IP Library › Granted Patent US 12,595,248
Granted Patent B2
US 12,595,248 · App. 17/783,975 · Granted Apr 7, 2026

PRMT5 inhibitors

Inventors: Michelle Machacek (Belmont, MA); Michael D. Altman (Needham, MA); Chunghui Huang (Arlington, MA); Michael H. Reutershan (Brighton, MA); David L. Sloman (Newton, MA); Phieng Siliphaivanh (Newton Highlands, MA); Sebastian E. Schneider (Cambridge, MA); Charles S. Yeung (Dedham, MA); David J. Witter (Toronto, CA); Craig R. Gibeau (Northborough, MA); Yingchun Ye (Belmont, MA)
Assignee: Merck Sharp & Dohme LLC
C07D401/14C07D405/14C07D413/14C07D451/04C07D471/04C07D487/04C07D498/08
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Quick Facts
Patent No.
US 12,595,248
App. No.
17/783,975
Granted
Apr 7, 2026
Kind
B2
Abstract

The present invention provides a compound of Formula (I) and the pharmaceutically acceptable salts, esters, and prodrugs thereof, which are PRMT5 inhibitors. Also provided are methods of making compounds of Formula I, pharmaceutical compositions comprising compounds of Formula I, and methods of using these compounds to treat cancer, sickle cell, and hereditary persistence of foetal hemoglobin (HPFH) mutations.

Claims (257)

1 . A compound of formula I,

or a pharmaceutically acceptable salt thereof, wherein

A is a 6 membered heterocycle containing 1 nitrogen ring atom and 5 carbon ring atoms,

wherein A is substituted with OH and optionally substituted with 0-2 R 2 ;

z 1 is

when present, W 1 is H, CHF 2 , NHW 2 , or OCHF 2 ;

when present, W 2 is

when present, R 1 is independently selected from hydrogen, halogen, ═O, C 1-6 alkyl, OC 0-6 alkyl, C 1-6 alkylOC 1-6 alkyl, tetrahydrofuran, cyclopropyl, triazole, thiazole or pyrazole, wherein the C 1-6 alkyl, OC 0-6 alkyl, C 1-6 alkylOC 1-6 alkyl, tetrahydrofuran, or cyclopropyl are optionally substituted with one to three substituents independently selected from halogen, CH 3 , CN, cyclopropyl, or ═O, or wherein the triazole, thiazole or pyrazole are optionally substituted with one to three substituents independently selected from halogen, CH 3 , CN, or cyclopropyl;

when present, R 2 is selected from H or CH 3 ;

each R 3 is selected from hydrogen or deuterium;

when present, R 6 is H, C 1-6 alkyl, C(O)C 1-6 alkyl, C(O)OC 1-6 alkyl, C(O)C 1-6 cycloalkyl, C(O)N(C 1-6 alkyl) 2 , or S(O) 2 C 1-6 alkyl;

when present, R 7 is H or ═O;

when present, R 9 is H, halogen or CH 3 ;

when present, Z 4 is N while Z 5 is C, or Z 4 is C while Z 5 is N;

when present, each X 1 is selected from N or CR 1 , provided no more than one X 1 is N;

when present, X 2 is independently selected from O, C═O, CHR 1 , C(R 1 ) 2 , or NR 1 , where two X 2 in the same ring cannot both be NR 1 ;

when present, t is 1 or 2;

when present, p is 0 or 1; and

when present, q is 1 or 2,

provided that the compound of formula (I) is not:

2 . A compound of Formula Ii,

or a pharmaceutically acceptable salt thereof, wherein

Z 1 is

when present, W 1 is H, CHF 2 , NHW 2 , or OCHF 2 ;

when present, W 2 is

when present, R 1 is independently selected from H, halogen, ═O, C 1-6 alkyl, OC 0-6 alkyl, C 1-6 alkylOC 1-6 alkyl, tetrahydrofuran, cyclopropyl, triazole, thiazole or pyrazole, wherein the C 1-6 alkyl, OC 0-6 alkyl, C 1-6 alkylOC 1-6 alkyl, tetrahydrofuran, or cyclopropyl are optionally substituted with one to three substituents independently selected from halogen, CH 3 , CN, cyclopropyl, or ═O, or wherein the triazole, thiazole or pyrazole are optionally substituted with one to three substituents independently selected from halogen, CH 3 , CN, or cyclopropyl,

when present, R 2 is independently selected from H or CH 3 ;

each R 3 is selected from hydrogen or deuterium;

