# US 10,870,653 B2 · WNT pathway modulators

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 10,870,653 B2
- Document ID: US10870653B2
- Status: Granted
- Kind: B2
- Application number: 16/226,398
- Filed: 2018-12-19
- Published: 2019-06-20
- Granted: 2020-12-22
- Earliest claimed: 2013-12-17
- Assignees: Agency for Science, Technology and Research
- Applicants: Agency for Science, Technology and Research
- Inventors: Jenefer Alam; Soo Yei Ho; Wei Ling Wang; Athisayamani Jeyaraj Duraiswamy
- Web page: https://patentgrep.com/patent/US10870653B2

## CPC

- C07D 487/04: Ortho-condensed systems
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 1/18: for pancreatic disorders, e.g. pancreatic enzymes
- 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 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 11/00: Drugs for disorders of the respiratory system
- A61P 17/06: Antipsoriatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 19/04: for non-specific disorders of the connective tissue
- 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 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: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to compounds of formula (I), combinations and uses thereof for disease therapy, or a pharmaceutically acceptable salt, solvate or polymorph thereof, including all tautomers and stereoisomers thereof wherein each of R1, R2, R3, R4, R5, W, X, Y, Z, and n is as defined herein.

## Claims

### Claim 1

A method of modulating WNT activity comprising exposing a WNT protein or a WNT receptor to an effective amount of a compound of formula (I)
or a pharmaceutically acceptable salt, solvate, polymorph, tautomer, or stereoisomer thereof wherein:
R1 represents H; alkyl optionally substituted with one or more substituents each independently selected from the group consisting of C1-6alkoxy, NH2, —NHC1-3alkyl, and —N(C1-3alkyl)2; —C(O)Oalkyl; haloalkyl; haloalkoxy; or -alkylaryl;
each R2 independently represents H; alkyl optionally substituted with one or more substituents each independently selected from the group consisting of C1-6alkoxy, NH2, —NHC1-3alkyl, and —N(C1-3alkyl)2; -alkylaryl; carbocyclyl optionally substituted with one or more substituents each independently selected from the group consisting of C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, C1-6haloalkoxy and halo; heterocyclyl optionally substituted with one or more substituents each independently selected from the group consisting of C1-6alkyl, C1-6alkoxy, —C(O)OC1-6alkyl, —C(O)C1-6alkyl, and —C(O)NHC1-6alkyl; —NHalkyl; —N(alkyl)2; amino; hydroxyl; alkoxy; or halo;
n represents 0, 1, or 2;
R3 represents H or alkyl;
R4 represents H or alkyl;
R5 represents H or alkyl;
W and X each independently represent C═O; C═S; or CH2;
Y represents aryl; heteroaryl; carbocyclyl optionally substituted with one or more substituents each independently selected from the group consisting of C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, C1-6haloalkoxy, and halo; or heterocyclyl optionally substituted with one or more substituents each independently selected from the group consisting of C1-6alkyl, C1-6alkoxy, —C(O)OC1-6alkyl, —C(O)C1-6alkyl, and —C(O)NHC1-6alkyl; and
Z represents alkyl optionally substituted with one or more substituents each independently selected from the group consisting of C1-6alkoxy, NH2, —NHC1-3alkyl, and —N(C1-3alkyl)2; aryl; heteroaryl; -alkylaryl; -alkylheteroaryl; carbocyclyl optionally substituted with one or more substituents each independently selected from the group consisting of C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, C1-6haloalkoxy, and halo; heterocyclyl optionally substituted with one or more substituents each independently selected from the group consisting of C1-6alkyl, C1-6alkoxy, —C(O)OC1-6alkyl, —C(O)C1-6alkyl, and —C(O)NHC1-6alkyl; -alkylcarbocyclyl, wherein carbocyclyl is optionally substituted with one or more substituents each independently selected from the group consisting of C1-6alkyl, C1-6alkoxy, C1-6haloalkoxy and halo; -alkylheterocyclyl wherein heterocyclyl is optionally substituted with one or more substituents each independently selected from the group consisting of C1-6alkyl, —C(O)OC1-6alkyl, —C(O)C1-6alkyl, and —C(O)NHC1-6alkyl; -arylcarbocyclyl wherein carbocyclyl is optionally substituted with one or more substituents each independently selected from the group consisting of C1-6alkyl, C1-6alkoxy, C1-6haloalkoxy, and halo; or -arylheterocyclyl wherein heterocyclyl of the -arylheterocyclyl is optionally substituted with one or more substituents each independently selected from the group consisting of C1-6alkyl, —C(O)OC1-6alkyl, —C(O)C1-6alkyl, and —C(O)NHC1-6alkyl.

