# US 2019/0315745 A1 · Cdk4/6 inhibitor

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2019/0315745 A1
- Document ID: US20190315745A1
- Status: Published application
- Kind: A1
- Application number: 16/470,111
- Filed: 2017-12-15
- Published: 2019-10-17
- Earliest claimed: 2016-12-16
- Assignees: Cstone Pharmaceuticals; Medshine Discovery Inc.
- Applicants: Cstone Pharmaceuticals; Medshine Discovery Inc.
- Inventors: Zhaobing XU; Lihong HU; Charles Z. DING; Shuhui CHEN
- Web page: https://patentgrep.com/patent/US20190315745A1

## CPC

- C07D 471/04: Ortho-condensed systems
- A61P 35/00: Antineoplastic agents
- C07D 519/00: Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- A61K 31/4375: the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
- A61K 31/4965: Non-condensed pyrazines
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)

## Abstract

Disclosed is a series of compounds acting as CDK4/6 inhibitors. Specifically disclosed are compounds as represented by formula (I), pharmaceutically acceptable salts or isomers thereof, pharmaceutical compositions containing same, and the use thereof in the preparation of drugs for treating cancers.

## Claims

### Claim 1

A compound of formula (I), a pharmaceutically acceptable salt thereof or an isomer thereof,
wherein,
R1 is H, or selected from the group consisting of C1-3 alkyl, C1-3 heteroalkyl,
each of which is optionally substituted by 1, 2 or 3 R;
each of R2 is independently H, OH, CN, halogen, or selected from the group consisting of C1-5 alkyl, C1-5 heteroalkyl, C3-6 cycloalkyl and 3-6 membered heterocycloalkyl, each of which is optionally substituted by 1, 2 or 3 R;
ring A is 4-11 membered heterocycloalkyl;
ring B is selected from the group consisting of C3-6 cycloalkyl, 3-6 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 R;
R is halogen, OH, CN, NH2, NO2, or selected from the group consisting of C1-3 alkyl and C1-3 heteroalkyl, each of which is optionally substituted by 1, 2 or 3 R′;
R′ is selected from the group consisting of F, Cl, Br, I, OH, CN and NH2;
each of the “hetero” in the C1-3 heteroalkyl, C1-5 heteroalkyl, 3-6 membered heterocycloalkyl, 4-11 membered heterocycloalkyl and 5-6 membered heteroaryl is independently selected from the group consisting of N, —O—, —S—, —NH—, —(C═O)—, —(S═O— and —(S═O)2—;
in any of the above cases, the number of the heteroatom or the heteroatomic group is independently 1, 2 or 3.

### Claim 2 (depends on 1)

The compound of formula (I), the pharmaceutically acceptable salt thereof or the isomer thereof according to claim 1, wherein, R is selected from F, Cl, Br, OH, CN, NH2, CH3, CH3CH2, CH3O, CF3, CHF2, CH2F.

### Claim 3 (depends on 1)

The compound of formula (I), the pharmaceutically acceptable salt thereof or the isomer thereof according to claim 1, wherein, R1 is H, or selected from the group consisting of CH3, CH3CH2, CH3(C═O)—,
each of which is optionally substituted by 1, 2 or 3 R.

### Claim 4 (depends on 3)

The compound of formula (I), the pharmaceutically acceptable salt thereof or the isomer thereof according to claim 3, wherein, R1 is selected from CH3, CHF2, CH3(C═O)—,

### Claim 5 (depends on 1)

The compound of formula (I), the pharmaceutically acceptable salt thereof or the isomer thereof according to claim 1, wherein, ring B is selected from the group consisting of cyclobutyl, cyclopentyl, cyclohexyl and phenyl, each of which is optionally substituted by 1, 2 or 3 R.

### Claim 6 (depends on 5)

The compound of formula (I), the pharmaceutically acceptable salt thereof or the isomer thereof according to claim 5, wherein, ring B is selected from cyclopentyl, cyclohexyl, phenyl.

### Claim 7 (depends on 1)

The compound of formula (I), the pharmaceutically acceptable salt thereof or the isomer thereof according to claim 1, wherein, R2 is independently selected from H, OH, CN, F, Cl, or selected from the group consisting of CH3,
oxetanyl, piperazinyl and morpholinyl, each of which is optionally substituted by 1, 2 or 3 R.

### Claim 8 (depends on 7)

The compound of formula (I), the pharmaceutically acceptable salt thereof or the isomer thereof according to claim 7, wherein, R2 is independently H or selected from the group consisting of CH3,
each of which is optionally substituted by 1, 2 or 3 R.

### Claim 9 (depends on 8)

The compound of formula (I), the pharmaceutically acceptable salt thereof or the isomer thereof according to claim 8, wherein, R2 is independently selected from H, CH3,

### Claim 10 (depends on 1)

The compound of formula (I), the pharmaceutically acceptable salt thereof or the isomer thereof according to claim 1, wherein, ring A is 5-9 membered heterocycloalkyl.

### Claim 11 (depends on 10)

The compound of formula (I), the pharmaceutically acceptable salt thereof or the isomer thereof according to claim 10, wherein, the moiety
is selected from the group consisting of

### Claim 12 (depends on 11)

The compound of formula (I), the pharmaceutically acceptable salt thereof or the isomer thereof according to claim 11, wherein, the moiety
is selected from the group consisting of

### Claim 13 (depends on 11)

The compound of formula (I), the pharmaceutically acceptable salt thereof or the isomer thereof according to claim 11, wherein, the moiety
is selected from the group consisting of

### Claim 14 (depends on 1)

The compound of formula (I), the pharmaceutically acceptable salt thereof or the isomer thereof according to claim 1, wherein, the compound is selected from the group consisting of
wherein, R2 is as defined in claims 1,
R is as defined in claim 1;
ring A is as defined in claim 1.

### Claim 15 (depends on 1)

The compound of formula (I), the pharmaceutically acceptable salt thereof or the isomer thereof according to claim 1, wherein, the compound is
wherein, R1 is as defined in claim 1;
R2 is as defined in claim 1.

### Claim 16 (depends on 1)

The compound of formula (I), the pharmaceutically acceptable salt thereof or the isomer thereof according to claim 1, wherein, the compound is
wherein, R2 is as defined in claim 1.

### Claim 17

The compound, the pharmaceutically acceptable salt thereof or the isomer thereof represented by the following formulae:

### Claim 18 (depends on 1)

A pharmaceutical composition, comprising a therapeutically effective amount of the compound, the pharmaceutically acceptable salt thereof or the isomer thereof according to claim 1, and a pharmaceutically acceptable carrier.

### Claim 19

(canceled)

### Claim 20 (depends on 1)

A process for treating a cancer in a subject in need thereof, comprising:
administering an effective amount of the compound, the pharmaceutically acceptable salt thereof or the isomer thereof according to claim 1 to the subject.

### Claim 21 (depends on 17)

A process for treating a cancer in a subject in need thereof, comprising:
administering an effective amount of the compound, the pharmaceutically acceptable salt thereof or the isomer thereof according to claim 17 to the subject.