when present, R 6 is H, C 1-6 alkyl, C(O)C 1-6 alkyl, C(O)C 1-6 cycloalkyl, C(O)OC 1-6 alkyl, C(O)N(C 1-6 alkyl) 2 , or S(O) 2 C 1-6 alkyl;

when present, R 7 is H or ═O;

when present R 9 is H, halogen, or CH 3 ;

when present, Z 4 is N while Z 5 is C, or Z 4 is C while Z 5 is N;

when present, X 1 is selected from N or CR 1 , provided no more than one X 1 is N;

when present, X 2 is independently selected from O, C═O, CHR 1 , C(R 1 ) 2 , or NR 1 , where two X 2 in the same ring cannot both be NR 1 ;

when present, p is 0 or 1;

when present, t is 1 or 2; and

when present, q is 1 or 2.

3 . The compound of claim 2 , of formula Ia:

or a pharmaceutically acceptable salt thereof, wherein

X 2 is NR 1 or C(R 1 ) 2 ;

R 1 is independently selected from H, halogen, ═O, OH, CH 3 , CF 3 , OCH 3 , CH 2 CH 3 , CH(CH 3 )CN, CH 2 CF 3 , OCH 2 CF 3 , OCH 2 CH 3 , OCH 2 CF 3 , CH(CH 3 )OCH 3 , CH(CH 3 ) 2 , C(CH 3 ) 2 CN, cyclopropyl, tetrahydrofuran, triazole, thiazole or pyrazole, wherein the cyclopropyl or tetrahydrofuran are optionally substituted with one to three substituents independently selected from halogen, CH 3 , CN, cyclopropyl, or ═O, or wherein the triazole, thiazole or pyrazole are optionally substituted with one to three substituents independently selected from halogen, CH 3 , CN or cyclopropyl;

Z 4 is N while Z 5 is C, or Z 4 is C while Z 5 is N; and

R 9 is H, halogen or CH 3 .

4 . The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein X 2 is NR 1 or C(R 1 ) 2 .

5 . The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein Z 4 is N and Z 5 is C, or Z 4 is C and Z 5 is N.

6 . The compound of claim 2 , of formula Ib:

or a pharmaceutically acceptable salt thereof, wherein

R 1 is independently selected from H, halogen, OH, CH 3 , CF 3 , OCH 3 , CH 2 CH 3 , CH(CH 3 )CN, CH 2 CF 3 , OCH 2 CH 3 , OCH 2 CF 3 , CH(CH 3 )OCH 3 , CH(CH 3 ) 2 , C(CH 3 ) 2 CN, cyclopropyl, tetrahydrofuran, triazole, thiazole or pyrazole, wherein the cyclopropyl or tetrahydrofuran are optionally substituted with one to three substituents independently selected from halogen, CH 3 , CN, cyclopropyl, or ═O, or wherein the triazole, thiazole or pyrazole are optionally substituted with one to three substituents independently selected from halogen, CH 3 , CN or cyclopropyl; and

X 1 is independently selected from N or CR 1 , provided no more than one X 1 is N.

7 . The compound of claim 6 , or a pharmaceutically acceptable salt thereof, wherein one X 1 is N and two X 1 's are CR 1 , or wherein all three X 1 's are CR 1 .

8 . The compound of claim 2 of formula Ic:

or a pharmaceutically acceptable salt thereof, wherein

R 1 is independently selected from H, halogen, ═O, OH, CH 3 , CF 3 , OCH 3 , CH 2 CH 3 , CH(CH 3 )CN, CH 2 CF 3 , OCH 2 CF 3 , OCH 2 CH 3 , OCH 2 CF 3 , CH(CH 3 )OCH 3 , CH(CH 3 ) 2 , C(CH 3 ) 2 CN, or cyclopropyl, tetrahydrofuran, triazole, thiazole or pyrazole, wherein the cyclopropyl or tetrahydrofuran are optionally substituted with one to three substituents independently selected from halogen, CH 3 , CN, cyclopropyl, or ═O, or wherein the triazole, thiazole or pyrazole are optionally substituted with one to three substituents independently selected from halogen, CH 3 , CN or cyclopropyl;

q is 1, or 2; and

X 2 is independently selected from O, C═O, NR 1 , CHR 1 or C(R 1 ) 2 .

9 . The compound of claim 8 , or a pharmaceutically acceptable salt thereof, wherein at least one X 2 is O.

