US 2026/0217688 A1Published application

Inhibitors of jak2

OwnerAlexander Khvat, Igor Rezekin +2inventors

InventorsAlexander Khvat, Igor Rezekin, Ruben Abagyan, Nikolay Savchuk

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Abstract

The present invention is directed to the compounds of Formula (I)—inhibitors JAK2. The inhibitors described herein can be useful in the treatment of diseases or disorders associated with JAK2, such as blood diseases. In particular, the invention is concerned with compounds and pharmaceutical compositions inhibiting JAK2, methods of treating diseases or disorders associated with JAK2, and methods of synthesizing these compounds.

Claims19

Dependent claims

A compound of Formula (I):

or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein
Ring G is 5-10 membered monocyclic or bicyclic heteroaryl, comprising 1-3 heteroatoms selected from N, O, S;
R1 is selected from C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, heterocycle, aryl, and heteroaryl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycle, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, CN, NO2, OH, N(R8)2, C1-C6 alkyl, C1-C6 alkoxy, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, heterocyclyl, aryl, heteroaryl, wherein the C3-C10 cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from C1-C6 alkyl, halogen, OH, CN;
R2 is selected from H, C1-C6 alkyl;
R3 is selected from hydrogen, C1-C6 alkyl, C3-C10 cycloalkyl;
R4 is selected from H, C1-C6 alkyl;
R5 is selected from H, C1-C6 alkyl;
or R4 and R5 together with the atoms to which they are attached and any intervening atoms, form a 3-14 membered heterocycle optionally substituted with one or more substituents independently selected from halogen, C1-C6 alkyl, and C1-C6 alkoxy;
R6 is selected from H, C1-C6 alkyl;
each R7 is independently selected from oxo, C1-C6 alkyl, C3-C10 cycloalkyl, heterocyclyl, —NH-heteroaryl, —(CH2)m—NH—C(O)—R8, —(CH2)m—C(O)NH—R8, —(CH2)m—C(O)NH-heteroaryl, —(CH2)m—S(O)2N—R8, —(CH2)m—S(O)2N-heterocyclyl, wherein the alkyl, cycloalkyl, heterocyclyl or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, —CN, —OH, N(R8)2, C1-C6 alkyl, C1-C6 alkoxy, cycloalkyl;
each R8 is independently selected from H, C1-C6 alkyl, C3-C10 cycloalkyl;
n is an integer selected from 0, 1, 2 and 3;
m is an integer selected from 0, 1, and 2;
wherein,
cycloalkyl is a mono or polycyclic saturated carbon rings containing 3-18 carbon atoms;
aryl is a cyclic, aromatic hydrocarbon groups that have 1 to 3 aromatic rings;
heterocyclyl is a saturated or partially unsaturated 3-10 membered monocyclic, 7-12 membered bicyclic (fused, bridged, or spiro rings), or 11-14 membered tricyclic ring system (fused, bridged, or spiro rings) having one or more heteroatoms selected from O, N, S, P, Se, or B;
heteroaryl is a monovalent monocyclic or a polycyclic aromatic radical of 5 to 24 ring atoms, containing one or more ring heteroatoms selected from N, O, S, P, or B, the remaining ring atoms being C.

15 more elements

A compound selected from:

#
Structure
IUPAC Name
1
4-[2-methoxy-3-(1-methyl-1,2,4- triazol-3-yl)anilino]-2-[(1- methylpyrazol-4-yl)amino]pyrimidine- 5-carboxamide
2
4-[2-methoxy-3-(2-pyridyl)anilino]-2- [(1-methylpyrazol-4- yl)amino]pyrimidine-5-carboxamide
3
4-[2-methoxy-3-(5-methyl-1,3,4- oxadiazol-2-yl)anilino]-2-[(1- methylpyrazol-4-yl)amino]pyrimidine- 5-carboxamide
4
2-[(1-isopropylpyrazol-4-yl)amino]-4- [2-methoxy-3-(1-methyl-1,2,4-triazol- 3-yl)anilino]pyrimidine-5-carboxamide
5
2-[[1-[2-(dimethylamino)ethyl]pyrazol- 4-yl]amino]-4-[2-methoxy-3-(1- methyl-1,2,4-triazol-3- yl)anilino]pyrimidine-5-carboxamide
6
4-[2-methoxy-3-(1-methyl-1,2,4- triazol-3-yl)anilino]-2-[(1- phenylpyrazol-4-yl)amino]pyrimidine- 5-carboxamide
7
4-[2-methoxy-3-(1-methyl-1,2,4- triazol-3-yl)anilino]-2-[[1-(4- piperidyl)pyrazol-4- yl]amino]pyrimidine-5-carboxamide
8
4-[3-(1,3-benzoxazol-2-yl)-2-methoxy- anilino]-2-[[1-(4-piperidyl)pyrazol-4- yl]amino]pyrimidine-5-carboxamide
9
4-[3-(1,3-benzoxazol-2-yl)-2-methoxy- anilino]-2-[[1-[2- (dimethylamino)ethyl]pyrazol-4- yl]amino]pyrimidine-5-carboxamide
10
4-[2-methoxy-3-(1-methyl-1,2,4- triazol-3-yl)anilino]-2-[[1-(1-methyl-4- piperidyl)pyrazol-4- yl]amino]pyrimidine-5-carboxamide
11
2-[(1-cyclohexylpyrazol-4-yl)amino]- 4-[2-methoxy-3-(1-methyl-1,2,4- triazol-3-yl)anilino]pyrimidine-5- carboxamide
12
4-[3-(1,3-benzoxazol-2-yl)-2-methoxy- anilino]-2-[(1-methylpyrazol-4- yl)amino]pyrimidine-5-carboxamide
13
2-[(1,3-dimethylpyrazol-4-yl)amino]-4- [2-methoxy-3-(1-methyl-1,2,4-triazol- 3-yl)anilino]pyrimidine-5-carboxamide
14
4-[2-methoxy-3-(1-methyl-1,2,4- triazol-3-yl)anilino]-2-[(1- tetrahydropyran-4-ylpyrazol-4- yl)amino]pyrimidine-5-carboxamide
15
4-(2-methoxy-3-pyrimidin-2-yl- anilino)-2-[(1-methylpyrazol-4- yl)amino]pyrimidine-5-carboxamide
16
4-[3-(1,3-benzoxazol-2-yl)-2-methoxy- anilino]-2-[(1-isopropylpyrazol-4- yl)amino]pyrimidine-5-carboxamide
17
4-[2-methoxy-3-(1-methyl-1,2,4- triazol-3-yl)anilino]-2-[(1,3,5- trimethylpyrazol-4- yl)amino]pyrimidine-5-carboxamide
18
2-[(1-ethyl-3,5-dimethyl-pyrazol-4- yl)amino]-4-[2-methoxy-3-(1-methyl- 1,2,4-triazol-3-yl)anilino]pyrimidine-5- carboxamide
19
2-[(3,5-dimethyl-1-propyl-pyrazol-4- yl)amino]-4-[2-methoxy-3-(1-methyl- 1,2,4-triazol-3-yl)anilino]pyrimidine-5- carboxamide
20
2-[(1-isopropyl-3,5-dimethyl-pyrazol- 4-yl)amino]-4-[2-methoxy-3-(1- methyl-1,2,4-triazol-3- yl)anilino]pyrimidine-5-carboxamide
21
2-[(1-cyclopropylpyrazol-4-yl)amino]- 4-[2-methoxy-3-(1-methyl-1,2,4- triazol-3-yl)anilino]pyrimidine-5- carboxamide
22
2-[[1-(cyclohexylmethyl)pyrazol-4- yl]amino]-4-[2-methoxy-3-(1-methyl- 1,2,4-triazol-3-yl)anilino]pyrimidine-5- carboxamide
23
2-[[1-(1-adamantylmethyl)pyrazol-4- yl]amino]-4-[2-methoxy-3-(1-methyl- 1,2,4-triazol-3-yl)anilino]pyrimidine-5- carboxamide
24
2-[(1-isopentylpyrazol-4-yl)amino]-4- [2-methoxy-3-(1-methyl-1,2,4-triazol- 3-yl)anilino]pyrimidine-5-carboxamide
25
4-[2-methoxy-3-(1-methyl-1,2,4- triazol-3-yl)anilino]-2-[(1-octylpyrazol- 4-yl)amino]pyrimidine-5-carboxamide
26
2-[(1-hexylpyrazol-4-yl)amino]-4-[2- methoxy-3-(1-methyl-1,2,4-triazol-3- yl)anilino]pyrimidine-5-carboxamide