### Claim 2 (depends on 1)

A method according to claim 1 wherein the method is an in vivo method.

### Claim 3

A method of treating a tumor comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula (I)
or a pharmaceutically acceptable salt, solvate, polymorph, tautomer, or stereoisomer thereof wherein,
R1 represents H; alkyl optionally substituted with one or more substituents each independently selected from the group consisting of C1-6alkoxy, NH2, —NHC1-3alkyl, and —N(C1-3alkyl)2; —C(O)Oalkyl; haloalkyl; haloalkoxy; or -alkylaryl;
each R2 independently represents H; alkyl optionally substituted with one or more substituents each independently selected from the group consisting of C1-6alkoxy, NH2, —NHC1-3alkyl, and —N(C1-3alkyl)2; -alkylaryl; carbocyclyl optionally substituted with one or more substituents each independently selected from the group consisting of C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, C1-6haloalkoxy and halo; heterocyclyl optionally substituted with one or more substituents each independently selected from the group consisting of C1-6alkyl, C1-6alkoxy, —C(O)OC1-6alkyl, —C(O)C1-6alkyl, and —C(O)NHC1-6alkyl; -NHalkyl; —N(alkyl)2; amino; hydroxyl; alkoxy; or halo;
n represents 1;
R3 represents H or alkyl;
R4 represents H or alkyl;
R5 represents H or alkyl;
W and X each independently represent C═O; C═S; or CH2;
Y represents optionally substituted phenyl or optionally substituted 6-membered heteroaryl; and
Z represents optionally substituted aryl or optionally substituted heteroaryl.

### Claim 4 (depends on 3)

The method of claim 3, wherein the tumor is selected from the group consisting of cervical cancer, colon cancer, breast cancer, bladder cancer, head and neck cancer, gastric cancer, lung cancer, ovarian cancer, prostate cancer, thyroid cancer, non-small-cell lung cancer, mesothelioma, melanoma, pancreatic adenocarcinoma, basal cell carcinoma, osteosarcoma, hepatocellular carcinoma, Wilm's tumor, and medulloblastoma.

