US 2026/0224758 A1Published application

Alpha-synuclein binders and methods of use

AssigneeMerck Sharp & Dohme Corp.

InventorsIdriss BENNACEF, Maria V. FAWAZ, Eric D. HOSTETLER, Helen MITCHELL, Anthony J. ROECKER, Anthony W. SHAW, Craig A. STUMP, Ling TONG

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Abstract

The invention is directed to compounds of Formula I (I) or their pharmaceutically acceptable salts, which may be suitable for imaging alpha-synuclein pathology and hence are useful in binding and imaging alpha-synuclein aggregates in patients with Parkinson's Disease. More specifically, this invention relates to a method of using the compounds of this invention as tracers in positron emission tomography (PET) imaging to study alpha-synuclein in brain in vivo to allow diagnosis of Parkinson's Disease and other neurodegenerative diseases Specific characterized by alpha-synuclein pathology. The invention further relates to a method of measuring clinical efficacy of therapeutic agents for Parkinson's Disease and other neurodegenerative diseases characterized by alpha-synuclein pathology.

Claims20

Dependent claims

A compound of Formula I:

or a pharmaceutically acceptable salt thereof wherein;
may be absent or may represent a bond;
R is independently selected from H or —C1-6alkyl, where said alkyl is optionally substituted with one to three groups from —C1-6alkyl, ORa or halo;
Ra is independently selected from H, —C1-6alkyl, —(CH2)pOR, —(CH2)phalo, or —(CH2)pO(CH2)phalo;
Rb is independently selected from H, —C1-6alkyl, heterocyclyl, heteroaryl, —(CH2)pOR, —CN, —(CH2)thalo, —(CH2)sNR2 or —O(CH2)phalo;
Rc is independently selected from H, halo, OR, or —C1-6alkyl, where said alkyl is optionally substituted with one to three groups from —C1-6alkyl, ORa or halo;
R1 is selected —(CH2)sOR, —(CH2)sNR2, —(CH2)s[O(Rc2)p]x—Rc, or —(CH2)shalo;
R2 is independently selected from H, OR, CN, halo or —C1-6alkyl, where said alkyl is optionally substituted with one to three groups from —C1-6alkyl, ORa or halo;
R3 is independently selected from —C1-6alkyl, heteroaryl or heterocyclyl, wherein said alkyl, heteroaryl or heterocyclyl is optionally substituted with one to three groups from ORa or Rb;
Ring A1 is selected from pyridinyl, imidazo-pyrimidinyl, triazinyl, pyrimidinyl, imidazo-pyridinyl, pyrazinyl or pyridazinyl;
Ring A2 is selected from pyrimidinyl, pyridinyl, pyrazinyl or phenyl wherein said pyrimidinyl, pyridinyl, pyrazinyl or phenyl is optionally substituted with one to three groups from —C1-6alkyl, ORa or halo;
Ring A3 is selected from pyridinyl, pyrazinyl, pyrimidinyl, pyrrolopyrazinyl, triazinyl, indolyl, imidazolyl, oxadiazolyl, triazolyl, thiazolyl, isoxazolyl, oxazolyl, 3,4-dihydro-2H-pyrido[3,2,b][1,4]oxazine or phenyl;
m is selected from 0, 1, or 2;
n is selected from 1, 2, or 3;
p is independently selected from 1, 2 or 3;
r is selected from 1, 2 or 3;
s is independently selected from 0, 1, 2, 3, 4, 5 or 6;
t is independently selected from 0, 1, 2, 3, 4, 5 or 6;
and
x is independently selected from 1, 2, 3, 4, 5 or 6.

