Piperidinyl-methyl-purineamines as NSD2 inhibitors and anti-cancer agents
The present invention provides a compound of Formula (I): or an enantiomer, an enantiomeric mixture, or a pharmaceutically acceptable salt thereof; wherein the variables are as defined herein. The present invention further provides pharmaceutical compositions comprising such compounds; and methods of using such compounds for treating a disease or condition mediated by nuclear SET domain-containing protein 2 (NSD2).
1. A compound of Formula (I):
or an enantiomer, an enantiomeric mixture, or a pharmaceutically acceptable salt thereof; wherein:
A is N or CR 9 wherein R 9 is hydrogen or halo;
L is a bond;
R 1 is H; or
R 1 and R 2 together with NH forms a 5-8 membered heterocyclyl containing 1-2 heteroatoms selected from N, O and S as ring members; wherein said 5-8 membered heterocyclyl is unsubstituted or substituted by an oxo substituent;
R 2 is selected from the group consisting of:
(i) hydrogen, —C 1-6 alkyl, -haloC 1-6 alkyl, -hydroxyC 1-6 alkylene, -hydroxyhaloC 1-6 alkylene, —C 1-6 alkoxyC 1-6 alkylene, -haloC 1-6 alkoxyC 1-6 alkylene or —C 3-8 cycloalkoxy(C 1-6 alkyl);
(ii) cyano; -cyanoC 1-6 alkylene; —C 1-6 alkylthioC 1-6 alkyl; —C 2-6 alkenyl; -haloC 2-6 alkenyl; —C 2-6 alkynyl; —C 1-4 alkylSOC 1-4 alkyl; —C 1-4 alkylSO 2 C 1-4 alkyl; —SO 2 R 8 or —C(C 1-4 alkyl)=N—O(C 1-4 alkyl);
(iii) —C 1-4 alkylcarbonyl; —(CR a R b ) p —C(═O)—OR 10 ; or —C(═O)—(CR a R b ) q R 11 ; wherein R 11 is C 3-7 cycloalkyl, 5-6 membered heterocyclyl or 5-6 membered heteroaryl, each of which is independently unsubstituted or substituted with C 1-6 alkyl or C 1-6 alkoxy;
(iv) —(CR a R b ) r —C(═O)—NR 12 R 13 wherein R 12 is hydrogen or C 1-6 alkyl; R 13 is hydrogen, —C 1-6 alkyl or a 5-6 membered heterocyclic ring; or R 12 and R 13 together form a 5-6 membered heterocyclic ring; wherein said 5-6 membered heterocyclic ring is unsubstituted or substituted with C 1-4 alkyl;
(v) 5-6 membered heterocyclylC 0-6 alkyl or 5-6 membered heterocyclyl(haloC 1-4 alkyl) wherein each said heterocyclyl radical is unsubstituted or substituted by oxo; and
(vi) 5-9 membered heteroarylC 0-6 alkyl or 5-9 membered heteroaryl(haloC 1-4 alkyl), wherein each said heteroaryl radical is unsubstituted or substituted by —C 1-4 alkyl, -haloC 1-4 alkyl, -hydroxyC 1-4 alkylene, —C 1-4 alkoxy,-haloC 1-4 alkoxy, halo, hydroxy, cyano, oxido, -aminocarbonylC 0-6 alkyl, —C 1-4 alkylaminocarbonylC 0-6 alkyl, -diC 1-4 alkylaminocarbonylC 0-6 alkyl or —C 3-7 cycloalkyl;
R 3a , R 3b , R 4a , and R 4b are independently hydrogen, halo, cyano, hydroxyl, —C 1-6 alkyl, -haloC 1-6 alkyl, -hydroxyC 1-6 alkylene, —C 1-6 alkoxy, or —C 1-6 alkoxyC 1-6 alkylene;
R 5a and R 5b are independently hydrogen or —C 1-6 alkyl:
R 6a and R 6b are independently hydrogen, —C 1-6 alkyl, -hydroxyC 1-6 alkylene, —C 1-6 alkoxyC 1-6 alkylene, -haloC 1-6 alkoxyC 1-6 alkylene, -hydroxyhaloC 1-6 alkylene, aryl, —C(═O)—OR 14 , or —(CR a R b ) s —C(═O)—NR 15 R 16 ; or
R 3a and R 3b , R 4a and R 4b , R 5a and R 5b or R 6a and R 6b forms an oxo substituent;
R 7 is H, —C 1-4 alkoxy, halo or C 1-4 alkyl;
R 8 is C 3-8 cycloalkyl(C 0-6 alkyl); 4-6 membered heterocyclylC 0-6 alkyl comprising 1-3 heteroatoms selected from N, O and S; aryl or 5-9 membered heteroarylC 0-6 alkyl comprising 1-3 heteroatoms selected from N, O and S; wherein R 8 is unsubstituted or substituted by 1-3 R 17 ;
R 17 is halo, hydroxy, cyano, —C 1-6 alkyl, -haloC 1-6 alkyl, —C 1-6 alkoxy, -haloC 1-6 alkoxy, —NR a C(═O)CR c ═C(R c ) 2 or —(CR a R b ) t —NR a —C(═O)—R 18 ;
R a , R b , R c , R 10 , R 14 , R 15 and R 16 are independently hydrogen or —C 1-4 alkyl;
R 18 is —C 1-4 alkyl or —C 1-4 haloalkyl; and
p, q, r, s and t are independently 0-4.
2. The compound of Formula (I) in claim 1 or an enantiomer, an enantiomeric mixture, or a pharmaceutically acceptable salt thereof; wherein A is N.
3. The compound of Formula (I) in claim 2 , or an enantiomer, an enantiomeric mixture, or a pharmaceutically acceptable salt; wherein
R 3a is hydrogen or halo; and R 3b is hydrogen, halo, -hydroxyl, —C 1-6 alkoxy or cyano; or
R 4a is hydrogen or halo; and R 4b is hydrogen, halo, —C 1-6 alkoxyC 1-6 alkylene, —C 1-6 alkyl or -haloC 1-6 alkyl; or
R 5a is hydrogen and R 5b is hydrogen or —C 1-6 alkyl; or
R 5a and R 5b together form an oxo substituent.
