Flap modulators

• US 9,926,333 B2
• Filed: 05/22/2015
• Issued: 03/27/2018
• Est. Priority Date: 02/04/2013
• Status: Active Grant

• Current Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Original Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Inventors: Eccles, Wendy, Fitzgerald, Anne E., Hack, Michael D., Hawryluk, Natalie A., Jones, William M., Keith, John M., Krawczuk, Paul, Lebsack, Alec D., Liu, Jing, Mani, Neelakandha S., McClure, Kelly J., Meduna, Steven P., Rosen, Mark D.
• Primary Examiner(s): Shameem, Golam M
• Application Number:
  US14/719,476
• Publication Number:
  US 20150252008A1
• Time in Patent Office: 1,040 Days
• CPC Class Codes: A61K 31/4353 ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/4985 Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/5025 ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/06 Antigout agents, e.g. antihyperuricemic or uricosuric agents
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 213/73 : Unsubstituted amino or imino radicals
• CPC Class Codes: C07D 237/20 : Nitrogen atoms nitro radicals C07D237/12
• CPC Class Codes: C07D 239/42 : One nitrogen atom nitro radicals C07D239/30
• CPC Class Codes: C07D 239/47 : One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
• CPC Class Codes: C07D 241/20 : Nitrogen atoms nitro radicals C07D241/16
• CPC Class Codes: C07D 241/26 : with nitrogen atoms directly attached to ring carbon atoms
• CPC Class Codes: C07D 401/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 403/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 403/14 : containing three or more hetero rings
• CPC Class Codes: C07D 405/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/14 : containing three or more hetero rings
• CPC Class Codes: C07D 413/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 471/04 : Ortho-condensed systems
• CPC Class Codes: C07D 487/04 : Ortho-condensed systems
• CPC Class Codes: C07D 491/10 : Spiro-condensed systems
• CPC Class Codes: C07D 491/113 : with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
• CPC Class Codes: C07D 495/04 : Ortho-condensed systems
• CPC Class Codes: C07D 498/04 : Ortho-condensed systems
• CPC Class Codes: C07D 513/04 : Ortho-condensed systems
• CPC Class Codes: C07F 7/1804 : Compounds having Si-O-C linkages Si-O-acyl linkages C07F7/1896
• CPC Class Codes: C07F 7/188 : by reactions involving the formation of Si-O linkages
• CPC Class Codes: C07F 7/1892 : by reactions not provided for in C07F7/1876 - C07F7/1888

Abstract

The present invention relates to compounds of Formula (I),

or a form thereof, wherein ring A, R₁, L and R₂ are as defined herein, useful as FLAP modulators. The invention also relates to pharmaceutical compositions comprising compounds of Formula (I). Methods of making and using the compounds of Formula (I) are also within the scope of the invention.

Claims

1. A method of treating a subject suffering from or diagnosed with a disease and/or disorder mediated by FLAP activity, comprising administering to the subject a therapeutically effective amount of at least one compound of Formula (I), wherein said disease is selected from the group consisting of:

exacerbations, non-allergic asthma, fibrotic lung diseases, acute respiratory distress syndrome and chronic obstructive pulmonary disease, or associated symptoms or complications thereof;

myocardial infarction, atherosclerosis and stroke aortic aneurisms, atherosclerosis, or associated symptoms or complications thereof;

rheumatoid arthritis, inflammatory bowel disease, nephritis, spondyloarthritis, polymyositis, dermatomyositis, gouty effusions, systemic lupus erythematosus, systemic sclerosis, Alzheimer'"'"'s disease, multiple sclerosis, allergic rhinitis, allergic dermatitis and asthma, or associated symptoms or complications thereof;

tumor cell proliferation, differentiation, apoptosis, tumor-associated angiogenesis, and the migration or invasion of carcinoma cells

2. A method according to claim 1, wherein the disease and/or disorder is selected from the group consisting of:

exacerbations, non-allergic asthma, fibrotic lung diseases, acute respiratory distress syndrome and chronic obstructive pulmonary disease, or associated symptoms or complications thereof.

3. A method according to claim 1, wherein the disease and/or disorder is selected from the group consisting of:

myocardial infarction, atherosclerosis and stroke aortic aneurisms, atherosclerosis, or associated symptoms or complications thereof.

4. A method according to claim 1, wherein the disease and/or disorder is selected from the group consisting of:

rheumatoid arthritis, inflammatory bowel disease, nephritis, spondyloarthritis, polymyositis, dermatomyositis, gouty effusions, systemic lupus erythematosus, systemic sclerosis, Alzheimer'"'"'s disease, multiple sclerosis, allergic rhinitis, allergic dermatitis and asthma, or associated symptoms or complications thereof.

5. A method according to claim 1, wherein the disease and/or disorder is selected from the group consisting of:

tumor cell proliferation, differentiation, apoptosis, tumor-associated angiogenesis, and the migration or invasion of carcinoma cells.

6. The method of claim 1, wherein the therapeutically effective amount of the compound of Formula (I) is from about 0.1 mg/dose to about 5 g/dose.