27
4-[2-methoxy-3-(1-methyl-1,2,4- triazol-3-yl)anilino]-2-[[1-[2-(1- methyl-2-piperidyl)ethyl]pyrazol-4- yl]amino]pyrimidine-5-carboxamide
28
2-[[1-[3- (dimethylamino)propyl]pyrazol-4- yl]amino]-4-[2-methoxy-3-(1-methyl- 1,2,4-triazol-3-yl)anilino]pyrimidine-5- carboxamide
29
2-[[1-[2- (diisobutylamino)ethyl]pyrazol-4- yl]amino]-4-[2-methoxy-3-(1-methyl- 1,2,4-triazol-3-yl)anilino]pyrimidine-5- carboxamide
30
2-[[1-(1-adamantyl)pyrazol-4- yl]amino]-4-[2-methoxy-3-(1-methyl- 1,2,4-triazol-3-yl)anilino]pyrimidine-5- carboxamide
31
2-[(1-isopropylpyrazol-4-yl)amino]-4- [2-methoxy-3-(1-methyl-1,2,4-triazol- 3-yl)anilino]-N,N-dimethyl- pyrimidine-5-carboxamide
32
4-[3-(1,3-benzoxazol-2-yl)-2-methoxy- anilino]-2-[[1-(1-methyl-4- piperidyl)pyrazol-4- yl]amino]pyrimidine-5-carboxamide
33
4-[3-(1,3-benzoxazol-2-yl)-2-methoxy- anilino]-2-[[1-(1-isopropyl-4- piperidyl)pyrazol-4- yl]amino]pyrimidine-5-carboxamide
34
4-[3-(1,3-benzoxazol-2-yl)-2-methoxy- anilino]-2-[[1-[2- (diisobutylamino)ethyl]pyrazol-4- yl]amino]pyrimidine-5-carboxamide
35
2-[[1-(1-isopropyl-4-piperidyl)pyrazol- 4-yl]amino]-4-[2-methoxy-3-(1- methyl-1,2,4-triazol-3- yl)anilino]pyrimidine-5-carboxamide
36
4-[2-methoxy-3-(3-pyridyl)anilino]-2- [(1-methylpyrazol-4- yl)amino]pyrimidine-5-carboxamide
37
4-[2-methoxy-3-(4-pyridyl)anilino]-2- [(1-methylpyrazol-4- yl)amino]pyrimidine-5-carboxamide
38
2-[(1-isopropylpyrazol-4-yl)amino]-4- [2-methoxy-3-(2- pyridyl)anilino]pyrimidine-5- carboxamide
39
2-[(1-cyclohexylpyrazol-4-yl)amino]- 4-[2-methoxy-3-(2- pyridyl)anilino]pyrimidine-5- carboxamide
40
4-[2-methoxy-3-(2-pyridyl)anilino]-2- [(1-tetrahydropyran-4-ylpyrazol-4- yl)amino]pyrimidine-5-carboxamide
41
2-[[1-(1-adamantyl)pyrazol-4- yl]amino]-4-[2-methoxy-3-(2- pyridyl)anilino]pyrimidine-5- carboxamide
42
2-[[1-[2- (diisobutylamino)ethyl]pyrazol-4- yl]amino]-4-[2-methoxy-3-(2- pyridyl)anilino]pyrimidine-5- carboxamide
43
2-[[1-[3- (dimethylamino)propyl]pyrazol-4- yl]amino]-4-[2-methoxy-3-(2- pyridyl)anilino]pyrimidine-5- carboxamide
44
4-[3-(1,3-benzoxazol-2-yl)-2-methoxy- anilino]-2-[(1-tetrahydropyran-4- ylpyrazol-4-yl)amino]pyrimidine-5- carboxamide
45
4-[3-(1,3-benzoxazol-2-yl)-2-methoxy- anilino]-2-[(1-cyclohexylpyrazol-4- yl)amino]pyrimidine-5-carboxamide
46
4-[3-(1,3-benzoxazol-2-yl)-2-methoxy- anilino]-2-[[1-[3- (dimethylamino)propyl]pyrazol-4- yl]amino]pyrimidine-5-carboxamide
47
4-[2-methoxy-3-(2-pyridyl)anilino]-2- [[1-(1-methyl-4-piperidyl)pyrazol-4- yl]amino]pyrimidine-5-carboxamide
48
2-[[1-(1-isopropyl-4-piperidyl)pyrazol- 4-yl]amino]-4-[2-methoxy-3-(2- pyridyl)anilino]pyrimidine-5- carboxamide
49
2-[[1-(1-adamantyl)pyrazol-4- yl]amino]-4-[3-(1,3-benzoxazol-2-yl)- 2-methoxy-anilino]pyrimidine-5- carboxamide
50
4-[3-(1,3-benzoxazol-2-yl)-2-methoxy- anilino]-2-[[1-(2- methoxyethyl)pyrazol-4- yl]amino]pyrimidine-5-carboxamide
51
2-[[1-(2-methoxyethyl)pyrazol-4- yl]amino]-4-[2-methoxy-3-(1-methyl- 1,2,4-triazol-3-yl)anilino]pyrimidine-5- carboxamide
52
4-[3-(1,3-benzoxazol-2-yl)-2-methoxy- anilino]-2-[[1-(3- methoxypropyl)pyrazol-4- yl]amino]pyrimidine-5-carboxamide
53