4. The compound of Formula (I) in claim 2 or an enantiomer, an enantiomeric mixture, or a pharmaceutically acceptable salt; wherein:
R 6a is hydrogen;
R 6b is hydrogen, -haloC 1-6 alkoxyC 1-6 alkylene, -hydroxyC 1-6 alkylene, -hydroxyhaloC 1-6 alkylene, carboxyl, phenyl or —(CR a R b ) t —C(O)—NR 15 R 16 ;
R a , R b , R 15 and R 16 are independently hydrogen or —C 1-4 alkyl; and
t is 0-1; or
R 6a and R 6b together form an oxo substituent.
5. The compound of Formula (I) in claim 3 or an enantiomer, an enantiomeric mixture, or a pharmaceutically acceptable salt thereof; wherein R 7 is H, —C 1-4 alkoxy or halo.
6. The compound of Formula (I) in claim 2 or a pharmaceutically acceptable salt thereof; wherein R 1 , R 3a , R 3b , R 4a , R 4b , R 5a , R 5b , R 6a , R 6b and R 7 are hydrogen.
7. The compound of Formula (I) in claim 1 , wherein said compound is a compound of Formula (II):
or an enantiomer, an enantiomeric mixture, or a pharmaceutically acceptable salt thereof.
8. The compound according to claim 7 or an enantiomer, an enantiomeric mixture, or a pharmaceutically acceptable salt thereof; wherein R 2 is —C 1-6 alkyl, -haloC 1-6 alkyl, -hydroxyC 1-6 alkylene, -hydroxyhaloC 1-6 alkylene, —C 1-6 alkoxyC 1-6 alkylene, -haloC 1-6 alkoxyC 1-6 alkylene or —C 3-8 cycloalkoxy(C 1-6 alkyl).
9. The compound according to claim 7 or an enantiomer, an enantiomeric mixture, or a pharmaceutically acceptable salt thereof; wherein R 2 is 2,2-difluoroethyl; 2-methyl-propan-1-olyl; ethan-1-olyl; 2,2-difluoroethan-1-olyl; 2-fluoroethan-1-olyl; 2,2,2-trifluoroethan-1-olyl; difluoromethoxyl; or 2,2,2-trifluoroethoxyl.
10. The compound according to claim 2 or an enantiomer, an enantiomeric mixture, or a pharmaceutically acceptable salt thereof; wherein R 2 is 2,2-difluoroethyl; 2-methyl-propan-1-olyl; ethan-1-olyl; 2,2-difluoroethan-1-olyl; 2-fluoroethan-1-olyl; 2,2,2-trifluoroethan-1-olyl; difluoromethoxyl; or 2,2,2-trifluoroethoxyl.
11. The compound according to claim 7 or an enantiomer, an enantiomeric mixture, or a pharmaceutically acceptable salt thereof; wherein R 2 is
12. The compound according to claim 7 or an enantiomer, an enantiomeric mixture, or a pharmaceutically acceptable salt thereof; wherein R 8 is phenyl substituted with 1-3 R 17 ;
R 17 is halo, hydroxy, cyano, —C 1-6 alkyl, -haloC 1-6 alkyl, —C 1-6 alkoxy, -haloC 1-6 alkoxy, —NR d C(O)CR d ═C(R d ) 2 or —(CR a R b ) t —NR d —C(O)—R 18 ;
R a , R b and R d are independently hydrogen or —C 1-4 alkyl;
R 18 is C 1-4 haloalkyl; and
t is 0-1.
13. The compound according to claim 2 or an enantiomer, an enantiomeric mixture, or a pharmaceutically acceptable salt thereof; wherein R 8 is phenyl substituted with 1-3 R 17 ;
R 17 is halo, hydroxy, cyano, —C 1-6 alkyl, -haloC 1-6 alkyl, —C 1-6 alkoxy, -haloC 1-6 alkoxy, —NR d C(O)CR d ═C(R d ) 2 or —(CR a R b ) t —NR d —C(O)—R 18 ;
R a , R b and R d are independently hydrogen or —C 1-4 alkyl;
R 18 is C 1-4 haloalkyl; and
t is 0-1.
14. The compound according to claim 9 or an enantiomer, an enantiomeric mixture, or a pharmaceutically acceptable salt thereof; wherein R 8 is phenyl substituted with 1-3 R 17 ; and R 17 is halo, hydroxy, —C 1-6 alkyl, -haloC 1-6 alkyl, —C 1-6 alkoxy or -haloC 1-6 alkoxy.
15. The compound according to claim 2 or an enantiomer, an enantiomeric mixture, or a pharmaceutically acceptable salt thereof; wherein R 8 is phenyl substituted with 1-3 R 17 ; and R 17 is halo, hydroxy, —C 1-6 alkyl, -haloC 1-6 alkyl, —C 1-6 alkoxy or -haloC 1-6 alkoxy.
16. The compound according to claim 1 or an enantiomer, an enantiomeric mixture, or a pharmaceutically acceptable salt thereof; wherein said compound is selected from a compound in the following table, or a pharmaceutically acceptable salt thereof:
Ex No.