7. The method of claim 1, wherein the compound of Formula (I) is selected from:

5-(4-Cyclobutyl-2-fluoro-3-{[4-(trifluoromethyl)benzyl]oxy}phenyl)pyrazin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-{[3-(trifluoromethyl)benzyl]oxy}phenyl)pyrazin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-{[2-(trifluoromethyl)benzyl]oxy}phenyl)pyrazin-2-amine,

3-{[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]methyl}benzoic acid,

4-{[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]methyl}benzoic acid,

5-(4-Cyclobutyl-2-fluoro-3-{[3-(methylsulfonyl)benzyl]oxy}phenyl)pyrazin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-{[4-(methylsulfonyl)benzyl]oxy}phenyl)pyrazin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-{[2-(trifluoromethoxy)benzyl]oxy}phenyl)pyrazin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-{[3-(trifluoromethoxy)benzyl]oxy}phenyl)pyrazin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-{[4-(trifluoromethoxy)benzyl]oxy}phenyl)pyrazin-2-amine,

5-(3-{[4-Chloro-2-(methylsulfonyl)benzyl]oxy}-4-cyclobutyl-2-fluorophenyl)pyrazin-2-amine,

1-(4-{[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]-methyl}phenyl)-ethanone,

5-[4-Cyclobutyl-2-fluoro-3-(pyridin-3-ylmethoxy)phenyl]pyrazin-2-amine,

5-[4-Cyclobutyl-2-fluoro-3-(pyridin-4-ylmethoxy)phenyl]pyrazin-2-amine,

4-{[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]methyl}benzonitrile,

3-{[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]methyl}benzonitrile,

3-{[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]methyl}benzamide,

2-{[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]methyl}benzonitrile,

2-{[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]methyl}benzamide,

5-(4-Cyclobutyl-2-fluoro-3-{[4-(1H-tetrazol-5-yl)benzyl]oxy}phenyl)pyrazin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-{[3-(1H-tetrazol-5-yl)benzyl]oxy}phenyl)pyrazin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-{[2-(1H-tetrazol-5-yl)benzyl]oxy}phenyl)pyrazin-2-amine,

(4-{[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]methyl}phenyl)acetic acid,

5-[4-Cyclobutyl-2-fluoro-3-(pyridin-2-ylmethoxy)phenyl]pyrazin-2-amine,

4-{[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]methyl}-N,N-dimethyl-benzenesulfonamide,

4-{[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]-methyl}-benzenesulfonamide,

4-{[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]methyl}-N-methylbenzenesulfonamide,

5-{4-Cyclobutyl-2-fluoro-3-[(4-fluorobenzyl)oxy]phenyl}pyrazin-2-amine,

5-{4-Cyclobutyl-2-fluoro-3-[(3-fluorobenzyl)oxy]phenyl}pyrazin-2-amine,

5-{4-Cyclobutyl-2-fluoro-3-[(2-fluorobenzyl)oxy]phenyl}pyrazin-2-amine,

5-{4-Cyclobutyl-3-[(2,6-difluorobenzyl)oxy]-2-fluorophenyl}pyrazin-2-amine,

5-{4-Cyclobutyl-3-[(2,3-difluorobenzyl)oxy]-2-fluorophenyl}pyrazin-2-amine,

5-{4-Cyclobutyl-3-[(3,4-difluorobenzyl)oxy]-2-fluorophenyl}pyrazin-2-amine,

5-{3-[(2-Chlorobenzyl)oxy]-4-cyclobutyl-2-fluorophenyl}pyrazin-2-amine,

5-{3-[(3-Chlorobenzyl)oxy]-4-cyclobutyl-2-fluorophenyl}pyrazin-2-amine,

5-{3-[(4-Chlorobenzyl)oxy]-4-cyclobutyl-2-fluorophenyl}pyrazin-2-amine,

5-{4-Cyclobutyl-3-[(2,6-dichlorobenzyl)oxy]-2-fluorophenyl}pyrazin-2-amine,

5-{4-Cyclobutyl-3-[(2,5-dichlorobenzyl)oxy]-2-fluorophenyl}pyrazin-2-amine,

5-{4-Cyclobutyl-3-[(2,3-dichlorobenzyl)oxy]-2-fluorophenyl}pyrazin-2-amine,

5-{4-Cyclobutyl-3-[(2,4-dichlorobenzyl)oxy]-2-fluorophenyl}pyrazin-2-amine,

5-{4-Cyclobutyl-3-[(3,4-dimethylbenzyl)oxy]-2-fluorophenyl}pyrazin-2-amine,

5-(3-{[2-Chloro-3-(trifluoromethyl)benzyl]oxy}-4-cyclobutyl-2-fluorophenyl)pyrazin-2-amine,

5-(3-{[5-Chloro-2-(trifluoromethyl)benzyl]oxy}-4-cyclobutyl-2-fluorophenyl)pyrazin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-{[4-fluoro-2-(trifluoromethyl)benzyl]oxy}phenyl)pyrazin-2-amine,

5-{3-[(2-Chloro-5-fluorobenzyl)oxy]-4-cyclobutyl-2-fluorophenyl}pyrazin-2-amine,

2-{[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]methyl}benzoic acid,

5-{4-Cyclobutyl-2-fluoro-3-[(1-methyl-1H-pyrazol-3-yl)methoxy]phenyl}pyrazin-2-amine,

