# US 8,772,316 B2 · Substituted 6,7-dialkoxy-3-isoquinolinol derivatives as inhibitors of phosphodiesterase 10 (PDE10A)

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- Number: US 8,772,316 B2
- Document ID: US8772316B2
- Status: Granted
- Kind: B2
- Application number: 13/399,351
- Filed: 2012-02-17
- Published: 2012-08-23
- Granted: 2014-07-08
- Earliest claimed: 2011-02-18
- Assignees: Allergan, Inc.; Exonhit Therapeutics SA
- Applicants: Bertrand Leblond; John E. Donello; Cédric Chauvignac; Thierry Taverne; Eric Beausoleil; Anne-Sophie Casagrande; Laurent Désiré; Matthew P. Pando; Rong Yang
- Inventors: Bertrand Leblond; John E. Donello; Cédric Chauvignac; Thierry Taverne; Eric Beausoleil; Anne-Sophie Casagrande; Laurent Désiré; Matthew P. Pando; Rong Yang
- Web page: https://patentgrep.com/patent/US8772316B2

## CPC

- C07D 401/14: containing three or more hetero rings
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- 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 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 19/00: Drugs for skeletal disorders
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- A61P 25/16: Anti-Parkinson drugs
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A61P 25/22: Anxiolytics
- A61P 25/24: Antidepressants
- 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 25/30: for treating abuse or dependence
- A61P 27/02: Ophthalmic agents
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 217/24: Oxygen atoms
- C07D 401/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 405/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 491/056: with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The invention relates to compounds of the formula wherein R′, R1, through R7 and Ar are as defined herein. These compounds are useful as inhibitors of phosphodiesterase 10 (PDE10A) which are useful in treating central nervous system diseases such as psychosis and also in treating, for example, obesity, type II diabetes, metabolic syndrome, glucose intolerance, pain and ophthalmic diseases.

## Claims

### Claim 1

A compound of Formula (I)
a pharmaceutically acceptable salt or a tautomer form thereof; wherein:
R1 is a (C1-C4)alkyl group optionally substituted with a —(C1-C4)alkoxy or a RaNH group, Ra being selected from the group consisting of (C1-C4)alkyl-C(═O)— and (C1-C4)alkyl-S(═O)2—;
R2 is a hydrogen atom;
R3 and R4 independently represent a (C1-C3)alkyl group;
R5 is a hydrogen atom;
R6 and R7 independently represent a hydrogen atom, a halogen atom, or R6 and R7 together with the carbon atom to which they are shown attached form a —C(═O)— group;
R′ is —NH2 or —OR, wherein R is a hydrogen atom, a (C1-C3)alkyl group or a (C1-C3)alkyl-C(═O)— group
Ar is an aryl or heteroaryl group optionally substituted with one to four substituents independently selected from the group consisting of halogen, azido, hydroxy, (C1-C4)alkyl, (C1-C4)alkoxy, —O—(C1-C4)alkyl-(C1-C6)cycloalkyl, aryl, (C1-C4)alkyl-aryl-, (C1-C4)alkoxy-aryl-, amino-substituted aryl, N((C1-C4)alkyl)2-substituted aryl, aryloxy, heteroaryl, (C1-C4)alkyl-heteroaryl-, and RbRcN, or wherein two substituents at adjacent positions of the aryl or heteroaryl together with the atoms to which they are attached form a heterocyclic ring; and
Rb and Rc, are independently selected from the group consisting of hydrogen, (C1-C4)alkyl, halogeno(C1-C4)alkyl-, (C1-C4)alkoxy(C1-C4)alkyl-, aryl(C1-C4)alkyl- and acetylamino(C1-C4)alkyl-.

### Claim 2 (depends on 1)

The compound according to claim 1, wherein R3 and R4 both represent a methyl group.

### Claim 3 (depends on 1)

The compound according to claim 1, wherein R1 is selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, CH3C(═O)NHCH2—, CH3S(═O)2NHCH2—, and CH3OCH2—.

### Claim 4 (depends on 1)

The compound according to claim 1, wherein R′ is selected from the group consisting of —NH2, —OH, —OCH3, and —OC(═O)CH3.