Chemical Name
1
(R)-9-((5-(3-aminopiperidin-1-yl)-2-(3-fluoro-4-methoxyphenyl)pyridin-4-
yl)methyl)-9H-purin-6-amine
2
9-((5-((3S,4R)-3-amino-4-fluoropiperidin-1-yl)-2-(2-fluorophenyl)pyridin-4-
yl)methyl)-9H-purin-6-amine
3
(3S,4R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-4-ol
4
(R)-9-((5-(3-aminopiperidin-1-yl)-2-(3-fluorophenyl)pyridin-4-yl)methyl)-9H-
purin-6-amine
5
9-((5-((3S,4R)-3-amino-4-fluoropiperidin-1-yl)-2-(3-fluoro-4-
methoxyphenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
6
(R)-9-((5-(3-aminopiperidin-1-yl)-2-(2-fluoro-4-methoxyphenyl)pyridin-4-
yl)methyl)-9H-purin-6-amine
7
(R)-4-(4-((6-amino-9H-purin-9-yl)methyl)-5-(3-aminopiperidin-1-yl)pyridin-
2-yl)-2-chlorobenzonitrile
8
9-((5-((3S,4R)-3-amino-4-fluoropiperidin-1-yl)-2-(3-fluorophenyl)pyridin-4-
yl)methyl)-9H-purin-6-amine
9
4-(5-((2S,3R)-3-amino-2-(methoxymethyl)piperidin-1-yl)-4-((6-amino-9H-
purin-9-yl)methyl)pyridin-2-yl)-2-fluorobenzonitrile
10
9-((5-((3S,4R)-3-amino-4-fluoropiperidin-1-yl)-2-(2-fluoro-4-
methoxyphenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
11
(R)-9-((5-(3-aminopiperidin-1-yl)-2-(4-methoxyphenyl)pyridin-4-yl)methyl)-
9H-purin-6-amine
12
9-((5-((3S,4R)-3-amino-4-fluoropiperidin-1-yl)-2-(3-chlorophenyl)pyridin-4-
yl)methyl)-9H-purin-6-amine
13
4-(5-((3S,4R)-3-amino-4-fluoropiperidin-1-yl)-4-((6-amino-9H-purin-9-
yl)methyl)pyridin-2-yl)-2-fluorobenzonitrile
14
9-((5-((3S,4R)-3-amino-4-fluoropiperidin-1-yl)-2-(2,3-dihydrobenzofuran-5-
yl)pyridin-4-yl)methyl)-9H-purin-6-amine
15
9-((5-(3-amino-4-methoxypiperidin-1-yl)-2-(3-fluoro-4-
methoxyphenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
16
(R)-9-((5-(5-amino-3,3-difluoropiperidin-1-yl)-2-(3-fluoro-4-
methoxyphenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
17
9-((5-(3-amino-4,4-difluoropiperidin-1-yl)-2-(3-fluorophenyl)pyridin-4-
yl)methyl)-9H-purin-6-amine
18
3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-difluorophenyl)pyridin-
3-yl)piperidine-4-carbonitrile
19
(R)-1-((5-(3-aminopiperidin-1-yl)-2-(3-fluoro-4-methoxyphenyl)pyridin-4-
yl)methyl)-7-chloro-1H-imidazo[4,5-c]pyridin-4-amine
20
(R)-9-((5-(3-amino-3-methylpiperidin-1-yl)-2-(3-fluoro-4-
methoxyphenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
21
(R)-1-((5-(3-aminopiperidin-1-yl)-2-(3-fluoro-4-methoxyphenyl)pyridin-4-
yl)methyl)-1H-imidazo[4,5-c]pyridin-4-amine
22
(R)-9-((5-(3-amino-3-(cyclopropoxymethyl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
23
(R)-9-((5-(3-amino-3-(methoxymethyl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
24
(R)-9-((5-(3-amino-3-(methoxymethyl)piperidin-1-yl)-2-(3-
fluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
25
(R)-9-((5-(3-amino-3-(isopropoxymethyl)piperidin-1-yl)-2-(3-fluoro-4-
methoxyphenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
26
(R)-9-((5-(3-amino-3-(methoxymethyl)piperidin-1-yl)-2-(5-chloro-2-
fluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
27
(R)-9-((5-(3-amino-3-(methoxymethyl)piperidin-1-yl)-2-(3-
chlorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
28
(R)-9-((5-(3-amino-3-(methoxymethyl)piperidin-1-yl)-2-(3-chloro-4-
fluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
29
(R)-9-((5-(3-amino-3-(methoxymethyl)piperidin-1-yl)-2-(2,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
30
(R)-9-((5-(3-amino-3-(cyclobutoxymethyl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
31
(R)-9-((5-(3-amino-3-(cyclopropoxymethyl)piperidin-1-yl)-2-(3-fluoro-4-
methoxyphenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
32
(R)-9-((5-(3-amino-3-(cyclobutoxymethyl)piperidin-1-yl)-2-(3-fluoro-4-
methoxyphenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
33
(R)-9-((5-(3-amino-3-(methoxymethyl)piperidin-1-yl)-2-(2-fluoro-4-
methoxyphenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
34
(R)-9-((5-(3-amino-3-(isopropoxymethyl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
35
(R)-9-((5-(3-amino-3-(cyclobutoxymethyl)piperidin-1-yl)-2-(3-
fluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
36
(R)-9-((5-(3-amino-3-(cyclobutoxymethyl)piperidin-1-yl)-2-(4-
fluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
37
(R)-9-((5-(3-amino-3-(isopropoxymethyl)piperidin-1-yl)-2-(4-
fluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
38
(R)-9-((5-(3-amino-3-(methoxymethyl)piperidin-1-yl)-2-(3-fluoro-4-
methoxyphenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
39
(R)-9-((5-(3-amino-3-((2,2,2-trifluoroethoxy)methyl)piperidin-1-yl)-2-(3-
fluoro-4-methoxyphenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
40
(R)-9-((5-(3-amino-3-((difluoromethoxy)methyl)piperidin-1-yl)-2-(3-
fluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
41
(R)-9-((5-(3-amino-3-((difluoromethoxy)methyl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
42
(R)-9-((5-(3-amino-3-((difluoromethoxy)methyl)piperidin-1-yl)-2-(3-fluoro-4-
methoxyphenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
43
(R)-9-((5-(3-amino-3-((2,2,2-trifluoroethoxy)methyl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
44
(R)-9-((5-(3-amino-3-((difluoromethoxy)methyl)piperidin-1-yl)-2-(4-
fluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
45
(R)-9-((5-(3-amino-3-((2,2,2-trifluoroethoxy)methyl)piperidin-1-yl)-2-(4-
fluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
46
(R)-1-((5-(3-amino-3-(methoxymethyl)piperidin-1-yl)-2-(3-fluoro-4-
methoxyphenyl)pyridin-4-yl)methyl)-1H-imidazo[4,5-c]pyridin-4-amine
47
(S)-9-((5-(3-amino-3-(2,2-difluoroethyl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
48
(S)-1-((5-(3-amino-3-(thiazol-2-ylmethyl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-1H-imidazo[4,5-c]pyridin-4-amine
49
(S)-1-((5-(3-amino-3-((1-methyl-1H-pyrazol-3-yl)methyl)piperidin-1-yl)-2-(4-
fluorophenyl)pyridin-4-yl)methyl)-1H-imidazo[4,5-c]pyridin-4-amine
50
(S)-1-((5-(3-amino-3-(pyridin-2-ylmethyl)piperidin-1-yl)-2-(3-fluoro-4-
methoxyphenyl)pyridin-4-yl)methyl)-1H-imidazo[4,5-c]pyridin-4-amine
51
(S)-1-((5-(3-amino-3-(pyridin-2-ylmethyl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-1H-imidazo[4,5-c]pyridin-4-amine
52
(S)-9-((5-(3-amino-3-(oxazol-2-ylmethyl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
53
(S)-9-((5-(3-amino-3-(thiazol-2-ylmethyl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
54
(S)-9-((5-(3-amino-3-(pyridin-2-ylmethyl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
55
(S)-9-((5-(3-amino-3-((6-methylpyridin-2-yl)methyl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
56
(S)-9-((5-(3-amino-3-((l-methyl-1H-pyrazol-3-yl)methyl)piperidin-1-yl)-2-
(3,4-difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
57
(S)-1-((5-(3-amino-3-(thiazol-2-ylmethyl)piperidin-1-yl)-2-(3-fluoro-4-
methoxyphenyl)pyridin-4-yl)methyl)-1H-imidazo[4,5-c]pyridin-4-amine
58
(S)-2-(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3-
