# US 11,306,078 B2 · Piperidine CXCR7 receptor modulators

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- Number: US 11,306,078 B2
- Document ID: US11306078B2
- Status: Granted
- Kind: B2
- Application number: 16/928,787
- Filed: 2020-07-14
- Published: 2020-12-10
- Granted: 2022-04-19
- Earliest claimed: 2016-07-28
- Assignees: Idorsia Pharmaceuticals Ltd
- Applicants: Idorsia Pharmaceuticals Ltd.
- Inventors: Hamed Aissaoui; Philippe Guerry; Francois Lehembre; Julien Pothier; Laetitia Pouzol; Sylvia Richard-Bildstein; Shuguang Yuan
- Web page: https://patentgrep.com/patent/US11306078B2

## CPC

- C07D 413/14: containing three or more hetero rings
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 401/14: containing three or more hetero rings
- C07D 413/12: linked by a chain containing hetero atoms as chain links
- C07D 417/14: containing three or more hetero rings
- C07B 2200/07: Optical isomers
- C07B 2200/09: Geometrical isomers
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- 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 relates to piperidine derivatives of formula (I) wherein Ar1, Ar2, RAr1, R1, R2, and R3 are as described in the description, their preparation, to pharmaceutically acceptable salts thereof, and to their use as pharmaceuticals, to pharmaceutical compositions containing one or more compounds of formula (I), and especially to their use as CXCR7 receptor modulators.

## Claims

### Claim 1

A compound of formula (I)
wherein
the two substituents of the piperidine ring: R1—CO— and —NH—CO—Ar1—Ar2, are in relative trans-configuration;
Ar1 represents an unsubstituted 5-membered heteroarylene group containing one sulfur ring atom and one or two nitrogen ring atoms, wherein the —NH—CO— group and Ar2 are attached in meta arrangement to ring atoms of Ar1;
Ar2 represents phenyl, or 6-membered heteroaryl; wherein said phenyl or 6-membered heteroaryl independently is mono-, di- or tri-substituted, wherein the substituents are independently selected from fluoro, chloro, methyl, cyano, methoxy, or (C1)fluoroalkyl;
R1 represents RN1RN2N—, wherein
RN1 represents
hydrogen;
(C1-6)alkyl;
(C1-6)alkyl which is mono-substituted with
hydroxy;
(C1-3)alkoxy;
2-hydroxy-ethoxy;
—CO—NH2;
—SO2—(C1-3)alkyl;
cyano;
(C1-3)fluoroalkoxy;
—NRN3RN4, wherein RN3 and RN4 independently represent hydrogen or (C1-4)alkyl;
(C2-6)alkynyl;
(C2-5)fluoroalkyl;
(C1-4)alkoxy;
2-(2-oxo-pyrrolidin-1-yl)-ethyl;
a group -L1-Cy1; wherein
L1 represents a direct bond, —(C1-3)alkylene-, or —(C3-5)cycloalkylene-; and
Cy1 represents (C3-6)cycloalkyl, wherein said (C3-6)cycloalkyl optionally contains one ring oxygen atom; wherein said (C3-6)cycloalkyl independently is unsubstituted; or mono-substituted with fluoro, methyl, or hydroxy, —CO—(C1-4)alkoxy, or cyano; or di-substituted with fluoro, or tri-substituted with methyl and two fluoro;
a group -L2-Ar3, wherein
L2 represents a direct bond, —(C1-4)alkylene-; *—(C3-5)cycloalkylene-(C0-2)alkylene- wherein said (C3-5)cycloalkylene optionally contains one ring oxygen atom, wherein the asterisk indicates the bond to which Ar3 is attached; *—(C1-2)alkylene-(C3-5)cycloalkylene- wherein said (C3-5)cycloalkylene optionally contains one ring oxygen atom, wherein the asterisk indicates the bond to which Ar3 is attached;
or —(C1-3)alkylene- which is mono-substituted with hydroxy, trifluoromethyl, or —CO—(C1-4)alkoxy; and
Ar3 represents phenyl, or 5- or 6-membered heteroaryl; wherein said phenyl or 5- or 6-membered heteroaryl independently is unsubstituted, or mono-, or di-substituted; wherein the substituents are independently selected from (C1-4)alkyl, (C1-4)alkoxy, halogen, hydroxy, (C1-3)fluoroalkyl, or (C1-3)fluoroalkoxy; wherein, in case Ar3 represents 6-membered heteroaryl which is pyridyl or pyrimidinyl, such pyridyl or pyrimidinyl may additionally be present in form of the respective N-oxide;
and RN2 independently represents hydrogen, (C1-4alkyl, or (C2-3)fluoroalkyl;
or RN1 and RN2 together with the nitrogen atom to which they are attached to form a 4- to 6-membered ring selected from
azetidinyl, pyrrolidinyl or piperidinyl; each independently
unsubstituted;
or mono-substituted with fluoro, methyl, or hydroxy;
or di-substituted with fluoro;
or mono-substituted with Ar4, wherein Ar4 represents phenyl, or 5- or 6-membered heteroaryl; wherein said phenyl or 5- or 6-membered heteroaryl independently is unsubstituted, or mono-, or di-substituted; wherein the substituents are independently selected from (C1-4)alkyl, (C1-4)alkoxy, halogen, (C1-3)fluoroalkyl, or (C1-3)fluoroalkoxy; or
morpholinyl;
R2 represents
hydrogen;
(C1-6)alkyl;
(C2-6)alkyl which is mono-substituted with (C1-3)alkoxy, or hydroxy;
(C3-5)alkenyl;
cyano-methyl;
(C2-3)fluoroalkyl;
(C3-8)cycloalkyl-(C0-3)alkyl; wherein the (C3-8)cycloalkyl is unsubstituted, or mono- or di-substituted wherein the substituents are independently selected from (C1-3)alkyl, fluoro, hydroxy, hydroxy-(C1-3)alkyl, (C1-3)alkoxy, or (C1-3)fluoroalkyl;
thietan-3-yl;
(C3-8)cycloalkenyl-(C1-3)alkyl; or
Ar5—CH2— wherein Ar5 represents phenyl, or 5- or 6-membered heteroaryl, wherein the phenyl or 5- or 6-membered heteroaryl independently is unsubstituted, or mono- or di-substituted wherein the substituents are independently selected from (C1-4)alkyl, (C1-4)alkoxy, halogen, (C1-3)fluoroalkyl, or (C1-3)fluoroalkoxy; and
R3 represents hydrogen, or methyl;
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The compound of formula (I) as defined for claim 1 which are also compounds of Formula (IS), wherein the two substituents of the piperidine ring: R1—CO— and —NH—CO—Ar1—Ar2, are in relative trans-configuration, wherein the absolute configuration of the two chiral carbon atoms in position 3 and 4 of the piperidine ring is (3S,4S):
or a pharmaceutically acceptable salt thereof.