10 . The compound of claim 8 , or a pharmaceutically acceptable salt thereof, wherein at least one X 2 is NR 1 .

11 . The compound of claim 8 , or a pharmaceutically acceptable salt thereof, wherein at least one X 2 is C(R 1 ) 2 .

12 . The compound of claim 8 , or a pharmaceutically acceptable salt thereof, wherein at least one X 2 is CHR 1 .

13 . The compound of claim 8 , or a pharmaceutically acceptable salt thereof, wherein R 1 is independently selected from H, CH 3 , CF 3 , CH 2 CH 3 , CH 2 CF 3 , ═O, or CH(CH 3 ) 2 .

14 . The compound of claim 8 , or a pharmaceutically acceptable salt thereof, wherein q is 1.

15 . The compound of claim 2 , of formula Id:

or a pharmaceutically acceptable salt thereof, wherein

R 1 is independently selected from H, halogen, ═O, OH, CH 3 , CF 3 , OCH 3 , CH 2 CH 3 , CH(CH 3 )CN, CH 2 CF 3 , OCH 2 CF 3 , OCH 2 CH 3 , OCH 2 CF 3 , CH(CH 3 )OCH 3 , CH(CH 3 ) 2 , C(CH 3 ) 2 CN, cyclopropyl, tetrahydrofuran, triazole, thiazole or pyrazole, wherein the cyclopropyl or tetrahydrofuran are optionally substituted with one to three substituents independently selected from halogen, CH 3 , CN, cyclopropyl, or ═O, or wherein the triazole, thiazole or pyrazole are optionally substituted with one to three substituents independently selected from halogen, CH 3 , CN or cyclopropyl.

16 . The compound of claim 15 , or a pharmaceutically acceptable salt thereof, wherein R 1 is H, cyclopropyl, or CH 2 CF 3 .

17 . The compound of claim 2 , of formula Ie:

or a pharmaceutically acceptable salt thereof, wherein

W 1 is H, CHF 2 , NHW 2 , or OCHF 2 ;

W 2 is

X 1 is independently selected from N or CR 1 , provided no more than one X 1 is N;

R 1 is independently selected from H, halogen, ═O, OH, CH 3 , CF 3 , OCH 3 , CH 2 CH 3 , CH(CH 3 )CN, CH 2 CF 3 , OCH 2 CF 3 , OCH 2 CH 3 , OCH 2 CF 3 , CH(CH 3 )OCH 3 , CH(CH 3 ) 2 , C(CH 3 ) 2 CN, cyclopropyl, tetrahydrofuran, triazole, thiazole or pyrazole, wherein the cyclopropyl or tetrahydrofuran are optionally substituted with one to three substituents independently selected from halogen, CH 3 , CN, cyclopropyl, or ═O, or wherein the triazole, thiazole or pyrazole are optionally substituted with one to three substituents independently selected from halogen, CH 3 , CN or cyclopropyl, R 6 is H, C 1-6 alkyl, C(O)C 1-6 alkyl, C(O)C 1-6 cycloalkyl, C(O)OC 1-6 alkyl, C(O)N(C 1-6 alkyl) 2 , or S(O) 2 C 1-6 alkyl;

R 7 is H or ═O;

R 9 is H, halogen or CH 3 ; and

R 2 is independently selected from H or CH 3 .

18 . The compound of claim 17 , or a pharmaceutically acceptable salt thereof,

wherein W 2 is

19 . The compound of claim 17 , or a pharmaceutically acceptable salt thereof, wherein R 1 is independently selected from H, F, Cl, ═O, OCH 2 CF 3 , OCH 3 , OCH 2 CH 3 , C(CH 3 ) 2 CN, tetrahydrofuran optionally substituted with cyclopropyl.

20 . The compound of claim 17 , or a pharmaceutically acceptable salt thereof, wherein R 6 is H, CH 3 , C(O)CH 2 CH 3 , C(O)N(CH 3 ) 2 , C(O)CH 3 , C(O)OC(CH 3 ) 3 , S(O) 2 CH 3 , C(O)OCH 2 CH 3 , C(O)OCH 2 CH 3 , C(O)cyclopropyl, or C(O)OCH 3 .

