# US 8,772,305 B2 · Substituted pyridinyl-pyrimidines and their use as medicaments

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- Number: US 8,772,305 B2
- Document ID: US8772305B2
- Status: Granted
- Kind: B2
- Application number: 13/357,734
- Filed: 2012-01-25
- Published: 2013-01-24
- Granted: 2014-07-08
- Earliest claimed: 2011-01-28
- Assignees: Boehringer Ingelheim International GmbH
- Applicants: Georg Dahmann; Dennis Fiegen; Martin Fleck; Matthias Hoffmann; Jasna Klicic; Stephen Peter East; Spencer Charles R. Napier; John Scott
- Inventors: Georg Dahmann; Dennis Fiegen; Martin Fleck; Matthias Hoffmann; Jasna Klicic; Stephen Peter East; Spencer Charles R. Napier; John Scott
- Web page: https://patentgrep.com/patent/US8772305B2

## CPC

- C07D 401/14: containing three or more hetero rings
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 7/04: Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
- A61P 7/06: Antianaemics
- A61P 7/10: Antioedematous agents; Diuretics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/02: Nasal agents, e.g. decongestants
- A61P 11/06: Antiasthmatics
- A61P 11/08: Bronchodilators
- A61P 13/12: of the kidneys
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/04: Antipruritics
- A61P 17/06: Antipsoriatics
- A61P 19/00: Drugs for skeletal disorders
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 19/10: for osteoporosis
- A61P 21/04: for myasthenia gravis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 27/02: Ophthalmic agents
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/02: Immunomodulators
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 405/14: containing three or more hetero rings
- C07D 409/14: containing three or more hetero rings
- C07D 413/14: containing three or more hetero rings
- C07D 417/14: containing three or more hetero rings
- C07D 471/04: Ortho-condensed systems
- C07D 471/08: Bridged systems
- C07D 471/10: Spiro-condensed systems
- C07D 487/04: Ortho-condensed systems
- C07D 487/10: Spiro-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The invention relates to new substituted pyridinyl-pyrimidines of formula 1 wherein ring A is a five-membered saturated or unsaturated carbocyclic ring which optionally comprises one, two or three heteroatoms each independently from each other selected from the group N, S and O, wherein R1, R2, R4, R3, R5 and R6 are defined as in claim 1 and wherein ring A is further optionally substituted by one or two further substituents and the pharmaceutically acceptable salts, diastereomers, enantiomers, racemates, hydrates and solvates of the aforementioned compounds.