### Claim 3 (depends on 2)

The compound according to claim 2; wherein R3 represents hydrogen;
or a pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 3)

The compound according to claim 3; wherein Ar1 represents [1,3,4]thiadiazol-2,5-diyl or isothiazol-3,5-diyl;
or a pharmaceutically acceptable salt thereof.

### Claim 5 (depends on 4)

The compound according to claim 4; wherein Ar2 represents phenyl which is mono-, di- or tri-substituted; wherein one or two of said substituents is/are independently selected from fluoro, chloro, and methyl, and the remaining, if present, is/are fluoro;
or a pharmaceutically acceptable salt thereof.

### Claim 6 (depends on 1)

The compound according to claim 1; wherein R1 represents RN1RN2N—, wherein
RN1 represents
(C1-6)alkyl;
(C1-6)alkyl which is mono-substituted with
hydroxy;
(C1-3)alkoxy;
2-hydroxy-ethoxy;
—CO—NH2;
—SO2—(C1-3)alkyl;
cyano;
(C1-3)fluoroalkoxy;
—NRN3RN4, wherein RN3 and RN4 independently represent hydrogen or (C1-4)alkyl;
(C2-6)alkynyl;
(C2-s)fluoroalkyl;
2-(2-oxo-pyrrolidin-1-yl)-ethyl;
a group -L1-Cy1; wherein
L1 represents a direct bond, —(C1-3)alkylene-, or —(C3-5)cycloalkylene-; and
Cy1 represents (C3-6)cycloalkyl, wherein said (C3-6)cycloalkyl optionally contains one ring oxygen atom; wherein said (C3-6)cycloalkyl independently is unsubstituted: or mono-substituted with fluoro, methyl, hydroxy, CO—(C1-4)alkoxy, or cyano; or di-substituted with fluoro, or tri-substituted with methyl and two fluoro;
a group -L2-Ar3, wherein
L2 represents a —(C1-4)alkylene-; —(C3-5)cycloalkylene- wherein said (C3-5)cycloalkylene optionally contains one ring oxygen atom; *—(C3-5)cycloalkylene-(C1-2)alkylene- wherein said (C3-5)cycloalkylene optionally contains one ring oxygen atom, wherein the asterisk indicates the bond to which Ar3 is attached; *—(C1-2)alkylene-(C3-5)cycloalkylene- wherein said (C3-5)cycloalkylene optionally contains one ring oxygen atom, wherein the asterisk indicates the bond to which Ar3 is attached;
or —(C1-3)alkylene- which is mono-substituted with hydroxy or trifluoromethyl; and
Ar3 represents phenyl, or 5-membered heteroaryl containing one oxygen atom and one or two nitrogen atoms, or 6-membered heteroaryl containing one or two nitrogen atoms; wherein said phenyl or 5- or 6-membered heteroaryl independently is unsubstituted, or mono-, or di-substituted; wherein the substituents are independently selected from (C1-4)alkyl, (C1-4)alkoxy, halogen, (C1-3)fluoroalkyl, or (C1-3)fluoroalkoxy; wherein, in case Ar3 represents 6-membered heteroaryl which is pyridyl or pyrimidinyl, such pyridyl or pyrimidinyl may additionally be present in form of the respective N-oxide;
and RN2 independently represents hydrogen, or (C1-4)alkyl;
or a pharmaceutically acceptable salt thereof.

### Claim 7 (depends on 1)

The compound according to claim 1; wherein
R1 represents RN1RN2N—, wherein
RN1 represents
(C3-6)cycloalkyl, wherein said (C3-6)cycloalkyl optionally contains one ring oxygen atom; wherein said (C3-6)cycloalkyl independently is unsubstituted, or mono-substituted with fluoro, methyl, or hydroxy, or di-substituted with fluoro, or tri-substituted with methyl and two fluoro;
