# US 11,028,079 B2 · Small molecule BET bromodomain inhibitors 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 11,028,079 B2
- Document ID: US11028079B2
- Status: Granted
- Kind: B2
- Application number: 16/685,128
- Filed: 2019-11-15
- Published: 2020-07-16
- Granted: 2021-06-08
- Earliest claimed: 2015-11-25
- Assignees: ConverGene LLC; The United States of America, as represented by the Secretary, Department of Health and Human Services
- Applicants: ConverGene LLC; The United States of America, as represented by the Secretary, Department of Health and Human Service
- Inventors: Jeffrey William Strovel; Makoto Yoshioka; David J. Maloney; Shyh Yang; Ajit Jadhav; Daniel Jason Urban
- Web page: https://patentgrep.com/patent/US11028079B2

## CPC

- C07D 413/04: directly linked by a ring-member-to-ring-member bond
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 31/18: for HIV
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 39/00: General protective or antinoxious agents
- C07D 239/84: Nitrogen atoms
- C07D 239/95: with hetero atoms directly attached in positions 2 and 4
- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- C07D 401/14: containing three or more hetero rings
- C07D 403/04: directly linked by a ring-member-to-ring-member bond
- C07D 413/14: containing three or more hetero rings
- C07D 417/14: containing three or more hetero rings
- C07D 471/04: Ortho-condensed systems
- C07D 471/10: Spiro-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to compounds that bind to and otherwise modulate the activity of bromodomain-containing proteins, to processes for preparing these compounds, to pharmaceutical compositions containing these compounds, and to methods of using these compounds for treating a wide variety of conditions and disorders.

## Claims

### Claim 1

A compound of Formula I, or a-pharmaceutically acceptable salt or isomer thereof:
wherein:
X is N;
Z is N;
R1 and R2, together with the included nitrogen atom and L1, form
Y is pyrazolyl and may optionally be substituted with 1 or 2 independently selected R8,
R3 is 2-oxopyridinyl and is optionally substituted by one or two methyl groups;
R4 is H;
each R8 is independently selected from the group consisting of H, C3-6 cycloalkyl, phenyl, and C1-6 alkyl, wherein said phenyl or C1-6 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R14; and
R14 is H, OH, or halogen.

### Claim 2 (depends on 1)

The compound of claim 1, wherein
R1 and R2, together with the included nitrogen atom and L1, form
R8 is selected from the group consisting of C3-6cycloalkyl and phenyl, wherein said phenyl is optionally substituted with R14; and
R14 is H, or halogen.

### Claim 3 (depends on 1)

The compound of claim 1, wherein
Y is
each R8 is independently selected from the group consisting of H and C1-6 alkyl, wherein said C1-6 alkyl is optionally substituted with R14; and
R14 is OH.

### Claim 4 (depends on 1)

The compound of claim 1, wherein
Y is

### Claim 5 (depends on 1)

The compound of claim 1, wherein
R3 is
and is optionally substituted with one methyl groups.

### Claim 6 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 and R2, together with the included nitrogen atom and L1, form:
wherein the phenyl may optionally be substituted with F, Cl, or Br.

### Claim 7 (depends on 1)

The compound of claim 1, wherein
R1 and R2, together with the included nitrogen atom and L1, form
R8 is selected from the group consisting of C3-6 cycloalkyl and phenyl, wherein said phenyl is optionally substituted with R14; and R14 is H, or halogen;
R3 is
and is optionally substituted with one methyl groups;
Y is

### Claim 8 (depends on 1)

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

### Claim 9 (depends on 1)

A method for the treatment of a disease or condition associated with the activity of bromodomain-containing proteins comprising administering a compound of claim 1, or a pharmaceutically acceptable salt thereof.

### Claim 10 (depends on 9)

The method of claim 9, wherein the compound or a pharmaceutically acceptable salt thereof inhibits the activity of bromodomain-containing proteins by inhibiting binding to acetylated proteins.

### Claim 11 (depends on 10)

The method of claim 10, wherein the acetylated protein is an acetylated histone involved in the regulation or dysregulation of gene expression.

### Claim 12 (depends on 9)

The method of claim 9, wherein the disease or condition is selected from the group consisting of human NUT midline carcinoma, multiple myeloma, Burkitt's lymphoma, myeloid leukemia, NPM1c mutant leukemia, T-cell lymphoblastic leukemia, hepatocellular carcinoma, glioblastoma, neuroblastoma, sarcoma, breast cancer, colorectal cancer, lung cancer, pancreatic cancer, ovarian cancer, chordoma, neuroendocrine tumors, Merkel cell carcinoma, prostate cancer, osteoarthritis, rheumatoid arthritis, Alzheimer's disease, and HIV infection.

### Claim 13 (depends on 9)

The method according to claim 9, wherein the disease or condition is a fibrotic condition.

### Claim 14 (depends on 9)

The method according to claim 9, wherein the fibrotic condition is idiopathic pulmonary fibrosis, renal fibrosis or cardiac fibrosis.