IP Library › Granted Patent US 12,595,262
Granted Patent B2
US 12,595,262 · App. 17/787,113 · Granted Apr 7, 2026

PRMT5 inhibitors

Inventors: Michelle Machacek (Boston, MA); Michael D. Altman (Boston, MA); Chunhui Huang (Boston, MA); Michael H. Reutershan (Boston, MA); David L. Sloman (Boston, MA); David J. Witter (Toronto, CA); Craig R. Gibeau (Boston, MA)
Assignee: Merck Sharp & Dohme LLC
C07D487/04C07D401/14C07B2200/05
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Quick Facts
Patent No.
US 12,595,262
App. No.
17/787,113
Granted
Apr 7, 2026
Kind
B2
Abstract

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

Claims (20)

1 . A compound selected from:

or a pharmaceutically acceptable salt thereof.

2 . A compound of claim 1 selected from:

or a pharmaceutically acceptable salt thereof.

3 . A compound of claim 1 , which is:

or a pharmaceutically acceptable salt thereof.

4 . A compound of claim 1 , which is:

or a pharmaceutically acceptable salt thereof.

5 . A compound of claim 1 , which is:

or a pharmaceutically acceptable salt thereof.

6 . A compound of claim 1 , which is:

or a pharmaceutically acceptable salt thereof.

7 . The compound of claim 1 , which is: 1-{4-[(4-{[(3S,4S)-4-(3,4-dihydroisoquinolin-2(1H)-yl)-3-hydroxypiperidin-1-yl]carbonyl}-5-fluoropyridin-2-yl)amino]piperidin-1-yl}ethanone or a pharmaceutically acceptable salt thereof.

8 . The compound of claim 1 , which is: (6-(2,2-difluorocyclopropyl)imidazo[1,2-a]pyrimidin-2-yl)((3S,4S)-4-(3,4-dihydroisoquinolin-2(1H)-yl)-3-hydroxypiperidin-1-yl)methanone, or a pharmaceutically acceptable salt thereof.

9 . The compound of claim 1 , which is: (6-cyclopropylimidazo[1,2-a]pyrimidin-2-yl)((3S,4S)-4-(3,4-dihydroisoquinolin-2(1H)-yl)-3-hydroxypiperidin-1-yl)methanone, or a pharmaceutically acceptable salt thereof.

10 . The compound of claim 1 , which is: (6-bromo-7-ethylimidazo[1,2-a]pyrimidin-2-yl)((3S,4S)-4-(3,4-dihydroisoquinolin-2(1H)-yl)-3-hydroxypiperidin-1-yl)methanone, or a pharmaceutically acceptable salt thereof.

11 . A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

12 . The method for treating cancer comprising administering to a patient in need thereof a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

13 . The method for treating sickle cell disease comprising administering to a patient in need thereof a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

14 . The method for treating hereditary persistence of foetal hemoglobin (HPFH) mutations comprising administering to a patient in need thereof a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

Assignments (2)
MERGER AND CHANGE OF NAME Recorded Jun 17, 2022
From: MERCK SHARP & DOHME CORP; MERCK SHARP & DOHME LLC
To: MERCK SHARP & DOHME LLC
Reel/Frame 060241/0718 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 17, 2022
From: MACHACEK, MICHELLE; ALTMAN, MICHAEL D; HUANG, CHUNHUI; REUTERSHAN, MICHAEL H; SLOMAN, DAVID L.; WITTER, DAVID J; GIBEAU, CRAIG R.
To: MERCK SHARP & DOHME CORP
Reel/Frame 060455/0492 →
Continuity (4)
Provisional Application 63025629 · May 15, 2020
Provisional Application 62949242 · Dec 17, 2019
Provisional Application 62949248 · Dec 17, 2019
Related Publication 20230108452A1 · Apr 6, 2023
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