5-{4-Cyclobutyl-3-[(3-cyclopropyl-1,2,4-oxadiazol-5-yl)methoxy]-2-fluorophenyl}pyrazin-2-amine,

tert-Butyl[3-(5-aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]acetate,

[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]acetic acid,

(racemic) 1-(3-(3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)-2-hydroxypropyl)pyridin-2(1H)-one,

(racemic) 3-(3-(3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)-2-hydroxypropyl)pyrimidin-4(3H)-one,

(racemic) 2-(3-(3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)-2-hydroxypropyl)pyridazin-3(2H)-one,

(racemic) 1-(3-(3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)-2-hydroxypropyl)pyrazin-2(1H)-one,

(racemic) 1-(3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)-3-(pyrimidin-5-ylamino)propan-2-ol,

(racemic) 1-(3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)-3-(pyrimidin-2-ylamino)propan-2-ol,

(racemic) 1-(3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)-3-(pyrazin-2-ylamino)propan-2-ol,

(racemic) 1-(3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)-3-((5-aminopyrimidin-2-yl)amino)propan-2-ol,

(racemic) 1-(3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)-3-((6-aminopyrimidin-4-yl)amino)propan-2-ol,

(racemic) 1-(3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)-3-(1H-pyrazol-1-yl)propan-2-ol,

(racemic) 1-(3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)-3-(1H-imidazol-1-yl)propan-2-ol,

(racemic) 1-(3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)-3-(1H-1,2,4-triazol-1-yl)propan-2-ol,

(racemic) 1-(3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)-3-(1H-1,2,3-triazol-1-yl)propan-2-ol,

(racemic) 1-(3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)-3-(2H-1,2,3-triazol-2-yl)propan-2-ol,

(racemic) 5-Amino-1-(3-(3-(5-aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)-2-hydroxypropyl)-1H-pyrazole-4-carbonitrile,

(racemic) 1-(5-Amino-1H-1,2,3-triazol-1-yl)-3-(3-(5-aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)propan-2-ol,

(racemic) 1-((1H-Pyrazol-5-yl)amino)-3-(3-(5-aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)propan-2-ol,

5-(4-Cyclobutyl-2-fluoro-3-{[1-(methylsulfonyl)piperidin-4-yl]methoxy}-phenyl)-pyrazin-2-amine,

5-{4-Cyclobutyl-2-fluoro-3-[(4-methylpyrimidin-2-yl)-oxy]-phenyl}pyrazin-2-amine,

5-{4-Cyclobutyl-2-fluoro-3-[(5-methyl-1,2,4-oxadiazol-3-yl)methoxy]phenyl}pyrazin-2-amine,

5-[4-Cyclobutyl-3-(cyclohexylmethoxy)-2-fluorophenyl]pyrazin-2-amine,

5-[4-Cyclobutyl-3-(cyclopropylmethoxy)-2-fluorophenyl]pyrazin-2-amine,

Ethyl 5-{[3-(5-aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]methyl}furan-2-carboxylate,

tert-Butyl 4-{[3-(5-aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]-methyl}-piperidine-1-carboxylate,

5-{4-Cyclobutyl-2-fluoro-3-[(3-methyl-1,2,4-oxadiazol-5-yl)-methoxy]-phenyl}-pyrazin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-{[2-methoxy-5-(pentafluoro-lambda˜

6˜

-sulfanyl)-benzyl]-oxy}-phenyl)pyrazin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-{[2-fluoro-5-(pentafluoro-lambda˜

6˜

-sulfanyl)benzyl]-oxy}-phenyl)pyrazin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-{[2-fluoro-4-(pentafluoro-lambda˜

6˜

-sulfanyl)benzyl]-oxy}-phenyl)pyrazin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-{[4-(pentafluoro-lambda˜

6˜

-sulfanyl)benzyl]-oxy}-phenyl)pyrazin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-{[3-(pentafluoro-lambda˜

6˜

-sulfanyl)benzyl]-oxy}-phenyl)pyrazin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-{[2-(pentafluoro-lambda˜

6˜

-sulfanyl)benzyl]-oxy}-phenyl)-pyrazin-2-amine,

5-[4-Cyclobutyl-3-(cyclobutylmethoxy)-2-fluorophenyl]pyrazin-2-amine,

5-[3-(Benzyloxy)-4-cyclobutyl-2-fluorophenyl]pyrazin-2-amine,

4-{2-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]ethyl}benzoic acid,

5-{[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]methyl}furan-2-carboxylic acid,

2-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]-6-methylpyrimidin-4-amine,

5-{4-Cyclobutyl-2-fluoro-3-[(4-phenylpyrimidin-2-yl)oxy]phenyl}pyrazin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-{[4-(methylsulfanyl)pyrimidin-2-yl]oxy}phenyl)pyrazin-2-amine,

5-{4-Cyclobutyl-3-[(4,6-dimethylpyrimidin-2-yl)oxy]-2-fluorophenyl}pyrazin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-{[4-(1-methylethyl)pyrimidin-2-yl]oxy}phenyl)pyrazin-2-amine,

5-{4-Cyclobutyl-2-fluoro-3-[(4-thiophen-2-ylpyrimidin-2-yl)oxy]phenyl}pyrazin-2-amine,

2-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]pyrimidine-4-carbonitrile,