### Claim 5 (depends on 3)

The method of claim 3, wherein the compound of formula (I), is selected from the group consisting of:
Compound
ID
Structure
IUPAC Name
14
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4-oxo- N-(4′-(trifluoromethyl)-[1,1′- biphenyl]-4-yl)butanamide
24
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(4- (oxazol-5-yl)phenyl)-4- oxobutanamide
25
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(4- (oxazol-5-yl)phenyl)-4- oxobutanamide
26
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4-oxo- N-(5-(thiazol-2-yl)pyridin-2- yl)butanamide
27
N-(4-(1H-imidazol-1- yl)phenyl)-4-(2-methyl-6,7- dihydropyrazoIo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
28
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(4- (2-methylthiazol-4- yl)phenyl)-4-oxobutanamide
29
N-(4-(1-methyl-1H-pyrazol- 5-yl)phenyl)-4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
32
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(4- (2-methylthiazol-4- yl)phenyl)-4-oxobutanamide
33
N-([1,1′-biphenyl]-4-yl)-4-(2- methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
34
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4-oxo- N-(4-(pyridin-2- yl)phenyl)butanamide
35
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4-oxo- N-(4-(pyridin-3- yl)phenyl)butanamide
36
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4-oxo- N-(4-(pyridin-4- yl)phenyl)butanamide
37
4-{2-methyl-5H,6H,7H- pyrazolo[1,5-a]pyrimidin-4- yl}-4-oxo-N-[4-(pyridazin-3- yl)phenyl]butanamide
38
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4-oxo- N-(4-(pyrimidin-4- yl)phenyl)butanamide
39
4-{2-methyl-5H,6H,7H- pyrazolo[1,5-a]pyrimidin-4- yl}-4-oxo-N-[4-(pyrimidin-5- yl)phenyl]butanamide
40
4-{2-methyl-5H,6H,7H- pyrazolo[1,5-a]pyrimidin-4- yl}-4-oxo-N-[4-(pyrimidin-2- yl)phenyl]butanamide
41
N-([2,3′-bipyridin]-6′-yl)-4- (2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
42
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4-oxo- N-(4-(pyrazin-2- yl)phenyl)butanamide
43
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4-oxo- N-(6-phenylpyridin-3- yl)butanamide
44
44Synthesis of 4-(2-methyl- 6,7-dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4-oxo- N-(5-phenylpyridin-2- yl)butanamide
45
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4-oxo- N-(6-phenylpyridazin-3- yl)butanamide
46
4-{2-methyl-5H,6H,7H- pyrazolo[1,5-a]pyrimidin-4- yl}-4-oxo-N-(5- phenylpyrimidin-2- yl)butanamide
47
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4-oxo- N-(5-phenylpyrazin-2- yl)butanamide
48
N-([2,3′-bipyridin]-5-yl)-4-(2- methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
49
4-{2-methyl-5H,6H,7H- pyrazolo[1,5-a]pyrimidin-4- yl}-4-oxo-N-[5-(pyridin-3- yl)pyridin-2-yl]butanamide
50
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4-oxo- N-(5-(pyrazin-2-yl)pyridin-2- yl)butanamide
51
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4-oxo- N-(6-(pyridin-3-yl)pyridazin- 3-yl)butanamide
52
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4-oxo- N-(5-(pyridin-3-yl)pyrazin-2- yl)butanamide
53
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(3- methyl-[1,1′-biphenyl]-4-yl)- 4-oxobutanamide
54
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(2- methyl-[1,1′-biphenyl]-4-yl)- 4-oxobutanamide
55
N-(3-methoxy-[1,1′- biphenyl]-4-yl)-4-(2-methyl 6,7-dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
56
N-(2-methoxy-[1,1′- biphenyl]-4-yl)-4-(2-methyl- 6,7-dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
57
N-(2-fluorobiphenyl-4-yl)-4- (2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
58
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(2′- methyl-[1,1′-biphenyl]-4-yl)- 4-oxobutanamide
59
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(3′- methyl-[1,1′-biphenyl]-4-yl)- 4-oxobutanamide
60
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(4′- methyl-[1,1′-biphenyl]-4-yl)- 4-oxobutanamide
61
N-(2′-methoxy-[1,1′- biphenyl]-4-yl)-4-(2-methyl 6,7-dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
62
N-(3′-methoxy-[1,1′- biphenyl]-4-yl)-4-(2-methyl- 6,7-dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
63
N-(4′-methoxy-[1,1- biphenyl]-4-yl)-4-(2-methyl- 6,7-dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
64
N-(2′-fluoro-[1,1′-biphenyl]- 4-yl)-4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
65
N-(3′-fluoro-[1,1′-biphenyl]- 4-yl)-4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
66
N-(4′-fluorobiphenyl-4-yl)-4- (2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
67
4′-(4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamido)-[1,1′- biphenyl]-3-carboxylic acid
68
N,N-dimethyl-4′-(4-(2- methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamido)-[1,1′- biphenyl]-3-carboxamide
69
N-(2′-amino-[1,1′-biphenyl]- 4-yl)-4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
70
N-(3′-amino-[1,1′-biphenyl]- 4-yl)-4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
71
N-(4′-amino-[1,1′-biphenyl]- 4-yl)-4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
72
N-(3′-(dimethylamino)-[1,1′- biphenyl]-4-yl)-4-(2-methyl- 6,7-dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
73
4-(2-methyl-6.7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(3′- morpholinobiphenyl-4-yl)-4- oxobutanamide
74
N-(3′-acetamido-[1,1′- biphenyl]-4-yl)-4-(2-methyl- 6,7-dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
83
N-(6-(3- chlorophenyl)pyridin-3-yl)-4- (2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
84
N-(6-(3-fluorophenyl)pyridin- 3-yl)-4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
85
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4-oxo- N-(6-(m-tolyl)pyridin-3- yl)butanamide
86
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(5- methyl-6-phenylpyridin-3-yl)- 4-oxobutanamide
87
N-(6-(4-fluorophenyl)pyridin- 3-yl)-4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
88
N-(6-(3- fluorophenyl)pyridazin-3-yl)- 4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
89
N-(5-(3-fiuorophenyl)pyridin- 2-yl)-4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
90
N-(5-(4-fluorophenyl)pyridin- 2-yl)-4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
91
N-(3-methyl-5-phenylpyridin- 2-yl)-4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutana
92
N-(4-methyl-5-phenylpyridin- 2-yl)-4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
93
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4-oxo- N-(5-(m-tolyl)pyridin-2- yl)butanamide
94
N-(5-fluoro-2,3′-bipyridin-6′- yl)-4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
95
N-(4-fluoro-2,3′-bipyridin-6′- yl)-4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
96
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(6- methyl-[2,3′-bipyridin]-6′-yl)- 4-oxobutanamide
97
N-(6-(3- chlorophenyl)pyridazin-3-yl)- 4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
98
N-(6-(3- fluorophenyl)pyridazin-3-yl)- 4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
99
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4-oxo- N-(6-(m-lolyl)pyridazin-3- yl)butanamide
