# US 11,999,713 B2 · Methionine adenosyltransferase 2a (MAT2A) inhibitors and uses thereof

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- Number: US 11,999,713 B2
- Document ID: US11999713B2
- Status: Granted
- Kind: B2
- Application number: 18/509,658
- Filed: 2023-11-15
- Published: 2024-04-25
- Granted: 2024-06-04
- Earliest claimed: 2021-10-20
- Assignees: Insilico Medicine IP Limited
- Applicants: Insilico Medicine IP Limited
- Inventors: Chiachun Chen; Xiao Ding; Xiaosong Liu; Feng Ren; Hailong Wang
- Web page: https://patentgrep.com/patent/US11999713B2

## CPC

- A61P 35/00: Antineoplastic agents
- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- A61K 31/517: ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- C07D 239/95: with hetero atoms directly attached in positions 2 and 4
- C07D 403/04: directly linked by a ring-member-to-ring-member bond
- C07D 413/14: containing three or more hetero rings
- C07D 471/04: Ortho-condensed systems
- C07D 487/04: Ortho-condensed systems
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

Described herein are MAT2A inhibitors and pharmaceutical compositions comprising said inhibitors. The subject compounds and compositions are useful for the treatment of a disease or disorder associated with MAT2A.

## Claims

### Claim 1

A compound of Formula (I) or Formula (II), or a pharmaceutically acceptable salt thereof:
wherein:
is selected from pyridyl, pyrazinyl, pyrimidyl, and pyridazinyl;
Z1 is CR7;
Z2 is CR9;
Z3 is CR6;
Z4 is CR6a;
X is —N(R4)—;
Y is —N(R4a);
R1 is hydrogen;
R1a and R1b are hydrogen;
R2 and R3 are each independently selected from hydrogen and C1-6alkyl;
or R2 and R3, together with the carbon to which they are attached, form a C3-6cycloalkyl;
R4 is hydrogen;
R4a is hydrogen;
R6 is selected from hydrogen, halogen, and —OR10;
R6a is selected from hydrogen and —OR10;
R7 is hydrogen;
R8 is selected from hydrogen, halogen, and C1-6haloalkyl;
R9 is hydrogen;
each R10 is independently selected from hydrogen, C1-6alkyl, and C1-6haloalkyl;
each R14 is independently C1-6alkyl;
m is 0, 1, or 2; and
n is 1.

### Claim 2 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R10 is C1-6alkyl.

### Claim 3 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R2 is hydrogen and R3 is hydrogen.

### Claim 4 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R2 and R3, together with the carbon to which they are attached, form a C3-6cycloalkyl.

### Claim 5 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, having the structure of Formula (Ia):

### Claim 6 (depends on 1)

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

### Claim 7 (depends on 1)

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

### Claim 8 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R8 is halogen or C1-6haloalkyl.

### Claim 9 (depends on 1)

The compound of claim 1 selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.

### Claim 10 (depends on 1)

The compound of claim 1 that is
or a pharmaceutically acceptable salt thereof.

### Claim 11 (depends on 1)

The compound of claim 1 that is
or a pharmaceutically acceptable salt thereof.

### Claim 12 (depends on 1)

The compound of claim 1 that is
or a pharmaceutically acceptable salt thereof.

### Claim 13 (depends on 1)

The compound of claim 1 that is
or a pharmaceutically acceptable salt thereof.

### Claim 14 (depends on 1)

The compound of claim 1 that is
or a pharmaceutically acceptable salt thereof.

### Claim 15 (depends on 1)

The compound of claim 1 that is
or a pharmaceutically acceptable salt thereof.

### Claim 16 (depends on 1)

The compound of claim 1 that is
or a pharmaceutically acceptable salt thereof.

### Claim 17 (depends on 1)

The compound of claim 1 that is
or a pharmaceutically acceptable salt thereof.

### Claim 18 (depends on 1)

The compound of claim 1 that is
or a pharmaceutically acceptable salt thereof.

### Claim 19 (depends on 1)

A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

### Claim 20

A method of treating cancer in a mammal in need thereof, comprising administering to the mammal a compound of Formula (I) or Formula (II), or a pharmaceutically acceptable salt thereof:
wherein:
is selected from pyridyl, pyrazinyl, pyrimidyl, and pyridazinyl;
Z1 is CR7;
Z2 is CR9;
Z3 is CR6;
Z4 is CR6a;
X is —N(R4)—;
Y is —N(R4a)—;
R1 is hydrogen;
R1a and R1b are hydrogen;
R2 and R3 are each independently selected from hydrogen and C1-6alkyl;
or R2 and R3, together with the carbon to which they are attached, form a C3-6cycloalkyl;
R4 is hydrogen;
R4a is hydrogen;
R6 is selected from hydrogen, halogen, and —OR10;
R6a is selected from hydrogen and —OR10;
R7 is hydrogen;
R8 is selected from hydrogen, halogen, and C1-6haloalkyl;
R9 is hydrogen;
each R10 is independently selected from hydrogen, C1-6alkyl, and C1-6haloalkyl;
each R14 is independently C1-6alkyl;
m is 0, 1, or 2; and
n is 1.