IP Library › Granted Patent US 12,435,090
Granted Patent B2
US 12,435,090 · App. 17/937,977 · Granted Oct 7, 2025

Compounds, pharmaceutical compositions, and methods of preparing compounds and of their use

Inventors: Janek Szychowski (Montreal, CA); Bingcan Liu (Montreal, CA); Evelyne Dietrich (Laval, CA); Frédéric Vallée (Montreal, CA); Alexander Perryman (Pointe-Claire, CA); Jean-François Truchon (Saint-Laurent, CA); Robert Papp (St-Laurent, CA); Patrick Beaulieu (Saint-Romuald, CA); Vouy Linh Truong (Pierrefonds, CA); Kaveh Matinkhoo (Montreal, CA); Sheldon N. Crane (Notre Dame de l'Ile Perrot, CA)
Assignee: Repare Therapeutics Inc.
C07D487/04C07D209/12C07D471/04
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Quick Facts
Patent No.
US 12,435,090
App. No.
17/937,977
Granted
Oct 7, 2025
Kind
B2
Abstract

Disclosed are compounds and pharmaceutically acceptable salts thereof that may be used in the treatment of subjects in need thereof. The compounds disclosed herein may be inhibitors of tyrosine and threonine-specific cdc2-inhibitory kinase (Myt1). Also disclosed are pharmaceutical compositions containing the compounds or pharmaceutically acceptable salts thereof and methods of their preparation and use.

Claims (45)

1. A compound of formula (I):

or a pharmaceutically acceptable salt thereof,

wherein

each is a single or double bond;

one, two, or three X groups are N, and the remaining X groups are C;

each Y is independently N or CR 2 ;

each Z is independently N or CH;

R 1 is OH, and R 3 is optionally substituted C 3-8 cycloalkyl;

or R 1 and R 3 combine to form —CR 9 ═N—NH—;

each R 2 is independently hydrogen, optionally substituted C 1-6 alkyl, optionally substituted C 2-6 alkenyl, optionally substituted C 2-6 alkynyl, optionally substituted C 3-8 cycloalkyl, optionally substituted C 3-8 cycloalkenyl, optionally substituted C 2-9 heterocyclyl, optionally substituted C 2-9 heterocyclyl C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-9 heteroaryl, optionally substituted C 1-9 heteroaryl C 1-6 alkyl, halogen, cyano, —N(R 7 ) 2 , —OR 7 , —C(O)N(R 8 ) 2 , —SO 2 N(R 8 ) 2 , —SO 2 R 7A , or -Q-R 7B ;

R 4 is independently hydrogen, optionally substituted C 1-6 alkyl, or halogen;

R 5 is hydrogen, halogen, or —N(R 7 ) 2 ;

R 6 is —C(O)NH(R 8 ) or —C(O)R 7A ;

each R 7 is independently hydrogen, optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl C 1-6 alkyl, optionally substituted C 3-8 cycloalkyl, optionally substituted C 6-10 aryl, optionally substituted C 2-9 heterocyclyl, optionally substituted C 1-9 heteroaryl, optionally substituted C 1-9 heteroaryl C 1-6 alkyl, or —SO 2 R 7A ; or two R 7 groups, together with the atom to which both are attached, combine to form an optionally substituted C 2-9 heterocyclyl;

each R 7A is independently optionally substituted C 1-6 alkyl or optionally substituted C 3-8 cycloalkyl;

each R 7B is independently hydroxyl, optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 2-9 heterocyclyl, optionally substituted C 1-9 heteroaryl, —N(R 7 ) 2 , —C(O)N(R 8 ) 2 , —SO 2 N(R 8 ) 2 , —SO 2 R 7A , or optionally substituted alkoxy;

each R 8 is independently hydrogen, optionally substituted C 1-6 alkyl, optionally substituted C 2-6 alkoxyalkyl, optionally substituted C 6-10 aryl C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 3-8 cycloalkyl, or optionally substituted C 1-9 heteroaryl; or two R 8 , together with the atom to which they are attached, combine to form an optionally substituted C 2-9 heterocyclyl;

R 9 is hydrogen or halogen; and

Q is optionally substituted C 1-6 alkylene, optionally substituted C 2-6 alkenylene, optionally substituted C 2-6 alkynylene, optionally substituted C 3-8 cycloalkylene, optionally substituted C 3-8 cycloalkenylene optionally substituted C 6-10 arylene, optionally substituted C 2-9 heterocyclylene, or optionally substituted C 1-9 heteroarylene.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein one X group is N, and the remaining X groups are C.

