# US 10,479,786 B2 · Protein kinase inhibitors

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- Number: US 10,479,786 B2
- Document ID: US10479786B2
- Status: Granted
- Kind: B2
- Application number: 15/839,469
- Filed: 2017-12-12
- Published: 2018-04-12
- Granted: 2019-11-19
- Earliest claimed: 2016-12-13
- Assignees: Princeton Drug Discovery Inc
- Applicants: Princeton Drug Discovery Inc
- Inventors: Kan He
- Web page: https://patentgrep.com/patent/US10479786B2

## CPC

- C07D 417/14: containing three or more hetero rings
- A61K 31/506: not condensed and containing further heterocyclic rings
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- 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 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 37/00: Drugs for immunological or allergic disorders
- C07B 59/002: {Heterocyclic compounds}
- C07D 417/12: linked by a chain containing hetero atoms as chain links
- C07B 2200/05: Isotopically modified compounds, e.g. labelled
- 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
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

The present invention concerns novel deuterated and non-deuterated cyclic chemical compounds and their corresponding salts thereof active on protein kinases in general, and in particular as inhibitors of protein kinases. Additionally, methods of treating mammals with protein kinase-mediated diseases or conditions by administering a therapeutically effective amount of the novel deuterated or non-deuterated cyclic chemical compound and their corresponding salts thereof.

## Claims

### Claim 1

A compound of formula I:
and/or a salt, an enantiomer or an enantiomeric mixture thereof;
wherein
W1, W2, and W3 are independently hydrogen or deuterium;
Y is C—H or nitrogen;
R1 is
-Q-A
wherein
Q is a single bond directly attaching A to a ring carbon atom, or a methylene or ethylene group connecting A to a ring carbon atom; and
A is
wherein
Y1 is C—H or nitrogen and Y2 is carbon and wherein A is a five or six membered ring;
Z1 and Z2 are independently hydrogen, —(CH2)n—OR5, or [—NR7R6], where n is an integer number from 0 to 4, and R5 R6 are independently hydrogen, lower alkyl, or lower alkenyl;
T1 and T2 are independently an integer number from 0 to 4 with the provisos that when T1 or T2 is 0, —(CH2)T1 or —(CH2)T2 is a single bond;
R2 and R3 are independently hydrogen; halogen; alkoxyl; lower alkyl or lower alkenyl, wherein the lower alkyl or lower alkenyl is optionally substituted with one or more substituents selected from —OH and alkoxyl, wherein alkoxyl is methoxy, ethoxy, propyloxy, or tert-butoxy; or optionally substituted heterocyclo, wherein optionally substituted includes [—NR7R6], wherein R6 and R7 are independently hydrogen, lower alkyl, or lower alkenyl;
and wherein the positions of R1, R2 and R3 are exchangeable.

### Claim 2

A compound of formula II:
and/or a salt, an enantiomer or an enantiomeric mixture thereof:
wherein W1, W2, and W3 are independently hydrogen or deuterium;
wherein Y is C—H or nitrogen;
wherein R2, R3, and R4 are independently hydrogen; halogen; alkoxyl; lower alkyl or lower alkenyl, wherein the lower alkyl or lower alkenyl is optionally substituted with one or more substituents selected from —OH and alkoxyl, wherein alkoxyl is methoxy, ethoxy, propyloxy, or tert-butoxy; or optionally substituted heterocyclo, wherein optionally substituted includes [—NR7R6], wherein R6 and R7 are independently hydrogen, lower alkyl, or lower alkenyl; and
wherein X is independently hydrogen, —(CH2)n—OR5, or [—NR7R6], wherein n is an integer number from 0 to 4 and R5 R6 are independently hydrogen, lower alkyl, or lower alkenyl.

### Claim 3

A compound of formula III:
and/or a salt, an enantiomer or an enantiomeric mixture thereof:
wherein W1, W2, and W3 are independently hydrogen or deuterium;
wherein Y is C—H or nitrogen;
wherein R2, R3, and R4 are independently H; halogen; alkoxyl; lower alkyl or lower alkenyl, wherein the lower alkyl or lower alkenyl is optionally substituted with one or more substituents selected from —OH and alkoxyl, wherein alkoxyl is methoxy, ethoxy, propyloxy, or tert-butoxy; or optionally substituted heterocyclo, wherein optionally substituted includes [NR7R6], wherein R6 are independently hydrogen, lower alkyl, or lower alkenyl.

### Claim 4 (depends on 1)

The compound of claim 1, wherein W2 is deuterium, and W1 and W3 are hydrogen.

### Claim 5 (depends on 4)

The compound of claim 4, wherein said compound is compound I:
and/or a salt thereof.

