# US 10,479,784 B2 · Substituted pyrazin-2-amines as inhibitors of ATR kinase

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- Number: US 10,479,784 B2
- Document ID: US10479784B2
- Status: Granted
- Kind: B2
- Application number: 15/967,110
- Filed: 2018-04-30
- Published: 2019-02-14
- Granted: 2019-11-19
- Earliest claimed: 2008-12-19
- Assignees: Vertex Pharmaceuticals Incorporated
- Applicants: Vertex Pharmaceuticals Incorporated
- Inventors: Jean-Damien Charrier; Steven John Durrant; David Kay; Ronald Marcellus Alphonsus Knegtel; Somhairle MacCormick; Michael Paul Mortimore; Michael Edward O'Donnell; Joanne Pinder; Alistair Rutherford; Anisa Nizarali Virani; Stephen Clinton Young; Philip Michael Reaper
- Web page: https://patentgrep.com/patent/US10479784B2

## CPC

- C07D 413/14: containing three or more hetero rings
- A61P 35/00: Antineoplastic agents
- C07D 241/28: in which said hetero-bound carbon atoms have double bonds to oxygen, sulfur or nitrogen atoms
- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- C07D 401/10: linked by a carbon chain containing aromatic rings
- C07D 401/14: containing three or more hetero rings
- C07D 403/04: directly linked by a ring-member-to-ring-member bond
- C07D 403/10: linked by a carbon chain containing aromatic rings
- C07D 403/12: linked by a chain containing hetero atoms as chain links
- C07D 403/14: containing three or more hetero rings
- C07D 405/04: directly linked by a ring-member-to-ring-member bond
- C07D 405/12: linked by a chain containing hetero atoms as chain links
- C07D 405/14: containing three or more hetero rings
- C07D 409/04: directly linked by a ring-member-to-ring-member bond
- C07D 409/14: containing three or more hetero rings
- C07D 413/04: directly linked by a ring-member-to-ring-member bond
- C07D 413/12: linked by a chain containing hetero atoms as chain links
- C07D 417/04: directly linked by a ring-member-to-ring-member bond
- C07D 417/12: linked by a chain containing hetero atoms as chain links
- C07D 417/14: containing three or more hetero rings
- C07D 471/04: Ortho-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to pyrazine compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. The compounds of this invention have formula I: wherein the variables are as defined herein.

## Claims

### Claim 1

A compound selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

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

### Claim 3 (depends on 1)

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

### Claim 4 (depends on 1)

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

### Claim 5 (depends on 1)

A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 1, or a pharmaceutically acceptable salt thereof.

### Claim 6 (depends on 1)

A method of sensitizing a cancer cell in a patient to a DNA damaging agent, comprising administering to a patient in need thereof an effective amount of the compound of claim 1.

### Claim 7 (depends on 6)

The method of claim 6, wherein the cancer cell expresses a DNA damaging oncogene.

### Claim 8 (depends on 7)

The method of claim 7, wherein the cancer cell has altered expression or activity of one or more proteins selected from the group consisting of K-Ras, N-Ras, H-Ras, Raf, Myc, Mos, E2F, Cdc25A, CDC4, CDK2, Cyclin E, Cyclin A and Rb.

### Claim 9 (depends on 6)

The method of claim 6, wherein the cancer cell has a defect in ataxia telangiectasia mutated signaling cascade.

### Claim 10 (depends on 9)

The method of claim 9, wherein the defect is altered expression or activity of one or more proteins selected from the group consisting of ataxia telangiectasia mutated, p53, checkpoint kinase 2, MRE11, RAD50, NBS1, 53BP1, MDC1 and H2AX.