C6)alkylene-R′,
C(O)N[(C1-C6)alkyl]2 or
R2 is (C1-C6)alkyl, provided that in said alkyl residue at least one hydrogen is substituted by OH, OCH3, COOH, COOCH3, NH2, NHCH3, N(CH3)2, CONH2, CONHCH3 or CON(CH3)2; or
R2 is a (C1-C4)alkylene bound to the cyclic amine, in which the (C1-C4) alkylene forms a second bond to a different carbon atom of the cyclic amine ring and forms, together with carbon atoms of cyclic amine, a second, 4-8 membered ring;
R3 is
H,
halogen,
(C1-C6)alkyl,
(C1-C6)alkylene-R′,
OH,
O—R″,
NH2,
NHR″,
NR″R″ or
NH—C(O)—R″,
R4 is
H,
halogen,
hydroxy,
CN,
(C1-C6)alkyl;
R5 is
H,
halogen,
CN,
NO2,
(C1-C6)alkyl,
(C2-C6)alkenyl,
CH(OH)—(C1-C6)alkyl,
NH2,
NH—SO2H,
NH—SO2—(C1-C6)alkyl,
NH—C(O)—(C1-C6)alkyl,
C(O)N[(C1-C6)alkyl]2,
C(O)OH, or
C(O)O—(C1-C6)alkyl;
R6 is
H,
R′,
(C1-C8)alkyl,
(C1-C6)alkylene-R′,
(C1-C6)alkylene-O—(C1-C6)alkyl,
(C1-C6)alkylene-O—R′,
(C1-C6)alkylene-CH[R′]2,
(C1-C6)alkylene-C(O)—R′,
(C1-C6)alkylene-C(O)NH2,
(C1-C6)alkylene-C(O)NH—R′,
(C1-C6)alkylene-C(O)NH—(C1-C6)alkyl,
(C1-C6)alkylene-C(O)N[(C1-C6)alkyl]2,
(C1-C6)alkylene-C(O)N[R′]2;
(C1-C6)alkylene-C(O)O—(C1-C6)alkyl,
C(O)O—(C1-C6)alkyl,
C(O)OR′,
C(O)(C1-C6)alkyl,
C(O)R′,
C(O)NH—(C1-C6)alkyl,
C(O)NHR′,
C(O)N[(C1-C6)alkyl]R′
C(O)N[(C1-C6)alkyl]2,
C(O)—(C1-C6)alkylene-R′, or
C(O)O(C1-C6)alkylene-R′;
R7 is
H,
halogen,
CN,
NO2,
(C1-C6)alkyl,
O—(C1-C6)alkyl,
(C2-C6)alkenyl,
CH(OH)—(C1-C6)alkyl,
NH2,
NH—SO2H,
NH—SO2—(C1-C6)alkyl,
SO2—NH2,
NH—C(O)—(C1-C6)alkyl,
C(O)N[(C1-C6)alkyl]2,
C(O)OH, or
C(O)O—(C1-C6)alkyl;
R8 is H, halogen or (C1-C6)alkyl;
n is 1;
m is 3;
L is O—(CH2)p, S(CH2)p, S(O)(CH2)p, S(O)(CH2)p, SO2(CH2)p, NH(CH2)p, N(C1-C6)alkyl-(CH2)p, N(C3-C6)cycloalkyl-(CH2)p, N[CO(C1-C6)alkyl]-(CH2)p or N[(C1-C3)alkylene-R′]-(CH2)p;
p is 0, 1, 2, 3, or 4;
R′ is
(C3-C8)cycloalkyl,
(C5-C10)heterocyclyl,
(C6-C10)aryl;
R″ is
(C3-C8)cycloalkyl,
(C5-C10)heterocyclyl,
(C6-C10)aryl,
(C1-C6)alkyl,
(C1-C6)alkylene-R′,
(C1-C6)alkylene-O—(C1-C6)alkyl,
(C1-C6)alkylene-O—R′, or
(C1-C6)alkylene-NRxRy; and
Rx and Ry are independently of each other
(C1-C6)alkyl,
(C5-C10)heterocyclyl,
(C6-C10)aryl,
(C1-C4)alkylene-(C5-C10)heterocyclyl,
(C1-C4)alkylene-(C6-C10)aryl,
(C1-C4)alkylene-NH(C1-C6)alkyl,
(C1-C4)alkylene-N[(C1-C6)alkyl]2,
(C1-C4)alkylene-N[(C6-C10)aryl]2, or
(C1-C4)alkylene-N[(C5-C10)heterocyclyl]2;
wherein in residues R2, R4, R5, R6, R7 and R8 as alkyl, alkylene or cycloalkyl can optionally be substituted one or more times by OH, OCH3, COOH, COOCH3, NH2, NHCH3, N(CH3)2, CONH2, CONHCH3 or CON(CH3)2;
wherein in residues R2 to R8 as alkyl or alkylene can optionally be substituted one or more times by halogen;
wherein in residues R2, R3, R6 as (C6-C10)aryl and (C5-C10)heterocyclyl are unsubstituted or substituted one or more times by suitable groups independently selected from halogen, OH, NO2, N3, CN, C(O)—(C1-C6)alkyl, COOH, COO(C1-C6)alkyl, CONH2, CONH(C1-C6)alkyl, CON[(C1-C6)alkyl]2, (C1-C6)alkyl, (C1-C6)alkylene-OH, (C1-C6)alkylene-NH2, (C1-C6)alkylene-NH(C1-C6)alkyl, (C1-C6)alkylene-N[(C1-C6)alkyl]2, (C2-C6)alkenyl, (C2-C6)alkynyl, O—(C1-C6)alkyl, O—C(O)—(C1-C6)alkyl, PO3H2, SO3H, SO2—NH2, SO2NH(C1-C6)alkyl, SO2N[(C1-C6)alkyl]2, S—(C1-C6)alkyl; SO—(C1-C6)alkyl, SO2—(C1-C6)alkyl, SO2—N═CH—N[(C1-C6)alkyl]2, C(NH)(NH2), NH2, NH—(C1-C6)alkyl, N[(C1-C6)alkyl]2, NH—C(O)—(C1-C6)alkyl, NH—C(O)O—(C1-C6)alkyl, NH—SO2—(C1-C6)alkyl, N(C1-C6)alkyl-C(O)—(C1-C6)alkyl, N(C1-C6)alkyl-C(O)O—(C1-C6)alkyl, N(C1-C6)alkyl-C(O)—NH—(C1-C6)alkyl]; or
stereoisomeric form thereof and/or tautomeric form thereof and/or pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The compound according to claim 1, having the formula (II)

