# US 2013/0156826 A1 · Respiratory formulations and compounds for use therein

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- Number: US 2013/0156826 A1
- Document ID: US20130156826A1
- Status: Published application
- Kind: A1
- Application number: 13/805,471
- Filed: 2011-06-17
- Published: 2013-06-20
- Earliest claimed: 2010-06-17
- Assignees: Respivert Limited
- Inventors: Peter John Murray; Stuart Thomas Onions; Jonathan Gareth Williams; Kevin Joly
- Web page: https://patentgrep.com/patent/US20130156826A1

## CPC

- C07D 471/04: Ortho-condensed systems
- A61K 9/0075: {for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles}
- A61K 31/437: the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
- A61K 31/4985: Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/02: Nasal agents, e.g. decongestants
- A61P 11/06: Antiasthmatics
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/12: Antivirals
- A61P 31/16: for influenza or rhinoviruses
- 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 473/30: attached in position 6, e.g. hypoxanthine
- C07D 475/02: with an oxygen atom directly attached in position 4
- C07D 487/04: Ortho-condensed systems
- Y10T 428/2982: Particulate matter [e.g., sphere, flake, etc.]
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION

## Abstract

The present invention relates to respiratory formulations comprising a compound of formula (I): and use of said compounds and compositions in treatment, for example in the treatment of an inflammatory disease or a respiratory disorder, in particular an inflammatory mediated and/or virally mediated respiratory disorder such as asthma and COPD or the treatment or prevention of viral infection, for example infection by influenza virus, rhinovirus or RSV. The invention also extends to certain novel compounds of formula (I).

## Claims

### Claim 1

A pharmaceutical formulation for topical administration by inhalation comprising a population of particles of compound of formula (I):
J represents:
Q is N or —CH—;
X is O or O—CH2—;
Y is CH═ or N;
Z is O, NR4, —CR4a═N— or N═CR4a— whereby the latter two groups, together with the atoms to which they are attached, form a 6 membered ring;
R1 is C1-6 alkyl, branched or unbranched, or C3-6 cycloalkyl, each optionally substituted by a hydroxyl group;
R2a is H, halo, saturated or unsaturated branched or unbranched C1-8 alkylene chain, wherein one or more carbons (for example 1 to 3, such as 1, 2 or 3 carbons) are optionally replaced by a heteroatom(s) independently selected from —O—, —N— and/or S(O)m and the chain is optionally substituted by one or more halogen atoms (for example 1 to 6);
R2b is H, halo, C1-6 alkoxy or C1-6 alkyl optionally substituted by OH;
R2 and R3 each independently represent H, C1-4 alkyl, halogen; C1-4 haloalkyl, O(C1-4 alkyl), O(C1-4haloalkyl), CN, SO2R5, C(O)OR6 with the proviso that R2 and R3 do not both represent H concomitantly, or
R2 and R3 together with the carbons to which they are attached form a six membered aromatic ring or a heteroaromatic ring comprising a nitrogen atom;
R4 is H, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, C3-6 cycloalkyl, C3-6 cycloalkenyl, C6 aryl, a 5 or 6 membered heteroaryl or a 5 or 6 membered heterocyclic group, wherein said aryl, heteroaryl or heterocyclic group is substituted with 0 to 3 substituents selected from halogen, hydroxyl, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, amino, C1-4 mono or di-alkyl amino, C1-4 mono or di-acyl amino, S(O)qC1-6 alkyl, C0-6 alkylC(O)C1-6 alkyl or C0-6 alkylC(O)C1-6 heteroalkyl;
R4a is H or C1-3 alkyl;
R5 is H or C1-4 alkyl;
R6 is H or C1-4 alkyl;
m is 0, 1 or 2;
q is 0, 1 or 2;
a pharmaceutically acceptable salt thereof, including all stereoisomers, tautomers and isotopic derivatives thereof in particulate form, wherein the mass mean aerodynamic diameter (MMAD) of the population of particles is in the range 1 to 20 microns, for example 1 to 10 microns, such as 1 to 4 microns.

### Claim at position 2

2-20. (canceled)

### Claim 21 (depends on 1)

A formulation according to claim 1, wherein the MMAD of the particles of the population is in the range 5 to 10 μm.

### Claim 22 (depends on 1)

A formulation according to claim 1, wherein 50% of the particles of the population by number have a particle size within the specified range.

### Claim 23

(canceled)

### Claim 24 (depends on 1)

A formulation according to claim 1, wherein the formulation further comprises an excipient or carrier.

### Claim 25 (depends on 24)

A formulation according to claim 24, wherein the excipient is lactose.

### Claim 26 (depends on 24)

A formulation according to claim 24, wherein the MMAD of the excipient is in the range 5 to 75 μm.

### Claim 27 (depends on 26)

A formulation according to claim 26, wherein 50, 60, 70, 80 or 90% of the excipient has a mean particle size within the range.