5-{4-Cyclobutyl-2-fluoro-3-[(4-methoxypyrimidin-2-yl)oxy]phenyl}pyrazin-2-amine,

5-{4-Cyclobutyl-2-fluoro-3-[(5-methoxypyrimidin-2-yl)oxy]phenyl}pyrazin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-{[4-(methylsulfonyl)pyrimidin-2-yl]oxy}phenyl)pyrazin-2-amine,

4-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]-6-methylpyrimidin-2-amine,

5-{4-Cyclobutyl-2-fluoro-3-[(6-methoxypyrimidin-4-yl)oxy]phenyl}pyrazin-2-amine,

6-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]pyrimidin-4-ol,

4-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]-6-methoxypyrimidin-2-amine,

6-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]-2-methoxypyrimidin-4-amine,

4-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]benzonitrile,

5-(4-Cyclobutyl-2-fluoro-3-{[6-(trifluoromethyl)pyridin-2-yl]oxy}phenyl)pyrazin-2-amine,

Methyl 4-[3-(5-aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]benzoate,

5-(4-Cyclobutyl-2-fluoro-3-{[5-(trifluoromethyl)pyrimidin-2-yl]oxy}phenyl)pyrazin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-{[5-(trifluoromethyl)pyrazin-2-yl]oxy}phenyl)pyrazin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-{[6-(trifluoromethyl)pyridazin-3-yl]oxy}phenyl)pyrazin-2-amine,

Methyl 6-[3-(5-aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]pyridine-3-carboxylate,

5-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]pyridine-2-carbonitrile,

4-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]pyridine-2-carbonitrile,

2-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]pyridine-3-carbonitrile,

6-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]pyridine-2-carbonitrile,

3-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]pyridine-2-carbonitrile,

5-(4-Cyclobutyl-2-fluoro-3-{[5-(trifluoromethyl)pyridin-2-yl]oxy}phenyl)pyrazin-2-amine,

6-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]pyridine-3-carbonitrile,

5-{4-Cyclobutyl-2-fluoro-3-[4-(pentafluoro-lambda˜

6˜

-sulfanyl)phenoxy]-phenyl}-pyrazin-2-amine,

5-{4-Cyclobutyl-2-fluoro-3-[4-(methylsulfonyl)phenoxy]phenyl}pyrazin-2-amine,

5-{4-Cyclobutyl-2-fluoro-3-[2-(methylsulfonyl)phenoxy]phenyl}pyrazin-2-amine,

5-[4-Cyclobutyl-2-fluoro-3-(pyrimidin-2-yloxy)phenyl]pyrazin-2-amine,

2-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]pyrimidin-4-amine,

5-{3-[3,4-Bis(trifluoromethyl)phenoxy]-4-cyclobutyl-2-fluorophenyl}pyrazin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-{[3-(trifluoromethyl)pyridin-2-yl]oxy}phenyl)pyrazin-2-amine,

5-{3-[(3-Chloropyridin-2-yl)oxy]-4-cyclobutyl-2-fluorophenyl}pyrazin-2-amine,

5-{3-[2-Chloro-4-(methylsulfonyl)phenoxy]-4-cyclobutyl-2-fluorophenyl}pyrazin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-{[2-(trifluoromethyl)pyrimidin-4-yl]oxy}phenyl)pyrazin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-{[6-(trifluoromethyl)pyrimidin-4-yl]oxy}phenyl)pyrazin-2-amine,

5-{4-Cyclobutyl-2-fluoro-3-[3-methyl-4-(methylsulfonyl)phenoxy]phenyl}pyrazin-2-amine,

5-(4-cyclobutyl-2-fluoro-3-(4-(methylsulfonyl)-2-(trifluoromethyl)phenoxy)-phenyl)-pyrazin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-{[6-(trifluoromethyl)pyridin-3-yl]oxy}phenyl)pyrazin-2-amine,

5-{4-Cyclobutyl-2-fluoro-3-[(3-methoxypyridin-2-yl)oxy]phenyl}pyrazin-2-amine,

4-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]pyrimidin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-{[4-(trifluoromethyl)pyrimidin-2-yl]oxy}phenyl)pyrazin-2-amine,

2-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]-5-(methylsulfonyl)-benzonitrile,

5-{4-Cyclobutyl-2-fluoro-3-[4-(methylsulfonyl)-3-(trifluoromethyl)-phenoxy]-phenyl}-pyrazin-2-amine,

5-{4-Cyclobutyl-2-fluoro-3-[(2-methylpyrimidin-4-yl)oxy]phenyl}pyrazin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-{[2-(1-methylethyl)pyrimidin-4-yl]oxy}phenyl)pyrazin-2-amine,

6-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]pyrimidin-4-amine,

5-{3-[(2-Chloropyrimidin-4-yl)oxy]-4-cyclobutyl-2-fluorophenyl}pyrazin-2-amine,

5-{3-[(6-Azetidin-1-ylpyrimidin-4-yl)oxy]-4-cyclobutyl-2-fluorophenyl}pyrazin-2-amine,

6-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]-N,N-dimethyl-2-(trifluoromethyl)pyrimidin-4-amine,

6-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]-2-methylpyrimidin-4-amine,

5-{4-Cyclobutyl-3-[(6-cyclopropylpyrimidin-4-yl)oxy]-2-fluorophenyl}pyrazin-2-amine,

4-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]-6-(methoxymethyl)pyrimidin-2-amine,