21 . The compound of claim 2 , of formula Ie:

or a pharmaceutically acceptable salt thereof, wherein

R 1 is independently selected from H, halogen, ═O, OH, CH 3 , CF 3 , OCH 3 , CH 2 CH 3 , CH(CH 3 )CN, CH 2 CF 3 , OCH 2 CF 3 , OCH 2 CH 3 , OCH 2 CF 3 , CH(CH 3 )OCH 3 , CH(CH 3 ) 2 , C(CH 3 ) 2 CN, cyclopropyl, tetrahydrofuran, triazole, thiazole or pyrazole, wherein the cyclopropyl or tetrahydrofuran are optionally substituted with one to three substituents independently selected from halogen, CH 3 , CN, cyclopropyl, or ═O, or wherein the triazole, thiazole or pyrazole are optionally substituted with one to three substituents independently selected from halogen, CH 3 , CN or cyclopropyl;

p is 0 or 1;

R 6 is H, C 1-6 alkyl, C(O)C 1-6 alkyl, C(O)C 1-6 cycloalkyl, C(O)OC 1-6 alkyl, C(O)N(C 1-6 alkyl) 2 , or S(O) 2 C 1-6 alkyl;

R 7 is H or ═O;

R 9 is H, halogen or CH 3 ; and

R 2 is independently selected from H or CH 3 .

22 . The compound of claim 21 , or a pharmaceutically acceptable salt thereof, wherein

R 1 is independently selected from H, F, CI, OCH 2 CF 3 , CHF 2 , OCHF 2 , OCH 3 , OCH 2 CH 3 , or C(CH 3 ) 2 CN,

R 7 is H,

p is 1, and

R 6 is H, CH 3 , C(O)CH 2 CH 3 , C(O)N(CH 3 ) 2 , C(O)CH 3 , C(O)OC(CH 3 ) 3 , S(O) 2 CH 3 , C(O)OCH 2 CH 3 , C(O)OCH 2 CH 3 , C(O)cyclopropyl, or C(O)OCH 3 .

23 . The compound of claim 2 , of formula Ig:

or a pharmaceutically acceptable salt thereof, wherein

R 6 is H, C(O)CH 3 or C(O)OC(CH 3 ) 3 .

24 . The compound of claim 2 , of formula Ih:

or a pharmaceutically acceptable salt thereof, wherein

R 1 is H or F;

R 6 is H or C(O)CH 3 .

25 . The compound of claim 2 , of formula Ij:

or a pharmaceutically acceptable salt thereof, wherein

X 1 is independently selected from N or CR 1 , provided no more than one X 1 is N;

R 1 is independently selected from H, halogen, ═O, OH, CH 3 , CF 3 , OCH 3 , CH 2 CH 3 , CH(CH 3 )CN, CH 2 CF 3 , OCH 2 CF 3 , OCH 2 CH 3 , OCH 2 CF 3 , CH(CH 3 )OCH 3 , CH(CH 3 ) 2 , C(CH 3 ) 2 CN, cyclopropyl, tetrahydrofuran, triazole, thiazole or pyrazole, wherein the cyclopropyl or tetrahydrofuran are optionally substituted with one to three substituents independently selected from halogen, CH 3 , CN, cyclopropyl, or ═O, or wherein the triazole, thiazole or pyrazole are optionally substituted with one to three substituents independently selected from halogen, CH 3 , CN or cyclopropyl; and

R 2 is independently selected from H or CH 3 .

26 . The compound of claim 25 , or a pharmaceutically acceptable salt thereof, wherein R 1 is independently selected from H, F, Cl, ═O, OCH 2 CF 3 , OCHF 2 , OCH 3 , OCH 2 CH 3 , C(CH 3 ) 2 CN, or tetrahydrofuran optionally substituted with cyclopropyl.

27 . The compound of claim 2 , of formula Ik:

or a pharmaceutically acceptable salt thereof, wherein

R 1 is H or CH 2 CF 3 ;

R 9 is H, halogen or CH 3 ; and

R 2 is independently selected from H or CH 3 .

28 . The compound of claim 2 , of formula Im:

or a pharmaceutically acceptable salt thereof, wherein

R 1 is H or OCH 2 CH 3 ,

R 2 is H,

R 3 is H or deuterium, and

R 9 is H, halogen, or CH 3 .

29 . The compound of claim 2 , of formula In:

or a pharmaceutically acceptable salt thereof, wherein

X 1 is independently selected from N or CR 1 , provided no more than one X 1 is N, and

R 1 is H or halogen.