(C3-6)cycloalkyl-(C1-3)alkylene-, wherein said (C3-6)cycloalkyl optionally contains one ring oxygen atom;
(C3-6)cycloalkyl-(C3-5)cycloalkylene-;
phenyl-(C1-4)alkylene- wherein said phenyl is unsubstituted, or mono-, or di-substituted; wherein the substituents are independently selected from (C1-4)alkyl, (C1-4)alkoxy, halogen, (C1-3)fluoroalkyl, or (C1-3)fluoroalkoxy;
phenyl-(C1-3)alkylene- wherein said —(C1-3)alkylene- is mono-substituted with hydroxy;
phenyl-(C3-5)cycloalkylene-; wherein said (C3-5)cycloalkylene optionally contains one ring oxygen atom, and wherein said phenyl is unsubstituted, or mono-, or di-substituted; wherein the substituents are independently selected from (C1-4)alkyl, (C1-4)alkoxy, halogen, hydroxy, (C1-3)fluoroalkyl, or (C1-3)fluoroalkoxy;
phenyl-(C3-5)cycloalkylene-(C1-2)alkylene- wherein said (C3-5)cycloalkylene optionally contains one ring oxygen atom, and wherein said phenyl is unsubstituted, or mono-substituted with halogen;
phenyl-(C1-2)alkylene-(C3-5)cycloalkylene- wherein said (C3-5)cycloalkylene optionally contains one ring oxygen atom;
5-membered heteroaryl-(C1-3)alkylene-, wherein said 5-membered heteroaryl contains one oxygen atom and one or two nitrogen atoms; and wherein said 5-membered heteroaryl is unsubstituted, or mono-, or di-substituted; wherein the substituents are independently selected from (C1-4)alkyl, (C1-4)alkoxy, halogen, (C1-3)fluoroalkyl, or (C1-3)fluoroalkoxy;
6-membered heteroaryl-(C1-4)alkylene-, wherein said 6-membered heteroaryl contains one or two nitrogen atoms; and wherein said 6-membered heteroaryl is unsubstituted, or mono-, or di-substituted; wherein the substituents are independently selected from (C1-4)alkyl, (C1-4)alkoxy, halogen, (C1-3)fluoroalkyl, or (C1-3)fluoroalkoxy; wherein, in case Ar3 represents pyridyl or pyrimidinyl, such pyridyl or pyrimidinyl may additionally be present in form of the respective N-oxide;
6-membered heteroaryl-(C1-3)alkylene-, wherein said —(C1-3)alkylene- is mono-substituted with hydroxy or trifluoromethyl; wherein said 6-membered heteroaryl contains one or two nitrogen atoms; or
6-membered heteroaryl-(C3-5)cycloalkylene-, wherein said 6-membered heteroaryl contains one or two nitrogen atoms; and wherein said 6-membered heteroaryl is unsubstituted, or mono-, or di-substituted; wherein the substituents are independently selected from (C1-4)alkyl, (C1-4)alkoxy, halogen, (C1-3)fluoroalkyl, or (C1-3)fluoroalkoxy; wherein, in case Ar3 represents pyridyl or pyrimidinyl, such pyridyl or pyrimidinyl may additionally be present in form of the respective N-oxide;
6-membered heteroaryl-(C3-5)cycloalkylene-(C1-2)alkylene- wherein said 6-membered heteroaryl contains one or two nitrogen atoms; and wherein said 6-membered heteroaryl is unsubstituted;
and RN2 independently represents hydrogen, or (C1-4)alkyl;
or RN1 represents (C1-3)alkyl; and RN2 represents hydrogen, or methyl;
or a pharmaceutically acceptable salt thereof.