4-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]-6-chloropyrimidin-2-amine,

5-{4-Cyclobutyl-2-fluoro-3-[(2-phenylpyrimidin-4-yl)oxy]phenyl}pyrazin-2-amine,

5-{4-Cyclobutyl-2-fluoro-3-[(6-phenylpyrimidin-4-yl)oxy]phenyl}pyrazin-2-amine,

6-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]-2-benzylpyrimidin-4-amine,

5-(4-Cyclobutyl-2-fluoro-3-{[6-(1-methylethyl)pyrimidin-4-yl]oxy}phenyl)pyrazin-2-amine,

3-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]-1-methyl-5-(trifluoromethyl)-1H-pyrazole-4-carbonitrile,

tert-Butyl[2-({2-[3-(5-aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]pyrimidin-4-yl}amino)ethyl]carbamate,

N-{4-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]pyrimidin-2-yl}ethane-1,2-diamine,

Methyl 2-[3-(5-aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]pyrimidine-4-carboxylate,

2-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]pyrimidine-4-carboxylic acid,

4-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]benzoic acid,

6-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]pyridine-3-carboxylic acid,

4-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]benzamide,

N′

-{4-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]pyrimidin-2-yl}-N,N-dimethylethane-1,2-diamine,

2-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]pyrimidine-4-carboxamide,

2-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]pyrimidin-5-amine,

5-[4-Cyclobutyl-2-fluoro-3-(pyrimidin-2-yloxy)phenyl]pyrimidin-2-amine,

5-{3-[(4-Aminopyrimidin-2-yl)oxy]-4-cyclobutyl-2-fluorophenyl}pyrimidin-2-amine,

4-[3-(2-Aminopyrimidin-5-yl)-6-cyclobutyl-2-fluorophenoxy]-6-(methoxymethyl)pyrimidin-2-amine,

5-{4-Cyclobutyl-2-fluoro-3-[(4-methylpyrimidin-2-yl)oxy]phenyl}pyrimidin-2-amine,

5-{3-[(6-Aminopyrimidin-4-yl)oxy]-4-cyclobutyl-2-fluorophenyl}pyrimidin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-{[4-(1-methylethyl)pyrimidin-2-yl]oxy}phenyl)pyrimidin-2-amine,

4-[3-(2-Aminopyrimidin-5-yl)-6-cyclobutyl-2-fluorophenoxy]pyrimidin-2-amine,

5-{4-Cyclobutyl-3-[(4,6-dimethylpyrimidin-2-yl)oxy]-2-fluorophenyl}pyrimidin-2-amine,

4-(3-(2-aminopyrimidin-5-yl)-6-cyclobutyl-2-fluorophenoxy)-6-isopropylpyrimidin-2-amine,

2-[3-(2-Aminopyrimidin-5-yl)-6-cyclobutyl-2-fluorophenoxy]pyrimidine-4-carboxamide,

5-(4-Cyclobutyl-2-fluoro-3-((6-methoxypyrimidin-4-yl)oxy)phenyl)pyrimidin-2-amine,

6-[3-(2-Aminopyrimidin-5-yl)-6-cyclobutyl-2-fluorophenoxy]pyrimidin-4-ol,

3-{[3-(5-Amino-3-cyanopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]methyl}benzoic acid,

5-Methyl-4-((3-(6-aminopyridin-3-yl)-6-cyclobutyl-2-fluorophenoxy)methyl)benzoate,

4-((3-(6-Aminopyridin-3-yl)-6-cyclobutyl-2-fluorophenoxy)methyl)benzoic acid,

5-(4-tert-Butyl-3-{[tert-butyl(dimethyl)silyl]oxy}-2-fluorophenyl)pyrazin-2-amine,

5-[4-tert-Butyl-2-fluoro-3-(pyrimidin-2-yloxy)phenyl]pyrazin-2-amine,

6-[3-(5-Aminopyrazin-2-yl)-6-tert-butyl-2-fluorophenoxy]pyrimidin-4-amine,

2-[3-(5-Aminopyrazin-2-yl)-6-tert-butyl-2-fluorophenoxy]pyrimidin-4-amine,

5-{4-tert-Butyl-2-fluoro-3-[(6-methoxypyrimidin-4-yl)oxy]phenyl}pyrazin-2-amine,

3-(2-Aminopyrimidin-5-yl)-6-tert-butyl-2-fluorophenol,

5-(4-tert-Butyl-3-{[tert-butyl(dimethyl)silyl]oxy}-2-fluorophenyl)pyrimidin-2-amine,

5-[4-tert-Butyl-2-fluoro-3-(pyrimidin-2-yloxy)phenyl]pyrimidin-2-amine,

5-{3-[(6-Aminopyrimidin-4-yl)oxy]-4-tert-butyl-2-fluorophenyl}pyrimidin-2-amine,

5-{3-[(4-Aminopyrimidin-2-yl)oxy]-4-tert-butyl-2-fluorophenyl}pyrimidin-2-amine,

5-[3-(Benzyloxy)-4-cyclopentyl-2-fluorophenyl]pyrazin-2-amine,

6-(4-Cyclobutyl-2-fluoro-3-(pyrimidin-2-yloxy)phenyl)pyridazin-3-amine,

6-(4-yclobutyl-2-fluoro-3-((6-methoxypyrimidin-4-yl)oxy)phenyl)pyridazin-3-amine,