fluorophenyl)pyridin-3-yl)piperidin-3-yl)acetic acid
59
(S)-2-(3-amino-1-(4-((4-amino-1H-imidazo[4,5-c]pyridin-1-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)-N,N-dimethylacetamide
60
9-((5-(3-amino-3-(2-methoxyethyl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
61
(S)-9-((5-(3-amino-3-(2,2-difluoroethyl)piperidin-1-yl)-2-(3-fluoro-4-
methoxyphenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
62
(S)-2-(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)acetamide
63
(S)-1-((5-(3-amino-3-(oxazol-2-ylmethyl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-1H-imidazo[4,5-c]pyridin-4-amine
64
N-(4-(5-(3-amino-3-(2,2-difluoroethyl)piperidin-1-yl)-4-((6-amino-9H-purin-
9-yl)methyl)pyridin-2-yl)phenyl)-3-bromopropanamide
65
9-((5-((S)-3-amino-3-((R)-1-(pyridin-2-yl)ethyl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
66
2-(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3-fluorophenyl)pyridin-
3-yl)piperidin-3-yl)-N-methylacetamide
67
2-(3-amino-1-(4-((4-amino-7-chloro-1H-imidazo[4,5-c]pyridin-1-yl)methyl)-6-
(3,4-difluorophenyl)pyridin-3-yl)piperidin-3-yl)-N-methylacetamide
68
2-(3-amino-1-(4-((4-amino-7-chloro-1H-imidazo[4,5-c]pyridin-1-yl)methyl)-6-
(3,4-difluorophenyl)pyridin-3-yl)piperidin-3-yl)-N,N-dimethylacetamide
69
9-((5-(3-amino-3-((6-fluoropyridin-2-yl)methyl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
70
(S)-2-(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3-
fluorophenyl)pyridin-3-yl)piperidin-3-yl)-N,N-dimethylacetamide
71
(S)-9-((5-(3-amino-3-(2,2-difluoroethyl)piperidin-1-yl)-2-(4-
fluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
72
2-(3-amino-1-(4-((4-amino-1H-imidazo[4,5-c]pyridin-1-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)-N-methylacetamide
73
methyl (S)-2-(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3-
fluorophenyl)pyridin-3-yl)piperidin-3-yl)acetate
74
(S)-9-((5-(3-amino-3-(pyrazin-2-ylmethyl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
75
N-(4-(5-(3-amino-3-(2,2-difluoroethyl)piperidin-1-yl)-4-((6-amino-9H-purin-
9-yl)methyl)pyridin-2-yl)benzyl)-2-chloroacetamide
76
N-(4-(5-(3-amino-3-(2,2-difluoroethyl)piperidin-1-yl)-4-((6-amino-9H-purin-
9-yl)methyl)pyridin-2-yl)phenyl)acrylamide
77
2-(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)acetonitrile
78
(R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3-fluorophenyl)pyridin-
3-yl)-N-methylpiperidine-3-carboxamide
79
methyl (R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3-
fluorophenyl)pyridin-3-yl)piperidine-3-carboxylate
80
(R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3-fluoro-4-
methoxyphenyl)pyridin-3-yl)-N,N-dimethylpiperidine-3-carboxamide
81
isopropyl (R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3-fluoro-4-
methoxyphenyl)pyridin-3-yl)piperidine-3-carboxylate
82
(R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)-N-(tetrahydro-2H-pyran-4-yl)piperidine-3-
carboxamide
83
tert-butyl (R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3-fluoro-4-
methoxyphenyl)pyridin-3-yl)piperidine-3-carboxylate
84
(R)-(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone
85
3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-difluorophenyl)pyridin-
3-yl)-N-(tetrahydrofuran-3-yl)piperidine-3-carboxamide
86
(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)(piperidin-1-yl)methanone
87
(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)(2-methylpiperidin-1-yl)methanone
88
(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)(2-methylpyrrolidin-1-
yl)methanone
89
1-(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)-2,3-dimethylbutan-1-one
90
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3-fluoro-4-
methoxyphenyl)pyridin-3-yl)piperidin-3-yl)ethan-1-ol
91
9-((5-((R)-3-amino-3-((S)-fluoro(pyridin-2-yl)methyl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
92
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3-fluoro-4-
methoxyphenyl)pyridin-3-yl)piperidin-3-yl)ethan-1-ol
93
9-((5-((R)-3-amino-3-((S)-1-methoxyethyl)piperidin-1-yl)-2-(3-fluoro-4-
methoxyphenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
94
9-((5-((R)-3-amino-3-((R)-1-methoxyethyl)piperidin-1-yl)-2-(3-fluoro-4-
methoxyphenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
95
9-((5-((R)-3-amino-3-((S)-1-methoxyethyl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
96
(E)-1-(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3-fluoro-4-
methoxyphenyl)pyridin-3-yl)piperidin-3-yl)ethan-1-one O-methyl oxime
97
9-((5-((R)-3-amino-3-((R)-1-methoxyethyl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
98
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)-2-methylpropan-1-ol
99
9-((5-(3-amino-3-((R)-1-ethoxyethyl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
100
(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)(cyclopentyl)methanone
101
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)-2-methylbutan-1-one
102
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)-2-methylbutan-1-one
103
1-(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)-2-cyclopropylpropan-1-one
104
(R)-1-(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)-2-methylpropan-1-one
105
(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)(cyclobutyl)methanone
106
(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)(3-methoxycyclopentyl)methanone
107
(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)(1-methylcyclopropyl)methanone
108
(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)(tetrahydro-2H-pyran-4-
yl)methanone
109
(R)-1-(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)-2,2-dimethylpropan-1-one
110
(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)(1-methyl-1H-pyrazol-3-
yl)methanone
111
(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)(tetrahydrofuran-3-yl)methanone
112
(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)(3-methyloxetan-3-yl)methanone
113
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol; or
114
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
115
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(4-
(difluoromethyl)-2-methylphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-
difluoroethan-1-ol
116
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(4-
(difluoromethoxy)-3-fluorophenyl)pyridin-3-yl)piperidin-3-yl)-2,2-
difluoroethan-1-ol
117
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(4,5-difluoro-2-
methylphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
118
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)-5-methoxypyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
119
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(4-
(difluoromethoxy)-3-fluorophenyl)pyridin-3-yl)piperidin-3-yl)-2,2-
difluoroethan-1-ol
120
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(4-
(difluoromethyl)-2,5-difluorophenyl)pyridin-3-yl)piperidin-3-yl)-2,2-
