# US 12,595,248 B2 · PRMT5 inhibitors

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- Number: US 12,595,248 B2
- Document ID: US12595248B2
- Status: Granted
- Kind: B2
- Application number: 17/783,975
- Filed: 2020-12-14
- Published: 2023-04-06
- Granted: 2026-04-07
- Earliest claimed: 2019-12-17
- Assignees: Merck Sharp & Dohme Corp.
- Applicants: Merck Sharp & Dohme LLC
- Inventors: Michelle Machacek; Michael D. Altman; Chunghui Huang; Michael H. Reutershan; David L. Sloman; Phieng Siliphaivanh; Sebastian E. Schneider; Charles S. Yeung; David J. Witter; Craig R. Gibeau; Yingchun Ye
- Web page: https://patentgrep.com/patent/US12595248B2

## CPC

- C07D 401/14: containing three or more hetero rings
- A61P 35/00: Antineoplastic agents
- C07D 405/14: containing three or more hetero rings
- C07D 413/14: containing three or more hetero rings
- C07D 451/04: with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- C07D 471/04: Ortho-condensed systems
- C07D 471/08: Bridged systems
- C07D 487/04: Ortho-condensed systems
- C07D 498/08: Bridged systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## 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

### Claim 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 R2;
z1 is
when present, W1 is H, CHF2, NHW2, or OCHF2;
when present, W2 is
when present, R1 is independently selected from hydrogen, halogen, ═O, C1-6alkyl, OC0-6alkyl, C1-6alkylOC1-6alkyl, tetrahydrofuran, cyclopropyl, triazole, thiazole or pyrazole, wherein the C1-6alkyl, OC0-6alkyl, C1-6alkylOC1-6alkyl, tetrahydrofuran, or cyclopropyl are optionally substituted with one to three substituents independently selected from halogen, CH3, CN, cyclopropyl, or ═O, or wherein the triazole, thiazole or pyrazole are optionally substituted with one to three substituents independently selected from halogen, CH3, CN, or cyclopropyl;
when present, R2 is selected from H or CH3;
each R3 is selected from hydrogen or deuterium;
when present, R6 is H, C1-6alkyl, C(O)C1-6alkyl, C(O)OC1-6alkyl, C(O)C1-6cycloalkyl, C(O)N(C1-6alkyl)2, or S(O)2C1-6alkyl;
when present, R7 is H or ═O;
when present, R9 is H, halogen or CH3;
when present, Z4 is N while Z5 is C, or Z4 is C while Z5 is N;
when present, each X1 is selected from N or CR1, provided no more than one X1 is N;
when present, X2 is independently selected from O, C═O, CHR1, C(R1)2, or NR1, where two X2 in the same ring cannot both be NR1;
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:

### Claim 2

A compound of Formula Ii,
or a pharmaceutically acceptable salt thereof, wherein
Z1 is
when present, W1 is H, CHF2, NHW2, or OCHF2;
when present, W2 is
when present, R1 is independently selected from H, halogen, ═O, C1-6alkyl, OC0-6alkyl, C1-6alkylOC1-6alkyl, tetrahydrofuran, cyclopropyl, triazole, thiazole or pyrazole, wherein the C1-6alkyl, OC0-6alkyl, C1-6alkylOC1-6alkyl, tetrahydrofuran, or cyclopropyl are optionally substituted with one to three substituents independently selected from halogen, CH3, CN, cyclopropyl, or ═O, or wherein the triazole, thiazole or pyrazole are optionally substituted with one to three substituents independently selected from halogen, CH3, CN, or cyclopropyl,
when present, R2 is independently selected from H or CH3;
each R3 is selected from hydrogen or deuterium;
when present, R6 is H, C1-6alkyl, C(O)C1-6alkyl, C(O)C1-6cycloalkyl, C(O)OC1-6alkyl, C(O)N(C1-6alkyl)2, or S(O)2C1-6alkyl;
when present, R7 is H or ═O;
when present R9 is H, halogen, or CH3;
when present, Z4 is N while Z5 is C, or Z4 is C while Z5 is N;
when present, X1 is selected from N or CR1, provided no more than one X1 is N;
when present, X2 is independently selected from O, C═O, CHR1, C(R1)2, or NR1, where two X2 in the same ring cannot both be NR1;
when present, p is 0 or 1;
when present, t is 1 or 2; and
when present, q is 1 or 2.