### Claim 3 (depends on 1)

The compound according to claim 1, having the formula (III)

### Claim 4 (depends on 1)

The compound according to claim 1, having the formula (III′)

### Claim 5 (depends on 1)

The compound according to claim 1 wherein R1 is NH2.

### Claim 6 (depends on 1)

The compound according to claim 1, wherein R3 is H, halogen, (C1-C4)alkylene-R′, O—R″ or NHR″.

### Claim 7 (depends on 6)

The compound according to claim 6, wherein R3 is H or NHR″.

### Claim 8 (depends on 7)

The compound according to claim 7, wherein R3 is H; NH—(C5-C6)heterocyclyl, or NH-phenyl.

### Claim 9 (depends on 8)

The compound according to claim 8, wherein R3 is H.

### Claim 10 (depends on 1)

The compound according to claim 1, wherein R8 is H, halogen or (C1-C4)alkyl.

### Claim 11 (depends on 10)

The compound according to claim 10, wherein R8 is H, Cl, F, methyl or ethyl.

### Claim 12 (depends on 11)

The compound according to claim 11, wherein R8 is H.

### Claim 13 (depends on 1)

The compound according to claim 1, wherein R4 is H, halogen or (C1-C6)alkyl.

### Claim 14 (depends on 13)

The compound according to claim 13, wherein R4 is H, halogen or (C1-C4)alkyl.

### Claim 15 (depends on 14)

The compound according to claim 14, wherein R4 is H.

### Claim 16 (depends on 1)

The compound according to claim 1, wherein R5 is H, halogen, CN, (C1-C6)alkyl, (C2-C6)alkenyl.

