# US 2014/0194441 A1 · 3-(benzoimidazol-2-yl)-indazole inhibitors of the wnt signaling pathway and therapeutic uses thereof

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- Number: US 2014/0194441 A1
- Document ID: US20140194441A1
- Status: Published application
- Kind: A1
- Application number: 14/149,948
- Filed: 2014-01-08
- Published: 2014-07-10
- Earliest claimed: 2013-01-08
- Assignees: Samumed, LLC
- Applicants: Samumed, LLC
- Inventors: Sunil Kumar KC; John Hood
- Web page: https://patentgrep.com/patent/US20140194441A1

## CPC

- C07D 401/14: containing three or more hetero rings
- A61P 1/02: Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- 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 11/00: Drugs for disorders of the respiratory system
- A61P 13/12: of the kidneys
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 17/00: Drugs for dermatological disorders
- A61P 19/00: Drugs for skeletal disorders
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 19/10: for osteoporosis
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- A61P 25/16: Anti-Parkinson drugs
- 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 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 35/04: specific for metastasis
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 405/14: containing three or more hetero rings
- C07D 409/14: containing three or more hetero rings
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present disclosure concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease, lung disease and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions/disorders/diseases due to mutations or dysregulation of the Wnt pathway and/or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.

## Claims

### Claim 1

A compound, or pharmaceutically acceptable salt thereof, of Formula I:
wherein:
R1 is -heteroarylR3R4;
R2 is selected from the group consisting of H, halide, C1-3 alkyl, —CN, —OR8, —OH, —(C1-3 alkyl)OR8, —NR9R10, —(C1-3 alkyl)NR9R10, -heteroarylR5, -heterocyclylR6 and -arylR7;
R3 is 1 substituent attached to the heteroaryl ring and is selected from the group consisting of H, C1-3 alkyl, —CF3, —NR9R10, —NHC(═O)R8, —(C1-3 alkyl)heterocyclylR6 and —(C1-3 alkyl)NR9R10;
R4 is 1 substituent attached to the heteroaryl ring and is selected from the group consisting of H, C1-3 alkyl, —CF3, halide, —CN, —OR8, —OH, —(C1-3 alkyl)OR8, —NR9R10, —(C1-3 alkyl)NR9R10 and —OCF3;
R5 is 1-3 substituents attached to the heteroaryl ring and each is independently selected from the group consisting of H, C1-3 alkyl, —CF3, halide, —CN, —OR8, —OH, —(C1-3 alkyl)OR8, —NR9R10, —(C1-3 alkyl)NR9R10 and —OCF3;
R6 is 1-3 substituents attached to the heterocyclyl ring and each is independently selected from the group consisting of H, C1-3 alkyl, —CF3, halide, —CN, —OR8, —OH, —(C1-3 alkyl)OR8, —NR9R10, —(C1-3 alkyl)NR9R10 and —OCF3;
R7 is 1-3 substituents attached to the aryl ring and each is independently selected from the group consisting of H, C1-3 alkyl, —CF3, halide, —CN, —OR8, —OH, —(C1-3 alkyl)OR8, —NR9R10, —(C1-3 alkyl)NR9R10 and —OCF3;
each R8 is independently selected from the group consisting of C1-9 alkyl, -heteroarylR12, -heterocyclylR13, -arylR14, carbocyclylR11, —(C1-3 alkyl)heteroarylR12, —(C1-3 alkyl)heterocyclylR13, —(C1-3 alkyl)arylR14 and —(C1-3 alkyl)carbocyclylR11;
each R9 is independently selected from the group consisting of H, C1-6 alkyl, -heteroarylR12, -heterocyclylR13, -arylR14, carbocyclylR11, —(C1-3 alkyl)heteroarylR12, —(C1-3 alkyl)heterocyclylR13, —(C1-3 alkyl)arylR14 and —(C1-3 alkyl)carbocyclylR11;
each R10 is independently selected from the group consisting of H and C1-6 alkyl;
R9 and R10 are optionally linked to form a five or six membered heterocyclyl ring;
R11 is 1-3 substituents attached to the carbocyclyl ring and each independently selected from the group consisting of H, C1-3 alkyl, —CF3, halide, —CN, —O(R10), —(C1-3 alkyl)OR10, —N(R10)2, —(C1-3 alkyl)N(R10)2 and —OCF3;
R12 is 1-3 substituents attached to the heteroaryl ring and each is independently selected from the group consisting of H, C1-3 alkyl, —CF3, halide, —CN, —O(R10), —(C1-3 alkyl)OR10, —N(R10)2, —(C1-3 alkyl)N(R10)2 and —OCF3;
R13 is 1-3 substituents attached to the heterocyclyl ring and each is independently selected from the group consisting of H, C1-3 alkyl, —CF3, halide, —CN, —O(R10), —(C1-3 alkyl)OR10, —N(R10)2, —(C1-3 alkyl)N(R10)2 and —OCF3;
R14 is 1-3 substituents attached to the aryl ring and each is independently selected from the group consisting of H, C1-3 alkyl, —CF3, halide, —CN, —O(R10), —(C1-3 alkyl)OR10, —N(R10)2, —(C1-3 alkyl)N(R10)2 and —OCF3;
with the proviso that a compound of Formula I is not a compound selected from the group consisting of:

### Claim 2

A compound, or pharmaceutically acceptable salt thereof, of Formula Ia:
wherein:
R1 is -pyridineR3R4;
R2 is selected from the group consisting of H, halide, C1-3 alkyl, —CN, —OR8, —OH, —(C1-3 alkyl)OR8, —NR9R10, —(C1-3 alkyl)NR9R10, -heteroarylR5, -heterocyclylR6 and -arylR7;
R3 is 1 substituent attached to the heteroaryl ring and is selected from the group consisting of H, C1-3 alkyl, —CF3, —NR9R10, —NHC(═O)R8, —(C1-3 alkyl)heterocyclylR6 and —(C1-3 alkyl)NR9R10;
R4 is H;
R5 is 1-3 substituents attached to the heteroaryl ring and is each independently selected from the group consisting of H, C1-3 alkyl, —CF3, halide, —CN, —OR8, —OH, —(C1-3 alkyl)OR8, —NR9R10, —(C1-3 alkyl)NR9R10 and —OCF3;
R6 is 1-3 substituents attached to the heterocyclyl ring and is each independently selected from the group consisting of H, C1-3 alkyl, —CF3, halide, —CN, —OR8, —OH, —(C1-3 alkyl)OR8, —NR9R10, —(C1-3 alkyl)NR9R10 and —OCF3;
R7 is 1-3 substituents attached to the aryl ring and each is independently selected from the group consisting of H, C1-3 alkyl, —CF3, halide, —CN, —OR8, —OH, —(C1-3 alkyl)OR8, —NR9R10, —(C1-3 alkyl)NR9R10 and —OCF3;
each R8 is independently selected from the group consisting of C1-9 alkyl, -heteroarylR12, -heterocyclylR13, -arylR14, carbocyclylR11, —(C1-3 alkyl)heteroarylR12, —(C1-3 alkyl)heterocyclylR13, —(C1-3 alkyl)arylR14 and —(C1-3 alkyl)carbocyclylR11;
each R9 is independently selected from the group consisting of H, C1-6 alkyl, -heteroarylR12, -heterocyclylR13, -arylR14, carbocyclylR11, —(C1-3 alkyl)heteroarylR12, —(C1-3 alkyl)heterocyclylR13, —(C1-3 alkyl)arylR14 and —(C1-3 alkyl)carbocyclylR11;
each R10 is independently selected from the group consisting of H and C1-6 alkyl;
R9 and R10 are optionally linked to form a five or six membered heterocyclyl ring;
R11 is 1-3 substituents attached to the carbocyclyl ring and each independently selected from the group consisting of H, C1-3 alkyl, —CF3, halide, —CN, —O(R10), —(C1-3 alkyl)OR10, —N(R10)2, —(C1-3 alkyl)N(R10)2 and —OCF3;
R12 is 1-3 substituents attached to the heteroaryl ring and each is independently selected from the group consisting of H, C1-3 alkyl, —CF3, halide, —CN, —O(R10), —(C1-3 alkyl)OR10, —N(R10)2, —(C1-3 alkyl)N(R10)2 and —OCF3;
R13 is 1-3 substituents attached to the heterocyclyl ring and each is independently selected from the group consisting of H, C1-3 alkyl, —CF3, halide, —CN, —O(R10), —(C1-3 alkyl)OR10, —N(R10)2, —(C1-3 alkyl)N(R10)2 and —OCF3;
R14 is 1-3 substituents attached to the aryl ring and each is independently selected from the group consisting of H, C1-3 alkyl, —CF3, halide, —CN, —O(R10), —(C1-3 alkyl)OR10, —N(R10)2, —(C1-3 alkyl)N(R10)2 and —OCF3;
with the proviso that a compound of Formula Ia is not a compound selected from the group consisting of:

### Claim 3 (depends on 1)

The compound of claim 1, wherein R1 is pyridineR3R4.

### Claim 4 (depends on 3)

The compound of claim 3, wherein R1 is pyridin-3-ylR3R4.

### Claim 5 (depends on 4)

The compound of claim 4, wherein R3 and R4 are both H.

### Claim 6 (depends on 4)

The compound of claim 4, wherein R3 is —C1-2 alkyl and R4 is H.

### Claim 7 (depends on 4)

The compound of claim 4, wherein R3 is —CH2NR9R10.

### Claim 8 (depends on 7)

The compound of claim 7, wherein R9 is —C1-2 alkyl; R10 is —(C1-2 alkyl); and R4 is H.

### Claim 9 (depends on 7)

The compound of claim 7, wherein R4 and R10 are both H; and R9 is selected from the group consisting of —C1-2 alkyl, —CH2phenyl and —CH2-carbocyclyl.

### Claim 10 (depends on 7)

The compound of claim 7, wherein R9 and R10 are linked to form a five or six membered heterocyclyl ring; and R4 is H.

### Claim 11 (depends on 4)

The compound of claim 4, wherein R3 is —NHC(═O)R8.

### Claim 12 (depends on 11)

The compound of claim 11, wherein R4 is H and R8 is selected from the group consisting of —C1-5 alkyl, —CH2phenyl, phenyl and -carbocyclyl.

### Claim 13 (depends on 4)

The compound of claim 4, wherein R3 is —NR9R10.

### Claim 14 (depends on 4)

The compound of claim 4, wherein R3 is —NH2 and R4 is H.

### Claim 15 (depends on 13)

The compound of claim 13, wherein R9 is —C1-2 alkyl; R10 is —C1-2 alkyl; and R4 is H.

### Claim 16 (depends on 13)

The compound of claim 13, wherein R4 and R9 are both H; and R10 is —C1-4 alkyl.

### Claim at position 17

-20. (canceled)

### Claim 21 (depends on 8)

The compound of claim 8, wherein R2 is H.

### Claim 22 (depends on 9)

The compound of claim 9, wherein R2 is H.

### Claim 23 (depends on 10)

The compound of claim 10, wherein R2 is H.

### Claim 24

(canceled)

### Claim 25 (depends on 12)

The compound of claim 12, wherein R2 is H.

### Claim 26

(canceled)

### Claim 27 (depends on 14)

The compound of claim 14, wherein R2 is H.

### Claim at position 25

-46. (canceled)

### Claim 47 (depends on 8)

The compound of claim 8, wherein R2 is -pyridine.