### Claim 3 (depends on 2)

The compound of claim 2, of formula Ia:
or a pharmaceutically acceptable salt thereof, wherein
X2 is NR1 or C(R1)2;
R1 is independently selected from H, halogen, ═O, OH, CH3, CF3, OCH3, CH2CH3, CH(CH3)CN, CH2CF3, OCH2CF3, OCH2CH3, OCH2CF3, CH(CH3)OCH3, CH(CH3)2, C(CH3)2CN, cyclopropyl, tetrahydrofuran, triazole, thiazole or pyrazole, wherein the cyclopropyl or tetrahydrofuran are optionally substituted with one to three substituents independently selected from halogen, CH3, CN, cyclopropyl, or ═O, or wherein the triazole, thiazole or pyrazole are optionally substituted with one to three substituents independently selected from halogen, CH3, CN or cyclopropyl;
Z4 is N while Z5 is C, or Z4 is C while Z5 is N; and
R9 is H, halogen or CH3.

### Claim 4 (depends on 3)

The compound of claim 3, or a pharmaceutically acceptable salt thereof, wherein X2 is NR1 or C(R1)2.

### Claim 5 (depends on 3)

The compound of claim 3, or a pharmaceutically acceptable salt thereof, wherein Z4 is N and Z5 is C, or Z4 is C and Z5 is N.

### Claim 6 (depends on 2)

The compound of claim 2, of formula Ib:
or a pharmaceutically acceptable salt thereof, wherein
R1 is independently selected from H, halogen, OH, CH3, CF3, OCH3, CH2CH3, CH(CH3)CN, CH2CF3, OCH2CH3, OCH2CF3, CH(CH3)OCH3, CH(CH3)2, C(CH3)2CN, cyclopropyl, tetrahydrofuran, triazole, thiazole or pyrazole, wherein the cyclopropyl or tetrahydrofuran are optionally substituted with one to three substituents independently selected from halogen, CH3, CN, cyclopropyl, or ═O, or wherein the triazole, thiazole or pyrazole are optionally substituted with one to three substituents independently selected from halogen, CH3, CN or cyclopropyl; and
X1 is independently selected from N or CR1, provided no more than one X1 is N.

### Claim 7 (depends on 6)

The compound of claim 6, or a pharmaceutically acceptable salt thereof, wherein one X1 is N and two X1's are CR1, or wherein all three X1's are CR1.

### Claim 8 (depends on 2)

The compound of claim 2 of formula Ic:
or a pharmaceutically acceptable salt thereof, wherein
R1 is independently selected from H, halogen, ═O, OH, CH3, CF3, OCH3, CH2CH3, CH(CH3)CN, CH2CF3, OCH2CF3, OCH2CH3, OCH2CF3, CH(CH3)OCH3, CH(CH3)2, C(CH3)2CN, or cyclopropyl, tetrahydrofuran, triazole, thiazole or pyrazole, wherein the cyclopropyl or tetrahydrofuran are optionally substituted with one to three substituents independently selected from halogen, CH3, CN, cyclopropyl, or ═O, or wherein the triazole, thiazole or pyrazole are optionally substituted with one to three substituents independently selected from halogen, CH3, CN or cyclopropyl;
q is 1, or 2; and
X2 is independently selected from O, C═O, NR1, CHR1 or C(R1)2.

### Claim 9 (depends on 8)

The compound of claim 8, or a pharmaceutically acceptable salt thereof, wherein at least one X2 is O.

### Claim 10 (depends on 8)

The compound of claim 8, or a pharmaceutically acceptable salt thereof, wherein at least one X2 is NR1.