### Claim 8 (depends on 5)

The compound according to claim 5; wherein R1 represents RN1RN2N—, wherein
RN1 represents
(C3-6)cycloalkyl-(C1-3)alkylene-, wherein said (C3-6)cycloalkyl optionally contains one ring oxygen atom;
phenyl-(C1-4)alkylene- wherein said phenyl is unsubstituted, or mono-, or di-substituted; wherein the substituents are independently selected from (C1-4)alkyl, (C1-4)alkoxy, halogen, (C1-3)fluoroalkyl, or (C1-3)fluoroalkoxy;
phenyl-(C3-5)cycloalkylene- wherein said (C3-5)cycloalkylene optionally contains one ring oxygen atom, and wherein said phenyl is unsubstituted, or mono-, or di-substituted; wherein the substituents are independently selected from (C1-4)alkyl, (C1-4)alkoxy, halogen, hydroxy, (C1-3)fluoroalkyl, or (C1-3)fluoroalkoxy;
6-membered heteroaryl-(C1-4)alkylene-, wherein said 6-membered heteroaryl contains one or two nitrogen atoms; and wherein said 6-membered heteroaryl is unsubstituted, or mono-, or di-substituted; wherein the substituents are independently selected from (C1-4)alkyl, (C1-4)alkoxy, halogen, (C1-3)fluoroalkyl, or (C1-3)fluoroalkoxy; wherein, in case Ar3 represents pyridyl or pyrimidinyl, such pyridyl or pyrimidinyl may additionally be present in form of the respective N-oxide;
6-membered heteroaryl-(C3-5)cycloalkylene-, wherein said 6-membered heteroaryl contains one or two nitrogen atoms; and wherein said 6-membered heteroaryl is unsubstituted, or mono-, or di-substituted; wherein the substituents are independently selected from (C1-4)alkyl, (C1-4)alkoxy, halogen, (C1-3)fluoroalkyl, or (C1-3)fluoroalkoxy; wherein, in case Ar3 represents pyridyl or pyrimidinyl, such pyridyl or pyrimidinyl may additionally be present in form of the respective N-oxide;
and RN2 independently represents hydrogen, or (C1-4)alkyl;
or a pharmaceutically acceptable salt thereof.