100
N-[6-(4- chlorophenyl)pyridazin-3-yl]- 4-{2-methyl-5H,6H,7H- pyrazolo[1,5-a]pyrimidin-4- yl}-4-oxobutanamide
101
N-(6-(4- fluorophenyl)pyridazin-3-yl)- 4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
102
N-(6-(5-chloropyridin-3- yl)pyridazin-3-yl)-4-(2- methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
103
N-(6-(5-fluoropyridin-3- yl)pyridazin-3-yl)-4-(2- methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
104
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(6- (5-methylpyridin-3- yl)pyridazin-3-yl)-4- oxobutanamide
105
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4-oxo- N-(6-(5- (trifluoromethyl)pyridin-3- yl)pyridazin-3-yl)butanamide
106
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(5- methyl-6-(pyridin-3- yl)pyridazin-3-yl)-4- oxobutanamide
107
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(6- (6-methylpyridin-3- yl)pyridazin-3-yl)-4- oxobutanamide
108
N-(5′-chloro-[2,3′-bipyridin]- 5-yl)-4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
109
N-(5′-fluoro-[2,3′-bipyridin]- 5-yl)-4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
110
N-(5′-methyl-2,3′-bipyridin-5- yl)-4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
111
N-(3-fluoro-2,3′-bipyridin-5- yl)-4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
112
N-(5′-amino-2,3′-bipyridin-5- yl)-4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
113
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(6′- methyl-[2,3′-bipyridin]-5-yl)- 4-oxobutanamide
114
N-(5′-chloro-[3,3′-bipyridin]- 6-yl)-4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
115
N-(5′-fluoro-[3,3′-bipyridin]- 6-yl)-4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
116
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(5′- methyl-[3,3′-bipyridin]-6-yl)- 4-oxobutanamide
117
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4-oxo- N-(4-(piperazin-1- yl)phenyl)butanamide
118
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4-oxo- N-(5′-(trifluoromethyl)-[3,3′- bipyridin]-6-yl)butanamide
119
N-(4-methyl-3,3′-bipyridin-6- yl)-4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
120
N-(4,5′-dimethyl-3,3′- bipyridin-6-yl)-4-(2-methyl- 6,7-dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
121
N-(6′-methyl-3,3′-bipyridin-6- yl)-4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
122
N-(5-(5-fluoropyridin-3- yl)pyrazin-2-yl)-4-(2-methyl- 6,7-dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
123
N-(5-(3- fluorophenyl)pyrazin-2-yl)-4- (2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
124
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(5- (5-methylpyridin-3- yl)pyrazin-2-yl)-4- oxobutanamide
125
N-(6-methyl-5-(pyridin-3- yl)pyrazin-2-yl)-4-(2-methyl- 6,7-dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
126
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4-oxo- N-(5-(m-tolyl)pyrazin-2- yl)butanamide
127
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(5- (6-methylpyridin-3- yl)pyrazin-2-yl)-4- oxobutanamide
128
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(5- (6-methylpyrazin-2- yl)pyridin-2-yl)-4- oxobutanamide
129
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4-oxo- N-(4-(pyrazin-2- yl)phenyl)butanamide
139
4-(2,6-dimethyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4-oxo- N-(6-phenylpyridazin-3- yl)butanamide
140
N-(2,3′-bipyridin-5-yl)-4-(2,6- dimethyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
141
4-(2,6-dimethyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4-oxo- N-(6-(pyridin-3-yl)pyridazin- 3-yl)butanamide
142
4-(2,6-dimethyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(5′- methyl-[3,3′-bipyridin]-6-yl)- 4-oxobutanamide
143
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(6- methyl-[2,3′-bipyridin]-6′-yl)- 4-oxobutanamide
144
4-(2,6-dimethyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(5′- methyl-[2,3′-bipyridin]-5-yl)- 4-oxobutanamide
145
N-([2,3′-bipyridin]-5-yl)-2- methyl-4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
146
2-methyl-4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4-oxo- N-(6-phenylpyridazin-3- yl)butanamide
147
N-([3,3′-bipyridin]-6-yl)-2- methyl-4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
148
N-(4-methyl-2,3′-bipyridin-6′- yl)-4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
149
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(5- (5-methylpyrazin-2- yl)pyridin-2-yl)-4- oxobutanamide
150
2-methyl-4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(5′- methyl-[2,3′-bipyridin]-5-yl)- 4-oxobutanamide
151
2-methyl-4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(5- (6-methylpyrazin-2- yl)pyridin-2-yl)-4- oxobutanamide
152
2-methyl-4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(5′- methyl-[3,3′-bipyridin]-6-yl)- 4-oxobutanamide
153
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4-oxo- N-(5-(pyrimidin-5-yl)pyridin- 2-yl)butanamide
154
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4-oxo- N-(6-(pyrimidin-5-yl)pyridin- 3-yl)butanamide
155
N-(2-fluorobiphenyl-4-yl)-4- (2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
156
N-(5-fluoro-6-phenylpyridin- 3-yl)-4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
157
4-(2,6-dimethyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(5- (6-methylpyrazin-2- yl)pyridin-2-yl)-4- oxobutanamide
158
N-(3-fluoro-5′-methyl-[2,3′- bipyridin]-5-yl)-4-(2-methyl- 6,7-dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
160
(S)-4-(2,6-dimethyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(5′- methyl-[3,3′-bipyridin]-6-yl)- 4-oxobutanamide
161
(R)-4-(2,6-dimethyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(5′- methyl-[3,3′-bipyridin]-6-yl)- 4-oxobutanamide
162
4-(2,6-dimethyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(5′- fluoro-[2,3′-bipyridin]-5-yl)- 4-oxobutanamide
163
4-(2,6-dimethyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(5′- fluoro-[3,3′-bipyridin]-6-yl)- 4-oxobutanamide
164
4-(2,6-dimethyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(5- fluoro-[2,3′-bipyridin]-6′-yl)- 4-oxobutanamide
165
4-(2,6-dimethyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(4- fluoro-[3,3′-bipyridin]-6-yl)- 4-oxobutanamide
166
4-(2-methyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4-oxo- N-(6-(pyrazin-2-yl)pyridin-3- yl)butanamide
167
4-(2,6-dimethyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-N-(6- (5-fluoropyridin-3- yl)pyridazin-3-yl)-4- oxobutanamide
168
N-(3,5′-dimethyl-[2,3′- bipyridin]-5-yl)-4-(2-methyl- 6,7-dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
169
(S)-N-([3,3′-bipyridin]-6-yl)- 4-(2,6-dimethyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
170
(R)-N-([3,3′-bipyridin]-6-yl)- 4-(2,6-dimethyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
171
N-([2,3′-bipyridin]-6′-yl)-4- (2,6-dimethyl-6,7- dihydropyrazolo[1,5- a]pyrimidin-4(5H)-yl)-4- oxobutanamide
or a pharmaceutically acceptable salt, polymorph, tautomer, or stereoisomer thereof.