difluoroethan-1-ol
121
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3-chloro-4-
methoxyphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
122
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3-chloro-4-
fluorophenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
123
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(6-fluoro-1-
methyl-1H-indazol-5-yl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
124
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(4-chloro-3-
fluorophenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
125
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3-chloro-4-
methoxyphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
126
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2,4-
dimethylphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
127
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3-fluoro-4-
methoxyphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
128
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(4-
(difluoromethoxy)-2,5-difluorophenyl)pyridin-3-yl)piperidin-3-yl)-2,2-
difluoroethan-1-ol
129
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(4-
(difluoromethyl)-5-fluoro-2-methylphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-
difluoroethan-1-ol
130
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-
cyclohexylpyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
131
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3-fluoro-4-
methoxyphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
132
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(4-
(difluoromethyl)-2-fluorophenyl)pyridin-3-yl)piperidin-3-yl)-2,2-
difluoroethan-1-ol
133
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(4-chloro-2-
fluorophenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
134
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(4-
(difluoromethyl)-2,5-difluorophenyl)pyridin-3-yl)piperidin-3-yl)-2,2-
difluoroethan-1-ol
135
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-5-fluoro-6-(2-
fluoro-4-methoxyphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
136
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(1,6-dimethyl-
1H-indazol-5-yl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
137
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(4-
(difluoromethyl)-2-fluorophenyl)pyridin-3-yl)piperidin-3-yl)-2,2-
difluoroethan-1-ol
138
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(4-
(difluoromethoxy)-2-fluorophenyl)pyridin-3-yl)piperidin-3-yl)-2,2-
difluoroethan-1-ol
139
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3-chloro-4-
fluorophenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
140
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(4-
(difluoromethyl)-2-methylphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-
difluoroethan-1-ol
141
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2-fluoro-4-
(trifluoromethyl)phenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
142
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2,4-
difluorophenyl)-5-fluoropyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
143
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(6-fluoro-1-
methyl-1H-indazol-5-yl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
144
4-(5-((R)-3-amino-3-((S)-2,2-difluoro-1-hydroxyethyl)piperidin-1-yl)-4-((6-
amino-9H-purin-9-yl)methyl)pyridin-2-yl)-2,5-difluorophenol
145
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-
cyclohexylpyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
146
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2-
(difluoromethyl)-4,5-difluorophenyl)pyridin-3-yl)piperidin-3-yl)-2,2-
difluoroethan-1-ol
147
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
148
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(4-chloro-2-
fluorophenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
149
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2,5-difluoro-4-
methoxyphenyl)-5-fluoropyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
150
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(4-
(difluoromethoxy)-2,5-difluorophenyl)pyridin-3-yl)piperidin-3-yl)-2,2-
difluoroethan-1-ol
151
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
152
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(4-chloro-3-
fluorophenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
153
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(4-
(difluoromethoxy)-2-fluorophenyl)pyridin-3-yl)piperidin-3-yl)-2,2-
difluoroethan-1-ol
154
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3-
(difluoromethyl)-2,5-difluorophenyl)pyridin-3-yl)piperidin-3-yl)-2,2-
difluoroethan-1-ol
155
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-5′-fluoro-[2,2′-
bipyridin]-5-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
156
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2,4,5-
trifluorophenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol; or
157
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2,4,5-
trifluorophenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
158
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2-
(difluoromethyl)-4-fluorophenyl)pyridin-3-yl)piperidin-3-yl)-2,2-
difluoroethan-1-ol; or
159
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2-
(difluoromethyl)-4-fluorophenyl)pyridin-3-yl)piperidin-3-yl)-2,2-
difluoroethan-1-ol
160
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2,5-difluoro-4-
methoxyphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol; or
161
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2,5-difluoro-4-
methoxyphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
162
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2-
(difluoromethyl)-4-methoxyphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-
difluoroethan-1-ol; or
163
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2-
(difluoromethyl)-4-methoxyphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-
difluoroethan-1-ol
164
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,5-difluoro-4-
methoxyphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol; or
165
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,5-difluoro-4-
methoxyphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
166
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(4-methoxy-2-
(trifluoromethyl)phenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol; or
167
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(4-methoxy-2-
(trifluoromethyl)phenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
168
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2-chloro-4-
methoxyphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol; or
169
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2-chloro-4-
methoxyphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
170