30 . A compound or a pharmaceutically acceptable salt thereof, which is:

(6-Bromoimidazo [1,2-a]pyridin-2-yl)((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)methanone,

(6-Bromoimidazo [1,2-a]pyridin-2-yl)((3R,4R)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)methanone,

((3S,4S)-3-hydroxy-4-(6-methyl-3,4-dihydroisoquinolin-2 (1H)-yl)piperidin-1-yl)(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)methanone,

((3R,4R)-3-hydroxy-4-(6-methyl-3,4-dihydroisoquinolin-2 (1H)-yl)piperidin-1-yl)(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)methanone,

1-(-4-((4-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)pyridin-2-yl)amino)-3,3-difluoropiperidin-1-yl)ethan-1-one,

1-(-4-((4-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)pyridin-2-yl)amino)-3,3-difluoropiperidin-1-yl)ethan-1-one,

1-(-4-((4-((3R,4R)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)pyridin-2-yl)amino)-3,3-difluoropiperidin-1-yl)ethan-1-one,

1-(-4-((4-((3R,4R)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)pyridin-2-yl)amino)-3,3-difluoropiperidin-1-yl)ethan-1-one,

6-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-2-ethyl-2H-benzo[b][1,4]oxazin-3 (4H)-one,

6-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-2-ethyl-2H-benzo[b][1,4]oxazin-3 (4H)-one,

6-((3R,4R)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-2-ethyl-2H-benzo[b][1,4]oxazin-3 (4H)-one,

6-((3R,4R)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-2-ethyl-2H-benzo[b][1,4]oxazin-3 (4H)-one,

1-(-4-((4-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-3-fluoropyridin-2-yl)amino)-3,3-difluoropiperidin-1-yl)ethan-1-one,

1-(-4-((4-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-3-fluoropyridin-2-yl)amino)-3,3-difluoropiperidin-1-yl)ethan-1-one,

1-(-4-((4-((3R,4R)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-3-fluoropyridin-2-yl)amino)-3,3-difluoropiperidin-1-yl)ethan-1-one,

1-(-4-((4-((3R,4R)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-3-fluoropyridin-2-yl)amino)-3,3-difluoropiperidin-1-yl)ethan-1-one,

1-(4-((4-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-3-fluoropyridin-2-yl)amino)piperidin-1-yl)ethan-1-one,

1-(4-((4-((3R,4R)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-3-fluoropyridin-2-yl)amino)piperidin-1-yl)ethan-1-one,

1-(4-((4-(4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxy-2-methylpiperidine-1-carbonyl)pyridin-2-yl)amino)piperidin-1-yl)ethan-1-one,

1-(4-((4-(4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxy-2-methylpiperidine-1-carbonyl)pyridin-2-yl)amino)piperidin-1-yl)ethan-1-one,

1-(4-((4-(4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxy-2,2-dimethylpiperidine-1-carbonyl)pyridin-2-yl)amino)piperidin-1-yl)ethan-1-one,

1-(4-((4-(4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxy-2,2-dimethylpiperidine-1-carbonyl)pyridin-2-yl)amino)piperidin-1-yl)ethan-1-one,

1-(4-((4-(-4-(4,4-difluoro-3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-5-fluoropyridin-2-yl)amino)piperidin-1-yl)ethan-1-one,

1-(4-((5-chloro-4-(-4-(4,4-difluoro-3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)pyridin-2-yl)amino)piperidin-1-yl)ethan-1-one,

(-4-(4,4-difluoro-3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)methanone,

1-(4-((5-fluoro-4-(-4-(4,4-difluoro-3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)pyridin-2-yl)amino)piperidin-1-yl)ethan-1-one,

1-(4-((5-chloro-4-(-4-(4,4-difluoro-3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)pyridin-2-yl)amino)piperidin-1-yl)ethan-1-one,

(-4-(4,4-difluoro-3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)methanone,

1-{4-[(4-{[(1R,4R)-5-(3,4-dihydroisoquinolin-2 (1H)-yl)-6-hydroxy-2-azabicyclo[2.2.1]hept-2-yl]carbonyl}-5-fluoropyridin-2-yl)amino]piperidin-1-yl}ethenone,

4-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-1-(2,2,2-trifluoroethyl)pyridin-2(1H)-one,

4-((3R,4R)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-1-(2,2,2-trifluoroethyl)pyridin-2(1H)-one,

(4-(3-oxa-8-azabicyclo[3.2.1]octane-8-carbonyl)-2-ethoxyphenyl)((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)methanone,

(4-(3-oxa-8-azabicyclo[3.2.1]octane-8-carbonyl)-2-ethoxyphenyl)((3R,4R)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)methanone,

(4-(3-oxa-8-azabicyclo[3.2.1]octane-8-carbonyl)phenyl)((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)methanone,