### Claim 11 (depends on 8)

The compound of claim 8, or a pharmaceutically acceptable salt thereof, wherein at least one X2 is C(R1)2.

### Claim 12 (depends on 8)

The compound of claim 8, or a pharmaceutically acceptable salt thereof, wherein at least one X2 is CHR1.

### Claim 13 (depends on 8)

The compound of claim 8, or a pharmaceutically acceptable salt thereof, wherein R1 is independently selected from H, CH3, CF3, CH2CH3, CH2CF3, ═O, or CH(CH3)2.

### Claim 14 (depends on 8)

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

### Claim 15 (depends on 2)

The compound of claim 2, of formula Id:
or a pharmaceutically acceptable salt thereof, wherein
R1 is independently selected from H, halogen, ═O, OH, CH3, CF3, OCH3, CH2CH3, CH(CH3)CN, CH2CF3, OCH2CF3, OCH2CH3, OCH2CF3, CH(CH3)OCH3, CH(CH3)2, C(CH3)2CN, cyclopropyl, tetrahydrofuran, triazole, thiazole or pyrazole, wherein the cyclopropyl or tetrahydrofuran are optionally substituted with one to three substituents independently selected from halogen, CH3, CN, cyclopropyl, or ═O, or wherein the triazole, thiazole or pyrazole are optionally substituted with one to three substituents independently selected from halogen, CH3, CN or cyclopropyl.

### Claim 16 (depends on 15)

The compound of claim 15, or a pharmaceutically acceptable salt thereof, wherein R1 is H, cyclopropyl, or CH2CF3.

### Claim 17 (depends on 2)

The compound of claim 2, of formula Ie:
or a pharmaceutically acceptable salt thereof, wherein
W1 is H, CHF2, NHW2, or OCHF2;
W2 is
X1 is independently selected from N or CR1, provided no more than one X1 is N;
R1 is independently selected from H, halogen, ═O, OH, CH3, CF3, OCH3, CH2CH3, CH(CH3)CN, CH2CF3, OCH2CF3, OCH2CH3, OCH2CF3, CH(CH3)OCH3, CH(CH3)2, C(CH3)2CN, cyclopropyl, tetrahydrofuran, triazole, thiazole or pyrazole, wherein the cyclopropyl or tetrahydrofuran are optionally substituted with one to three substituents independently selected from halogen, CH3, CN, cyclopropyl, or ═O, or wherein the triazole, thiazole or pyrazole are optionally substituted with one to three substituents independently selected from halogen, CH3, CN or cyclopropyl, R6 is H, C1-6alkyl, C(O)C1-6alkyl, C(O)C1-6cycloalkyl, C(O)OC1-6alkyl, C(O)N(C1-6alkyl)2, or S(O)2C1-6alkyl;
R7 is H or ═O;
R9 is H, halogen or CH3; and
R2 is independently selected from H or CH3.

### Claim 18 (depends on 17)

The compound of claim 17, or a pharmaceutically acceptable salt thereof,
wherein W2 is

### Claim 19 (depends on 17)

The compound of claim 17, or a pharmaceutically acceptable salt thereof, wherein R1 is independently selected from H, F, Cl, ═O, OCH2CF3, OCH3, OCH2CH3, C(CH3)2CN, tetrahydrofuran optionally substituted with cyclopropyl.

### Claim 20 (depends on 17)

The compound of claim 17, or a pharmaceutically acceptable salt thereof, wherein R6 is H, CH3, C(O)CH2CH3, C(O)N(CH3)2, C(O)CH3, C(O)OC(CH3)3, S(O)2CH3, C(O)OCH2CH3, C(O)OCH2CH3, C(O)cyclopropyl, or C(O)OCH3.