## Claims

### Claim 1

A compound of formula 1
wherein
ring A is a five-membered saturated or unsaturated carbocyclic ring which optionally comprises one, two or three heteroatoms each independently from each other selected from the group N, S and O,
wherein ring A may optionally be further substituted by one or two residues which are both independently from each other selected from the group consisting of H, halogen, C1-3-alkyl, -oxo, —NH2, —CO—(C1-3-alkyl), —CO—NH(C1-3-alkyl), —CO—N(C1-3-alkyl)2, —SO2-phenyl and —SO2—(C1-3-alkyl),
and wherein
R1 is selected from the group consisting of
H, -halogen, SH, -oxo, —NH2, —CO—Y, —CO—N(CH3)—Y, —CO—N(CH3)—(C1-3-alkylene)-Y, —CS—Y, —CS—N(CH3)—Y, —CS—N(CH3)—(C1-3-alkylene)-Y, —C1-6-alkyl, —C1-3-haloalkyl, —CO—NH—Y, —CO—NH—C1-4-alkylene-Y, —CO—NH—C1-4-alkylene-(Y)2, —CO—N(CH3)—(C2-3-alkylene)-O—(C1-3-alkyl), —NH2, —C1-6-alkylene-L, —SO2-phenyl, —SO2—(C1-3-alkyl), —CO—N(C1-4-alkyl)2, —CO—N(C2-4-alkylene-O—C1-3-alkyl)2, a five- or six-membered heteroaromatic group comprising 1, 2 or 3 heteroatoms each independently selected from the group N, S and O,
with Y being a group selected from the group consisting of —NH2, —NH(CH3), —N(CH3)2, —C1-6-alkylene-N(CH3)2, —O—C1-3-alkyl, —OH and —N(ethyl)2,
or with Y being a group selected from the group consisting of a four-, five-, six- or seven-membered monocyclic fully saturated or partially unsaturated heterocycle comprising 1, 2 or 3 heteroatoms each independently selected from the group N, S and O, with the proviso that this heterocycle comprises at least one N-atom and that this heterocycle is directly attached to the molecule via this N-atom, a five- or six-membered monocyclic heteroaromatic group comprising 1, 2 or 3 heteroatoms each independently selected from the group of N, S and O, and a C3-6-cycloalkyl,
or with Y being a 9- to 11-membered bicyclic annellated fully saturated or partially unsaturated heterocycle comprising 1, 2, 3 or 4 heteroatoms each independently from each other selected from the group N, S and O,
or with Y being an 8- to 11-membered bicyclic fully saturated spiro-heterocycle comprising 1, 2 or 3 heteroatoms each independently selected from the group N, S and O, with the proviso that this spiro-heterocycle comprises at least one N-atom and that this heterocycle is directly attached to the molecule via this N-atom,
or with Y being a six- or seven-membered fully saturated heterocycle comprising 1, 2 or 3 heteroatoms each independently selected from the group N, S and O, which is bridged by an additional C1-3-alkylene-unit,
whereby each Y may optionally be substituted by one or more groups Z each independently from each other selected from the group consisting of halogen, -oxo, OH, C1-5-alkyl, —C1-5-alkanol, —O—C1-3-alkyl, a five-, six- or seven-membered fully saturated or partially unsaturated heterocycle comprising 1, 2 or 3 heteroatoms each independently selected from the group N, S and O; a fully saturated or partially unsaturated C3-6-cycloalkyl, a five- to six-membered heteroaromatic group comprising 1, 2 or 3 heteroatoms each independently selected from the group N, S and O; —CO-L, —C1-3-alkylene-CO-L, —C1-3-alkylene-O—C1-3-alkyl, —N(CH3)2 and —N(ethyl)2,
whereby each group Z may optionally be further substituted by one, two or three groups T each independently selected from the group consisting of -oxo, OH, halogen, —C1-3-alkyl, —O—C1-3-alkyl, —N(methyl)2, —N(ethyl)2, 5- to 6-membered fully saturated, partially unsaturated or aromatic heterocycle comprising 1 or 2 heteroatoms each independently selected from the group N, O and S, a C3-6-cycloalkyl and —CN,
wherein each group T may also optionally be substituted by a group selected from the group consisting of C1-3-alkyl, halogen, OH, oxo and —O—C1-3-alkyl,
whereby L denotes a 5- or 6-membered fully saturated or partially unsaturated heterocycle comprising 1 or 2 heteroatoms each independently selected from the group N, O and S, which said heterocycle may optionally be substituted by one, two or three groups independently selected from among methyl, halogen, OH and -oxo,
wherein R2 denotes a group selected from the group consisting of hydrogen, —OH, halogen, —CO—NH—NH2 and —CO—NH2,
or R2 denotes a group selected from the group consisting of linear or branched C1-6-alkyl, —C1-6-haloalkyl, —R3, —O—R3, —O—C1-3-alkylene-R3, —C1-3-alkylene-O—C1-3-alkyl, linear or branched —O—C2-8-alkanol, linear or branched —O—C1-3-haloalkyl, —C3-6-cycloalkyl, —O—C2-4-alkylene-O—C1-3-alkyl, —CO—R3, —C1-4-alkylene-R3, —O—C2-6-alkenyl, —O—C2-4-alkylene-N(CH3)—C1-3-alkyl, —CO—N(C1-3-alkyl)2 and —CO—NH(C1-3-alkyl), which may optionally be substituted by one, two or three substituents each independently selected from the group consisting of —CN, —NH2, —C1-2-alkylene-CN, —OH, —C1-2-alkylene-OH, halogen, -oxo, —C1-3-alkyl, —O—R3, —C1-3-alkylene-O—R3, —CO—C1-6-alkyl, —CO—NH2, —CO—N(CH3)2, —C1-3-alkylene-NH2, phenyl, —C1-2-alkylene-OH and —CO—C1-2-alkyl,
wherein each R3 denotes independently from each other a group selected from a linear or branched C1-10-alkyl, linear or branched C1-4-haloalkyl, fully saturated or partially unsaturated C3-8-cycloalkyl, —C1-3-alkylene-C3-6-cycloalkyl, a four-, five- or six-membered monocyclic either fully saturated or partially unsaturated heterocycle comprising 1, 2 or 3 heteroatoms each independently selected from N, S or O, a five- to six-membered heteroaromatic group comprising 1, 2 or 3 heteroatoms each independently selected from the group N, S and O, linear or branched —C2-5-alkenyl, phenyl and a nine- or ten-membered fully saturated, aromatic or partially unsaturated, bicyclic heterocycle comprising 1, 2 or 3 heteroatoms each independently selected from the group N, S and O
wherein R4 denotes a group selected from H, F, Cl, Br, OH, —O—C1-3-alkyl, —C1-4-alkyl, —C1-3-alkylene-OH and —CN,
wherein R5 denotes a group selected from H, F, Cl, Br, OH, —O—C1-3-alkyl, —C1-4-alkyl, —C1-3-alkylene-OH and —CN,
wherein R6 denotes a group selected from H, halogen, C1-3-alkyl, —NH2, —C1-3-haloalkyl and —C1-4-alkoxy
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The compound of formula 1 according to claim 1, wherein ring A is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.