### Claim 5 (depends on 1)

The compound according to claim 1, wherein Ar represents
a pyridinyl group optionally substituted with one or two substituents independently selected from the group consisting of aryl, (C1-C4)alkylaryl, heteroaryl, (C1-C4)heteroaryl and (C1-C4)alkoxy-aryl-;
a phenyl group optionally substituted with one or two substituents selected from the group consisting of (C1-C4)alkyloxy, aryloxy, (C1-C4)alkoxy-aryl-, and aminoaryl;
a naphthyl group optionally substituted with one or two substituents selected from the group consisting of (C1-C4)alkyloxy, aryloxy, (C1-C4)alkoxy-aryl and aminoaryl;
a quinolinyl group optionally substituted with one or more substituents, in particular one or two substituents, selected from the group consisting of (C1-C4)alkyl, (C1-C4)alkyloxy and RbRcN;
-[1,3]dioxolo[4,5-g]quinolyn group, optionally substituted with a RbRcN-substituent;
an isoquinolinyl group; or
a dibenzofuran group.

### Claim 6 (depends on 1)

The compound of claim 1, wherein Ar is an aryl or heteroaryl group which can optionally be substituted with one to four substituents independently selected from the group consisting of fluoro, azido, hydroxyl, methyl, ethyl, hydroxy, methoxy, ethoxy, —O—CH2-cyclopropyl, phenyl, methoxyphenyl, aminophenyl, phenoxy, pyridinyl, methylamino, ethylamino, N,N-dimethylamino, ethylamino, n-propylamino, n-butylamino, isopropylamino, trifluoromethyl, 2,2,2-trifluoroethylamino, benzylamino, and acetyl-2-aminoethylamino.

