# US 8,569,306 B2 · JNK modulators

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

- Number: US 8,569,306 B2
- Document ID: US8569306B2
- Status: Granted
- Kind: B2
- Application number: 13/202,779
- Filed: 2010-02-19
- Published: 2011-12-15
- Granted: 2013-10-29
- Earliest claimed: 2009-02-24
- Assignees: Hoffmann-La Roche Inc.
- Applicants: Bernd Buettelmann; Bindu Goyal; Wylie Solang Palmer
- Inventors: Bernd Buettelmann; Bindu Goyal; Wylie Solang Palmer
- Web page: https://patentgrep.com/patent/US8569306B2

## CPC

- C07D 471/04: Ortho-condensed systems
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/06: Antiasthmatics
- A61P 17/00: Drugs for dermatological disorders
- A61P 19/00: Drugs for skeletal disorders
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 19/06: Antigout agents, e.g. antihyperuricemic or uricosuric agents
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/04: Antibacterial agents
- A61P 31/12: Antivirals
- A61P 31/22: for herpes viruses
- A61P 33/06: Antimalarials
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Compounds of formula (I) modulate JNK wherein X1 and X2 are each simultaneously N or CH; X3 is CH—R2 Or N—SO2R, where R is lower alkyl; R1 is aryl or heteroaryl, substituted with 0-3 lower alkyl radicals; R2 is (II), where R3 is H, lower acyl, or an amino acid, or a pharmaceutically acceptable salt thereof.

## Claims

### Claim 1

A compound of formula I:
wherein
R1 is —OH, —OR, or hydroxy-lower alkyl, where R is lower alkyl, benzyl, aryl-lower alkyl, or methylsulfonyl-lower alkyl;
R2 is —OH, —NH2, —CH2SO2R4, —SO2R4—NHSO2R4, —CO2R5, or
where R3 is H, lower acyl, or an amino acid; R4 is lower alkyl, —NH2, lower alkyl-amino, or di(lower alkyl)amino; R5 is H or lower alkyl;
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The compound of claim 1, wherein
R1 is —OH, —OR, or hydroxy-lower alkyl, where R is lower alkyl, benzyl, aryl-lower alkyl, or methylsulfonyl-lower alkyl;
R2 is —OH, —NH2, —SO2R4, —NHSO2R4, —CO2R5, or
where R3 is H, lower acyl, or an amino acid; R4 is lower alkyl, —NH2, lower alkyl-amino, or di(lower alkyl)-amino; R5 is H or lower alkyl;
or a pharmaceutically acceptable salt thereof.

### Claim 3 (depends on 2)

The compound according to claim 2, wherein R2 is —NHSO2CH3.

### Claim 4 (depends on 2)

The compound according to claim 2, wherein R1 is 2-hydroxy-prop-2-yl.

### Claim 5 (depends on 2)

The compound according to claim 2, wherein R1 benzyloxy.

### Claim 6 (depends on 2)

The compound according to claim 2, wherein R2 is 4-hydroxy-piperidin-1-carbonyl.

### Claim 7 (depends on 6)

The compound of claim 6, wherein R1 is 2-hydroxy-prop-2-yl.

### Claim 8 (depends on 6)

The compound of claim 6, wherein R1 is benzyloxy.

### Claim 9 (depends on 6)

The compound of claim 6, wherein R1 is 3-methanesulfonylpropoxy.

### Claim 10 (depends on 1)

The compound of claim 1, wherein R2 is —NHSO2N(CH3)2.

### Claim 11 (depends on 1)

The compound of claim 1, selected from the group consisting of:
2-{3-[2-(4-methanesulfonylmethyl-cyclohexylamino)-pyrimidin-4-yl]-imidazo[1,2-a]pyridine-8-yl}-propan-2-ol;
(4-{4-[8-(1-hydroxy-1-methyl-ethyl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-cyclohexyl)-(4-hydroxy-piperidin-1-yl)-methanone;
N-(4-{4-[8-(1-hydroxy-1-methyl-ethyl)-imidazo[1,2-a]pyridine-3-yl]-pyrimidin-2-ylamino}-cyclohexyl)-methanesulfonamide;
N-(4-{4-[8-(1-hydroxy-1-methyl-ethyl)-imidazo[1,2-a]pyridine-3-yl]-pyrimidin-2-ylamino}-cyclohexyl)-(N,N-dimethylamino)sulfonamide;
(4-hydroxy-piperidin-1-yl)-(4-{4-[8-(3-methanesulfonyl-propoxy)-imidazo[1,2-a]pyridin-3-yl]-pyridmidin-2-ylamino}-cyclohexyl)-methanone;
{4-[4-(8-benzyloxy-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-2-ylamino]-cyclohexyl}-(4-hydroxy-piperidin-1-yl)-methanone;
N-{4-[4-(8-benzyloxy-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-2-ylamino]-cyclohexyl}-methanesulfonamide;
4-[4-(8-benzyloxy-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-2-ylamino]-cyclohexanecarboxylic acid ethyl ester; and
4-[4-(8-benzyloxy-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-2-ylamino]-cyclohexanol.

### Claim 12

A pharmaceutical composition for treating inflammation, comprising: an effective amount of a compound of Formula I:
wherein
R1 is —OH, —OR, or hydroxy-lower alkyl, where R is lower alkyl, benzyl, aryl-lower alkyl, or methylsulfonyl-lower alkyl;
R2 is —OH, —NH2, —SO2R4, —NHSO2R4, —CO2R5, or
where R3 is H, lower acyl, or an amino acid; R4 is lower alkyl, —NH2, lower alkyl-amino, or di(lower alkyl)amino; R5 is H or lower alkyl;
or a pharmaceutically acceptable salt thereof;
and a pharmaceutically acceptable excipient.

### Claim 13

A method of treating a subject for inflammation, said method comprising:
administering to a subject in need thereof an effective amount of a compound of formula I:
wherein
R1 is —OH, —OR, or hydroxy-lower alkyl, where R is lower alkyl, benzyl, aryl-lower alkyl, or methylsulfonyl-lower alkyl;
R2 is —OH, —NH2, —SO2R4, —NHSO2R4, —CO2R5, or
where R3 is H, lower acyl, or an amino acid; R4 is lower alkyl, —NH2, lower alkyl-amino, or di(lower alkyl)-amino; R5 is H or lower alkyl;
or a pharmaceutically acceptable salt thereof.

### Claim 14

A method of inhibiting the activity of JNK, comprising:
contacting said JNK with an effective concentration of a compound of formula I:
wherein
R1 is —OH, —OR, or hydroxy-lower alkyl, where R is lower alkyl, benzyl, aryl-lower alkyl, or methylsulfonyl-lower alkyl;
R2 is —OH, —NH2, —SO2R4, —NHSO2R4, —CO2R5, or
where R3 is H, lower acyl, or an amino acid; R4 is lower alkyl, —NH2, lower alkyl-amino, or di(lower alkyl)-amino; R5 is H or lower alkyl;
or a pharmaceutically acceptable salt thereof.