6-(3-(6-Aminopyridazin-3-yl)-6-cyclobutyl-2-fluorophenoxy)pyrimidin-4-ol,

4-(3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)pyrimidine-2-carbonitrile,

6-(3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)-N,N,2-trimethylpyrimidin-4-amine,

4-(3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)-N,N,6-trimethylpyrimidin-2-amine,

6-(3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)-N,N-dimethylpyrimidin-4-amine,

Ethyl 5-(3-(5-aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxylate,

5-(4-Cyclobutyl-2-fluoro-3-((5-(methylsulfonyl)pyridin-2-yl)oxy)phenyl)pyrazin-2-amine,

4-(3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)-6-(tert-butyl)pyrimidin-2-amine,

5-(3-((4-(1,5-Dioxa-9-azaspiro[5.5]undecan-9-yl)pyrimidin-2-yl)oxy)-4-cyclobutyl-2-fluorophenyl)pyrazin-2-amine,

4-(3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)-6-isobutylpyrimidin-2-amine,

N-(2-(3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)-ethyl)-methane-sulfonamide,

5-(4-Cyclobutyl-2-fluoro-3-(2-morpholinoethoxy)phenyl)pyrazin-2-amine,

Ethyl 4-(3-(5-aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)butanoate,

tert-Butyl 3-((3-(5-aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)methyl)-azetidine-1-carboxylate,

tert-Butyl 3-((3-(5-aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)methyl)-pyrrolidine-1-carboxylate,

tert-Butyl 2-((3-(5-aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)methyl)-pyrrolidine-1-carboxylate,

tert-Butyl 3-((3-(5-aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)-methyl)-piperidine-1-carboxylate,

2-(3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)ethanol,

4-(3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)butanoic acid,

5-(4-Cyclobutyl-2-fluoro-3-((tetrahydrofuran-2-yl)methoxy)phenyl)pyrazin-2-amine,

3-(3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)propane-1,2-diol,

1-(3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)-3-morpholinopropan-2-ol,

4-(3-(3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)-2-hydroxypropyl)-thiomorpholine 1,1-dioxide,

5-(4-Cyclobutyl-2-fluoro-3-(pyridazin-4-yloxy)phenyl)pyrazin-2-amine,

3-(3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)pyrazin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-(pyrazin-2-yloxy)phenyl)pyrazin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-(pyrimidin-4-yloxy)phenyl)pyrazin-2-amine,

4-(3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)-N-isobutylpyrimidin-2-amine trifluoroacetic acid salt

Methyl 3-({[3-(5-aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]acetyl}amino)-4-hydroxybenzoate,

5-[4-Cyclobutyl-2-fluoro-3-(tetrahydro-2H-pyran-4-ylmethoxy)phenyl]pyrazin-2-amine,

4-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]-3-(methylsulfonyl)benzonitrile,

5-{3-[2,4-Bis(trifluoromethyl)phenoxy]-4-cyclobutyl-2-fluorophenyl}pyrazin-2-amine,

2-Amino-5-[3-(5-aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]pyrimidine-4-carbonitrile,

Methyl 3-({[3-(5-aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]acetyl}amino)-4-hydroxybenzoate,

5-[4-Cyclobutyl-2-fluoro-3-(pyridazin-3-yloxy)phenyl]pyrazin-2-amine,

5-[4-Cyclopropyl-2-fluoro-3-(pyrimidin-2-yloxy)phenyl]pyrazin-2-amine,

2-[3-(5-Aminopyrazin-2-yl)-6-cyclopropyl-2-fluorophenoxy]pyrimidin-4-amine,

5-{4-Cyclobutyl-2-fluoro-3-[(1-methyl-1H-imidazol-2-yl)methoxy]phenyl}pyrazin-2-amine,

Methyl 2-{[3-(5-aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]methyl}-1,3-oxazole-4-carboxylate,

2-{[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]methyl}-1,3-oxazole-4-carboxylic acid,

5-{4-Cyclobutyl-2-fluoro-3-[(1-methyl-1H-imidazol-4-yl)methoxy]phenyl}pyrazin-2-amine,

5-{4-Cyclobutyl-2-fluoro-3-[(1-methyl-1H-imidazol-5-yl)methoxy]phenyl}pyrazin-2-amine,

2-{[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]methyl}pyridine-3-carbonitrile,

5-{4-Cyclobutyl-2-fluoro-3-[(2-methyl-1,3-thiazol-4-yl)methoxy]phenyl}pyrazin-2-amine,

5-[4-Cyclobutyl-2-fluoro-3-(pyridazin-3-ylmethoxy)phenyl]pyrazin-2-amine,

5-{3-[(5-Chloropyridin-2-yl)methoxy]-4-cyclobutyl-2-fluorophenyl}pyrazin-2-amine,

5-{[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]methyl}pyridine-2-carbonitrile,

5-{4-Cyclobutyl-2-fluoro-3-[(5-methylisoxazol-3-yl)methoxy]phenyl}pyrazin-2-amine,

6-{[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]methyl}pyridine-2-carbonitrile,