### Claim 3 (depends on 2)

The compound of formula 1 according to claim 2, wherein ring A is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 3)

The compound of formula 1 according to claim 3, wherein
R2 denotes a group selected from the group consisting of hydrogen, —OH, F, Cl, —CO—NH—NH2 and —CO—NH2,
or wherein
R2 denotes a group selected from the group consisting of linear or branched C1-6-alkyl, —C1-6-fluoroalkyl, —C1-6-chloroalkyl, —R3, —O—R3, —O—C1-3-alkylene-R3, —C1-3-alkylene-O—C1-3-alkyl, linear or branched —O—C2-8-alkanol, linear or branched —O—C1-3-haloalkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, —O—C2-4-alkylene-O—C1-3-alkyl, —CO—R3, —C1-4-alkylene-R3, —O—C2-6-alkenyl, —O—C2-3-alkylene-N(CH3)—C1-3-alkyl, —CO—N(CH3)2 and —CO—NH—C1-3-alkyl, which may optionally be substituted by one, two or three substituents each independently selected from the group consisting of —CN, —NH2, —C1-2-alkylene-CN, —OH, —C1-2-alkylene-OH, F, Cl, -oxo, —C1-3-alkyl, —O—R3, —C1-3-alkylene-O—R3, —CO—C1-6-alkyl, —CO—NH2, —CO—N(CH3)2, —C1-3-alkylene-NH2, phenyl, —C1-2-alkylene-OH and —CO—C1-2-alkyl,
wherein each R3 denotes independently from each other a group selected from a linear or branched C1-6-alkyl, linear or branched C1-4-fluoroalkyl, linear or branched C1-4-chloroalkyl, linear or branched C2-5-alkenyl, fully saturated or partially unsaturated C3-8-cycloalkyl, —C1-3-alkylene-C3-6-cycloalkyl, a four-, five- or six-membered monocyclic, either fully saturated or partially unsaturated heterocycle comprising 1, 2 or 3 heteroatoms each independently selected from the group N, S and O, a five- to six-membered heteroaromatic group comprising 1, 2 or 3 heteroatoms each independently selected from the group N, S and O, phenyl and a nine- or ten-membered fully saturated, aromatic or partially unsaturated, bicyclic heterocycle comprising 1, 2 or 3 heteroatoms each independently selected from the group N, S and O,
or a pharmaceutically acceptable salt thereof.