### Claim 7

A compound selected from the group consisting of:
4-benzyl-6,7-dimethoxy-1-methylisoquinolin-3-ol hydrochloride 1,
4-(3,4-dimethoxybenzyl)-6,7-dimethoxy-1-methylisoquinolin-3-ol hydrochloride 2,
4-(3,4-dimethoxybenzyl)-3,6,7-trimethoxy-1-methylisoquinoline hydrochloride 3,
6,7-dimethoxy-1-methyl-4-(3-phenoxybenzyl)isoquinolin-3-ol hydrochloride 4,
6,7-dimethoxy-1-methyl-4-(4-phenoxybenzyl)isoquinolin-3-ol hydrochloride 5,
4-(dibenzo[b,d]furan-2-ylmethyl)-1-ethyl-6,7-dimethoxyisoquinolin-3-ol hydrochloride 6,
4-(dibenzo[b,d]furan-2-ylmethyl)-6,7-dimethoxy-1-propylisoquinolin-3-ol hydrochloride 7,
4-((3′-amino-[1,1′-biphenyl]-3-yl)methyl)-1-ethyl-6,7-dimethoxyisoquinolin-3-ol dihydrochloride 10,
6,7-dimethoxy-1-methyl-4-(pyridin-4-ylmethyl)isoquinolin-3-ol hydrochloride 11,
6,7-dimethoxy-1-methyl-4-((6-phenylpyridin-2-yl)methyl)isoquinolin-3-ol dihydrochloride
6,7-dimethoxy-4-((6-(4-methoxyphenyl)pyridin-2-yl)methyl)-1-methylisoquinolin-3-ol dihydrochloride 13,
4-([2,4′-bipyridin]-6-ylmethyl)-6,7-dimethoxy-1-methylisoquinolin-3-ol trihydrochloride 14,
6,7-dimethoxy-1-methyl-4-((5-phenylpyridin-3-yl)methyl)isoquinolin-3-ol dihydrochloride 15,
6,7-dimethoxy-4-((5-(4-methoxyphenyl)pyridin-3-yl)methyl)-1-methylisoquinolin-3-ol dihydrochloride 16,
6,7-dimethoxy-1-methyl-4-(naphthalen-2-ylmethyl)isoquinolin-3-ol hydrochloride 17,
1-ethyl-6,7-dimethoxy-4-(naphthalen-2-ylmethyl)isoquinolin-3-ol hydrochloride 19,
6,7-dimethoxy-4-(naphthalen-2-ylmethyl)-1-propylisoquinolin-3-ol hydrochloride 20,
4-(isoquinolin-6-ylmethyl)-6,7-dimethoxy-1-methylisoquinolin-3-ol dihydrochloride 21,
4-(isoquinolin-5-ylmethyl)-6,7-dimethoxy-1-methylisoquinolin-3-ol 22,
6,7-dimethoxy-1-methyl-4-(quinolin-2-ylmethyl)isoquinolin-3-ol dihydrochloride 23,
6,7-dimethoxy-1-methyl-4-(quinolin-6-ylmethyl)isoquinolin-3-ol dihydrochloride 24,
6,7-dimethoxy-1-methyl-4-(quinolin-4-ylmethyl)isoquinolin-3-ol dihydrochloride 25,
6,7-dimethoxy-1-methyl-4-(quinolin-3-ylmethyl)isoquinolin-3-ol dihydrochloride 26,
6,7-dimethoxy-4-((5-methoxyquinolin-3-yl)methyl)-1-methylisoquinolin-3-ol dihydrochloride 27,
4-((5-ethoxyquinolin-3-yl)methyl)-6,7-dimethoxy-1-methylisoquinolin-3-ol dihydrochloride 28,
6,7-dimethoxy-4-((7-methoxyquinolin-3-yl)methyl)-1-methylisoquinolin-3-ol dihydrochloride 29,
4-((7-ethoxyquinolin-3-yl)methyl)-6,7-dimethoxy-1-methylisoquinolin-3-ol dihydrochloride 30,
1-ethyl-6,7-dimethoxy-4-((7-methoxyquinolin-3-yl)methyl)isoquinolin-3-ol dihydrochloride 31,
6,7-dimethoxy-4-((7-methoxyquinolin-3-yl)methyl)-1-propylisoquinolin-3-ol dihydrochloride 32,
6,7-dimethoxy-1-methyl-4-((6-methyl-2-(methylamino)quinolin-3-yl)methyl)isoquinolin-3-ol dihydrochloride 33,
6,7-dimethoxy-4-((6-methyl-2-(methylamino)quinolin-3-yl)methyl)-1-propylisoquinolin-3-ol dihydrochloride 34,
4-((2-(ethylamino)-6-methylquinolin-3-yl)methyl)-6,7-dimethoxy-1-propylisoquinolin-3-ol dihydrochloride 35,
