# US 12,599,671 B2 · Compounds, compositions, and methods for protein degradation

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- Number: US 12,599,671 B2
- Document ID: US12599671B2
- Status: Granted
- Kind: B2
- Application number: 17/799,000
- Filed: 2021-02-11
- Published: 2023-03-30
- Granted: 2026-04-14
- Earliest claimed: 2020-02-12
- Assignees: Dana-Farber Cancer Institute, Inc.
- Applicants: Dana-Farber Cancer Institute, Inc.
- Inventors: Deyao Li; Lingling Dai; Jun Qi
- Web page: https://patentgrep.com/patent/US12599671B2

## CPC

- A61K 47/55: the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug
- C07D 401/14: containing three or more hetero rings
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/545: {Heterocyclic compounds (A61K47/558 takes precedence)}
- A61P 35/00: Antineoplastic agents
- C07D 417/14: containing three or more hetero rings
- 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)
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Disclosed herein are compounds that target SMARCA2, SMARCA4 or BRM, causing their degradation. Also disclosed herein are compositions and methods of use in treating associated disorders and diseases.

## Claims

### Claim 1

A compound of Formula I:
or a pharmaceutically acceptable salt or stereoisomer thereof, wherein
A is
E is
X1 and X2 are each independently selected from O, NR3, and S; or X1 or X2 combine with L to form a heterocyclyl or heteroaryl; or both of X1 and X2 combine with L to form a heterocyclyl or heteroaryl;
L comprises an alkylene, cycloalkylene, heterocyclylene, arylene, or heteroarylene chain, or a combination thereof, comprising 1 to 35 carbon atoms, optionally wherein:
if L comprises an alkylene comprising 1 to 35 —CH2— moieties, then at least one, but no more than ten, —CH2— moieties of L are independently replaced with a moiety selected from —C(═O)—, —C(═O)—NR4—, —NR4—C(═O)—, —C(═O)—O—, —O—C(═O)—, —NR4—C(═O)—NR3—, —O—C(═O)—NR4—, —NR4—C(═O)—O—, —O—, —S—, and —NR4—, provided that the number of —CH2— moieties of L is larger than the collective number of —C(═O)—, —C(═O)—NR4—, —NR4—C(═O)—, —C(═O)—O—, —O—C(═O)—, —NR4—C(═O)—NR3—, —O—C(═O)—NR4—, —NR4—C(═O)—O—, —O—, —S—, and —NR3— moieties of L, and provided there is at least one —CH2— between each —C(═O)—, —C(═O)—NR4—, —NR4—C(═O)—, —C(═O)—O—, —O—C(═O)—, —NR4—C(═O)—NR3—, —O—C(═O)—NR4—, —NR4—C(═O)—O—, —O—, —S—, and —NR4— moiety of L;
R1 is halo;
R2 is H;
R3 and R4 are each independently selected from H and alkyl; and
n is 1-5.

### Claim 2 (depends on 1)

The compound of claim 1, wherein R3 or R4 is H.

### Claim 3 (depends on 1)

The compound of claim 1, wherein the compound is:
or a pharmaceutically acceptable salt or stereoisomer thereof.

### Claim 4 (depends on 3)

The compound of claim 3, wherein X1 is NH or O.

### Claim 5 (depends on 3)

The compound of claim 3, wherein X3 is NH or O.

### Claim 6 (depends on 3)

The compound of claim 3, wherein X2 is NH or O.

### Claim 7 (depends on 3)

The compound of claim 3, wherein X2 combines with L to form a heterocyclyl.

### Claim 8 (depends on 3)

The compound of claim 3, wherein L is alkylene or cycloalkylene.

### Claim 9 (depends on 8)

The compound of claim 8, wherein the alkylene comprises 2-25 carbon atoms.

### Claim 10 (depends on 7)

The compound of claim 7, wherein the heterocyclyl is piperidinyl.

### Claim 11 (depends on 8)

The compound of claim 8, wherein the cycloalkylene is cyclohexylene.

### Claim 12 (depends on 2)

The compound of claim 2, wherein R1 is fluoro or chloro.

### Claim 13 (depends on 8)

The compound of claim 8, wherein at least one, but no more than five methylene moieties of the alkylene are replaced with an amide moiety or an oxygen atom.

### Claim 14 (depends on 8)

The compound of claim 8, wherein one, two, three, or six methylene moieties of the alkylene are replaced with one, two, three, or six amide moieties.

### Claim 15 (depends on 13)

The compound of claim 13, wherein at least one, but no more than five methylene moieties of the alkylene are replaced with an amide moiety, and the amide moieties are separated by at least one carbon atom.

### Claim 16 (depends on 1)

The compound of claim 1, wherein the compound is selected from:
or a pharmaceutically acceptable salt or stereoisomer thereof.

### Claim 17 (depends on 1)

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