### Claim 5 (depends on 4)

The compound of formula 1 according to claim 4, wherein
R1 is selected from the group consisting of H, F, Cl, SH, -oxo, —NH2, —CO—Y, —CO—N(CH3)—Y, —CO—N(CH3)—(C1-3-alkylene)-Y, —CS—Y, —CS—N(CH3)—Y, —CS—N(CH3)—(C1-3-alkylene)-Y, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, —C1-3-fluoroalkyl, —C1-3-chloroalkyl, —CO—NH—Y, —CO—NH—C1-4-alkylene-Y, —CO—NH—C1-4-alkylene-(Y)2, —CO—N(CH3)—(C2-3-alkylene)-O—(C1-3-alkyl), —NH2, —C1-6-alkylene-L, —SO2-phenyl, —SO2—(C1-3-alkyl), —CO—N(C1-4-alkyl)2, —CO—N(C2-4-alkylene-O—C1-3-alkyl)2, a five- or six-membered heteroaromatic group comprising 1, 2 or 3 heteroatoms each independently selected from the group N, S and O,
with Y being a group selected from the group consisting of —NH2, —NH(CH3), —N(CH3)2, —C1-6-alkylene-N(CH3)2; —O—C1-3-alkyl, OH and —N(ethyl)2,
or with Y being a group selected from the group consisting of a four-, five-, six- or seven-membered monocyclic fully saturated or partially unsaturated heterocycle comprising 1, 2 or 3 heteroatoms each independently selected from the group N, S and O with the proviso hat this heterocycle comprises at least one N-atom and that this heterocycle is directly attached to the molecule via this N-atom, a five- or six-membered monocyclic heteroaromatic group comprising 1, 2 or 3 heteroatoms each independently selected from the group of N, S and O, and a C3-6-cycloalkyl,
or with Y being a 9- to 11-membered bicyclic annellated fully saturated or partially unsaturated heterocycle comprising 1, 2, 3 or 4 heteroatoms each independently from each other selected from the group N, S and O,
or with Y being an 8- to 11-membered bicyclic fully saturated spiro-heterocycle comprising 1, 2 or 3 heteroatoms each independently selected from the group N, S and O with the proviso that this spiro-heterocycle comprises at least one N-atom and that this heterocycle is directly attached to the molecule via this N-atom,
or with Y being a six- or seven-membered fully saturated heterocycle comprising 1, 2 or 3 heteroatoms each independently selected from the group N, S and O, which is bridged by an additional —C1-3-alkylene-unit,
whereby each Y may optionally be substituted by one or more groups Z each independently from each other selected from the group consisting of F, Cl, -oxo, OH, C1-5-alkyl, —C1-5-alkanol, —O—C1-3-alkyl, a five-, six- or seven-membered fully saturated or partially unsaturated heterocycle comprising 1, 2 or 3 heteroatoms each independently selected from the group N, S and O; a fully saturated or partially unsaturated C3-6-cycloalkyl, a five- to six-membered heteroaromatic group comprising 1, 2 or 3 heteroatoms each independently selected from the group N, S and O; —CO-L, —C1-3-alkylene-CO-L, —C1-3-alkylene-O—C1-3-alkyl, —N(CH3)2 and —N(ethyl)2,
whereby each group Z may optionally be further substituted by one, two or three groups T each independently selected from the group consisting of -oxo, OH, F, Cl, methyl, ethyl, propyl, —O-methyl, —O-ethyl, —O-propyl, —O-isopropyl, —N(methyl)2, —N(ethyl)2, 5- to 6-membered fully saturated, partially unsaturated or aromatic heterocycle comprising 1 or 2 heteroatoms each independently selected from the group N, O and S; a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and —CN,
wherein each group T may also optionally be substituted by a group selected from the group consisting of methyl, ethyl, propyl, isopropyl, F, Cl, OH, oxo, —O-methyl, —O-ethyl, —O-propyl and —O-isopropyl,
whereby L denotes a 5- or 6-membered fully saturated or partially unsaturated heterocycle comprising 1 or 2 heteroatoms each independently selected from the group N, O and S, which said heterocycle may optionally be substituted by one, two or three groups independently selected from among methyl, F, Cl, OH and -oxo,
or a pharmaceutically acceptable salt thereof.