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2-
(difluoromethyl)-4,5-difluorophenyl)pyridin-3-yl)piperidin-3-yl)-2,2-
difluoroethan-1-ol; or
171
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2-
(difluoromethyl)-4,5-difluorophenyl)pyridin-3-yl)piperidin-3-yl)-2,2-
difluoroethan-1-ol
172
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2,3,4-
trifluorophenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
173
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(4-fluoro-2-
methoxyphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol; or
174
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(4-fluoro-2-
methoxyphenyl)pyridin-3-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
175
(S)-1-((R)-3-amino-1-(44(6-amino-9H-purin-9-yl)methyl)-6′-chloro-5′-fluoro-
[2,2′-bipyridin]-5-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol; or
176
(R)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6′-chloro-5′-fluoro-
[2,2′-bipyridin]-5-yl)piperidin-3-yl)-2,2-difluoroethan-1-ol
177
9-((5-(3-amino-3-(6-methylpyridin-2-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
178
(R)-9-((5-(3-amino-3-(6-methoxypyridin-2-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
179
9-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-2-(1,3-
dihydroisobenzofuran-5-yl)pyridin-4-yl)methyl)-9H-purin-6-amine
180
(R)-9-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-5′-chloro-6′-fluoro-
[2,3′-bipyridin]-4-yl)methyl)-9H-purin-6-amine
181
(R)-9-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-2-(2-fluoro-4-
methoxyphenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
182
(R)-9-((5-(3-amino-3-(6-cyclopropylpyridin-2-yl)piperidin-1-yl)-2-(4-
fluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
183
9-((5-((R)-3-amino-3-(6-((S)-1-fluoroethyl)pyridin-2-yl)piperidin-1-yl)-2-(4-
fluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
184
9-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-2-(4-
(difluoromethoxy)phenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
185
(R)-9-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-2-(2,3-
dihydrobenzofuran-5-yl)pyridin-4-yl)methyl)-9H-purin-6-amine
186
9-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-2-(benzo[d][1,3[dioxol-
5-yl)pyridin-4-yl)methyl)-9H-purin-6-amine
187
(R)-9-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-2-(2,5-difluoro-4-
methoxyphenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
188
(R)-9-((5-(3-amino-3-(6-chloro-5-fluoropyridin-2-yl)piperidin-1-yl)-2-(3-
fluoro-4-methoxyphenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
189
9-((5-(3-amino-3-(5-fluoropyridin-2-yl)piperidin-1-yl)-2-(4-
fluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
190
(R)-9-((5-(3-amino-3-(5-fluoro-6-methylpyridin-2-yl)piperidin-1-yl)-2-(4-
fluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
191
(R)-9-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-6′-chloro-5′-fluoro-
[2,2′-bipyridin]-4-yl)methyl)-9H-purin-6-amine
192
(R)-9-((5-(3-amino-3-(6-chloro-3-fluoropyridin-2-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
193
9-((5-(3-amino-3-(5-fluoro-6-(fluoromethyl)pyridin-2-yl)piperidin-1-yl)-2-(4-
fluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
194
(R)-9-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-6′-chloro-5′-
methoxy-[2,2′-bipyridin]-4-yl)methyl)-9H-purin-6-amine
195
6-(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)picolinamide
196
(R)-9-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-5′-fluoro-[2,2′-
bipyridin]-4-yl)methyl)-9H-purin-6-amine
197
(R)-9-((5-(3-amino-3-(6-(1,1-difluoroethyl)pyridin-2-yl)piperidin-1-yl)-2-(4-
fluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
198
(R)-9-((5-(3-amino-3-(pyridin-2-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
199
(R)-9-((5-(3-amino-3-(3-fluoropyridin-2-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
200
(R)-9-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
201
(R)-9-((5-(3-amino-3-(6-fluoropyridin-2-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
202
(R)-9-((5-(3-amino-3-(6-ethylpyridin-2-yl)piperidin-1-yl)-2-(4-
fluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
203
(R)-9-((5-(3-amino-3-(6-(difluoromethyl)pyridin-2-yl)piperidin-1-yl)-2-(4-
fluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
204
(R)-9-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-2-
cyclopropylpyridin-4-yl)methyl)-9H-purin-6-amine
205
9-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-2-(4-
fluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
206
(R)-2-(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)-6-fluoropyridin-4-ol
207
(R)-9-((5-(3-amino-3-(5-fluoro-6-methylpyridin-2-yl)piperidin-1-yl)-2-(3-
fluoro-4-methoxyphenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
208
6-(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)picolinonitrile
209
(R)-9-((5-(3-amino-3-(5-(difluoromethoxy)pyridin-2-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
210
9-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-2-(imidazo[1,2-
a]pyridin-6-yl)pyridin-4-yl)methyl)-9H-purin-6-amine
211
(R)-9-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-2-(4-
methoxyphenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
212
9-((5-((R)-3-amino-3-(6-((R)-1-fluoroethyl)pyridin-2-yl)piperidin-1-yl)-2-(4-
fluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
213
(R)-9-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-2-(3-fluoro-4-
methoxyphenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
214
6-(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)-2-fluoropyridin-3-01
215
1-(6-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)-2-fluoropyridin-3-yl)ethan-1-ol
216
(R)-9-((5-(3-amino-3-(6-chloro-5-fluoropyridin-2-yl)piperidin-1-yl)-2-(4-
methoxyphenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
217
(R)-6-(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)pyridin-2-ol
218
(R)-9-((5-(3-amino-3-(6-(difluoromethyl)-5-fluoropyridin-2-yl)piperidin-1-yl)-
2-(4-fluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
219
(R)-2-(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)-6-chloropyridin-4-ol
220
9-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-2-(1-methyl-1H-
benzo[d[imidazol-6-yl)pyridin-4-yl)methyl)-9H-purin-6-amine
221
(R)-9-((5-(3-amino-3-(6-chloro-5-fluoropyridin-2-yl)piperidin-1-yl)-2-(4-
fluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
222
9-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-2-(pyrazolo[1,5-
a]pyridin-6-yl)pyridin-4-yl)methyl)-9H-purin-6-amine
223
9-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-2-(pyrazolo[1,5-
a]pyridin-6-yl)pyridin-4-yl)methyl)-9H-purin-6-amine
224
(R)-9-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-6′-fluoro-5′-
methoxy-[2,2′-bipyridin]-4-yl)methyl)-9H-purin-6-amine
225