(4-(3-oxa-8-azabicyclo[3.2.1]octane-8-carbonyl)phenyl)((3R,4R)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)methanone,

(4-(3-oxa-8-azabicyclo[3.2.1]octane-8-carbonyl)phenyl)((3S,4S)-4-(5-fluoro-3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)methanone,

(4-(3-oxa-8-azabicyclo[3.2.1]octane-8-carbonyl)phenyl)((3R,4R)-4-(5-fluoro-3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)methanone,

(4-(3-oxa-8-azabicyclo[3.2.1]octane-8-carbonyl)phenyl)((3S,4S)-4-(6-fluoro-3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)methanone,

(4-(3-oxa-8-azabicyclo[3.2.1]octane-8-carbonyl)phenyl)((3R,4R)-4-(6-fluoro-3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)methanone,

(4-(3-oxa-8-azabicyclo[3.2.1]octane-8-carbonyl)phenyl)((3S,4S)-4-(7-fluoro-3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)methanone,

(4-(3-oxa-8-azabicyclo[3.2.1]octane-8-carbonyl)phenyl)((3R,4R)-4-(7-fluoro-3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)methanone,

((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)methanone,

((3R,4R)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)methanone,

((3R,4R or 3S,4S)-3-hydroxy-4-(7-methyl-3,4-dihydroisoquinolin-2 (1H)-yl)piperidin-1-yl)(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)methanone,

((3S,4S or 3R,4R)-3-hydroxy-4-(7-methyl-3,4-dihydroisoquinolin-2 (1H)-yl)piperidin-1-yl)(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)methanone,

1-{4-[(5-chloro-4-{[(3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl]carbonyl}pyridin-2-yl)amino]piperidin-1-yl}ethenone,

((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)(5-(2,2,2-trifluoroethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-yl)methanone,

(6-bromo-8-ethoxyimidazo [1,2-a]pyrazin-2-yl)((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)methanone,

(2-(difluoromethyl)pyridin-4-yl)((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)methanone,

(2-(difluoromethoxy)pyridin-4-yl)((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)methanone,

[(3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl][6-(2,4-dimethyl-1,3-thiazol-5-yl)imidazo [1,2-a]pyrimidin-2-yl]methanone,

[(3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl][6-(1-methyl-1H-pyrazol-5-yl)imidazo [1,2-a]pyrimidin-2-yl]methanone,

[(3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl]{8-[(1R)-1-methoxyethyl]-6-(propan-2-yl)imidazo [1,2-a]pyridin-2-yl}methanone,

[(3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl]{8-[(1R)-1-methoxyethyl]-6-methylimidazo [1,2-a]pyridin-2-yl}methanone,

(4-(1-cyclopropyl-1H-1,2,4-triazol-5-yl)phenyl)((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)methanone,

(4-(1-cyclopropyl-1H-1,2,4-triazol-5-yl)phenyl)((3R,4R)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)methanone,

8-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-4-isopropyl-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diazepin-5-one,

(3-cyclopropyl-4-hydroxyquinolin-7-yl)((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)methanone,

8-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-4-ethyl-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diazepin-5-one,

8-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-4-(tetrahydrofuran-3-yl)-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diazepin-5-one,

(6-bromo-5-methylimidazo [1,2-a]pyrimidin-2-yl)((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)methanone,

(6-bromo-7-methylimidazo [1,2-a]pyrimidin-2-yl)((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)methanone,

(6-bromo-8-((R or S)-1-methoxyethyl)imidazo [1,2-a]pyridin-2-yl)((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)methanone,

(6-bromo-7-methoxyimidazo [1,2-a]pyrimidin-2-yl)((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)methanone,

(6-bromo-7-hydroxyimidazo [1,2-a]pyrimidin-2-yl)((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)methanone,

(6-bromoimidazo [1,2-a]pyrimidin-2-yl)[(3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl]methanone,

[(3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl](6-methylimidazo [1,2-a]pyrimidin-2-yl)methanone,

(6-bromo-7-methylimidazo [1,2-a]pyrimidin-3-yl)[(3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl]methanone,

(6-bromo-5-methylimidazo [1,2-a]pyrimidin-3-yl)[(3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl]methanone,

2-{2-[(3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl]imidazo [1,2-a]pyrimidin-6-yl}propanenitrile,

(6-bromo-7-cyclopropylimidazo [1,2-a]pyrimidin-2-yl)[(3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl]methanone,