### Claim 9 (depends on 5)

The compound according to claim 5; wherein R1 represents RN1RN2N—, wherein
RN1 represents
6-membered heteroaryl-(C1-4)alkylene-, wherein said 6-membered heteroaryl contains one or two nitrogen atoms; and wherein said 6-membered heteroaryl is unsubstituted, or mono-, or di-substituted; wherein the substituents are independently selected from (C1-4)alkyl, (C1-4)alkoxy, halogen, (C1-3)fluoroalkyl, or (C1-3)fluoroalkoxy; wherein, in case Ar3 represents pyridyl or pyrimidinyl, such pyridyl or pyrimidinyl may additionally be present in form of the respective N-oxide;
6-membered heteroaryl-(C3-5)cycloalkylene-, wherein said 6-membered heteroaryl contains one or two nitrogen atoms; and wherein said 6-membered heteroaryl is unsubstituted, or mono-, or di-substituted; wherein the substituents are independently selected from (C1-4)alkyl, (C1-4)alkoxy, halogen, (C1-3)fluoroalkyl, or (C1-3)fluoroalkoxy; wherein, in case Ar3 represents pyridyl or pyrimidinyl, such pyridyl or pyrimidinyl may additionally be present in form of the respective N-oxide;
and RN2 independently represents hydrogen or methyl;
or a pharmaceutically acceptable salt thereof.

### Claim 10 (depends on 7)

The compound according to claim 7; wherein R2 represents
(C3-8)cycloalkyl-(C1-3)alkyl, wherein the (C3-8)cycloalkyl is unsubstituted; or mono-substituted wherein the substituent is (C1-3)alkyl, fluoro, or (C1-3)fluoroalkyl; or di-substituted with fluoro; or
(C3-8)cycloalkyl, wherein the (C3-8)cycloalkyl is unsubstituted, or mono- or di-substituted wherein the substituents are independently selected from (C1-3)alkyl, or fluoro;
or a pharmaceutically acceptable salt thereof.

### Claim 11 (depends on 8)

The compound according to claim 8; wherein R2 represents
unsubstituted (C3-8)cycloalkyl-(C1-3)alkyl; or
unsubstituted (C3-6)cycloalkyl; or
(C3-8)cycloalkyl, wherein the (C3-8)cycloalkyl is di-substituted with fluoro; or
(C3-8)cycloalkyl-(C1-3)alkyl; wherein the (C3-8)cycloalkyl is mono-substituted with methyl, fluoro, or (C1)fluoroalkyl; or di-substituted with fluoro;
or a pharmaceutically acceptable salt thereof.

### Claim 12 (depends on 1)

The compound according to claim 1 which is:
(3S,4S)-1-Cyclobutyl-4-{[5-(2,4-difluoro-phenyl)-[1,3,4]thiadiazole-2-carbonyl]-amino}-piperidine-3-carboxylic acid (1-pyrimidin-2-yl-cyclopropyl)-amide;
(3S,4S)-4-{[5-(2,4-difluoro-phenyl)-[1,3,4]thiadiazole-2-carbonyl]-amino}-1-(1-fluoro-cyclopropylmethyl)-piperidine-3-carboxylic acid (1-pyrimidin-2-yl-cyclopropyl)-amide; or
(3S,4S)-1-Cyclopropylmethyl-4-{[5-(2,4-difluoro-phenyl)-[1,3,4]thiadiazole-2-carbonyl]-amino}-piperidine-3-carboxylic acid (1-pyrimidin-2-yl-cyclopropyl)-amide; or a pharmaceutically acceptable salt thereof.

### Claim 13 (depends on 1)

The compound according to claim 1 which is (3S,4S)-1-Cyclopropylmethyl-4-{[5-(2,4-difluoro-phenyl)-[1,3,4]thiadiazole-2-carbonyl]-amino}-piperidine-3-carboxylic acid (1-pyrimidin-2-yl-cyclopropyl)-amide; or a pharmaceutically acceptable salt thereof.

### Claim 14 (depends on 1)

The compound according to claim 1 which is (3S,4S)-1-Cyclopropylmethyl-4-{[5-(2,4-difluoro-phenyl)-[1,3,4]thiadiazole-2-carbonyl]-amino}-piperidine-3-carboxylic acid (1-pyrimidin-2-yl-cyclopropyl)-amide; wherein said compound is in free form.