### Claim 6 (depends on 5)

The compound of formula 1 according to claim 5,
wherein
R6 denotes a group selected from H, Br, Cl, F, methyl,
or a pharmaceutically acceptable salt thereof.

### Claim 7 (depends on 6)

The compound of formula 1 according to claim 6,
wherein R4 denotes a group selected from H, F, Cl, OH, —OCH3, —CH2—OH, —CN
wherein R5 denotes a group selected from H, F, Cl, OH, —OCH3, —C1-4-alkyl, —CH2—OH and —CN,
or a pharmaceutically acceptable salt thereof.

### Claim 8 (depends on 7)

The compound of formula 1 according to claim 7,
wherein R1 is not hydrogen and wherein R1 is attached to a C-atom of ring A,
or a pharmaceutically acceptable salt thereof.

### Claim 9 (depends on 7)

The compound of formula 1 according to claim 7,
wherein ring A is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.

### Claim 10 (depends on 7)

The compound of formula 1 according to claim 7,
wherein
R1 is selected from the group consisting of
—CO—Y, —CO—N(CH3)—Y, —CO—N(CH3)—(C1-3-alkylene)-Y, —CO—NH—Y,
with Y being a group selected from the group consisting of —NH2, —NH(CH3), —N(CH3)2, —C1-4-alkylene-N(CH3)2, —O-methyl, —O-ethyl, —OH and —N(ethyl)2,
or with Y being selected from the group consisting of a five- or six-membered monocyclic fully saturated or partially unsaturated heterocycle comprising 1, 2 or 3 heteroatoms each independently selected from the group N, S and O with the proviso hat this heterocycle comprises at least one N-atom and that this heterocycle is directly attached to the molecule via this N-atom, a five- or six-membered monocyclic heteroaromatic group comprising 1, 2 or 3 heteroatoms each independently selected from the group of N, S and O; —C3-6-cycloalkyl and a 9- to 10-membered bicyclic fully saturated spiro-heterocycle comprising 1, 2 or 3 heteroatoms each independently selected from the group N, S and O, with the proviso that this heterocycle is directly attached to the molecule via this N-atom,
whereby each Y may optionally be substituted by one or more groups Z,
whereby each group Z may optionally be further substituted by one, two or three groups T,
wherein each group T may also optionally be substituted by a group selected from the group consisting of methyl, ethyl, propyl, isopropyl, F, Cl, OH, oxo, —O-methyl, —O-ethyl, —O-propyl and —O-isopropyl,
or a pharmaceutically acceptable salt thereof.

### Claim 11 (depends on 10)

The compound of formula 1 according to claim 10,
wherein
Y is selected from the group consisting of —NH2, —NH(CH3), —N(CH3)2, —C1-4-alkylene-N(CH3)2, —O-methyl, —O-ethyl and —N(ethyl)2,
or wherein
Y is selected from the group consisting of
piperazine-1-yl, piperidine-1-yl, morpholine-4-yl, pyrrolidine-1-yl, azetidine-1-yl, [1,4]oxazepane-4-yl, [1,4]diazepane-1-yl), pyridine-1-yl, 4-Oxa-1,9-diaza-spiro[5.5]undecan-9-yl and cyclohexyl,
whereby each Y may optionally be substituted by one or more groups Z,
whereby each group Z may optionally be further substituted by one, two or three groups T,
wherein each group T may also optionally be substituted by a group selected from the group consisting of methyl, ethyl, propyl, isopropyl, F, Cl, OH, oxo, —O-methyl, —O-ethyl, —O-propyl and —O-isopropyl,
or a pharmaceutically acceptable salt thereof.