### Claim 48 (depends on 9)

The compound of claim 9, wherein R2 is -pyridine.

### Claim 49 (depends on 10)

The compound of claim 10, wherein R2 is -pyridine.

### Claim 50

(canceled)

### Claim 51 (depends on 12)

The compound of claim 12, wherein R2 is -pyridine.

### Claim 52

(canceled)

### Claim 53 (depends on 14)

The compound of claim 14, wherein R2 is -pyridine.

### Claim at position 33

-59. (canceled)

### Claim 60 (depends on 8)

The compound of claim 8, wherein R2 is thiophene.

### Claim 61 (depends on 9)

The compound of claim 9, wherein R2 is thiophene.

### Claim 62 (depends on 10)

The compound of claim 10, wherein R2 is thiophene.

### Claim 63

(canceled)

### Claim 64 (depends on 12)

The compound of claim 12, wherein R2 is thiophene.

### Claim 65

(canceled)

### Claim 66 (depends on 14)

The compound of claim 14, wherein R2 is thiophene.

### Claim at position 41

-72. (canceled)

### Claim 73 (depends on 8)

The compound of claim 8, wherein R2 is furan.

### Claim 74 (depends on 9)

The compound of claim 9, wherein R2 is furan.

### Claim 75 (depends on 10)

The compound of claim 10, wherein R2 is furan.

### Claim 76

(canceled)

### Claim 77 (depends on 12)

The compound of claim 12, wherein R2 is furan.

### Claim 78

(canceled)

### Claim 79 (depends on 14)

The compound of claim 14, wherein R2 is furan.

### Claim at position 49

-85. (canceled)

### Claim 86 (depends on 8)

The compound of claim 8, wherein R2 is -imidazolylR5; and R5 is 1 substituent selected from the group consisting of H or —C1-2 alkyl.

### Claim 87 (depends on 9)

The compound of claim 9, wherein R2 is -imidazolylR5; and R5 is 1 substituent selected from the group consisting of H or —C1-2 alkyl.

### Claim 88 (depends on 10)

The compound of claim 10, wherein R2 is -imidazolylR5; and R5 is 1 substituent selected from the group consisting of H or —C1-2 alkyl.

### Claim 89

(canceled)

### Claim 90 (depends on 12)

The compound of claim 12, wherein R2 is -imidazolylR5; and R5 is 1 substituent selected from the group consisting of H or —C1-2 alkyl.

### Claim 91

(canceled)

### Claim 92 (depends on 14)

The compound of claim 14, wherein R2 is -imidazolylR5; and R5 is 1 substituent selected from the group consisting of H or —C1-2 alkyl.

### Claim at position 57

-111. (canceled)

### Claim 112 (depends on 8)

The compound of claim 8, wherein R2 is -piperidine.

### Claim 113 (depends on 9)

The compound of claim 9, wherein R2 is -piperidine.

### Claim 114 (depends on 10)

The compound of claim 10, wherein R2 is -piperidine.

### Claim 115

(canceled)

### Claim 116 (depends on 12)

The compound of claim 12, wherein R2 is -piperidine.

### Claim 117

(canceled)

### Claim 118 (depends on 14)

The compound of claim 14, wherein R2 is -piperidine.

### Claim at position 65

-124. (canceled)

### Claim 125 (depends on 8)

The compound of claim 8, wherein R2 is -piperazineR6; and R6 is 1 substituent selected from the group consisting of H or —C1-2 alkyl.

### Claim 126 (depends on 9)

The compound of claim 9, wherein R2 is -piperazineR6; and R6 is 1 substituent selected from the group consisting of H or —C1-2 alkyl.

### Claim 127 (depends on 10)

The compound of claim 10, wherein R2 is -piperazineR6; and R6 is 1 substituent selected from the group consisting of H or —C1-2 alkyl.