9-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-2-(1-methyl-1H-
indazol-5-yl)pyridin-4-yl)methyl)-9H-purin-6-amine
226
(R)-9-((5-(3-amino-3-(6-(fluoromethyl)pyridin-2-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
227
(R)-9-((5-(3-amino-3-(6-(difluoromethyl)pyridin-2-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
228
9-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-2-(4-
(difluoromethoxy)-3-fluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
229
9-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-6′-methyl-[2,3′-
bipyridin]-4-yl)methyl)-9H-purin-6-amine
230
(R)-9-((5-(3-amino-3-(6-chloro-3-methoxypyridin-2-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
231
(R)-9-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-5′-fluoro-6′-
methoxy-[2,3′-bipyridin]-4-yl)methyl)-9H-purin-6-amine
232
(R)-2-(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)-6-methylpyridine 1-oxide
233
(R)-9-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-2-(3,5-difluoro-4-
methoxyphenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
234
1-(6-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)-2-chloropyridin-3-yl)ethan-1-ol
235
(R)-9-((5-(3-amino-3-(6-fluoro-4-methoxypyridin-2-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
236
(R)-9-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-2-(2,6-difluoro-4-
methoxyphenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
237
(R)-9-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-2-(2,6-difluoro-4-
methoxyphenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
238
(R)-9-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-2-(2,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
239
(R)-2-(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)-6-fluoropyridin-3-01
240
9-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-5′,6′-difluoro-[2,3′-
bipyridin]-4-yl)methyl)-9H-purin-6-amine
241
(R)-9-((5-(3-amino-3-(5-fluoro-6-methylpyridin-2-yl)piperidin-1-yl)-2-(4-
methoxyphenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
242
(R)-9-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-2-(2,3-difluoro-4-
methoxyphenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
243
(R)-9-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-4′-fluoro-5′-
methoxy-[2,2′-bipyridin]-4-yl)methyl)-9H-purin-6-amine
244
5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-4-((6-amino-9H-purin-9-
yl)methyl)-5′-fluoro-[2,3′-bipyridin]-6′-ol
245
(S)-9-((5-(3-amino-3-(pyridin-4-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
246
(S)-9-((5-(3-amino-3-(2-chloropyridin-4-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
247
(S)-9-((5-(3-amino-3-(2-methylpyridin-4-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
248
(S)-9-((5-(3-amino-3-(3-fluoropyridin-4-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
249
9-((5-(3-amino-3-(6-chloropyridazin-3-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
250
(R)-9-((5-(3-amino-3-(6-ethylpyrazin-2-yl)piperidin-1-yl)-2-(4-
fluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
251
(R)-9-((5-(3-amino-3-(2-ethylpyrimidin-4-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
252
(R)-1-((5-(3-amino-3-(6-ethylpyridin-2-yl)piperidin-1-yl)-2-
cyclopropylpyridin-4-yl)methyl)-1H-imidazo[4,5-c]pyridin-4-amine
253
9-((5-(3-amino-3-(pyridazin-3-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
254
9-((5-(3-amino-3-(6-chloropyrazin-2-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
255
9-((5-(3-amino-3-(pyrimidin-4-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
256
(R)-1-((5-(3-amino-3-(6-ethylpyrazin-2-yl)piperidin-1-yl)-2-(4-
fluorophenyl)pyridin-4-yl)methyl)-1H-imidazo[4,5-c]pyridin-4-amine
257
(R)-9-((5-(3-amino-3-(2-methylpyrimidin-4-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
258
(R)-9-((5-(3-amino-3-(6-methylpyrazin-2-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
259
9-((5-(3-amino-3-(pyrazin-2-yl)piperidin-1-yl)-2-(3,4-difluorophenyl)pyridin-
4-yl)methyl)-9H-purin-6-amine
260
(R)-1-((5-(3-amino-3-(6-(difluoromethyl)pyridin-2-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-1H-imidazo[4,5-c]pyridin-4-amine
261
(R)-1-((5-(3-amino-3-(6-methylpyridin-2-yl)piperidin-1-yl)-2-(4-
fluorophenyl)pyridin-4-yl)methyl)-1H-imidazo[4,5-c]pyridin-4-amine
262
1-((5-(3-amino-3-(6-fluoropyridin-2-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-1H-imidazo[4,5-c]pyridin-4-amine
263
1-((5-(3-amino-3-(6-methylpyridin-2-yl)piperidin-1-yl)-2-cyclopropylpyridin-
4-yl)methyl)-1H-imidazo[4,5-c]pyridin-4-amine
264
(R)-1-((5-(3-amino-3-(6-(difluoromethyl)pyridin-2-yl)piperidin-1-yl)-2-
cyclopropylpyridin-4-yl)methyl)-1H-imidazo[4,5-c]pyridin-4-amine
265
1-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-2-(azetidin-1-
yl)pyridin-4-yl)methyl)-1H-imidazo[4,5-c]pyridin-4-amine
266
1-((5-(3-amino-3-(pyridin-2-yl)piperidin-1-yl)-2-(4-fluorophenyl)pyridin-4-
yl)methyl)-1H-imidazo[4,5-c]pyridin-4-amine
267
1-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-2-cyclobutylpyridin-4-
yl)methyl)-1H-imidazo[4,5-c]pyridin-4-amine
268
1-((5-(3-amino-3-(6-chloropyridin-2-yl)piperidin-1-yl)-2-cyclobutylpyridin-4-
yl)methyl)-1H-imidazo[4,5-c]pyridin-4-amine
269
(S)-9-((5-(3-amino-3-(1-methyl-1H-pyrazol-4-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
270
1-((5-(3-amino-3-(1-methyl-1H-pyrazol-4-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-1H-imidazo[4,5-c]pyridin-4-amine
271
9-((5-(3-amino-3-(pyridin-3-yl)piperidin-1-yl)-2-(3,4-difluorophenyl)pyridin-
4-yl)methyl)-9H-purin-6-amine
272
(S)-3-(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)pyridin-2(1H)-one
273
(R)-9-((5-(3-amino-3-(1-(difluoromethyl)-1H-pyrazol-3-yl)piperidin-1-yl)-2-
(4-fluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
274
(R)-9-((5-(3-amino-3-(1-isopropyl-1H-pyrazol-3-yl)piperidin-1-yl)-2-(4-
fluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
275
(R)-9-((5-(3-amino-3-(1-methyl-1H-pyrazol-3-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
276
(R)-1-((5-(3-amino-3-(1-ethyl-1H-pyrazol-3-yl)piperidin-1-yl)-2-
cyclopropylpyridin-4-yl)methyl)-1H-imidazo[4,5-c]pyridin-4-amine
277
1-((5-(3-amino-3-(1-ethyl-1H-pyrazol-3-yl)piperidin-1-yl)-2-(4-
fluorophenyl)pyridin-4-yl)methyl)-1H-imidazo[4,5-c]pyridin-4-amine
278
9-((5-(3-amino-3-(1-cyclopropyl-1H-pyrazol-3-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
279
(R)-1-((5-(3-amino-3-(1-(difluoromethyl)-1H-pyrazol-3-yl)piperidin-1-yl)-2-
(4-fluorophenyl)pyridin-4-yl)methyl)-1H-imidazo[4,5-c]pyridin-4-amine
280
1-((5-(3-amino-3-(1-cyclopropyl-1H-pyrazol-3-yl)piperidin-1-yl)-2-(4-
fluorophenyl)pyridin-4-yl)methyl)-1H-imidazo[4,5-c]pyridin-4-amine
281
9-((5-(3-amino-3-(2-chlorothiazol-4-yl)piperidin-1-yl)-2-(4-
fluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
282
9-((5-(3-amino-3-(1-methyl-1H-1,2,3-triazol-4-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