4-((2-(dimethylamino)-6-methylquinolin-3-yl)methyl)-6,7-dimethoxy-1-propylisoquinolin-3-ol dihydrochloride 36,
6,7-dimethoxy-4-((6-methoxy-2-(methylamino)quinolin-3-yl)methyl)-1-methyl-isoquinolin-3-ol dihydrochloride 37,
6,7-dimethoxy-4-((6-methoxy-2-(propylamino)quinolin-3-yl)methyl)-1-propylisoquinolin-3-ol dihydrochloride 38,
1-ethyl-6,7-dimethoxy-4-((6-methoxy-2-(methylamino)quinolin-3-yl)methyl)isoquinolin-3-ol 39,
1-ethyl-6,7-dimethoxy-4-((6-methoxy-2-(ethylamino)quinolin-3-yl)methyl)isoquinolin-3-ol dihydrochloride 40,
1-ethyl-6,7-dimethoxy-4-((6-ethoxy-2-(ethylamino)quinolin-3-yl)methyl)isoquinolin-3-ol dihydrochloride 41,
1-ethyl-6,7-dimethoxy-4-((6-methoxy-2-(propylamino)quinolin-3-yl)methyl)isoquinolin-3-ol dihydrochloride 42,
1-ethyl-4-((2-(isopropylamino)-6-methoxyquinolin-3-yl)methyl)-6,7-dimethoxyisoquinolin-3-ol dihydrochloride 43,
4-((2-(benzylamino)-6-methoxyquinolin-3-yl)methyl)-1-ethyl-6,7-dimethoxyisoquinolin-3-ol dihydrochloride 44,
1-ethyl-6,7-dimethoxy-4-((6-methoxy-2-(2,2,2-trifluoroethylamino)quinolin-3-yl)methyl)isoquinolin-3-ol dihydrochloride 45,
4-((6-ethoxy-2-(ethylamino)quinolin-3-yl)methyl)-1-isopropyl-6,7-dimethoxyisoquinolin-3-ol dihydrochloride 46,
4-((2-(ethylamino)-6-methoxyquinolin-3-yl)methyl)-1-isopropyl-6,7-dimethoxyisoquinolin-3-ol dihydrochloride 47,
6,7-dimethoxy-4-((6-methoxy-2-(methylamino)quinolin-3-yl)methyl)-1-propylisoquinolin-3-ol dihydrochloride 48,
4-((6-ethoxy-2-(ethylamino)quinolin-3-yl)methyl)-6,7-dimethoxy-1-propylisoquinolin-3-ol dihydrochloride 49,
4-((2-(ethylamino)-6-methoxyquinolin-3-yl)methyl)-6,7-dimethoxy-1-propylisoquinolin-3-ol dihydrochloride 50,
1-isopropyl-6,7-dimethoxy-4-((6-methoxy-2-(2,2,2-trifluoroethylamino)quinolin-3-yl)methyl)isoquinolin-3-ol dihydrochloride 51,
6,7-dimethoxy-4-((6-methoxy-2-(propylamino)quinolin-3-yl)methyl)-1-propylisoquinolin-3-ol dihydrochloride 52,
4-((2-(isopropylamino)-6-methoxyquinolin-3-yl)methyl)-6,7-dimethoxy-1-propylisoquinolin-3-ol dihydrochloride 53,
6,7-dimethoxy-4-((6-methoxy-2-((2,2,2-trifluoroethyl)amino)quinolin-3-yl)methyl)-1-propylisoquinolin-3-ol dihydrochloride 54,
N-(2-((3-((3-hydroxy-6,7-dimethoxy-1-propylisoquinolin-4-yl)methyl)-6-methoxyquinolin-2-yl)amino)ethyl)acetamide dihydrochloride 55,
1-(acetamidomethyl)-4-((2-(ethylamino)-6-methoxyquinolin-3-yl)methyl)-6,7-dimethoxyisoquinolin-3-yl acetate 56,
N-((4-((2-(ethylamino)-6-methoxyquinolin-3-yl)methyl)-3-hydroxy-6,7-dimethoxyisoquinolin-1-yl)methyl)acetamide dihydrochloride 57,
N-((4-((2-(ethylamino)-6-methoxyquinolin-3-yl)methyl)-3-hydroxy-6,7-dimethoxyisoquinolin-1-yl)methyl)methanesulfonamide dihydrochloride 58,
3-((3-hydroxy-6,7-dimethoxy-1-methylisoquinolin-4-yl)methyl)-2-(methylamino)quinoline-6,7-diol dihydrochloride 59,
6,7-dimethoxy-1-methyl-4-((6-(methylamino)-[1,3]dioxolo[4,5-g]quinolin-7-yl)methyl)isoquinolin-3-ol dihydrochloride 60,
1-ethyl-6,7-dimethoxy-4-((6-(methylamino)-[1,3]dioxolo[4,5-g]quinolin-7-yl)methyl)isoquinolin-3-ol dihydrochloride 61,