### Claim 17 (depends on 16)

The compound according to claim 16, wherein R5 is H, halogen, (C1-C6)alkyl, (C2-C6)alkenyl.

### Claim 18 (depends on 17)

The compound according to claim 17, wherein R5 is H, halogen, methyl, ethyl, vinyl.

### Claim 19 (depends on 18)

The compound according to claim 18, wherein R5 is H, halogen, methyl, or ethyl.

### Claim 20 (depends on 19)

The compound according to claim 19, wherein R5 is H.

### Claim 21 (depends on 1)

The compound according to claim 1, wherein R7 is H, halogen, CN, (C1-C6)alkyl, O—(C1-C6)alkyl, (C2-C6)alkenyl.

### Claim 22 (depends on 21)

The compound according to claim 21, wherein R7 is H, halogen, CN, (C1-C4)alkyl, O—(C1-C4)alkyl, (C2-C4)alkenyl.

### Claim 23 (depends on 22)

The compound according to claim 22, wherein R7 is H, fluoro, chloro, bromo, methyl, ethyl, methoxy, CN, or vinyl.

### Claim 24 (depends on 23)

The compound according to claim 23, wherein R7 is H, fluoro, chloro, bromo, methyl or methoxy.

### Claim 25 (depends on 24)

The compound according to claim 24, wherein R7 is H.

### Claim 26 (depends on 1)

The compound according to claim 1, wherein R2 is (C6-C10)aryl, (C7-C8)alkyl, (C2-C6)alkenyl, (C1-C6)alkylene-C(O)NH2, (C1-C6)alkylene-C(O)NH—(C1-C6)alkyl, (C1-C6)alkylene-C(O)N[(C1-C6)alkyl]2, (C1-C6)alkylene-C(O)O—(C1-C6)alkyl, C(O)NH—(C1-C6)alkyl, C(O)NHR′, C(O)—NH(C2-C6)alkenyl, C(O)—NH(C2-C6)alkynyl, C(O)—NH(C1-C6)alkylene-R′, C(O)N[(C1-C6)alkyl]2, or
R2 is (C1-C6)alkyl, provided that in said alkyl residue at least one hydrogen is substituted by OH, OCH3, COOH, COOCH3, NH2, NHCH3, N(CH3)2, CONH2, CONHCH3 or CON(CH3)2; or
R2 is a (C1-C4)alkylene bound to the cyclic amine, in which the (C1-C4) alkylene forms a second bond to a different carbon atom of the cyclic amine ring and forms, together with carbon atoms of cyclic amine, a second, 4-8 membered ring.

### Claim 27 (depends on 26)

The compound according to claim 26, wherein R2 is
(C6-C10)aryl,
(C2-C6)alkenyl,
(C1-C6)alkylene-C(O)NH2,
(C1-C6)alkylene-C(O)NH—(C1-C6)alkyl,
C(O)NH—(C1-C6)alkyl,
C(O)NHR′,
C(O)—NH(C2-C6)alkenyl,
C(O)—NH(C2-C6)alkynyl, or
C(O)—NH(C1-C6)alkylene-R′, or
R2 is (C1-C3)alkyl, provided that in said alkyl residue at least one hydrogen is substituted by OH, OCH3, COOH, COOCH3, NH2, NHCH3, N(CH3)2, CONH2, CONHCH3 or CON(CH3)2; or
R2 is a (C1-C4)alkylene bound to the cyclic amine, in which the (C1-C4) alkylene forms a second bond to a different carbon atom of the cyclic amine ring and forms, together with carbon atoms of cyclic amine, a second, 4-8 membered ring.

### Claim 28 (depends on 27)

The compound according to claim 27, wherein R2 is
(C6-C10)aryl,
(C2-C6)alkenyl,
(C1-C6)alkylene-C(O)NH—(C1-C6)alkyl,
C(O)NH—(C1-C6)alkyl,
C(O)NHR′,
C(O)—NH(C2-C6)alkynyl, or
C(O)—NH(C1-C6)alkylene-R′, or
R2 is a (C1-C2)alkylene bound to the cyclic amine, in which the (C1-C4) alkylene forms a second bond to a different carbon atom of the cyclic amine ring and forms, together with carbon atoms of cyclic amine, a second, 4-8 membered ring.