283
(R)-9-((5-(3-amino-3-(2-methyl-2H-1,2,3-triazol-4-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
284
(R)-9-((5-(3-amino-3-(5-methylisoxazol-3-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
285
(R)-2-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)-2-fluoroethan-1-ol
286
(R)-2-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(2,4,5-
trifluorophenyl)pyridin-3-yl)piperidin-3-yl)-2-fluoroethan-1-ol
287
9-((5-(3-amino-3-(1,2-difluoroethyl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
288
9-((5-((R)-3-amino-3-((2R,6S)-6-methyl-1,4-dioxan-2-yl)piperidin-1-yl)-2-
(3,4-difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
289
9-((5-((R)-3-amino-3-((R)-1,4-dioxan-2-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
290
9-((5-((R)-3-amino-3-((R)-1,4-dioxan-2-yl)piperidin-1-yl)-2-(2,4,5-
trifluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
291
9-((5-((R)-3-amino-3-((R)-1,4-dioxan-2-yl)piperidin-1-yl)-2-(2-
(difluoromethyl)-4,5-difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
292
(R)-7-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-difluorophenyl)pyridin-3 -
yl)-3-oxa-1,7-diazaspiro[4.5]decan-2-one
293
(S)-9-((5-(3-amino-3-(1,1-difluoroprop-1-en-2-yl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
294
9-((5-(3-amino-3-(2,2-difluorovinyl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
295
9-((5-(3-amino-3-(1-fluoroethyl)piperidin-1-yl)-2-(3-fluoro-4-
methoxyphenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
296
(R)-9-((5-(3-((1H-pyrazol-1-yl)methyl)-3-aminopiperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
297
9-((5-(3-amino-3-((methylthio)methyl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
298
9-((5-(3-amino-3-((methylsulfonyl)methyl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
299
(S)-1-((R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)-2,2,2-trifluoroethan-1-ol
300
9-((5-(3-amino-3-(1,2,2-trifluoroethyl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
301
3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-difluorophenyl)pyridin-
3-yl)-3-(2,2-difluoroethyl)piperidin-4-ol
302
(3R,4R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)-3-(6-chloropyridin-2-yl)piperidin-4-ol
303
(S)-9-((5-(3-amino-3-(2,2,2-trifluoroethyl)piperidin-1-yl)-2-(3-fluoro-4-
methoxyphenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
304
(S)-9-((5-(3-amino-3-ethynylpiperidin-1-yl)-2-(3,4-difluorophenyl)pyridin-4-
yl)methyl)-9H-purin-6-amine
305
(R)-9-((5-(3-amino-3-(difluoromethyl)piperidin-1-yl)-2-(3-fluoro-4-
methoxyphenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
306
9-((5-((3R,5R)-3-amino-5-(fluoromethyl)piperidin-1-yl)-2-(3-fluoro-4-
methoxyphenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
307
9-((5-((35,55)-3-amino-3-(2,2-difluoroethyl)-5-methylpiperidin-1-yl)-2-(4-
fluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
308
9-((5-(3-amino-5-(methoxymethyl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
309
9-((5-((3R,5S)-3-amino-5-fluoropiperidin-1-yl)-2-(3,4-difluorophenyl)pyridin-
4-yl)methyl)-9H-purin-6-amine
310
9-((5-((2S,5R)-5-amino-2-methylpiperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
311
9-((5-((2S,3R)-3-amino-2-((difluoromethoxy)methyl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
312
((2S,3R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-2-yl)methanol
313
9-((5-((2S,3R)-3-amino-2-((2,2-difluoroethoxy)methyl)piperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
314
2-((2R,3R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-2-yl)ethan-1-ol
315
(2S,3R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)-N-methylpiperidine-2-carboxamide
316
(R)-1-((2S,3R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-2-yl)-2,2,2-trifluoroethan-1-ol
317
(2S,3R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)-N,N-dimethylpiperidine-2-carboxamide
318
(2S,3R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidine-2-carboxamide
319
(2S,3R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidine-2-carboxamide
320
2-((2R,3R)-3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-2-yl)acetamide
321
9-((2-(3,4-difluorophenyl)-5-(4-oxa-1,8-diazaspiro[5.5]undecan-8-yl)pyridin-
4-yl)methyl)-9H-purin-6-amine
322
(S)-3-(3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-3-yl)-N,N-dimethylpropanamide
323
9-((5-((2R,3R)-3-amino-2-phenylpiperidin-1-yl)-2-(3,4-
difluorophenyl)pyridin-4-yl)methyl)-9H-purin-6-amine
324
3-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-difluorophenyl)pyridin-
3-yl)piperidin-2-one
325
(R)-5-amino-1-(4-((6-amino-9H-purin-9-yl)methyl)-6-(3,4-
difluorophenyl)pyridin-3-yl)piperidin-2-one
17. The compound according to claim 1 or an enantiomer, an enantiomeric mixture, or a pharmaceutically acceptable salt thereof; wherein said compound has the following formula or a pharmaceutically acceptable salt thereof:
18. The compound according to claim 1 or an enantiomer, an enantiomeric mixture, or a pharmaceutically acceptable salt thereof; wherein said compound has the following formula or a pharmaceutically acceptable salt thereof:
19. A compound having the following formula or a pharmaceutically acceptable salt thereof:
20. The compound of claim 19 , wherein the compound has the formula:
21. A compound having the following formula or a pharmaceutically acceptable salt thereof:
22. The compound of claim 21 , wherein the compound has the formula:
23. A pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carrier.
24. A pharmaceutical composition comprising a compound according to claim 7 or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carrier.
25. A pharmaceutical composition comprising a compound according to claim 19 or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carrier.
26. A pharmaceutical composition comprising a compound according to claim 21 or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carrier.
27. A pharmaceutical composition comprising a compound according to claim 22 , and one or more pharmaceutically acceptable carrier.
28. A method for treating a disease or condition mediated by nuclear SET domain-containing protein 2 (NSD2), comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein the disease or condition mediated by NSD2 is breast cancer, cervical cancer, skin cancer, ovarian cancer, gastric cancer, prostate cancer, pancreatic cancer, lung cancer, hepatocellular carcinoma, head and neck cancer, peripheral nerve sheath tumor, osteosarcoma, multiple myeloma, neuroblastoma, leukemia, or non-Hodgkin's lymphoma.
29. The method of claim 28 , wherein said disease or condition mediated by NSD2 is breast cancer, cervical cancer, skin cancer, ovarian cancer, gastric cancer, prostate cancer, pancreatic cancer, lung cancer, hepatocellular carcinoma, multiple myeloma, leukemia, or non-Hodgkin's lymphoma.