# US 10,870,648 B2 · Inhibiting CREB binding protein (CBP)

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- Number: US 10,870,648 B2
- Document ID: US10870648B2
- Status: Granted
- Kind: B2
- Application number: 16/457,596
- Filed: 2019-06-28
- Published: 2020-01-02
- Granted: 2020-12-22
- Earliest claimed: 2018-06-29
- Assignees: FORMA Therapeutics, Inc.
- Applicants: FORMA Therapeutics, Inc.
- Inventors: Shawn E. R. Schiller; Torsten Herbertz; Hongbin Li; Bradford Graves; Steven Mischke; Angela West; Jennifer R. Downing; Anna Ericsson
- Web page: https://patentgrep.com/patent/US10870648B2

## CPC

- C07D 471/04: Ortho-condensed systems
- A61P 35/00: Antineoplastic agents
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present disclosure is directed to inhibitors of the CBP/p300 family of bromodomains. The compounds can be useful in the treatment of disease or disorders associated with the inhibition of the CBP/p300 family of bromodomains. For instance, the disclosure is concerned with compounds and compositions for inhibition of the CBP/p300 family of bromodomains, methods of treating, preventing, or ameliorating diseases or disorders associated with the inhibition of CBP/p300 family of bromodomains, and methods of synthesis of these compounds.

## Claims

### Claim 1

A compound of Formula (I):
or a pharmaceutically acceptable salt thereof, wherein:
R1 is —OR5;
R5 is —C1C6alkyl;
R6 is phenyl optionally substituted with one or more R10;
R10 is each independently, at each occurrence, —C1-C6alkyl, halogen, —OC1-C6alkyl, —OC3-C6cycloalkyl, wherein each alkyl or cycloalkyl is optionally substituted with one or more —R12; or wherein any two R10 when on non-adjacent atoms, can combine to form a bridging cycloalkyl or heterocyclyl; or wherein any two R10 when on adjacent atoms, can combine to form a cycloalkyl, heterocyclyl, aryl or heteroaryl;
R12 is independently, at each occurrence, —C1-C6alkyl, —OH, or halogen.

### Claim 2 (depends on 1)

The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein
R5 is —C1-C3alkyl;
R10 is each independently, at each occurrence halogen or —OC1-C6alkyl, —OC3-C6cycloalkyl, wherein each alkyl, or cycloalkyl, is optionally substituted with one or more —R12; and
R12 is halogen.

### Claim 3 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein any two R10 when on non-adjacent atoms, can combine to form a bridging cycloalkyl or heterocyclyl.

### Claim 4 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein any two R10 when on adjacent atoms, can combine to form a cycloalkyl, heterocyclyl, aryl or heteroaryl.

### Claim 5 (depends on 1)

The compound of claim 1, wherein R5 is methyl.

### Claim 6 (depends on 5)

The compound of claim 5, wherein at least one R10 is —OC1-C6alkyl optionally substituted with one or more —R12.

### Claim 7 (depends on 6)

The compound of claim 6, wherein R12 is halogen.

### Claim 8 (depends on 5)

The compound of claim 5, wherein at least one R10 is —C1-C6alkyl optionally substituted with one or more —R12.

### Claim 9 (depends on 8)

The compound of claim 8, wherein R12 is halogen.

### Claim 10 (depends on 5)

The compound of claim 5, wherein at least one R10 is —OC3-C6cycloalkyl optionally substituted with one or more —R12.

### Claim 11 (depends on 10)

The compound of claim 10, wherein R12 is halogen.

### Claim 12

A compound of Formula (IV-a):
or a pharmaceutically acceptable salt thereof, wherein
n is an integer of 0, 1, 2, 3, 4 or 5; and
each R10 is independently, at each occurrence, selected from the group consisting of: —C1-C6alkyl, halogen, —OC1-C6alkyl, and —OC3-C6cycloalkyl, wherein each alkyl or cycloalkyl is optionally substituted with one or more halogen or C1-C6alkyl; or
any two R10 when on non-adjacent atoms, can combine to form a bridging cycloalkyl or heterocyclyl; or
any two R10 when on adjacent atoms, can combine to form a cycloalkyl, heterocyclyl, aryl or heteroaryl.

### Claim 13 (depends on 1)

The compound of claim 1, wherein n is 0, 1 or 2.

### Claim 14 (depends on 13)

The compound of claim 13, wherein each R10 is independently, at each occurrence, selected from the group consisting of:
—C1-C6alkyl, halogen, —OC1-C6salkyl, and —OC3-C6cycloalkyl, wherein each alkyl or cycloalkyl is optionally substituted with one or more halogen or methyl.

### Claim 15 (depends on 14)

The compound of claim 14, wherein each halogen is independently selected from the group consisting of fluorine and chlorine.

### Claim 16 (depends on 15)

The compound of claim 15, wherein each —OC3-C6cycloalkyl is —O-cyclopropyl and each —C1-C6alkyl is methyl and each —OC1-C6alkyl is methoxy.

### Claim 17 (depends on 1)

The compound of claim 1, wherein each R10 is independently, at each occurrence, selected from the group consisting of:
—C1-C6alkyl, halogen, —OC1-C6alkyl, and —OC3-C6cycloalkyl, wherein each alkyl or cycloalkyl is optionally substituted with one or more halogen or methyl.

### Claim 18

A compound or a pharmaceutically acceptable salt thereof, wherein the compound is selected from

### Claim 19 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound has the structure

### Claim 20 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound has the structure

### Claim 21 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound has the structure

### Claim 22 (depends on 18)

The compound of claim 18, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from

### Claim 23 (depends on 18)

The compound of claim 18, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from

### Claim 24 (depends on 18)

The compound of claim 18, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from