### Claim 29 (depends on 1)

The compound according to claim 1, wherein
R6 is
H,
(C1-C6)alkyl,
R′,
(C1-C4)alkylene-(C6-C10)aryl,
(C1-C4)alkylene-(C3-C8)cycloalkyl,
(C1-C4)alkylene-(C5-C10)heterocyclyl,
(C1-C6)alkylene-O—(C1-C6)alkyl,
(C1-C4)alkylene-C(O)—(C5-C10)heterocyclyl,
(C1-C4)alkylene-C(O)—(C6-C10)aryl,
(C1-C6)alkylene-C(O)N[(C1-C6)alkyl]2,
(C1-C6)alkylene-C(O)NH—(C1-C6)alkyl,
(C1-C6)alkylene-C(O)O—(C1-C6)alkyl,
C(O)O—(C1-C6)alkyl,
C(O)(C1-C6)alkyl,
C(O)R′,
C(O)NH—(C1-C6)alkyl,
C(O)N[(C1-C6)alkyl]2, or
C(O)(C1-C6)alkylene-R′.

### Claim 30 (depends on 29)

The compound according to claim 29, wherein R6 is
H,
(C1-C6)alkyl,
(C5-C10)heterocyclyl,
(C3-C8)cycloalkyl,
(C6-C10)aryl,
(C1-C4)alkylene-(C3-C8)cycloalkyl,
(C1-C4)alkylene-(C5-C10)heterocyclyl,
(C1-C4)alkylene-(C6-C10)aryl,
(C1-C6)alkylene-O—(C1-C6)alkyl,
(C1-C6)alkylene-C(O)N[(C1-C6)alkyl]2,
(C1-C6)alkylene-C(O)NH—(C1-C6)alkyl,
(C1-C6)alkylene-C(O)O—(C1-C6)alkyl,
C(O)O—(C1-C6)alkyl,
C(O)(C1-C6)alkyl,
C(O)(C5-C10)heterocyclyl,
C(O)(C3-C8)cycloalkyl
C(O)NH—(C1-C6)alkyl,
C(O)N[(C1-C6)alkyl]2,
C(O)(C1-C6)alkylene-(C3-C8)cycloalkyl,
C(O)(C1-C6)alkylene-C5-C10)heterocyclyl, or
C(O)(C1-C6)alkylene-(C6-C10)aryl.

### Claim 31 (depends on 30)

The compound according to claim 30, wherein
R6 is
H,
(C1-C6)alkyl,
(C3-C8)cycloalkyl,
(C5-C10)heterocyclyl,
(C6-C10)aryl,
(C1-C4)alkylene-(C3-C8)cycloalkyl,
(C1-C4)alkylene-(C5-C10)heterocyclyl,
(C1-C4)alkylene-(C6-C10)aryl,
(C1-C6)alkylene-O—(C1-C6)alkyl,
(C1-C6)alkylene-C(O)NH—(C1-C6)alkyl,
(C1-C6)alkylene-C(O)N[(C1-C6)alkyl]2,
C(O)O—(C1-C6)alkyl,
C(O)(C1-C6)alkyl,
C(O)(C3-C8)cycloalkyl,
C(O)—(C5-C10)heterocyclyl,
C(O)NH—(C1-C6)alkyl,
C(O)N[(C1-C6)alkyl]2,
C(O)(C1-C6)alkylene-(C3-C8)cycloalkyl,
C(O)(C1-C6)alkylene-(C5-C10)heterocyclyl, or
C(O)(C1-C6)alkylene-(C6-C10)aryl.

### Claim 32 (depends on 31)

The compound according to claim 31, wherein
R6 is
H,
(C1-C6)alkyl,
(C3-C8)cycloalkyl,
(C6-C10)aryl,
(C1-C4)alkylene-(C3-C8)cycloalkyl,
(C1-C4)alkylene-(C5-C10)heterocyclyl,
(C1-C4)alkylene-(C6-C10)aryl,
(C1-C4)alkylene-O—(C1-C4)alkyl,
C(O)(C1-C6)alkyl,
C(O)(C3-C8)cycloalkyl,
C(O)—(C5-C10)heterocyclyl,
C(O)(C1-C4)alkylene-(C5-C10)heterocyclyl, or
C(O)(C1-C4)alkylene-(C6-C10)aryl.