17 more elements

A compound selected from

Ex
No.
Chemical Name
1
(R,E)-(4-(5-(2-(6-(1H-imidazol-1-yl)pyridin-3-yl)vinyl)pyrimidin-2-yl)-1-(pyrimidin-
2-yl)piperazin-2-yl)methanol;
2
(R,E)-5-(2-(6-(1H-imidazol-1-yl)pyridin-3-yl)vinyl)-2-(3-(methoxymethyl)-4-
(pyrimidin-2-yl)piperazin-1-yl)pyrimidine;
3
(R,E)-5-(2-(6-(1H-imidazol-1-yl)pyridin-3-yl)vinyl)-2-(3-((2-fluoroethoxy)methyl)-4-
(pyrimidin-2-yl)piperazin-1-yl)pyrimidine;
4
(R,E)-5-(2-(6-(1H-imidazol-1-yl)pyridin-3-yl)vinyl)-2-(3-((fluoromethoxy)methyl)-4-
(pyrimidin-2-yl)piperazin-1-yl)pyrimidine;
5
(R,E)-5-(2-(6-(4H-1,2,4-triazol-4-yl)pyridin-3-yl)vinyl)-2-(2-(methoxymethyl)-4-
(pyridin-2-yl)piperazin-1-yl)pyrimidine;
6
(R,E)-5-(2-(6-(1H-imidazol-1-yl)pyridin-3-yl)vinyl)-2-(2-((2-methoxyethoxy)methyl)-
4-(pyridin-2-yl)piperazin-1-yl)pyrimidine;
7
(R,E)-(2-(4-(5-(2-(6-(1H-imidazol-1-yl)pyridin-3-yl)vinyl)pyrimidin-2-yl)-2-
(methoxymethyl)piperazin-1-yl)pyrimidin-5-yl)methanol;
8
(R,E)-5-(2-(6-(1H-imidazol-1-yl)pyridin-3-yl)vinyl)-2-(4-(5-(fluoromethyl)pyrimidin-
2-yl)-3-(methoxymethyl)piperazin-1-yl)pyrimidine;
9
(R,E)-5-(2-(6-(1H-imidazol-1-yl)pyridin-3-yl)vinyl)-2-(2-(methoxymethyl)-4-(5-
(methoxymethyl)pyrimidin-2-yl)piperazin-1-yl)pyrimidine;
10
(R)-(4-(5-((6-(1H-imidazol-1-yl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)-1-(pyrimidin-2-
yl)piperazin-2-yl)methanol;
11
(R)-5-((6-(1H-imidazol-1-yl)pyridin-3-yl)ethynyl)-2-(3-(methoxymethyl)-4-
(pyrimidin-2-yl)piperazin-1-yl)pyrimidine;
12
(R)-5-((6-(1H-imidazol-1-yl)pyridin-3-yl)ethynyl)-2-(4-(6-fluoropyrimidin-4-yl)-3-
(methoxymethyl)piperazin-1-yl)pyrimidine;
13
(R,E)-5-(2-(6-(1H-imidazol-1-yl)pyridin-3-yl)vinyl)-2-(4-(6-fluoropyrimidin-4-yl)-2-
(methoxymethyl)piperazin-1-yl)pyrimidine;
14
(R,E)-5-(2-(6-(1H-imidazol-1-yl)pyridin-3-yl)vinyl)-2-(4-(6-chloropyrimidin-4-yl)-2-
(methoxymethyl)piperazin-1-yl)pyrimidine;
15
(R,E)-(1-(5-(2-(6-(1H-imidazol-1-yl)pyridin-3-yl)vinyl)pyrimidin-2-yl)-4-(6-
fluoropyrimidin-4-yl)piperazin-2-yl)methanol;
16
(R,E)-4-(5-(2-(2-(4-(4-fluoropyridin-2-yl)-2-(methoxymethyl)piperazin-1-
yl)pyrimidin-5-yl)vinyl)pyridin-2-yl)morpholine;
17
(R,E)-5-(2-(6-(1H-imidazol-1-yl)pyridin-3-yl)vinyl)-2-(4-(4-fluoropyridin-2-yl)-2-
(methoxymethyl)piperazin-1-yl)pyrimidine;
18
(R,E)-5-(2-(6-(1H-imidazol-1-yl)pyridin-3-yl)vinyl)-2-(2-(methoxymethyl)-4-