### Claim 128

(canceled)

### Claim 129 (depends on 12)

The compound of claim 12, wherein R2 is -piperazineR6; and R6 is 1 substituent selected from the group consisting of H or —C1-2 alkyl.

### Claim 130

(canceled)

### Claim 131 (depends on 14)

The compound of claim 14, wherein R2 is -piperazineR6; and R6 is 1 substituent selected from the group consisting of H or —C1-2 alkyl.

### Claim at position 73

132-137. (canceled)

### Claim 138 (depends on 8)

The compound of claim 8, wherein R2 is -phenylR7.

### Claim 139 (depends on 9)

The compound of claim 9, wherein R2 is -phenylR7.

### Claim 140 (depends on 10)

The compound of claim 10, wherein R2 is -phenylR7.

### Claim 141

(canceled)

### Claim 142 (depends on 12)

The compound of claim 12, wherein R2 is -phenylR7.

### Claim 143

(canceled)

### Claim 144 (depends on 14)

The compound of claim 14, wherein R2 is -phenylR7.

### Claim at position 81

-150. (canceled)

### Claim 151 (depends on 138)

The compound of claim 138, wherein R7 is 1-2 fluorine atoms.

### Claim 152 (depends on 139)

The compound of claim 139, wherein R7 is 1-2 fluorine atoms.

### Claim 153 (depends on 140)

The compound of claim 140, wherein R7 is 1-2 fluorine atoms.

### Claim 154

(canceled)

### Claim 155 (depends on 142)

The compound of claim 142, wherein R7 is 1-2 fluorine atoms.

### Claim 156

(canceled)

### Claim 157 (depends on 144)

The compound of claim 144, wherein R7 is 1-2 fluorine atoms.

### Claim at position 89

-159. (canceled)

### Claim 160 (depends on 1)

The compound of claim 1, wherein R1 is pyridin-3-ylR3R4; R2 is -phenyllR7; R3 is selected from the group consisting of H, —C1-2 alkyl, —CH2NR9R10; —NR9R10 and —NHC(═O)R8; R4 is H; R7 is 1-2 fluorine atoms; R8 is selected from the group consisting of —C1-5 alkyl, —CH2phenyl, phenyl and -carbocyclyl; R9 is selected from the group consisting of —C1-3 alkyl, —CH2phenyl and —CH2carbocyclyl; R10 is H or —C1-2 alkyl; or R9 and R10 are optionally linked to form a piperidine or pyrrolidine ring.

### Claim 161 (depends on 2)

The compound of claim 2, wherein R1 is pyridin-3-ylR3R4; R2 is -phenyllR7; R3 is selected from the group consisting of H, —C1-2 alkyl, —CH2NR9R10; —NR9R10 and —NHC(═O)R8; R4 is H; R7 is 1-2 fluorine atoms; R8 is selected from the group consisting of —C1-5 alkyl, —CH2phenyl, phenyl and -carbocyclyl; R9 is selected from the group consisting of —C1-3 alkyl, —CH2phenyl and —CH2carbocyclyl; R10 is H or —C1-2 alkyl; or R9 and R10 are optionally linked to form a piperidine or pyrrolidine ring.

### Claim 162 (depends on 1)

The compound of claim 1, wherein R1 is pyridin-3-ylR3R4; R2 is pyridine; R3 is selected from the group consisting of —C1-2 alkyl, —CH2NR9R10, NR9R10 and —NHC(═O)R8; R4 is H; R8 is selected from the group consisting of —C1-5 alkyl, —CH2phenyl and —carbocyclyl; R9 is selected from the group consisting of H, —C1-3 alkyl, —CH2phenyl and —CH2carbocyclyl; R10 is H or —C1-2 alkyl; or R9 and R10 are optionally linked to form a pyrrolidine ring.