6,7-dimethoxy-4-((6-(methylamino)-[1,3]dioxolo[4,5-g]quinolin-7-yl)methyl)-1-propylisoquinolin-3-ol dihydrochloride 62,
4-((6-(dimethylamino)-[1,3]dioxolo[4,5-g]quinolin-7-yl)methyl)-6,7-dimethoxy-1-propylisoquinolin-3-ol dihydrochloride 63,
4-((6-(ethylamino)-[1,3]dioxolo[4,5-g]quinolin-7-yl)methyl)-6,7-dimethoxy-1-propylisoquinolin-3-ol dihydrochloride 64,
4-((2-ethyl-6-methoxyquinolin-3-yl)methyl)-6,7-dimethoxy-1-propylisoquinolin-3-ol dihydrochloride 66,
4-((2-(ethylamino)-6-methoxyquinolin-3-yl)methyl)-6,7-dimethoxy-1-(methoxymethyl)isoquinolin-3-ol dihydrochloride 67,
4-((2-azido-6-methoxyquinolin-3-yl)methyl)-1-ethyl-6,7-dimethoxyisoquinolin-3-ol dihydrochloride 68,
N-(2-((3-((1-ethyl-3-hydroxy-6,7-dimethoxyisoquinolin-4-yl)methyl)-6-methoxyquinolin-2-yl)amino)ethyl)acetamide dihydrochloride 69,
4-((2-(ethylamino)-7-fluoro-6-methoxyquinolin-3-yl)methyl)-6,7-dimethoxy-1-propylisoquinolin-3-ol dihydrochloride 70,
4-((2-butyl-6-methoxyquinolin-3-yl)methyl)-6,7-dimethoxy-1-propylisoquinolin-3-ol dihydrochloride 71,
6,7-dimethoxy-4-((6-methoxy-2-(trifluoromethyl)quinolin-3-yl)methyl)-1-propylisoquinolin-3-ol hydrochloride 72,
N-(2-((3-((3-hydroxy-6,7-dimethoxy-1-methylisoquinolin-4-yl)methyl)-6-methoxyquinolin-2-yl)amino)ethyl)acetamide dihydrochloride 73,
6,7-dimethoxy-1-propyl-4-(quinolin-3-ylmethyl)isoquinolin-3-ol dihydrochloride 74,
6,7-dimethoxy-4-((6-methoxy-2-((2-methoxyethyl)amino)quinolin-3-yl)methyl)-1-propylisoquinolin-3-ol dihydrochloride 76,
1-ethyl-6,7-dimethoxy-4-((6-methoxy-2-((2-methoxyethyl)amino)quinolin-3-yl)methyl)isoquinolin-3-ol dihydrochloride 77,
1-ethyl-6,7-dimethoxy-4-(quinolin-3-ylmethyl)isoquinolin-3-ol dihydrochloride 78,
1-isopropyl-6,7-dimethoxy-4-(quinolin-3-ylmethyl)isoquinolin-3-ol dihydrochloride 79,
6,7-dimethoxy-4-((2-methylquinolin-6-yl)methyl)-1-propylisoquinolin-3-ol dihydrochloride 80,
1-ethyl-6,7-dimethoxy-4-((2-methylquinolin-6-yl)methyl)isoquinolin-3-ol dihydrochloride 81,
1-ethyl-4-((2-(ethylamino)-7-fluoro-6-methoxyquinolin-3-yl)methyl)-6,7-dimethoxyisoquinolin-3-ol dihydrochloride 82,
N-(2-((6-(cyclopropylmethoxy)-3-((3-hydroxy-6,7-dimethoxy-1-propylisoquinolin-4-yl)methyl)quinolin-2-yl)amino)ethyl)acetamide dihydrochloride 83,
6,7-dimethoxy-4-((6-methoxyquinolin-3-yl)methyl)-1-propylisoquinolin-3-ol dihydrochloride 84,
1-ethyl-6,7-dimethoxy-4-((6-methoxyquinolin-3-yl)methyl)isoquinolin-3-ol dihydrochloride 85,
4-((6-ethoxy-2-(ethylamino)-7-fluoroquinolin-3-yl)methyl)-6,7-dimethoxy-1-propylisoquinolin-3-ol dihydrochloride 86,
N-(2-((6-(cyclopropylmethoxy)-3-((1-ethyl-3-hydroxy-6,7-dimethoxyisoquinolin-4-yl)methyl)quinolin-2-yl)amino)ethyl)acetamide dihydrochloride 87, and
N-(2-((6-ethoxy-3-((3-hydroxy-6,7-dimethoxy-1-propylisoquinolin-4-yl)methyl)quinolin-2-yl)amino)ethyl)acetamide dihydrochloride 88; any other pharmaceutically acceptable salt, or a tautomer form thereof.