5-[4-Cyclobutyl-2-fluoro-3-(piperidin-4-ylmethoxy)phenyl]pyrazin-2-amine,

(racemic) 5-[4-Cyclobutyl-2-fluoro-3-(piperidin-3-ylmethoxy)phenyl]pyrazin-2-amine,

(racemic) 5-[4-Cyclobutyl-2-fluoro-3-(pyrrolidin-3-ylmethoxy)phenyl]pyrazin-2-amine,

5-[3-(Azetidin-3-ylmethoxy)-4-cyclobutyl-2-fluorophenyl]pyrazin-2-amine,

(racemic) 5-[4-Cyclobutyl-2-fluoro-3-(pyrrolidin-2-ylmethoxy)phenyl]pyrazin-2-amine,

(racemic) 5 1-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]-3-piperidin-1-ylpropan-2-ol,

(racemic) 1-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]-3-pyrrolidin-1-ylpropan-2-ol,

(diastereomeric mixture) 1-{3-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]-2-hydroxypropyl}pyrrolidin-3-ol,

(racemic) 1-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]-3-piperazin-1-ylpropan-2-ol,

(racemic) 1-{3-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]-2-hydroxypropyl}pyrimidin-2(1H)-one,

(racemic) 1-{3-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]-2-hydroxypropyl}imidazolidin-2-one,

2′

-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]-5,5′

-bipyrimidin-2-amine,

5-[2-Fluoro-4-methyl-3-(pyrimidin-2-yloxy)phenyl]pyrazin-2-amine,

2-[3-(5-Aminopyrazin-2-yl)-2-fluoro-6-methylphenoxy]pyrimidin-4-amine,

5-[4-Ethyl-2-fluoro-3-(pyrimidin-2-yloxy)phenyl]pyrazin-2-amine,

2-[3-(5-Aminopyrazin-2-yl)-6-ethyl-2-fluorophenoxy]pyrimidin-4-amine,

5-[2-Fluoro-4-(1-methylethyl)-3-(pyrimidin-2-yloxy)phenyl]pyrazin-2-amine,

5-[2-Fluoro-4-propyl-3-(pyrimidin-2-yloxy)phenyl]pyrazin-2-amine,

5-(4-Cyclohexyl-2-fluoro-3-(pyrimidin-2-yloxy)phenyl)pyrazin-2-amine,

5-(4-(Cyclohexylmethyl)-2-fluoro-3-(pyrimidin-2-yloxy)phenyl)pyrazin-2-amine,

5-(2-Fluoro-4-isopentyl-3-(pyrimidin-2-yloxy)phenyl)pyrazin-2-amine,

5-(2-Fluoro-4-isobutyl-3-(pyrimidin-2-yloxy)phenyl)pyrazin-2-amine,

5-(2-Fluoro-4-neopentyl-3-(pyrimidin-2-yloxy)phenyl)pyrazin-2-amine,

2-(3-(5-Aminopyrazin-2-yl)-6-cyclohexyl-2-fluorophenoxy)pyrimidin-4-amine,

2-(3-(5-Aminopyrazin-2-yl)-6-(cyclohexylmethyl)-2-fluorophenoxy)pyrimidin-4-amine,

2-(3-(5-Aminopyrazin-2-yl)-2-fluoro-6-isopentylphenoxy)pyrimidin-4-amine,

2-(3-(5-Aminopyrazin-2-yl)-2-fluoro-6-isobutylphenoxy)pyrimidin-4-amine,

5-(3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)pyrimidine-2-carboxamide,

5-(2-Fluoro-4-(pentan-3-yl)-3-(pyrimidin-2-yloxy)phenyl)pyrazin-2-amine,

5-(2-Fluoro-4-methyl-3-(pyrimidin-2-yloxy)phenyl)pyrimidin-2-amine,

5-(4-Ethyl-2-fluoro-3-(pyrimidin-2-yloxy)phenyl)pyrimidin-2-amine,

5-(2-Fluoro-4-propyl-3-(pyrimidin-2-yloxy)phenyl)pyrimidin-2-amine,

5-(2-Fluoro-4-isopropyl-3-(pyrimidin-2-yloxy)phenyl)pyrimidin-2-amine,

5-(4-Cyclopropyl-2-fluoro-3-(pyrimidin-2-yloxy)phenyl)pyrimidin-2-amine,

5-(2-Fluoro-4-isobutyl-3-(pyrimidin-2-yloxy)phenyl)pyrimidin-2-amine,

5-(2-Fluoro-4-neopentyl-3-(pyrimidin-2-yloxy)phenyl)pyrimidin-2-amine,

5-(2-Fluoro-4-(pentan-3-yl)-3-(pyrimidin-2-yloxy)phenyl)pyrimidin-2-amine,

5-(4-Cyclohexyl-2-fluoro-3-(pyrimidin-2-yloxy)phenyl)pyrimidin-2-amine,

5-(4-(Cyclohexylmethyl)-2-fluoro-3-(pyrimidin-2-yloxy)phenyl)pyrimidin-2-amine,

5-(2-Fluoro-4-isopentyl-3-(pyrimidin-2-yloxy)phenyl)pyrimidin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-(pyrimidin-2-yloxy)phenyl)-4-methylpyrimidin-2-amine,

5-(4-(tert-Butyl)-2-fluoro-3-(pyrimidin-2-yloxy)phenyl)-4-methylpyrimidin-2-amine,