(pyridin-2-yl)piperazin-1-yl)pyrimidine;
19
(R,E)-6-(2-(2-(2-(methoxymethyl)-4-(pyridin-2-yl)piperazin-1-yl)pyrimidin-5-
yl)vinyl)-2-methylimidazo[1,2-a]pyrimidine;
20
(R,E)-2-(5-(2-(2-(2-(methoxymethyl)-4-(pyridin-2-yl)piperazin-1-yl)pyrimidin-5-
yl)vinyl)pyridin-2-yl)oxazole;
21
(R,E)-7-(4-(5-(2-(6-(1H-pyrazol-1-yl)pyridin-3-yl)vinyl)pyrimidin-2-yl)-3-
(methoxymethyl)piperazin-1-yl)pyrrolo[1,2-a]pyrazine;
22
(R,E)-5-(2-(6-(1H-imidazol-1-yl)pyridin-3-yl)vinyl)-2-(3-(methoxymethyl)-4-
(pyridin-2-yl)piperazin-1-yl)pyrimidine;
23
(R,E)-(1-(5-(2-(6-(1H-imidazol-1-yl)pyridin-3-yl)vinyl)pyrimidin-2-yl)-4-(pyrazin-2-
yl)piperazin-2-yl)methanol;
24
(R,E)-(1-(5-(2-(6-(1H-imidazol-1-yl)pyridin-3-yl)vinyl)pyrimidin-2-yl)-4-(pyrimidin-
4-yl)piperazin-2-yl)methanol;
25
(R,E)-5-(2-(6-(1H-imidazol-1-yl)pyridin-3-yl)vinyl)-2-(2-(methoxymethyl)-4-(5-
methylpyrimidin-2-yl)piperazin-1-yl)pyrimidine;
26
(R,E)-5-(5-(2-(2-(2-(methoxymethyl)-4-(pyridin-2-yl)piperazin-1-yl)pyrimidin-5-
yl)vinyl)pyridin-2-yl)oxazole;
27
(R,E)-5-(2-(6-(1H-imidazol-1-yl)pyridin-3-yl)vinyl)-2-(4-(5-fluoropyrimidin-2-yl)-3-
(methoxymethyl)piperazin-1-yl)pyrimidine;
28
(R,E)-5-(2-(6-(1H-imidazol-1-yl)pyridin-3-yl)vinyl)-2-(2-(methoxymethyl)-4-
(pyrimidin-2-yl)piperazin-1-yl)pyrimidine;
29
(R,E)-5-(2-(6-(1H-imidazol-1-yl)pyridin-3-yl)vinyl)-2-(4-(2-fluoropyridin-4-yl)-2-
(methoxymethyl)piperazin-1-yl)pyrimidine;
30
(R,E)-5-(2-(6-(1H-imidazol-1-yl)pyridin-3-yl)vinyl)-2-(2-((2-fluoroethoxy)methyl)-4-
(pyrimidin-2-yl)piperazin-1-yl)pyrimidine;
31
(R,E)-5-(2-(6-(1H-imidazol-1-yl)pyridin-3-yl)vinyl)-2-(2-((2-fluoroethoxy)methyl)-4-
(pyridin-4-yl)piperazin-1-yl)pyrimidine;
32
(R,E)-5-(2-(6-(1H-imidazol-1-yl)pyridin-3-yl)vinyl)-2-(4-(6-fluoropyridin-3-yl)-2-
(methoxymethyl)piperazin-1-yl)pyrimidine;
33
(R,E)-(1-(5-(2-(6-(1H-imidazol-1-yl)pyridin-3-yl)vinyl)pyrimidin-2-yl)-4-(6-
fluoropyridin-3-yl)piperazin-2-yl)methanol;
34
(R,E)-4-(4-(5-(2-(6-(1H-imidazol-1-yl)pyridin-3-yl)vinyl)pyrimidin-2-yl)-2-
(methoxymethyl)piperazin-1-yl)-2-fluoropyrimidine;
and
35
(R,E)-5-(2-(6-(1H-imidazol-1-yl)pyridin-3-yl)vinyl)-2-(4-(5-(2-
fluoroethoxy)pyrimidin-2-yl)-3-(methoxymethyl)piperazin-1-yl)pyrimidine;
36
(R,E)-5-(5-(2-(2-(3-((2-fluoroethoxy)methyl)-4-(pyrimidin-2-yl)piperazin-1-
yl)pyrimidin-5-yl)vinyl)pyridin-2-yl)oxazole
37
(R,E)-5-(2-(6-(1-(2-fluoroethyl)-1H-pyrazol-4-yl)pyridin-3-yl)vinyl)-2-(3-
