# US 2021/0276960 A1 · Inhibitors of tissue transglutaminase 2 (tg2) and uses thereof

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2021/0276960 A1
- Document ID: US20210276960A1
- Status: Published application
- Kind: A1
- Application number: 17/249,519
- Filed: 2021-03-03
- Published: 2021-09-09
- Earliest claimed: 2020-03-04
- Assignees: Northwestern University; THE UNITED STATES GOVERMENT as represented by the DEPARTMENT OF VETERAN'S AFFAIRS
- Applicants: Northwestern University; United States Goverment as represented by the Department of Veterans Affairs
- Inventors: Gary E. Schiltz; Daniela E. Matei; Purav Vagadia
- Web page: https://patentgrep.com/patent/US20210276960A1

## CPC

- C07D 239/48: Two nitrogen atoms
- A61P 35/00: Antineoplastic agents
- C07D 239/42: One nitrogen atom (nitro radicals C07D239/30)
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 403/12: linked by a chain containing hetero atoms as chain links
- C07D 409/12: linked by a chain containing hetero atoms as chain links
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Disclosed are compounds, pharmaceutical compositions comprising the compounds, and methods of using the compounds and pharmaceutical compositions for treating a subject in need thereof. The disclosed compounds inhibit the activity of tissue transglutaminase 2 (TG2). As such, the disclosed compounds and pharmaceutical compositions may be utilized in methods for treating a subject having or at risk for developing a disease or disorder that is associated with TG2 activity which may be cell proliferative diseases and disorders such as cancer.

## Claims

### Claim 1

A compound of a formula:
or a salt or solvate thereof,
wherein:
Z is pyrimidinyl or 5,7-diazaindolinyl and Z optionally is substituted at one or more ring positions with alkyl, alkoxy, amino, alkylamino, dialkylamino, heteroaryl, or halo;
V is NR1 or O, wherein R1 is hydrogen or alkyl;
m is selected from 0-6;
Y is an aryl group, a diaryl group, or a heteroaryl group, and Y optionally is substituted at one or more ring positions with haloalkyl;
n is selected from 0-6;
W is NR2 or CH, wherein R2 is hydrogen or alkyl;
R3 and R3′ are hydrogen or R3 and R3′ together form oxo;
p is selected from 0-6; and
X is an aryl group or a heteroaryl group, and X optionally is substituted at one or more ring positions with one or more of alkyl, alkoxy, halo; amino; alkylamino, or aryl; and
optionally with the proviso that if m is 0, n is 0, and p is 1, then X is not N-imidazyl or indol-3-yl; and
optionally with the proviso that if m is 0, n is 0, and p is 1, then Z is not 4-dimethylamino-pyrimidin-2-yl or 4-pyrrolidin-1-yl-pyrimidin-2-yl.

### Claim 2 (depends on 1)

The compound of claim 1 having a formula Ia:

### Claim 3 (depends on 1)

The compound of claim 1 having a formula Ib:
wherein:
R4 is hydrogen or R4 has a formula,
wherein R7 and R8 independently are hydrogen, alkyl, or a moiety comprising a biotinyl group or R7 and R8 together form linked alkyl; and
R6 is hydrogen or alkyl.

### Claim 4 (depends on 1)

The compound of claim 1, wherein X has a formula selected from:

### Claim 5 (depends on 1)

The compound of claim 1, wherein Y has a formula selected from:

### Claim 6 (depends on 1)

The compound of claim 1, wherein Z has a formula selected from:

### Claim 7 (depends on 1)

The compound of claim 1, wherein R1 is hydrogen.

### Claim 8 (depends on 1)

The compound of claim 1, wherein R1 is methyl.

### Claim 9 (depends on 1)

The compound of claim 1, wherein R2 is hydrogen.

### Claim 10 (depends on 1)

The compound of claim 1, wherein R2 is methyl.

### Claim 11 (depends on 1)

The compound of claim 1, wherein R3 and R3′ together form oxo.

### Claim 12 (depends on 3)

The compound of claim 3, wherein R4 has a formula,
wherein R7 and R8 are hydrogen, methyl, or a moiety comprising a biotinyl group.

### Claim 13 (depends on 1)

The compound of claim 1, wherein X is a phenyl group optionally substituted at one or more ring positions with one or more alkyl, alkoxy and halo.

### Claim 14 (depends on 1)

The compound of claim 1 wherein: m is 0 or 1; n is 0 or 1; and/or p is 0 or 1.

### Claim 15 (depends on 3)

The compound of claim 3, wherein R1 is methyl, R4 has a formula
wherein R7 and R are methyl; and X is phenyl, optionally substituted with one or more alkyl, alkoxy and halo.

### Claim 16 (depends on 1)

The compound of claim 1 having a formula selected from:

### Claim 17 (depends on 1)

A pharmaceutical composition comprising the compound of claim 1.

### Claim 18 (depends on 17)

The pharmaceutical composition of claim 17, wherein the compound has a formula selected from:

### Claim 19 (depends on 1)

A method of treating or preventing a disease or disorder associated with tissue transglutaminase in a subject in need thereof, the method comprising administering to the subject of the compound of claim 1.

### Claim 20 (depends on 19)

The method of claim 19, wherein the disease or disorder is a cell proliferation diseases or disorder.

### Claim 21 (depends on 20)

The method of claim 20, wherein the cell proliferation disease or disorder is cancer.

### Claim 22 (depends on 20)

The method of claim 20, wherein the cell proliferation disease or disorder is ovarian cancer.