# US 11,028,066 B2 · Inhibitors of lysine specific demethylase-1

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- Number: US 11,028,066 B2
- Document ID: US11028066B2
- Status: Granted
- Kind: B2
- Application number: 16/780,704
- Filed: 2020-02-03
- Published: 2020-06-04
- Granted: 2021-06-08
- Earliest claimed: 2014-06-27
- Assignees: Celgene Quanticel Research, Inc.
- Applicants: Celgene Quanticel Research, Inc.
- Inventors: Young Chen; Toufike Kanouni; Jeffrey Alan Stafford; James Veal
- Web page: https://patentgrep.com/patent/US11028066B2

## CPC

- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- A61K 31/4523: containing further heterocyclic ring systems
- A61K 31/497: containing further heterocyclic rings
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 401/14: containing three or more hetero rings
- C07D 403/12: linked by a chain containing hetero atoms as chain links
- C07D 405/14: containing three or more hetero rings
- C07D 471/04: Ortho-condensed systems
- C07D 471/10: Spiro-condensed systems
- C07D 487/04: Ortho-condensed systems
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates generally to compositions and methods for treating cancer and neoplastic disease. Provided herein are substituted heterocyclic derivative compounds and pharmaceutical compositions comprising said compounds as exemplified as follows, The subject compounds and compositions are useful for inhibition of lysine specific demethylase-1. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, lung cancer and/or melanoma and the like.

## Claims

### Claim 1

A compound having the structure of Formula (I), or a pharmaceutically acceptable salt thereof,
wherein:
A is C—R, wherein R is optionally substituted alkyl;
W1 and W2 are independently chosen from N, C—H, or C—F;
X is hydrogen, halogen, optionally substituted alkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, optionally substituted aralkyl, optionally substituted heteroarylalkyl, optionally substituted alkynyl, optionally substituted carbocyclylalkynyl, optionally substituted aryl, or optionally substituted heteroaryl;
Y is optionally substituted alkyl, optionally substituted cycloalkylalkyl, heterocyclylalkyl or aralkyl; and
Z is an optionally substituted group chosen from N-heterocyclyl, —O-heterocyclylalkyl, —N(H)-heterocyclylalkyl, or —N(Me)-heterocyclylalkyl;
wherein if Z is an optionally substituted heterocyclylalkyl group selected from —O— heterocyclylalkyl, —N(H)-heterocyclylalkyl or —N(Me)-heterocyclylalkyl, then heterocyclylalkyl group has the formula —Rc-heterocyclyl, wherein Rc is an optionally substituted C1-C3 alkylene chain and the heterocyclyl is an optionally substituted nitrogen-containing 5-membered heterocyclyl.

### Claim 2 (depends on 1)

The compound or pharmaceutically acceptable salt of claim 1, wherein W2 is C—H.

### Claim 3 (depends on 1)

The compound or pharmaceutically acceptable salt of claim 1, wherein W1 is C—F.

### Claim 4 (depends on 1)

The compound or pharmaceutically acceptable salt of claim 1, wherein W1 is C—H.

### Claim 5 (depends on 1)

The compound or pharmaceutically acceptable salt of claim 1, wherein W1 is N.

### Claim 6 (depends on 1)

The compound or pharmaceutically acceptable salt of claim 1, wherein X is hydrogen.

### Claim 7 (depends on 1)

The compound or pharmaceutically acceptable salt of claim 1, wherein X is optionally substituted alkyl.

### Claim 8 (depends on 1)

The compound or pharmaceutically acceptable salt of claim 1, wherein X is optionally substituted alkynyl.

### Claim 9 (depends on 1)

The compound or pharmaceutically acceptable salt of claim 1, wherein X is optionally substituted carbocyclylalkynyl.

### Claim 10 (depends on 1)

The compound or pharmaceutically acceptable salt of claim 1, wherein X is optionally substituted aryl, or optionally substituted heteroaryl.

### Claim 11 (depends on 1)

The compound or pharmaceutically acceptable salt of claim 1, wherein X is optionally substituted aryl.

### Claim 12 (depends on 1)

The compound or pharmaceutically acceptable salt of claim 1, wherein the optionally substituted aryl is an optionally substituted phenyl.

### Claim 13 (depends on 1)

The compound or pharmaceutically acceptable salt of claim 1, wherein X is optionally substituted heteroaryl.

### Claim 14 (depends on 13)

The compound or pharmaceutically acceptable salt of claim 13, wherein the optionally substituted heteroaryl is chosen from an optionally substituted pyridinyl, optionally substituted pyrazolyl, or optionally substituted indazolyl.

### Claim 15 (depends on 1)

The compound or pharmaceutically acceptable salt of claim 1, wherein Z is an optionally substituted —O-heterocyclylalkyl.

### Claim 16 (depends on 1)

The compound or pharmaceutically acceptable salt of claim 1, wherein Z is an optionally substituted —N(H)-heterocyclylalkyl.

### Claim 17 (depends on 1)

The compound or pharmaceutically acceptable salt of claim 1, wherein Z is an optionally substituted —N(Me)-heterocyclylalkyl.

### Claim 18 (depends on 1)

The compound or pharmaceutically acceptable salt of claim 1, wherein Z is —O-heterocyclylalkyl, —N(H)-heterocyclylalkyl, or —N(Me)-heterocyclylalkyl; and the heterocyclylalkyl group has the formula —Rc-heterocyclyl and the Rc is an optionally substituted C1 alkylene chain.

### Claim 19 (depends on 1)

The compound or pharmaceutically acceptable salt of claim 1, wherein Z is an optionally substituted N-heterocyclyl.

### Claim 20 (depends on 19)

The compound or pharmaceutically acceptable salt of claim 19, wherein the optionally substituted N-heterocyclyl is a 4-, 5-, 6-, or 7-membered N-heterocyclyl.

### Claim 21 (depends on 19)

The compound or pharmaceutically acceptable salt of claim 19, wherein the optionally substituted N-heterocyclyl is a 6-membered N-heterocyclyl.

### Claim 22 (depends on 19)

The compound or pharmaceutically acceptable salt of claim 19, wherein the optionally substituted N-heterocyclyl is an optionally substituted piperidine.

### Claim 23 (depends on 22)

The compound or pharmaceutically acceptable salt of claim 22, wherein the optionally substituted piperidine is an optionally substituted 4-aminopiperidine.

### Claim 24 (depends on 1)

The compound or pharmaceutically acceptable salt of claim 1, wherein Y is optionally substituted cycloalkylalkyl.

### Claim 25 (depends on 1)

The compound or pharmaceutically acceptable salt of claim 1, wherein Y is optionally substituted alkyl.

### Claim 26 (depends on 1)

The compound or pharmaceutically acceptable salt of claim 1, wherein Y is optionally substituted heterocyclylalkyl.

### Claim 27 (depends on 1)

The compound or pharmaceutically acceptable salt of claim 1, wherein Y is optionally substituted aralkyl.

### Claim 28 (depends on 1)

A pharmaceutical composition comprising a compound of Formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

### Claim 29 (depends on 1)

A method of regulating gene transcription in a cell comprising inhibiting lysine-specific demethylase 1 activity by exposing the lysine-specific demethylase 1 enzyme to a compound of Formula (I) according to claim 1.