(methoxymethyl)-4-(pyrimidin-2-yl)piperazin-1-yl)pyrimidine
38
(R,E)-5-(5-(2-(2-(3-((2-(2-fluoroethoxy)ethoxy)methyl)-4-(1,3,5-triazin-2-
yl)piperazin-1-yl)pyrimidin-5-yl)vinyl)pyridin-2-yl)oxazole
39
1-((2-((R)-4-(5-((E)-2-(6-(1H-imidazol-1-yl)pyridin-3-yl)vinyl)pyrimidin-2-yl)-2-
(methoxymethyl)piperazin-1-yl)pyrimidin-5-yl)oxy)-3-fluoropropan-2-ol
40
(R,E)-2-(3-((2-fluoroethoxy)methyl)-4-(pyrimidin-2-yl)piperazin-1-yl)-5-(2-(6-(4-
methyl-1H-imidazol-1-yl)pyridin-3-yl)vinyl)pyrimidine
41
(R,E)-5-(5-(2-(2-(3-((2-fluoroethoxy)methyl)-4-(1,3,5-triazin-2-yl)piperazin-1-
yl)pyrimidin-5-yl)vinyl)pyridin-2-yl)oxazole
42
(R,E)-5-(5-(2-(2-(3-((2-fluoroethoxy)methyl)-4-(pyrimidin-4-yl)piperazin-1-
yl)pyrimidin-5-yl)vinyl)pyridin-2-yl)oxazole
43
(R,E)-2-(2-((2-fluoroethoxy)methyl)-4-(5-(2-(2-(1-methyl-1H-pyrazol-4-yl)pyrimidin-
5-yl)vinyl)pyrimidin-2-yl)piperazin-1-yl)-1,3,5-triazine
44
(R)-2-(2-((2-fluoroethoxy)methyl)-4-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyrimidin-5-
yl)ethynyl)pyrimidin-2-yl)piperazin-1-yl)-1,3,5-triazine
45
(R)-5-((6-(4H-1,2,4-triazol-4-yl)pyridin-3-yl)ethynyl)-2-(4-(6-fluoropyrimidin-4-yl)-
3-(methoxymethyl)piperazin-1-yl)pyrimidine
46
(R)-2-(4-(5-((2-(1-(2-fluoroethyl)-1H-pyrazol-4-yl)pyrimidin-5-yl)ethynyl)pyrimidin-
2-yl)-2-(methoxymethyl)piperazin-1-yl)-1,3,5-triazine
47
(R)-2-(4-(5-((6-(1-(2-fluoroethyl)-1H-pyrazol-4-yl)pyridin-3-yl)ethynyl)pyrimidin-2-
yl)-2-(methoxymethyl)piperazin-1-yl)-1,3,5-triazine
48
(R)-5-(5-((2-(3-((2-(2-fluoroethoxy)ethoxy)methyl)-4-(1,3,5-triazin-2-yl)piperazin-1-
yl)pyrimidin-5-yl)ethynyl)pyridin-2-yl)oxazole
49
(R)-2-(2-((2-fluoroethoxy)methyl)-4-(5-((2-(1-methyl-1H-pyrazol-3-yl)pyrimidin-5-
yl)ethynyl)pyrimidin-2-yl)piperazin-1-yl)-1,3,5-triazine
50
(R)-2-(2-((2-fluoroethoxy)methyl)-4-(5-((6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-
yl)ethynyl)pyrimidin-2-yl)piperazin-1-yl)-1,3,5-triazine
51
(R)-2-(3-((2-fluoroethoxy)methyl)-4-(pyrimidin-2-yl)piperazin-1-yl)-5-((2-(1-methyl-
1H-pyrazol-4-yl)pyrimidin-5-yl)ethynyl)pyrimidine
52
(R)-2-(3-((2-(2-fluoroethoxy)ethoxy)methyl)-4-(pyrimidin-2-yl)piperazin-1-yl)-5-((2-
(1-methyl-1H-pyrazol-4-yl)pyrimidin-5-yl)ethynyl)pyrimidine
53
(R)-2-(3-((2-fluoroethoxy)methyl)-4-(pyrimidin-4-yl)piperazin-1-yl)-5-((2-(1-methyl-
1H-pyrazol-4-yl)pyrimidin-5-yl)ethynyl)pyrimidine