### Claim 33 (depends on 32)

The compound according to claim 32, wherein
R6 is
H;
(C1-C6)alkyl;
(C3-C8)cycloalkyl;
(C1-C4)alkylene-(C3-C8)cycloalkyl;
(C1-C4)alkylene-(C5-C10)heterocyclyl wherein heterocyclyl is unsubstituted or substituted one or more times by (C1-C4)alkyl;
(C1-C4)alkylene-(C6-C10)aryl wherein aryl is unsubstituted or substituted one or more times by halogen, (C1-C4)alkyl, O—(C1-C4)alkyl, SO2—(C1-C4)alkyl or SO2-N[(C1-C6)alkyl]2.

### Claim 34 (depends on 33)

The compound according to claim 33, wherein R6 is H, (C1-C6)alkyl or (C3-C8)cycloalkyl.

### Claim 35 (depends on 34)

The compound according to claim 34, wherein R6 is H, unsubstituted (C1-C6)alkyl or unsubstituted (C3-C8)cycloalkyl.

### Claim 36 (depends on 35)

The compound according to claim 35, wherein R6 is H.

### Claim 37 (depends on 1)

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 piperidine ring.

### Claim 38 (depends on 1)

The compound according to claim 1, wherein m is 3 and L is attached to the 4-position of the piperidine ring.

### Claim 39 (depends on 1)

The compound according to claim 1, wherein L is S(CH2)p, S(O)(CH2)p or SO2(CH2)p.

### Claim 40 (depends on 1)

The compound according to claim 1, wherein L is NH(CH2)p or N(C1-C6)alkyl-(CH2)p.

### Claim 41 (depends on 1)

The compound according to claim 1, wherein L is O—(CH2)p.

### Claim 42 (depends on 1)

The compound according to claim 1, wherein p is 0.

### Claim 43 (depends on 1)

The compound according to claim 1, wherein
R1 is H or OH;
R2 is (C6-C10)aryl, (C7-C8)alkyl, (C2-C6)alkenyl, (C1-C6)alkylene-C(O)NH2, (C1-C6)alkylene-C(O)NH—(C1-C6)alkyl, (C1-C6)alkylene-C(O)N[(C1-C6)alkyl]2, (C1-C6)alkylene-C(O)O—(C1-C6)alkyl, C(O)NH—(C1-C6)alkyl, C(O)NHR′, C(O)—NH(C2-C6)alkenyl, C(O)—NH(C2-C6)alkynyl, C(O)—NH(C1-C6)alkylene-R′, C(O)N[(C1-C6)alkyl]2, or
R2 is (C1-C6)alkyl, provided that in said alkyl residue at least one hydrogen is substituted by OH, OCH3, COOH, COOCH3, NH2, NHCH3, N(CH3)2, CONH2, CONHCH3 or CON(CH3)2; or
R2 is a (C1-C4)alkylene bound to the cyclic amine, in which the (C1-C4) alkylene forms a second bond to a different carbon atom of the cyclic amine ring and forms, together with carbon atoms of cyclic amine, a second, 4-8 membered ring;
R3 is H, halogen, (C1-C4)alkylene-R′, O—R″ or NHR″;
R4 is H, halogen or (C1-C6)alkyl;
R5 is H, (C1-C6)alkyl, halogen, CN, (C2-C6)alkenyl;
R6 is H, R′, (C1-C8)alkyl, (C1-C6)alkylene-R′, (C1-C6)alkylene-O—(C1-C6)alkyl, (C1-C6)alkylene-O—R′, (C1-C6)alkylene-CH[R′]2, (C1-C6)alkylene-C(O)NH2, (C1-C6)alkylene-C(O)NH—R′, (C1-C6)alkylene-C(O)N[(C1-C4)alkyl]2, (C1-C6)alkylene-C(O)N[R′]2; C(O)O—(C1-C6)alkyl, C(O)(C1-C6)alkyl, C(O)(C3-C8)cycloalkyl, C(O)NH—(C1-C6)alkyl, C(O)N[(C1-C6)alkyl]2, C(O)(C1-C6)alkylene-(C3-C8)cycloalkyl, C(O)(C1-C6)alkylene-C5-C10)heterocyclyl, or C(O)(C1-C6)alkylene-(C6-C10)aryl; R7 is H, halogen, CN, (C1-C6)alkyl, O—(C1-C6)alkyl, (C2-C6)alkenyl;
m is 3
n is 1,
L is O—(CH2)p, S(CH2)p, NH(CH2)p or N(C1-C6)alkyl-(CH2)p, and
p is 0, 1 or 2.