4-[2-methoxy-3-[1-(3-methoxypropyl)- 1,2,4-triazol-3-yl]anilino]-2-[[1-(3- methoxypropyl)pyrazol-4- yl]amino]pyrimidine-5-carboxamide
54
4-[3-(1,3-benzoxazol-2-yl)-2-methoxy- anilino]-2-[[1-(2-ethoxyethyl)pyrazol- 4-yl]amino]pyrimidine-5-carboxamide
55
2-[[1-(2-ethoxyethyl)pyrazol-4- yl]amino]-4-[2-methoxy-3-(1-methyl- 1,2,4-triazol-3-yl)anilino]pyrimidine-5- carboxamide
56
4-[3-(1,3-benzoxazol-2-yl)-2-methoxy- anilino]-2-[(1-isobutylpyrazol-4- yl)amino]pyrimidine-5-carboxamide
57
4-[3-(1,3-benzoxazol-2-yl)-2-methoxy- anilino]-2-[[1-(2,2,2- trifluoroethyl)pyrazol-4- yl]amino]pyrimidine-5-carboxamide
58
2-[(1-isobutylpyrazol-4-yl)amino]-4- [2-methoxy-3-(1-methyl-1,2,4-triazol- 3-yl)anilino]pyrimidine-5-carboxamide
59
4-[2-methoxy-3-(1-methyl-1,2,4- triazol-3-yl)anilino]-2-[[1-(2,2,2- trifluoroethyl)pyrazol-4- yl]amino]pyrimidine-5-carboxamide
60
2-[(1-isopropylpyrazol-4-yl)amino]-4- [2-methoxy-3-(1-methylbenzimidazol- 2-yl)anilino]pyrimidine-5-carboxamide
61
4-[3-(1,3-benzothiazol-2-yl)-2- methoxy-anilino]-2-[(1- isopropylpyrazol-4- yl)amino]pyrimidine-5-carboxamide
62
4-[3-(5-tert-butyl-1,3-benzoxazol-2-yl)- 2-methoxy-anilino]-2-[(1- isopropylpyrazol-4- yl)amino]pyrimidine-5-carboxamide
63
4-[3-(5-bromo-1,3-benzoxazol-2-yl)-2- methoxy-anilino]-2-[(1- isopropylpyrazol-4- yl)amino]pyrimidine-5-carboxamide
64
4-[3-[4-(3-hydroxyoxetan-3-yl)oxazol- 2-yl]-2-methoxy-anilino]-2-[(1- isopropylpyrazol-4- yl)amino]pyrimidine-5-carboxamide
65
2-[(1-isopropylpyrazol-4-yl)amino]-4- [2-methoxy-3-(7-methyl-5-oxo-4H- oxazolo[4,5-b]pyridin-2- yl)anilino]pyrimidine-5-carboxamide
66
4-[3-[4-[2-[(4-cyano-2-pyridyl)amino]- 2-oxo-ethyl]oxazol-2-yl]-2-methoxy- anilino]-2-[(1-isopropylpyrazol-4- yl)amino]pyrimidine-5-carboxamide
67
4-[3-[4-[2-[(5-cyano-3-pyridyl)amino]- 2-oxo-ethyl]oxazol-2-yl]-2-methoxy- anilino]-2-[(1-isopropylpyrazol-4- yl)amino]pyrimidine-5-carboxamide
68
2-[(1-isopropylpyrazol-4-yl)amino]-4- [2-methoxy-3-[4- (methylsulfamoyl)oxazol-2- yl]anilino]pyrimidine-5-carboxamide
69
2-[(1-isopropylpyrazol-4-yl)amino]-4- [2-methoxy-3-(4-tetrahydrofuran-3- ylsulfonyloxazol-2- yl)anilino]pyrimidine-5-carboxamide
70
2-[(1-isopropylpyrazol-4-yl)amino]-4- [2-methoxy-3-[4- (methylsulfonylmethyl)oxazol-2- yl]anilino]pyrimidine-5-carboxamide
71
2-[(1-isopropylpyrazol-4-yl)amino]-4- [2-methoxy-3-(4- methylsulfonyloxazol-2- yl)anilino]pyrimidine-5-carboxamide
72
2-[(1-isopropylpyrazol-4-yl)amino]-4- [2-methoxy-3-(6-oxo-5,7-dihydro-4H- oxazolo[5,4-c]pyridin-2- yl)anilino]pyrimidine-5-carboxamide
73
4-[3-(4-acetamidooxazol-2-yl)-2- methoxy-anilino]-2-[(1- isopropylpyrazol-4- yl)amino]pyrimidine-5-carboxamide
74
4-[3-[4-(2-amino-2-oxo-ethyl)oxazol- 2-yl]-2-methoxy-anilino]-2-[(1- isopropylpyrazol-4- yl)amino]pyrimidine-5-carboxamide
75
2-[(1-isopropylpyrazol-4-yl)amino]-4- [2-methoxy-3-[4-[2-(methylamino)-2- oxo-ethyl]oxazol-2- yl]anilino]pyrimidine-5-carboxamide
76
2-[(1-isopropylpyrazol-4-yl)amino]-4- [3-[5-[(1-isopropylpyrazol-4- yl)amino]-1,3-benzoxazol-2-yl]-2- methoxy-anilino]pyrimidine-5- carboxamide
or a pharmaceutically acceptable salt, stereoisomer, solvate, or tautomer thereof.