### Claim 21 (depends on 2)

The compound of claim 2, of formula Ie:
or a pharmaceutically acceptable salt thereof, wherein
R1 is independently selected from H, halogen, ═O, OH, CH3, CF3, OCH3, CH2CH3, CH(CH3)CN, CH2CF3, OCH2CF3, OCH2CH3, OCH2CF3, CH(CH3)OCH3, CH(CH3)2, C(CH3)2CN, cyclopropyl, tetrahydrofuran, triazole, thiazole or pyrazole, wherein the cyclopropyl or tetrahydrofuran are optionally substituted with one to three substituents independently selected from halogen, CH3, CN, cyclopropyl, or ═O, or wherein the triazole, thiazole or pyrazole are optionally substituted with one to three substituents independently selected from halogen, CH3, CN or cyclopropyl;
p is 0 or 1;
R6 is H, C1-6alkyl, C(O)C1-6alkyl, C(O)C1-6cycloalkyl, C(O)OC1-6alkyl, C(O)N(C1-6alkyl)2, or S(O)2C1-6alkyl;
R7 is H or ═O;
R9 is H, halogen or CH3; and
R2 is independently selected from H or CH3.

### Claim 22 (depends on 21)

The compound of claim 21, or a pharmaceutically acceptable salt thereof, wherein
R1 is independently selected from H, F, CI, OCH2CF3, CHF2, OCHF2, OCH3, OCH2CH3, or C(CH3)2CN,
R7 is H,
p is 1, and
R6 is H, CH3, C(O)CH2CH3, C(O)N(CH3)2, C(O)CH3, C(O)OC(CH3)3, S(O)2CH3, C(O)OCH2CH3, C(O)OCH2CH3, C(O)cyclopropyl, or C(O)OCH3.

### Claim 23 (depends on 2)

The compound of claim 2, of formula Ig:
or a pharmaceutically acceptable salt thereof, wherein
R6 is H, C(O)CH3 or C(O)OC(CH3)3.

### Claim 24 (depends on 2)

The compound of claim 2, of formula Ih:
or a pharmaceutically acceptable salt thereof, wherein
R1 is H or F;
R6 is H or C(O)CH3.

### Claim 25 (depends on 2)

The compound of claim 2, of formula Ij:
or a pharmaceutically acceptable salt thereof, wherein
X1 is independently selected from N or CR1, provided no more than one X1 is N;
R1 is independently selected from H, halogen, ═O, OH, CH3, CF3, OCH3, CH2CH3, CH(CH3)CN, CH2CF3, OCH2CF3, OCH2CH3, OCH2CF3, CH(CH3)OCH3, CH(CH3)2, C(CH3)2CN, cyclopropyl, tetrahydrofuran, triazole, thiazole or pyrazole, wherein the cyclopropyl or tetrahydrofuran are optionally substituted with one to three substituents independently selected from halogen, CH3, CN, cyclopropyl, or ═O, or wherein the triazole, thiazole or pyrazole are optionally substituted with one to three substituents independently selected from halogen, CH3, CN or cyclopropyl; and
R2 is independently selected from H or CH3.

### Claim 26 (depends on 25)

The compound of claim 25, or a pharmaceutically acceptable salt thereof, wherein R1 is independently selected from H, F, Cl, ═O, OCH2CF3, OCHF2, OCH3, OCH2CH3, C(CH3)2CN, or tetrahydrofuran optionally substituted with cyclopropyl.

### Claim 27 (depends on 2)

The compound of claim 2, of formula Ik:
or a pharmaceutically acceptable salt thereof, wherein
R1 is H or CH2CF3;
R9 is H, halogen or CH3; and
R2 is independently selected from H or CH3.

### Claim 28 (depends on 2)

The compound of claim 2, of formula Im:
or a pharmaceutically acceptable salt thereof, wherein
R1 is H or OCH2CH3,
R2 is H,
R3 is H or deuterium, and
R9 is H, halogen, or CH3.

### Claim 29 (depends on 2)

The compound of claim 2, of formula In:
or a pharmaceutically acceptable salt thereof, wherein
X1 is independently selected from N or CR1, provided no more than one X1 is N, and
R1 is H or halogen.

### Claim 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.

### Claim 31 (depends on 1)

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

### Claim 32 (depends on 1)

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.