### Claim 44 (depends on 1)

The compound according to claim 1, wherein
R1 is H or OH;
R2 is (C6-C10)aryl, (C2-C6)alkenyl, (C1-C6)alkylene-C(O)NH2, C(O)—NH(C2-C6)alkynyl, (C1-C6)alkylene-C(O)NH—(C1-C6)alkyl, C(O)NH—(C1-C6)alkyl, C(O)NHR′ or C(O)—NH(C1-C6)alkylene-R′, or
R2 is (C1-C3)alkyl, provided that in said alkyl residue at least one hydrogen is substituted by OH, OCH3, COOH, COOCH3, NH2, NHCH3, N(CH3)2, CONH2, CONHCH3 or CON(CH3)2; or
R2 is a (C1-C4)alkylene bound to the cyclic amine, in which the (C1-C4) alkylene forms a second bond to a different carbon atom of the cyclic amine ring and forms, together with carbon atoms of cyclic amine, a second, 4-8 membered ring;
R3 is H, halogen or NHR″;
R4 is H, halogen or (C1-C4)alkyl;
R5 is H, (C1-C6)alkyl, halogen, (C2-C4)alkenyl;
R6 is H, (C3-C8)cycloalkyl, (C1-C8)alkyl, (C1-C3)alkylene-R′, C(O)O—(C1-C6)alkyl, C(O)(C1-C6)alkyl, C(O)(C3-C8)cycloalkyl, C(O)—(C5-C10)heterocyclyl, C(O)NH—(C1-C6)alkyl, C(O)N[(C1-C6)alkyl]2, C(O)(C1-C6)alkylene-(C3-C8)cycloalkyl, C(O)(C1-C6)alkylene-(C5-C10)heterocyclyl, or C(O)(C1-C6)alkylene-(C6-C10)aryl;
R7 is H, halogen, CN, (C1-C6)alkyl, O—(C1-C6)alkyl, (C2-C6)alkenyl;
m is 3
n is 1;
L is O—(CH2)p, S(CH2)p or NH(CH2)p, and
p is 0 or 1.

### Claim 45 (depends on 1)

The compound according to claim 1, wherein
R1 is H or OH;
R2 is
(C6-C10)aryl,
(C2-C6)alkenyl,
(C1-C6)alkylene-C(O)NH—(C1-C6)alkyl,
C(O)NH—(C1-C6)alkyl,
C(O)NHR′,
C(O)—NH(C2-C6)alkynyl or
C(O)—NH(C1-C6)alkylene-R′, or
R2 is a (C1-C2)alkylene bound to the cyclic amine, in which the (C1-C4) alkylene forms a second bond to a different carbon atom of the cyclic amine ring and forms, together with carbon atoms of cyclic amine, a second, 4-8 membered ring;
R3 is H, NH—(C5-C6)heteroaryl or NH-phenyl;
R4 is H, halogen or (C1-C4)alkyl;
R5 is H, (C1-C4)alkyl, halogen, (C2-C4)alkenyl;
R6 is H, (C3-C8)cycloalkyl, (C1-C8)alkyl, (C1-C3)alkylene-R′; C(O)(C1-C6)alkyl,
C(O)(C3-C8)cycloalkyl, C(O)—(C5-C10)heterocyclyl, C(O)(C1-C3)alkylene-(C5-C10)heterocyclyl or C(O)(C1-C3)alkylene-(C6-C10)aryl;
R7 is H, halogen, CN, (C1-C4)alkyl, O—(C1-C4)alkyl, (C2-C4)alkenyl;
R8 is H, halogen or (C1-C4)alkyl;
m is 3;
n is 1; and
L is O, NH or S.