[6-bromo-7-(propan-2-yl)imidazo [1,2-a]pyrimidin-2-yl][(3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl]methanone,

2-cyclopropyl-6-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-2H-benzo[b][1,4]oxazin-3 (4H)-one,

2-cyclopropyl-6-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-2H-benzo[b][1,4]oxazin-3 (4H)-one,

((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl) (-6-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo [1,2-a]pyridin-2-yl)methanone,

((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl) (-6-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo [1,2-a]pyridin-2-yl)methanone,

6-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-2-(-5,5-dimethyltetrahydrofuran-3-yl)-2H-benzo[b][1,4]oxazin-3 (4H)-one,

6-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-2-(-5,5-dimethyltetrahydrofuran-3-yl)-2H-benzo[b][1,4]oxazin-3 (4H)-one,

1-(4-((4-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-5-fluoropyridin-2-yl)amino)-3,3-difluoropiperidin-1-yl)ethan-1-one,

1-(4-((4-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-5-fluoropyridin-2-yl)amino)-3,3-difluoropiperidin-1-yl)ethan-1-one,

1-(4-((4-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-5-methoxypyridin-2-yl)amino)piperidin-1-yl)ethan-1-one,

2-(5-{[(3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl]carbonyl}pyridin-2-yl)-2-methylpropanenitrile,

2-(5-{[(3R,4R)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl]carbonyl}pyridin-2-yl)-2-methylpropanenitrile,

7-((3R,4R)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-4-methyl-1,4-dihydro-2H-benzo[d][1,3]oxazin-2-one,

7-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-4-methyl-1,4-dihydro-2H-benzo[d][1,3]oxazin-2-one,

7-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-4-methyl-1,4-dihydro-2H-benzo[d][1,3]oxazin-2-one,

7-((3R,4R)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-4-methyl-1,4-dihydro-2H-benzo[d][1,3]oxazin-2-one,

7-((3R,4R)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-4,4-dimethyl-3,4-dihydroquinolin-2 (1H)-one,

7-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-4,4-dimethyl-3,4-dihydroquinolin-2 (1H)-one,

7-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-4,4-dimethyl-1,4-dihydro-2H-benzo[d][1,3]oxazin-2-one,

7-((3R,4R)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-4,4-dimethyl-1,4-dihydro-2H-benzo[d][1,3]oxazin-2-one,

7-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-6-fluoro-4-methyl-1,4-dihydro-2H-benzo[d][1,3]oxazin-2-one,

7-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-6-fluoro-4-methyl-1,4-dihydro-2H-benzo[d][1,3]oxazin-2-one,

6-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-2,2-dimethyl-2H-benzo[b][1,4]oxazin-3 (4H)-one,

8-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-4-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diazepin-5-one,

tert-butyl-3-((4-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-5-fluoropyridin-2-yl)amino)-8-azabicyclo[3.2.1]octane-8-carboxylate,

((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)(5-fluoro-2-((1-(methylsulfonyl)piperidin-4-yl)amino)pyridin-4-yl)methanone,

ethyl 4-((4-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-5-fluoropyridin-2-yl)amino)piperidine-1-carboxylate,

1-(4-((4-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-5-ethoxypyridin-2-yl)amino)piperidin-1-yl)ethan-1-one,

(2-((1-(cyclopropanecarbonyl)piperidin-4-yl)amino)-5-fluoropyridin-4-yl)((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)methanone,

methyl 4-((4-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-5-fluoropyridin-2-yl)amino)piperidine-1-carboxylate,

4-((4-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-5-fluoropyridin-2-yl)amino)-N,N-dimethylpiperidine-1-carboxamide,

1-(4-((4-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-5-fluoropyridin-2-yl)amino)piperidin-1-yl) propan-1-one,

4-((4-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-5-fluoropyridin-2-yl)amino)-1-methylpiperidin-2-one,

1-(-3-((4-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-5-fluoropyridin-2-yl)amino) pyrrolidin-1-yl)ethan-1-one,

1-(-3-((4-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-5-fluoropyridin-2-yl)amino) pyrrolidin-1-yl)ethan-1-one,

7-[(4-{[(3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl]carbonyl}-5-fluoropyridin-2-yl)amino]hexahydroindolizin-3 (2H)-one,

7-[(4-{[(3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl]carbonyl}-5-fluoropyridin-2-yl)amino]hexahydroindolizin-3 (2H)-one,

7-[(4-{[(3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl]carbonyl}-5-fluoropyridin-2-yl)amino]hexahydroindolizin-3 (2H)-one,