### Claim 12 (depends on 11)

The compound of formula 1 according to claim 11,
wherein R1 is CO—Y,
wherein
Y is selected from the group consisting of —NH(CH3), —N(CH3)2,
whereby each Y may optionally be substituted by one or more groups Z, each Z independently from one another selected from the group consisting of methyl, oxo, CO-L, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, piperidinyl, piperazinyl, pyranyl and morpholinyl, whereby each group Z may optionally be further substituted by one, two or three groups T, each T independently from one another selected from the group consisting of methyl, oxo, F and Cl, whereby each L is selected from the group consisting of pyrrolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, piperidinyl, piperazinyl, pyranyl and morpholinyl,
or a pharmaceutically acceptable salt thereof.

### Claim 13 (depends on 1, 2, 3, 4, 5, 12)

The compound of formula 1 according to claim 12,
wherein
R2 is selected from the group consisting of H, —R3, —O—R3, —O—C1-3-alkylene-R3 and —C1-3-alkylene-O—C1-3-alkyl,
which may optionally be substituted by one, two or three substituents as defined in one of claims 1 to 5,
wherein R3 is selected from the group consisting of linear or branched C1-6-alkyl, linear or branched C1-4-haloalkyl,
or a pharmaceutically acceptable salt thereof.

### Claim 14 (depends on 13)

The compound of formula 1 according to claim 13,
wherein
R2 is H or
wherein R2 is selected from the group consisting of —R3, —O—R3, —O—C1-3-alkylene-R3 and —C1-3-alkylene-O—C1-3-alkyl,
which may optionally be substituted by one or more substituents selected from the group consisting of OH, oxo, methyl, —CN, F, Cl, —O—CH3,
wherein R3 is selected from the group consisting of linear or branched C1-6-alkyl and a linear or branched C1-4-haloalkyl,
or a pharmaceutically acceptable salt thereof.

### Claim 15 (depends on 14)

The compound of formula 1 according to claim 14,
wherein
R6 is selected from the group consisting of H, Cl and methyl
or a pharmaceutically acceptable salt thereof.

### Claim 16

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

### Claim 17 (depends on 1)

A method of treating diseases selected from among allergic rhinitis, asthma, COPD, adult respiratory distress syndrome, bronchitis, B-cell lymphoma, dermatitis, allergic dermatitis, rheumatoid arthritis, idiopathic thrombocytopenic purpura, lupus erythematodes, Lymphoma, Crohn's disease, multiple sclerosis, psoriasis, T cell lymphoma, comprising administering to a patient a therapeutically effective amount of a compound according to claim 1.

### Claim 18 (depends on 17)

The method according to claim 17 wherein the diseases are selected from among asthma, COPD, allergic rhinitis, adult respiratory distress syndrome, bronchitis, allergic dermatitis, idiopathic thrombocytopenic purpura, and rheumatoid arthritis.

### Claim 19 (depends on 17)

The method according to claim 17 wherein the diseases are selected from among asthma, COPD, allergic rhinitis, allergic dermatitis and rheumatoid arthritis.

### Claim 20 (depends on 1)

A pharmaceutical composition comprising therapeutically effective amount of a compound according to claim 1 and one or more pharmaceutically acceptable carriers and/or adjuvants.

### Claim 21 (depends on 20)

The pharmaceutical composition according to claim 20 further in combination with an active substance selected from among anticholinergics, betamimetics, corticosteroids, PDE4-inhibitors, EGFR-inhibitors, LTD4-antagonists, CCR3-inhibitors, iNOS-inhibitors, CRTH2-antagonists and HMG-CoA reductase inhibitors.

### Claim 22 (depends on 1)

A compounds selected from the group consisting of
wherein R1, R2, R4, R5, R6 and A are defined as in claim 1 and wherein RA is —CO—O—CH3 or —CO—O—CH2—CH3,
or a pharmaceutically acceptable salt thereof.