153 more elements

Dependencies are inferred from the claim text.

Facts

Application: 19/141,044Filed 18 Dec 2023
Priority: 21 Dec 2022
Published: 30 Jul 2026
Term ends: Not estimatedThe source records don’t support an estimate.

Classification9 codes

C07D 403/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group…
A61K 31/506
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: not condensed and containing further heterocyclic rings
C07D 401/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a…:…
C07D 405/14
Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having…:…

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Application63/434,412Us provisional application · filed 21 Dec 2022
US 2026/0217688 A1This patent

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Abstract

A compound of Formula (I):

or a pharmaceutically acceptable salt, prodrug, stereoisomer, solvate, or tautomer thereof, wherein
Ring G is 5-10 membered monocyclic or bicyclic heteroaryl, comprising 1-3 heteroatoms selected from N, O, S;
R1 is selected from C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, heterocycle, aryl, and heteroaryl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycle, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, CN, NO2, OH, N(R8)2, C1-C6 alkyl, C1-C6 alkoxy, C3-C10 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, heterocyclyl, aryl, heteroaryl, wherein the C3-C10 cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more substituents independently selected from C1-C6 alkyl, halogen, OH, CN;
R2 is selected from H, C1-C6 alkyl;
R3 is selected from hydrogen, C1-C6 alkyl, C3-C10 cycloalkyl;
R4 is selected from H, C1-C6 alkyl;
R5 is selected from H, C1-C6 alkyl;
or R4 and R5 together with the atoms to which they are attached and any intervening atoms, form a 3-14 membered heterocycle optionally substituted with one or more substituents independently selected from halogen, C1-C6 alkyl, and C1-C6 alkoxy;
R6 is selected from H, C1-C6 alkyl;
each R7 is independently selected from oxo, C1-C6 alkyl, C3-C10 cycloalkyl, heterocyclyl, —NH-heteroaryl, —(CH2)m—NH—C(O)—R8, —(CH2)m—C(O)NH—R8, —(CH2)m—C(O)NH-heteroaryl, —(CH2)m—S(O)2N—R8, —(CH2)m—S(O)2N-heterocyclyl, wherein the alkyl, cycloalkyl, heterocyclyl or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, —CN, —OH, N(R8)2, C1-C6 alkyl, C1-C6 alkoxy, cycloalkyl;
each R8 is independently selected from H, C1-C6 alkyl, C3-C10 cycloalkyl;
n is an integer selected from 0, 1, 2 and 3;
m is an integer selected from 0, 1, and 2;
wherein,
cycloalkyl is a mono or polycyclic saturated carbon rings containing 3-18 carbon atoms;
aryl is a cyclic, aromatic hydrocarbon groups that have 1 to 3 aromatic rings;
heterocyclyl is a saturated or partially unsaturated 3-10 membered monocyclic, 7-12 membered bicyclic (fused, bridged, or spiro rings), or 11-14 membered tricyclic ring system (fused, bridged, or spiro rings) having one or more heteroatoms selected from O, N, S, P, Se, or B;
heteroaryl is a monovalent monocyclic or a polycyclic aromatic radical of 5 to 24 ring atoms, containing one or more ring heteroatoms selected from N, O, S, P, or B, the remaining ring atoms being C.

15 more elements

Facts

Application

19/141,044Filed 18 Dec 2023

Priority

21 Dec 2022

Published

30 Jul 2026

Term ends

Not estimatedThe source records don’t support an estimate.

Classification9 codes

C07D 403/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group…
A61K 31/506
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: not condensed and containing further heterocyclic rings
C07D 401/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a…:…
C07D 405/14
Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having…:…