7-[(4-{[(3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl]carbonyl}-5-fluoropyridin-2-yl)amino]hexahydroindolizin-3 (2H)-one,

1-(5-((4-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-5-fluoropyridin-2-yl)amino)-2-azabicyclo[2.2.1]heptan-2-yl)ethan-1-one,

1-(5-((4-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-5-fluoropyridin-2-yl)amino)-2-azabicyclo[2.2.1]heptan-2-yl)ethan-1-one,

(2-((8-azabicyclo[3.2.1]octan-3-yl)amino)-5-fluoropyridin-4-yl)((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)methanone,

1-(3-((4-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-5-fluoropyridin-2-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)ethan-1-one,

1-((S)-3-(((4-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-5-fluoropyridin-2-yl)amino)methyl) pyrrolidin-1-yl)ethan-1-one,

1-((1R,5S)-8-((4-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)-5-fluoropyridin-2-yl)amino)-3-azabicyclo[3.2.1]octan-3-yl)ethan-1-one,

1-(2-((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidine-1-carbonyl)imidazo [1,2-a]pyridin-6-yl) cyclopropane-1-carbonitrile,

((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)(4-hydroxy-3-(2,2,2-trifluoroethyl) quinolin-7-yl)methanone,

1-(2-{[(3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl]carbonyl}imidazo [1,2-a]pyrimidin-6-yl)-2,2-dimethylcyclopropanecarbonitrile,

1-(2-{[(3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl]carbonyl}imidazo [1,2-a]pyrimidin-6-yl)-2,2-dimethylcyclopropanecarbonitrile,

((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)(6-(2-methylcyclopropyl)imidazo [1,2-a]pyrimidin-2-yl)methanone,

((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)(6-(2-methylcyclopropyl)imidazo [1,2-a]pyrimidin-2-yl)methanone,

((3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl)(6-(2-methylcyclopropyl)imidazo [1,2-a]pyrimidin-2-yl)methanone,

(6-chloroimidazo [1,2-a]pyridin-2-yl)[(3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl]methanone,

(6-bromo-3-chloropyrazolo[1,5-a]pyrimidin-2-yl)[(3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl]methanone,

(8-bromo-6-methylimidazo [1,2-a]pyridin-2-yl)[(3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl]methanone,

(6-bromo-8-methylimidazo [1,2-a]pyridin-2-yl)[(3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl]methanone,

(8-chloro-6-methylimidazo [1,2-a]pyridin-2-yl)[(3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl]methanone,

[8-chloro-6-(trifluoromethyl)imidazo [1,2-a]pyridin-2-yl][(3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl]methanone,

(8-bromo-6-chloroimidazo [1,2-a]pyridin-2-yl)[(3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl]methanone,

(6-bromo-8-iodoimidazo [1,2-a]pyridin-2-yl)[(3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl]methanone,

(6,8-dichloroimidazo [1,2-a]pyridin-2-yl)[(3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl]methanone,

(6-bromo-8-fluoroimidazo [1,2-a]pyridin-2-yl)[(3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl]methanone,

(6,8-dibromoimidazo [1,2-a]pyridin-2-yl)[(3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl]methanone, or

(6-bromopyrazolo[1,5-a]pyrimidin-2-yl)[(3S,4S)-4-(3,4-dihydroisoquinolin-2 (1H)-yl)-3-hydroxypiperidin-1-yl]methanone.

31 . A composition for treating cancer comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically carrier.

32 . A method for treating a PRMT5 mediated cancer comprising administering to a patient in need thereof a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

Assignments (2)
MERGER Recorded Jun 10, 2022
From: MERCK SHARP & DOHME CORP.
To: MERCK SHARP & DOHME LLC
Reel/Frame 060157/0589 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 10, 2022
From: MACHACEK, MICHELLE; ALTMAN, MICHAEL D.; HUANG, CHINHUI; REUTERSHAN, MICHAEL H.; SLOMAN, DAVID L.; SILIPHAIVANH, PHIENG; SCHNEIDER, SEBASTIAN E.; YEUNG, CHARLES S.; WITTER, DAVID J.; GIBEAU, CRAIG R.; YE, YINGCHUN
To: MERCK SHARP & DOHME CORP.
Reel/Frame 060329/0608 →
Continuity (3)
Provisional Application 63025561 · May 15, 2020
Provisional Application 62949245 · Dec 17, 2019
Related Publication 20230108114A1 · Apr 6, 2023
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