### Claim 6 (depends on 4)

The compound of claim 4, wherein said compound is compound II:
and/or a salt thereof.

### Claim 7 (depends on 4)

The compound of claim 4, wherein said compound is compound IV:
and/or a salt thereof.

### Claim 8 (depends on 4)

The compound of claim 4, wherein said compound is compound V:
and/or a salt thereof.

### Claim 9 (depends on 4)

The compound of claim 4, wherein said compound is compound VI:
and/or a salt thereof.

### Claim 10 (depends on 4)

The compound of claim 4, wherein said compound is compound VII:
and/or a salt hereof.

### Claim 11 (depends on 1)

The compound of claim 1, wherein W1, W2, and W3 are each hydrogen.

### Claim 12 (depends on 11)

The compound of claim 11, wherein said compound is compound VIII:
and/or a salt thereof.

### Claim 13 (depends on 11)

The compound of claim 11, wherein said compound is compound IX:
thereof.

### Claim 14 (depends on 11)

The compound of claim 11, wherein said compound is compound XII:
and/or a salt thereof.

### Claim 15 (depends on 11)

The compound of claim 11, wherein said compound is compound XIII:
and/or a salt thereof.

### Claim 16 (depends on 11)

The compound of claim 11, wherein said compound is compound XIV:
and/or a salt thereof.

### Claim 17

A pharmaceutical composition comprising a compound of formula 1
and/or a salt, an enantiomer or an enantiomeric mixture thereof;
wherein
W1, W2, and W3 are independently hydrogen or deuterium;
Y is C—H or nitrogen;
R1 is
-Q-A
wherein
Q is a single bond directly attaching A to a ring carbon atom, or a methylene or ethylene group connecting A to a ring carbon atom; and
A is
wherein
Y1 is C—H or nitrogen and Y2 is carbon and wherein A is a five or six membered ring;
Z1 and Z2 are independently hydrogen, —(CH2)n—OR5, or [—NR7R6], where n is an integer number from 0 to 4, and R5 R6 are independently hydrogen, lower alkyl, or lower alkenyl;
T1 and T2 are independently an integer number from 0 to 4 with the provisos that when T1 or T2 is 0, —(CH2)T1 or —(CH2)T2 is a single bond;
R2 and R3 are independently hydrogen; halogen; alkoxyl; lower alkyl or lower alkenyl, wherein the lower alkyl or lower alkenyl is optionally substituted with one or more substituents selected from —OH and alkoxyl, wherein alkoxyl is methoxy, ethoxy, propyloxy, or tert-butoxy; or optionally substituted heterocyclo, wherein optionally substituted includes [—NR7R6], wherein R6 and R7 are independently hydrogen, lower alkyl, or lower alkenyl;
and wherein the positions of R1, R2 and R3 are exchangeable;
and a pharmaceutically acceptable excipient or carrier.

### Claim 18 (depends on 17)

The pharmaceutical composition of claim 17, wherein W2 is deuterium, and W1 and W3 are hydrogen.

### Claim 19 (depends on 18)

The pharmaceutical composition of claim 18, wherein said compound is compound I:
and/or a salt thereof.

### Claim 20 (depends on 18)

The pharmaceutical composition of claim 18, wherein said compound is compound II:
and/or a salt thereof.

### Claim 21 (depends on 18)

The pharmaceutical composition of claim 18, wherein said compound is compound IV:
and/or a salt thereof.

### Claim 22 (depends on 18)

The pharmaceutical composition of claim 18, wherein said compound is compound V:
and/or a salt thereof.

### Claim 23 (depends on 18)

The pharmaceutical composition of claim 18, wherein said compound is compound VI:
and/or a salt thereof.

### Claim 24 (depends on 18)

The pharmaceutical composition of claim 18, wherein said compound is compound VII:
and/or a salt hereof.

### Claim 25 (depends on 17)

The pharmaceutical composition of claim 17, wherein W1, W2, and W3 are each hydrogen.

### Claim 26 (depends on 25)

The pharmaceutical composition of claim 25, wherein said compound is compound VIII:
and/or a salt thereof.

### Claim 27 (depends on 25)

The pharmaceutical composition of claim 25, wherein said compound is compound IX:
and/or a salt thereof.

### Claim 28 (depends on 25)

The pharmaceutical composition of claim 25, wherein said compound is compound XII:
and/or a salt thereof.

### Claim 29 (depends on 25)

The pharmaceutical composition of claim 25, wherein said compound is compound XIII:
and/or a salt thereof.

### Claim 30 (depends on 25)

The pharmaceutical composition of claim 25, wherein said compound is compound XIV:
and/or a salt thereof.