54
(R)-2-(1-(2-fluoroethyl)-1H-pyrazol-4-yl)-5-((2-(3-(methoxymethyl)-4-(pyrimidin-4-
yl)piperazin-1-yl)pyrimidin-5-yl)ethynyl)pyrimidine
55
(R)-5-(5-((2-(3-((2-fluoroethoxy)methyl)-4-(1,3,5-triazin-2-yl)piperazin-1-
yl)pyrimidin-5-yl)ethynyl)pyrimidin-2-yl)oxazole
56
(R)-2-(4-(5-((2-(1-(fluoromethyl)-1H-pyrazol-4-yl)pyrimidin-5-yl)ethynyl)pyrimidin-
2-yl)-2-(methoxymethyl)piperazin-1-yl)-1,3,5-triazine
57
(R)-2-(4-(5-((6-(1H-imidazol-1-yl)pyridin-3-yl)ethynyl)-6-fluoropyrazin-2-yl)-2-
(methoxymethyl)piperazin-1-yl)pyrimidine
58
(R)-5-((6-(4H-1,2,4-triazol-4-yl)pyridin-3-yl)ethynyl)-4-fluoro-2-(3-
(methoxymethyl)-4-(pyrimidin-4-yl)piperazin-1-yl)pyrimidine
59
(R)-5-((6-(3-fluoro-4H-1,2,4-triazol-4-yl)pyridin-3-yl)ethynyl)-2-(3-
(methoxymethyl)-4-(pyrimidin-2-yl)piperazin-1-yl)pyrimidine
60
(R)-2-(4-(5-((6-(1H-imidazol-1-yl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)-2-
(methoxymethyl)piperazin-1-yl)-4-fluoropyrimidine
61
(R)-4-(4-(5-((6-(1H-imidazol-1-yl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)-2-
(methoxymethyl)piperazin-1-yl)-2-fluoropyrimidine
62
(S)-5-(5-((2-(3-((2-fluoroethoxy)methyl)-4-(1,3,5-triazin-2-yl)piperazin-1-
yl)pyrimidin-5-yl)ethynyl)pyridin-2-yl)oxazole
63
3-(((R)-4-(5-((6-(1H-imidazol-1-yl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)-1-
(pyrimidin-2-yl)piperazin-2-yl)methoxy)-2-fluoropropan-1-ol
64
(R)-5-(5-((2-(4-(2-fluoropyridin-4-yl)-3-(methoxymethyl)piperazin-1-yl)pyrimidin-5-
yl)ethynyl)pyridin-2-yl)oxazole
65
1-(4-(6-fluoropyrimidin-4-yl)-1-(5-((6-(oxazol-5-yl)pyridin-3-yl)ethynyl)pyrimidin-2-
yl)piperazin-2-yl)-N-methylmethanamine
66
(R)-5-(5-((2-(4-(5-(2-fluoroethoxy)pyrimidin-2-yl)-3-(methoxymethyl)piperazin-1-
yl)pyrimidin-5-yl)ethynyl)pyridin-2-yl)oxazole
67
1-fluoro-3-(((R)-4-(5-((6-(oxazol-5-yl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)-1-(1,3,5-
triazin-2-yl)piperazin-2-yl)methoxy)propan-2-ol
68
(R)-5-((6-(3-fluoroazetidin-1-yl)pyridin-3-yl)ethynyl)-2-(3-(methoxymethyl)-4-
(pyrimidin-2-yl)piperazin-1-yl)pyrimidine
69
(R)-5-((6-(1H-imidazol-1-yl)pyridin-3-yl)ethynyl)-2-(4-(6-fluoropyrazin-2-yl)-3-
(methoxymethyl)piperazin-1-yl)pyrimidine
70
(R)-2-(4-(5-((6-(4H-1,2,4-triazol-4-yl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)-2-((2-
fluoroethoxy)methyl)piperazin-1-yl)-1,3,5-triazine
71