### Claim 8 (depends on 1)

A pharmaceutical composition comprising at least one compound of claim 1, a pharmaceutically acceptable salt, or a tautomer form thereof, and at least one pharmaceutically acceptable carrier.

### Claim 9 (depends on 1)

A method for inhibiting PDE10A in a mammal, comprising administering to said mammal in need thereof, a therapeutically effective amount of at least one compound of claim 1 a pharmaceutically acceptable salt, or a tautomer form thereof.

### Claim 10

A compound of the formula
a pharmaceutically acceptable salt, or tautomer form thereof, wherein:
Ar is a quinolinyl group optionally substituted with one or more substituents, selected from the group consisting of (C1-C4)alkyl, (C1-C4)alkyloxy and RbRcN;
R1 is a (C1-C4)alkyl group optionally substituted with a —(C1-C4)alkoxy or a RaNH group, Ra being selected from the group consisting of (C1-C4)alkyl-C(═O)— and (C1-C4)alkyl)-S(═)2—;
R2, R5, R6, R7 are hydrogen;
R3 and R4 are both methyl; and
R′ is —OH.

### Claim 11

A compound selected from the group consisting of:
6,7-dimethoxy-4-((6-methoxy-2-(methylamino)quinolin-3-yl)methyl)-1-methyl-isoquinolin-3-ol dihydrochloride 37,
6,7-dimethoxy-4-((6-methoxy-2-(propylamino)quinolin-3-yl)methyl)-1-propylisoquinolin-3-ol dihydrochloride 38,
1-ethyl-6,7-dimethoxy-4-((6-methoxy-2-(methylamino)quinolin-3-yl)methyl)isoquinolin-3-ol 39,
1-ethyl-6,7-dimethoxy-4-((6-methoxy-2-(ethylamino)quinolin-3-yl)methyl)isoquinolin-3-ol dihydrochloride 40,
1-ethyl-6,7-dimethoxy-4-((6-ethoxy-2-(ethylamino)quinolin-3-yl)methyl)isoquinolin-3-ol dihydrochloride 41,
1-ethyl-6,7-dimethoxy-4-((6-methoxy-2-(propylamino)quinolin-3-yl)methyl)isoquinolin-3-ol dihydrochloride 42,
1-ethyl-4-((2-(isopropylamino)-6-methoxyquinolin-3-yl)methyl)-6,7-dimethoxyisoquinolin-3-01 dihydrochloride 43,
4-((2-(ethylamino)-6-methoxyquinolin-3-yl)methyl)-1-isopropyl-6,7-dimethoxyisoquinolin-3-ol dihydrochloride 47,
6,7-dimethoxy-4-((6-methoxy-2-(methylamino)quinolin-3-yl)methyl)-1-propylisoquinolin-3-ol dihydrochloride 48,
4-((6-ethoxy-2-(ethylamino)quinolin-3-yl)methyl)-6,7-dimethoxy-1-propylisoquinolin-3-ol dihydrochloride 49,
4-((2-(ethylamino)-6-methoxyquinolin-3-yl)methyl)-6,7-dimethoxy-1-propylisoquinolin-3-ol dihydrochloride 50,
6,7-dimethoxy-4-((6-methoxy-2-(propylamino)quinolin-3-yl)methyl)-1-propylisoquinolin-3-ol dihydrochloride 52, and
4-((2-(isopropylamino)-6-methoxyquinolin-3-yl)methyl)-6,7-dimethoxy-1-propylisoquinolin-3-ol dihydrochloride 53; any other pharmaceutically acceptable salt, or a tautomer form thereof.

### Claim 12

The compound 6,7-dimethoxy-4-((6-methoxy-2-(propylamino)quinolin-3-yl)methyl)-1-propylisoquinolin-3-ol dihydrochloride, any other pharmaceutically acceptable salt, or a tautomer thereof.

### Claim 13 (depends on 7)

A pharmaceutical composition comprising at least one compound of claim 7, any other pharmaceutically acceptable salt, or a tautomer form thereof, and at least one pharmaceutically acceptable carrier.

### Claim 14 (depends on 10)

A pharmaceutical composition comprising at least one compound of claim 10, a pharmaceutically acceptable salt, or a tautomer form thereof, and at least one pharmaceutically acceptable carrier.

### Claim 15 (depends on 11)

A pharmaceutical composition comprising at least one compound of claim 11, any other pharmaceutically acceptable salt, or a tautomer form thereof, and at least one pharmaceutically acceptable carrier.

### Claim 16 (depends on 12)

A pharmaceutical composition comprising the compound of claim 12, any other pharmaceutically acceptable salt, or a tautomer form thereof, and at least one pharmaceutically acceptable carrier.

### Claim 17 (depends on 7)

A method of treating a disease selected from the group consisting of wet Age Related Macular Degeneration (ARMD) and dry ARMD in a mammal, comprising administering to said mammal, a therapeutically effective amount of at least one compound of claim 7, any other pharmaceutically acceptable salt, or a tautomer form thereof.

### Claim 18 (depends on 10)

A method of treating a disease selected from the group consisting of wet Age Related Macular Degeneration (ARMD) and dry ARMD in a mammal, comprising administering to said mammal, a therapeutically effective amount of at least one compound of claim 10, a pharmaceutically acceptable salt, or a tautomer form thereof.

### Claim 19 (depends on 11)

A method of treating a disease selected from the group consisting of wet Age Related Macular Degeneration (ARMD) and dry ARMD in a mammal, comprising administering to said mammal, a therapeutically effective amount of at least one compound of claim 11, any other pharmaceutically acceptable salt, or a tautomer form thereof.

### Claim 20 (depends on 12)

A method of treating a disease selected from the group consisting of wet Age Related Macular Degeneration (ARMD) and dry ARMD in a mammal, comprising administering to said mammal, a therapeutically effective amount of the compound of claim 12, any other pharmaceutically acceptable salt, or a tautomer thereof.