### Claim 163 (depends on 2)

The compound of claim 2, wherein R1 is pyridin-3-ylR3R4; R2 is pyridine; R3 is selected from the group consisting of —C1-2 alkyl, —CH2NR9R10, —NR9R10 and —NHC(═O)R8; R4 is H; R8 is selected from the group consisting of —C1-5 alkyl, —CH2phenyl and —carbocyclyl; R9 is selected from the group consisting of H, —C1-3 alkyl, —CH2phenyl and —CH2carbocyclyl; R10 is H or —C1-2 alkyl; or R9 and R10 are optionally linked to form a pyrrolidine ring.

### Claim 164 (depends on 1)

The compound of claim 1, wherein R1 is pyridin-3-ylR3R4; R2 is 1-methylpiperazinyl- or piperidinyl-; R3 is selected from the group consisting of H, —C1-2 alkyl, —CH2NR9R10, —NR9R10 and —NHC(═O)R8; R4 is H; R8 is selected from the group consisting of —C1-5 alkyl, —CH2phenyl, phenyl and -carbocyclyl; R9 is H or —C1-2 alkyl; R10 is —C1-3 alkyl; or R9 and R10 are optionally linked to form a piperidine or pyrrolidine ring.

### Claim 165 (depends on 2)

The compound of claim 2, wherein R1 is pyridin-3-ylR3R4; R2 is 1-methylpiperazinyl- or piperidinyl-; R3 is selected from the group consisting of H, —C1-2 alkyl, —CH2NR9R10, —NR9R10 and —NHC(═O)R8; R4 is H; R8 is selected from the group consisting of —C1-5 alkyl, —CH2phenyl, phenyl and -carbocyclyl; R9 is H or —C1-2 alkyl; R10 is —C1-3 alkyl; or R9 and R10 are optionally linked to form a piperidine or pyrrolidine ring.

### Claim 166 (depends on 1)

The compound of claim 1, wherein R1 is pyridin-3-ylR3R4; R2 is selected from the group consisting of furan, thiophene and -imidazolylR5; R3 is selected from the group consisting of —CH2NR9R10, —NR9R10 and —NHC(═O)R8; R4 is H; R5 is H or —C1-2 alkyl; R8 is selected from the group consisting of —C1-5 alkyl, —CH2phenyl and -carbocyclyl; R9 is selected from the group consisting of H, —C1-3 alkyl and —CH2phenyl; R10 is H or —C1-2 alkyl; or R9 and R10 are optionally linked to form a piperidine or pyrrolidine ring.

### Claim 167 (depends on 2)

The compound of claim 2, wherein R1 is pyridin-3-ylR3R4; R2 is selected from the group consisting of furan, thiophene and -imidazolylR5; R3 is selected from the group consisting of —CH2NR9R10, —NR9R10 and —NHC(═O)R8; R4 is H; R5 is H or —C1-2 alkyl; R8 is selected from the group consisting of —C1-5 alkyl, —CH2phenyl and -carbocyclyl; R9 is selected from the group consisting of H, —C1-3 alkyl and —CH2phenyl; R10 is H or —C1-2 alkyl; or R9 and R10 are optionally linked to form a piperidine or pyrrolidine ring.

### Claim 168 (depends on 1)

The compound of claim 1, wherein R1 is pyridin-3-ylR3R4; R2 is H; R3 is selected from the group consisting of —C1-2 alkyl, —CH2NR9R10 and —NHC(═O)R8; R4 is H; R8 is selected from the group consisting of —C1-5 alkyl, phenyl and -carbocyclyl; R9 is —CH2phenyl, R10 is H.

### Claim 169 (depends on 2)

The compound of claim 2, wherein R1 is pyridin-3-ylR3R4; R2 is H; R3 is selected from the group consisting of —C1-2 alkyl, —CH2NR9R10 and —NHC(═O)R8; R4 is H; R8 is selected from the group consisting of —C1-5 alkyl, phenyl and -carbocyclyl; R9 is —CH2phenyl, R10 is H.