### Claim 15 (depends on 1)

The compound according to claim 1 which is (3S,4S)-1-Cyclopropylmethyl-4-{[5-(2,4-difluoro-phenyl)-[1,3,4]thiadiazole-2-carbonyl]-amino}-piperidine-3-carboxylic acid (1-pyrimidin-2-yl-cyclopropyl)-amide; wherein said compound is in pharmaceutically acceptable salt form.

### Claim 16 (depends on 1)

A pharmaceutical composition comprising, as active principle, one or more compounds according to claim 1, or a pharmaceutically acceptable salt thereof, and at least one therapeutically inert excipient.

### Claim 17 (depends on 11)

A pharmaceutical composition comprising, as active principle, one or more compounds according to claim 11, or a pharmaceutically acceptable salt thereof, and at least one therapeutically inert excipient.

### Claim 18 (depends on 12)

A pharmaceutical composition comprising, as active principle, one or more compounds according to claim 12, or a pharmaceutically acceptable salt thereof, and at least one therapeutically inert excipient.

### Claim 19 (depends on 13)

A pharmaceutical composition comprising, as active principle, one or more compounds according to claim 13, or a pharmaceutically acceptable salt thereof, and at least one therapeutically inert excipient.

### Claim 20 (depends on 11)

A method for the treatment of cancer; comprising administering to a subject in need thereof an effective amount of a compound of formula (I) as defined in claim 11, or a pharmaceutically acceptable salt thereof.

### Claim 21 (depends on 11)

A method of treating tumors comprising administering an effective amount of the compound of formula (Ia) according to claim 11, or a pharmaceutically acceptable salt thereof, wherein said effective amount leads to a change of tumor properties, and wherein said modification is achieved by modulating the CXCL11/CXCL12 receptor pathway.

### Claim 22 (depends on 11)

A method for the treatment of fibrosis; comprising administering to a subject in need thereof an effective amount of a compound of formula (I) as defined in claim 11, or a pharmaceutically acceptable salt thereof.

### Claim 23 (depends on 11)

A method for the treatment of autoimmune disorders which have an inflammatory component selected from inflammatory demyelinating diseases, multiple sclerosis (MS), Guillain Barré syndrome, rheumatoid arthritis (RA), inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), lupus nephritis, and auto-immune encephalomyelitis; comprising administering to a subject in need thereof an effective amount of a compound of formula (I) as defined in claim 11, or a pharmaceutically acceptable salt thereof.

### Claim 24 (depends on 11)

A method for the treatment of inflammatory diseases selected from
lung inflammatory diseases selected from asthma, chronic obstructive pulmonary disorder (COPD), and acute lung injury; and
atherosclerosis;
comprising administering to a subject in need thereof an effective amount of a compound of formula (I) as defined in claim 11, or a pharmaceutically acceptable salt thereof.

### Claim 25 (depends on 13)

A method for the treatment of cancer; comprising administering to a subject in need thereof an effective amount of a compound of formula (I) as defined in claim 13, or a pharmaceutically acceptable salt thereof.

### Claim 26 (depends on 13)

A method of treating tumors comprising administering an effective amount of the compound of claim 13, or a pharmaceutically acceptable salt thereof, wherein said effective amount leads to a change of tumor properties, and wherein said modification is achieved by modulating the CXCL11/CXCL12 receptor pathway.

### Claim 27 (depends on 13)

A method for the treatment of fibrosis; comprising administering to a subject in need thereof an effective amount of a compound of formula (I) as defined in claim 13, or a pharmaceutically acceptable salt thereof.

### Claim 28 (depends on 13)

A method for the treatment of autoimmune disorders which have an inflammatory component selected from inflammatory demyelinating diseases, multiple sclerosis (MS), Guillain Barré syndrome, rheumatoid arthritis (RA), inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), lupus nephritis, and auto-immune encephalomyelitis; comprising administering to a subject in need thereof an effective amount of a compound of formula (I) as defined in claim 13, or a pharmaceutically acceptable salt thereof.

### Claim 29 (depends on 13)

A method for the treatment of inflammatory diseases selected from
lung inflammatory diseases selected from asthma, chronic obstructive pulmonary disorder (COPD), and acute lung injury; and
atherosclerosis;
comprising administering to a subject in need thereof an effective amount of a compound of formula (I) as defined in claim 13, or a pharmaceutically acceptable salt thereof.