(R)-5-((6-(4H-1,2,4-triazol-4-yl)pyridin-3-yl)ethynyl)-2-(3-((2-fluoroethoxy)methyl)-
4-(pyrimidin-2-yl)piperazin-1-yl)pyrimidine
72
5-((6-((S)-3-fluoropyrrolidin-1-yl)pyridin-3-yl)ethynyl)-2-((R)-3-(methoxymethyl)-4-
(pyrimidin-2-yl)piperazin-1-yl)pyrimidine
73
(R)-1-(5-((2-(3-((2-fluoroethoxy)methyl)-4-(1,3,5-triazin-2-yl)piperazin-1-
yl)pyrimidin-5-yl)ethynyl)pyrimidin-2-yl)-1H-pyrazol-4-amine
74
(R)-5-(5-((2-(3-((3-fluoropropoxy)methyl)-4-(1,3,5-triazin-2-yl)piperazin-1-
yl)pyrimidin-5-yl)ethynyl)pyridin-2-yl)oxazole
75
(R)-7-(5-((2-(3-((2-fluoroethoxy)methyl)-4-(1,3,5-triazin-2-yl)piperazin-1-
yl)pyrimidin-5-yl)ethynyl)pyridin-2-yl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-
a]pyrazine
76
(R)-5-((6-(4-(2H-1,2,3-triazol-2-yl)piperidin-1-yl)pyridin-3-yl)ethynyl)-2-(3-
(methoxymethyl)-4-(pyrimidin-2-yl)piperazin-1-yl)pyrimidine
77
(R)-2-(4-(5-((6-(1-(2-(2-fluoroethoxy)ethyl)-1H-pyrazol-4-yl)pyridin-3-
yl)ethynyl)pyrimidin-2-yl)-2-(methoxymethyl)piperazin-1-yl)-1,3,5-triazine
78
(R)-2-(2-((2-(2-fluoroethoxy)ethoxy)methyl)-4-(5-((2-(1-methyl-1H-pyrazol-4-
yl)pyrimidin-5-yl)ethynyl)pyrimidin-2-yl)piperazin-1-yl)-1,3,5-triazine
79
(R)-5-((2-(3-((2-(2-fluoroethoxy)ethoxy)methyl)-4-(1,3,5-triazin-2-yl)piperazin-1-
yl)pyrimidin-5-yl)ethynyl)-2,5′-bipyrimidine
80
(R)-2-(4-(5-((6-(1H-imidazol-1-yl)pyridin-3-yl)ethynyl)-4-fluoropyrimidin-2-yl)-2-
((2-methoxyethoxy)methyl)piperazin-1-yl)-1,3,5-triazine
81
(R)-2-(4-(5-((6-(6-fluoropyrimidin-4-yl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)-2-
(methoxymethyl)piperazin-1-yl)pyrimidine-5-carbonitrile
82
(R)-2-(3-((2-(2-(2-fluoroethoxy)ethoxy)ethoxy)methyl)-4-(pyrimidin-2-yl)piperazin-
1-yl)-5-((2-(1-methyl-1H-pyrazol-4-yl)pyrimidin-5-yl)ethynyl)pyrimidine
83
(R)-2-(3-(13-fluoro-2,5,8,11-tetraoxatridecyl)-4-(pyrimidin-2-yl)piperazin-1-yl)-5-((2-
(1-methyl-1H-pyrazol-4-yl)pyrimidin-5-yl)ethynyl)pyrimidine
84
(R)-2-(4-(5-((2-(1-(2-fluoroethyl)-1H-pyrazol-4-yl)pyrimidin-5-yl)ethynyl)pyrimidin-
2-yl)-3-(methoxymethyl)piperazin-1-yl)-1,3,5-triazine
85
(R)-2-(1-(2-fluoroethyl)-1H-pyrazol-4-yl)-5-((2-(4-(5-fluoropyridin-2-yl)-3-
(methoxymethyl)piperazin-1-yl)pyrimidin-5-yl)ethynyl)pyrimidine
86
(S)-5-((2-(4H-1,2,4-triazol-4-yl)pyrimidin-5-yl)ethynyl)-2-(4-(5-fluoropyridin-2-yl)-
2-methylpiperazin-1-yl)pyrimidine
87
(S)-2-(4-(5-((2-(1-(2-fluoroethyl)-1H-pyrazol-4-yl)pyrimidin-5-yl)ethynyl)pyrimidin-