### Claim 170 (depends on 1)

The compound of claim 1, wherein R2 is selected from the group consisting of:

### Claim 171 (depends on 2)

The compound of claim 2, wherein R2 is selected from the group consisting of:

### Claim 172 (depends on 1)

The compound of claim 1, wherein R3 is selected from the group consisting of:

### Claim 173 (depends on 2)

The compound of claim 2, wherein R3 is selected from the group consisting of:

### Claim 174 (depends on 1)

The compound of claim 1, wherein the compound of Formula (I) is selected from the group consisting of:

### Claim 175 (depends on 1)

The compound according to claim 1, having a structure selected from the group consisting of:

### Claim 176 (depends on 2)

The compound according to claim 2, having a structure selected from the group consisting of:

### Claim 177 (depends on 1)

A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

### Claim 178 (depends on 2)

A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 2, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

### Claim 179 (depends on 1)

A method of treating a disorder or disease selected from the group consisting of cancer, pulmonary fibrosis, a bone or cartilage disease, a neurological condition/disorder/disease, osteoarthritis, lung disease, a fibrotic disorder, the method comprising administering to the patient a therapeutically effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt thereof.

### Claim 180 (depends on 2)

A method of treating a disorder or disease selected from the group consisting of cancer, pulmonary fibrosis, a bone or cartilage disease, a neurological condition/disorder/disease, osteoarthritis, lung disease, a fibrotic disorder, the method comprising administering to the patient a therapeutically effective amount of a compound according to claim 2, or a pharmaceutically acceptable salt thereof.

### Claim 181 (depends on 1)

A method of treating a disorder or disease selected from the group consisting of: polyposis coli, osteoporosis-pseudoglioma syndrome, familial exudative vitreoretinopathy, retinal angiogenesis, early coronary disease, tetra-amelia syndrome, Müllerian-duct regression and virilization, SERKAL syndrome, diabetes mellitus type 2, Fuhrmann syndrome, Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome, odonto-onycho-dermal dysplasia, obesity, split-hand/foot malformation, caudal duplication syndrome, tooth agenesis, Wilms tumor, skeletal dysplasia, focal dermal hypoplasia, autosomal recessive anonychia, neural tube defects, alpha-thalassemia (ATRX) syndrome, fragile X syndrome, ICF syndrome, Angelman syndrome, Prader-Willi syndrome, Beckwith-Wiedemann Syndrome, Norrie disease, and Rett syndrome, the method comprising administering to the patient a therapeutically effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt thereof.

### Claim 182 (depends on 2)

A method of treating a disorder or disease selected from the group consisting of: polyposis coli, osteoporosis-pseudoglioma syndrome, familial exudative vitreoretinopathy, retinal angiogenesis, early coronary disease, tetra-amelia syndrome, Müllerian-duct regression and virilization, SERKAL syndrome, diabetes mellitus type 2, Fuhrmann syndrome, Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome, odonto-onycho-dermal dysplasia, obesity, split-hand/foot malformation, caudal duplication syndrome, tooth agenesis, Wilms tumor, skeletal dysplasia, focal dermal hypoplasia, autosomal recessive anonychia, neural tube defects, alpha-thalassemia (ATRX) syndrome, fragile X syndrome, ICF syndrome, Angelman syndrome, Prader-Willi syndrome, Beckwith-Wiedemann Syndrome, Norrie disease, and Rett syndrome, the method comprising administering to the patient a therapeutically effective amount of a compound according to claim 2, or a pharmaceutically acceptable salt thereof.

### Claim at position 113

-220. (canceled)

### Claim 221 (depends on 1)

A method of preventing or reducing angiogenesis in a patient, the method comprising administering to the patient a therapeutically effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt thereof.

### Claim 222 (depends on 2)

A method of preventing or reducing angiogenesis in a patient, the method comprising administering to the patient a therapeutically effective amount of a compound according to claim 2, or a pharmaceutically acceptable salt thereof.