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein zero, one, or two Y groups are N, and the remaining Y groups are CR 2 .

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is OH or R 1 and R 3 combine to form —CH═N—NH—.

5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 6 is —C(O)NH(R 8 ) or —C(O)NH 2 .

6. A pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

7. A compound of formula (II):

or a pharmaceutically acceptable salt thereof,

wherein

each is a single or double bond;

each Y is independently N or CR 2 ;

each Z is independently N or CH;

R 1 is OH, and R 3 is optionally substituted C 3-8 cycloalkyl;

or R 1 and R 3 combine to form —CR 9 ═N—NH—;

each R 2 is independently hydrogen, optionally substituted C 1-6 alkyl, optionally substituted C 2-6 alkenyl, optionally substituted C 2-6 alkynyl, optionally substituted C 3-8 cycloalkyl, optionally substituted C 3-8 cycloalkenyl, optionally substituted C 2-9 heterocyclyl, optionally substituted C 2-9 heterocyclyl C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-9 heteroaryl, optionally substituted C 1-9 heteroaryl C 1-6 alkyl, halogen, cyano, —N(R 7 ) 2 , —OR 7 , —C(O)N(R 8 ) 2 , —SO 2 N(R 8 ) 2 , —SO 2 R 7A , or -Q-R 7B ;

R 4 is independently hydrogen, optionally substituted C 1-6 alkyl, or halogen;

R 5 is hydrogen, halogen, or —N(R 7 ) 2 ;

R 6 is —C(O)NH(R 8 ), —C(O)R 7A , or —SO 2 R 7A ;

each R 7 is independently hydrogen, optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl C 1-6 alkyl, optionally substituted C 3-8 cycloalkyl, optionally substituted C 6-10 aryl, optionally substituted C 2-9 heterocyclyl, optionally substituted C 1-9 heteroaryl, optionally substituted C 1-9 heteroaryl C 1-6 alkyl, or —SO 2 R 7A ; or two R 7 groups, together with the atom to which both are attached, combine to form an optionally substituted C 2-9 heterocyclyl;

each R 7A is independently optionally substituted C 1-6 alkyl or optionally substituted C 3-8 cycloalkyl;

each R 7B is independently hydroxyl, optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 2-9 heterocyclyl, optionally substituted C 1-9 heteroaryl, —N(R 7 ) 2 , —C(O)N(R 8 ) 2 , —SO 2 N(R 8 ) 2 , —SO 2 R 7A , or optionally substituted alkoxy;

each R 8 is independently hydrogen, optionally substituted C 1-6 alkyl, optionally substituted C 2-6 alkoxyalkyl, optionally substituted C 6-10 aryl C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 3-8 cycloalkyl, or optionally substituted C 1-9 heteroaryl; or two R 8 , together with the atom to which they are attached, combine to form an optionally substituted C 2-9 heterocyclyl;

R 9 is hydrogen or halogen; and

Q is optionally substituted C 1-6 alkylene, optionally substituted C 2-6 alkenylene, optionally substituted C 2-6 alkynylene, optionally substituted C 3-8 cycloalkylene, optionally substituted C 3-8 cycloalkenylene optionally substituted C 6-10 arylene, optionally substituted C 2-9 heterocyclylene, or optionally substituted C 1-9 heteroarylene.

8. The compound of claim 7 , or a pharmaceutically acceptable salt thereof, wherein the compound is enriched for the atropisomer of formula (II-i):

9. The compound of claim 7 , or a pharmaceutically acceptable salt thereof, wherein the compound is of formula (IIB):

10. The compound of claim 9 , or a pharmaceutically acceptable salt thereof, wherein the compound is enriched for the atropisomer of (IIB-i):

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 26, 2022
From: SZYCHOWSKI, JANEK; LIU, BINGCAN; DIETRICH, EVELYNE; VALLÉE, FRÉDÉRIC; PERRYMAN, ALEXANDER; TRUCHON, JEAN-FRANÇOIS; PAPP, ROBERT; BEAULIEU, PATRICK; TRUONG, VOUY LINH; MATINKHOO, KAVEH; CRANE, SHELDON N.
To: REPARE THERAPEUTICS INC.
Reel/Frame 061547/0389 →
Continuity (3)
Provisional Application 63252961 · Oct 6, 2021
Provisional Application 63251942 · Oct 4, 2021
Related Publication 20230122909A1 · Apr 20, 2023
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