3-Chloro-5-(4-cyclobutyl-2-fluoro-3-(pyrimidin-2-yloxy)phenyl)pyridin-2-amine,

5-(4-(tert-Butyl)-2-fluoro-3-(pyrimidin-2-yloxy)phenyl)-3-chloropyridin-2-amine,

2-Amino-5-(4-cyclobutyl-2-fluoro-3-(pyrimidin-2-yloxy)phenyl)nicotinonitrile,

2-Amino-5-(4-(tert-butyl)-2-fluoro-3-(pyrimidin-2-yloxy)phenyl)nicotinonitrile,

5-(4-Cyclobutyl-2-fluoro-3-(pyrimidin-2-yloxy)phenyl)-3-fluoropyridin-2-amine,

5-(4-(tert-Butyl)-2-fluoro-3-(pyrimidin-2-yloxy)phenyl)-3-fluoropyridin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-(pyrimidin-2-yloxy)phenyl)-3-(trifluoromethyl)pyridin-2-amine,

5-(4-(tert-Butyl)-2-fluoro-3-(pyrimidin-2-yloxy)phenyl)-3-(trifluoromethyl)pyridin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-(pyrimidin-2-yloxy)phenyl)pyridine-2,3-diamine,

5-(4-(tert-Butyl)-2-fluoro-3-(pyrimidin-2-yloxy)phenyl)pyridine-2,3-diamine,

5-(4-Cyclobutyl-2-fluoro-3-(pyrimidin-2-yloxy)phenyl)-3-methylpyrazin-2-amine,

5-(4-(tert-Butyl)-2-fluoro-3-(pyrimidin-2-yloxy)phenyl)-3-methylpyrazin-2-amine,

3-Chloro-5-(4-cyclobutyl-2-fluoro-3-(pyrimidin-2-yloxy)phenyl)pyrazin-2-amine,

5-(4-(tert-Butyl)-2-fluoro-3-(pyrimidin-2-yloxy)phenyl)-3-chloropyrazin-2-amine,

3-Amino-6-(4-cyclobutyl-2-fluoro-3-(pyrimidin-2-yloxy)phenyl)pyrazine-2-carbonitrile,

3-Amino-6-(4-(tert-butyl)-2-fluoro-3-(pyrimidin-2-yloxy)phenyl)pyrazine-2-carbonitrile,

5-(4-Cyclobutyl-2-fluoro-3-(pyrimidin-2-yloxy)phenyl)-3-fluoropyrazin-2-amine,

5-(4-(tert-Butyl)-2-fluoro-3-(pyrimidin-2-yloxy)phenyl)-3-fluoropyrazin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-(pyrimidin-2-yloxy)phenyl)-3-methoxypyrazin-2-amine,

5-(4-(tert-Butyl)-2-fluoro-3-(pyrimidin-2-yloxy)phenyl)-3-methoxypyrazin-2-amine,

5-(4-Cyclobutyl-2-fluoro-3-(pyrimidin-2-yloxy)phenyl)pyrazine-2,3-diamine, and

5-(4-(tert-Butyl)-2-fluoro-3-(pyrimidin-2-yloxy)phenyl)pyrazine-2,3-diamine.

8. A method of treating a subject suffering from or diagnosed with a disease and/or disorder mediated by FLAP activity, Wherein said disease is selected from the group consisting of:

exacerbations, non-allergic asthma, fibrotic lung diseases, acute respiratory distress syndrome and chronic obstructive pulmonary disease, or associated symptoms or complications thereof;

myocardial infarction, atherosclerosis and stroke aortic aneurisms, atherosclerosis, or associated symptoms or complications thereof;

rheumatoid arthritis, inflammatory bowel disease, nephritis, spondyloarthritis, polymyositis, dermatomyositis, gouty effusions, systemic lupus erythematosus, systemic sclerosis, Alzheimer'"'"'s disease, sclerosis, allergic rhinitis, allergic dermatitis and asthma, or associated symptoms or complications thereof;

tumor cell proliferation, differentiation, apoptosis, tumor- associated angiogenesis, and the migration or invasion of carcinoma cells, comprising administering to the subject a therapeutically effective amount of at least one compound selected from the group consisting of;

5-[4-Cyclobutyl-2-fuoro-3-(pyrimidin-2-yloxy)phenyl]pyrazin-2-amine, 5-{3-[(4-Aminopyrimidin-2-yl)oxy]-4-cyclobutyl-2-fluorophenyl}pyrimidin-2-amine, 5-[4-tert-Butyl-2-fluoro-3-(pyrimidin-2-yloxy)phenyl]pyrazin-2-amine, 2-[3-(5-Aminopyrazin-2-yl)-6-tert-butyl-2-fluorophenoxy]pyrimidin-4-amine, 5-[4-tert-Butyl-2-fluoro-3-(pyrimidin-2-yloxy)phenyl]pyrimidin-2-amine, 5-{3-[(4-Aminopyrimidin-2-yl)oxy]-4-tert-butyl-2-fluorophenyl}pyrimidin-2-amine, 2-[3-(5-Aminopyrazin-2-yl)-6-cyclopentyl-2-fluorophenoxy]pyrimidin-4-amine, and 2-[3-(5-Aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy]pyrimidin-4-amine, and pharmaceutically acceptable salts thereof.