### Claim 6 (depends on 3)

The method of claim 3, wherein R1 represents H, methyl, ethyl, —C(O)OMe, or CF3.

### Claim 7 (depends on 3)

The method of claim 3, wherein each R2 independently represents H or alkyl.

### Claim 8 (depends on 3)

The method of claim 3, wherein each R2 independently represents H.

### Claim 9 (depends on 3)

The method of claim 3, wherein R3 represents H.

### Claim 10 (depends on 3)

The method of claim 3, wherein R4 represents H.

### Claim 11 (depends on 3)

The method of claim 3, wherein R5 represents H.

### Claim 12 (depends on 3)

The method of claim 3, wherein W and X each represent C═O.

### Claim 13 (depends on 3)

The method of claim 3, wherein Y represents phenyl.

### Claim 14 (depends on 3)

The method of claim 3, wherein Y is substituted by one or more substituents each independently selected from the group consisting of C1-6 alkyl, C1-6alkoxy, halo, and C1-6haloalkyl.

### Claim 15 (depends on 3)

The method of claim 3, wherein the tumor is pancreatic adenocarcinoma.

### Claim 16 (depends on 3)

The method of claim 3, wherein the tumor is osteosarcoma.

### Claim 17 (depends on 3)

The method of claim 3, wherein the tumor is hepatocellular carcinoma.

### Claim 18 (depends on 3)

The method of claim 3, wherein the tumor is Wilm's tumor.

### Claim 19 (depends on 3)

The method of claim 3, wherein the tumor is medulloblastoma.