### Claim 46

A compound selected from the group consisting of
(2R,4R)-4-(Isoquinolin-6-yloxy)-piperidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester,
(2R,4R)-4-(Isoquinolin-6-yloxy)-2-o-tolylcarbamoyl-piperidine-1-carboxylic acid tert-butyl ester,
(2R,4R)-4-(Isoquinolin-6-yloxy)-piperidine-2-carboxylic acid o-tolylamide,
(2R,4R)-4-(Isoquinolin-6-yloxy)-piperidine-2-carboxylic acid isobutyl-amide,
(2R,4R)-4-(Isoquinolin-6-yloxy)-piperidine-2-carboxylic acid 3-methoxy-benzylamide (11),
(2R,4R)-4-(Isoquinolin-6-yloxy)-piperidine-2-carboxylic acid 2-chloro-benzylamide (12),
(2R,4R)-4-(Isoquinolin-6-yloxy)-piperidine-2-carboxylic acid phenethyl-amide,
(2R,4R)-4-(Isoquinolin-6-yloxy)-piperidine-2-carboxylic acid (3-methoxy-propyl)-amide,
(2R,4R)-4-(Isoquinolin-6-yloxy)-piperidine-2-carboxylic acid (2-hydroxy-ethyl)-amide,
(2R,4R)-4-(Isoquinolin-6-yloxy)-piperidine-2-carboxylic acid (furan-2-ylmethyl)-amide,
(2S,4S)-4-(Isoquinolin-6-yloxy)-piperidine-2-carboxylic acid (furan-2-ylmethyl)-amide,
(2S,4S)-4-(Isoquinolin-6-yloxy)-piperidine-2-carboxylic acid (3-methoxy-propyl)-amide,
(2S,4S)-4-(Isoquinolin-6-yloxy)-piperidine-2-carboxylic acid (pyridin-2-ylmethyl)-amide,
(2S,4S)-4-(Isoquinolin-6-yloxy)-piperidine-2-carboxylic acid prop-2-ynylamide,
(2S,4S)-4-(Isoquinolin-6-yloxy)-piperidine-2-carboxylic acid phenethyl-amide,
(2S,4S)-4-(Isoquinolin-6-yloxy)-piperidine-2-carboxylic acid 2-chloro-benzylamide,
(2S,4S)-4-(Isoquinolin-6-yloxy)-piperidine-2-carboxylic acid isobutyl-amide,
6-(8-Methyl-8-aza-bicyclo[3.2.1]oct-3-yloxy)-isoquinoline, and
6-(1-benzyl-4-phenyl-piperidin-4-yloxy)-7-chloro-isoquinolin-1-one, or
stereoisomeric form thereof and/or tautomeric form thereof and/or pharmaceutically acceptable salt thereof.

### Claim 47

A compound selected from the group consisting of
6-(8-Methyl-8-aza-bicyclo[3.2.1]oct-3-yloxy)-2H-isoquinolin-1-one,
6-(8-Aza-bicyclo[3.2.1]oct-3-yloxy)-7-chloro-2H-isoquinolin-1-one,
6-(8-Methyl-8-aza-bicyclo[3.2.1]oct-3-yloxy)-2H-isoquinolin-1-one,
7-Chloro-6-(8-methyl-8-aza-bicyclo[3.2.1]oct-3-yloxy)-2H-isoquinolin-1-one,
7-Methyl-6-(8-methyl-8-aza-bicyclo[3.2.1]oct-3-yloxy)-2H-isoquinolin-1-one, and
N6-(4-Amino-4-phenyl-cyclohexyl)-isoquinoline-1,6-diamine, or
stereoisomeric form thereof and/or tautomeric form thereof and/or pharmaceutically acceptable salt thereof.

### Claim 48 (depends on 1)

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.