2-yl)-3-(methoxymethyl)piperazin-1-yl)-1,3,5-triazine
88
(R)-5-fluoro-2-(4-(5-((2-(1-(2-fluoroethyl)-1H-pyrazol-4-yl)pyrimidin-5-
yl)ethynyl)pyrimidin-2-yl)-2-(methoxymethyl)piperazin-1-yl)pyrimidine
89
(R)-5-((2-(4H-1,2,4-triazol-4-yl)pyrimidin-5-yl)ethynyl)-2-(4-(5-fluoropyridin-2-yl)-
3-(methoxymethyl)piperazin-1-yl)pyrimidine
90
(R)-5-fluoro-2-(4-(5-((6-(1-(2-fluoroethyl)-1H-pyrazol-4-yl)pyridin-3-
yl)ethynyl)pyrimidin-2-yl)-2-(methoxymethyl)piperazin-1-yl)pyrimidine
91
(R)-2-(4-(5-((2-(1-(3-fluoropropyl)-1H-pyrazol-4-yl)pyrimidin-5-
yl)ethynyl)pyrimidin-2-yl)-2-(methoxymethyl)piperazin-1-yl)-1,3,5-triazine
92
(R)-5-(2-fluoroethoxy)-2-(2-(methoxymethyl)-4-(5-((6-(1-methyl-1H-pyrazol-4-
yl)pyridin-3-yl)ethynyl)pyrimidin-2-yl)piperazin-1-yl)pyrimidine
93
(R)-5-(5-((2-(3-((2-fluoroethoxy)methyl)-4-(pyrimidin-2-yl)piperazin-1-yl)pyrimidin-
5-yl)ethynyl)pyrimidin-2-yl)oxazole
94
(R)-2-(4-(6-fluoropyrimidin-4-yl)-3-(methoxymethyl)piperazin-1-yl)-5-((2-(1-methyl-
1H-pyrazol-4-yl)pyrimidin-5-yl)ethynyl)pyrimidine
95
(R)-2-(2-((fluoromethoxy)methyl)-4-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyrimidin-5-
yl)ethynyl)pyrimidin-2-yl)piperazin-1-yl)-1,3,5-triazine
96
(S)-2-(3-((2-fluoroethoxy)methyl)-4-(5-((2-(1-methyl-1H-pyrazol-4-yl)pyrimidin-5-
yl)ethynyl)pyrimidin-2-yl)piperazin-1-yl)-1,3,5-triazine
97
(R)-5-fluoro-2-(2-((2-fluoroethoxy)methyl)-4-(5-((2-(1-methyl-1H-pyrazol-3-
yl)pyrimidin-5-yl)ethynyl)pyrimidin-2-yl)piperazin-1-yl)pyrimidine
98
(R)-2-(2-((2-fluoroethoxy)methyl)-4-(5-((2-(1-methyl-1H-pyrazol-5-yl)pyrimidin-5-
yl)ethynyl)pyrimidin-2-yl)piperazin-1-yl)-1,3,5-triazine
or a pharmaceutically acceptable salt thereof.

297 more elements

Dependencies are inferred from the claim text.

Facts

Application: 19/157,423Filed 29 Feb 2024
Priority: 6 Mar 2023
Published: 6 Aug 2026
Term ends: Not estimatedThe source records don’t support an estimate.

Classification18 codes

A61K 51/0461
Having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins: having six-membered rings with three nitrogens as the only ring hetero…
C07D 471/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61B 5/0042
Adapted for image acquisition of a particular organ or body part: for the brain
A61B 5/4848
Other medical applications: monitoring or testing the effects of treatment, e.g. of medication