### Claim 28 (depends on 1)

A formulation according to claim 1, wherein the formulation is a dry powder formulation.

### Claim 29

(canceled)

### Claim 30 (depends on 1)

A formulation according to claim 1, wherein the formulation is an aerosol formulation.

### Claim 31 (depends on 30)

A formulation according to claim 30, wherein the formulation comprises a carrier which is a liquefied propellant gas.

### Claim at position 14

32-60. (canceled)

### Claim 61

A compound of formula (I):
J represents:
Q is N or —CH—;
X is O or O—CH2—;
Y is CH═ or N;
Z is O, NR4, —CR4a═N— or N═CR4a—, whereby the latter two groups, together with the atoms to which they are attached, form a 6 membered ring;
R1 is C1-6 alkyl, branched or unbranched, or C3-6 cycloalkyl, each optionally substituted by a hydroxyl group;
R2a is H, halo, saturated or unsaturated branched or unbranched C1-8 alkylene chain, wherein one or more carbons (for example 1 to 3, such as 1, 2 or 3 carbons) are optionally replaced by a heteroatom(s) independently selected from —O—, —N— and/or S(O)m and the chain is optionally substituted by one or more halogen atoms (for example 1 to 6);
R2b is H, halo, C1-6 alkoxy or C1-6 alkyl optionally substituted by OH;
R2 and R3 each independently represent H, C1-4 alkyl, halogen; C1-4 haloalkyl, O(C1-4 alkyl), O(C1-4haloalkyl), CN, SO2R5, C(O)OR6 with the proviso that R2 and R3 do not both represent H concomitantly, or
R2 and R3 together with the carbons to which they are attached form a six membered aromatic ring or a heteroaromatic ring comprising a nitrogen atom;
R4 is H, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, C3-6 cycloalkyl, C3-6 cycloalkenyl, C6 aryl, a 5 or 6 membered heteroaryl or a 5 or 6 membered heterocyclic group, wherein said aryl, heteroaryl or heterocyclic group is substituted with 0 to 3 substituents selected from halogen, hydroxyl, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, amino, C1-4 mono or di-alkyl amino, C1-4 mono or di-acyl amino, S(O)qC1-6 alkyl, C0-6 alkylC(O)C1-6 alkyl or C0-6 alkylC(O)C1-6 heteroalkyl;
R4a is H or C1-3 alkyl;
R5 is H or C1-4 alkyl;
R6 is H or C1-4 alkyl;
m is 0, 1 or 2;
q is 0, 1 or 2;
a pharmaceutically acceptable salt thereof, including all stereoisomers, tautomers and isotopic derivatives thereof.

### Claim 62 (depends on 61)

A compound of formula (I) according to claim 61 wherein Z represents —N═CR4a—.

### Claim 63 (depends on 61)

A compound of formula (I) according to claim 61 wherein Z represents NH.

### Claim 64 (depends on 61)

A compound of formula (I) according to claim 61 wherein Z represents O.

### Claim 65 (depends on 61)

A compound of formula (I) according to claim 61 wherein J represents phenyl substituted by R2a and R2b.

### Claim 66 (depends on 61)

A compound of formula (I) according to claim 61 wherein J represents pyridinyl substituted by R2a and R2b.

### Claim 67 (depends on 61)

A compound of formula (I) according to claim 61 wherein J represents thienyl substituted by R2a.

### Claim 68 (depends on 61)

A compound of formula (I) according to claim 61 wherein Y represents —CH═.

### Claim 69 (depends on 61)

A compound of formula (I) according to claim 61 wherein Y represents N.

### Claim 70 (depends on 61)

A compound of formula (I) according to claim 61 which is a compound of formula (II):
wherein R1, R2, R2a, R3 and X are as defined above for compounds of formula (I) and Z represents NH.

### Claim 71 (depends on 1)

A compound of formula (I) according to claim 1 which is a compound of formula (IIIa):
wherein R1, R2, R2a, R3, R4a and X are as defined above for compounds of formula (I).

### Claim 72 (depends on 71)

A compound of formula (IIIa) according to claim 71 wherein R2a does not represent, F, Cl, Br, I, C1-4 alkyl, OH, OC1-4 alkyl, CF3, OCF3 and SO2C1-4 alkyl.

### Claim 73 (depends on 61)

A compound according to claim 61, wherein R1 represents tert-butyl.

### Claim 74 (depends on 61)

A compound according to claim 61, wherein R1 represents C1-6 alkyl or branched or unbranched, C3-6 cycloalkyl, each substituted by a hydroxyl group;

### Claim 75 (depends on 61)

A compound according to claim 61, wherein R2a represents methyl.

### Claim 76 (depends on 61)

A compound of formula (I) according to claim 61, wherein R2a represents methoxy.

### Claim 77 (depends on 61)

A compound according to claim 61, wherein R2a represents C1-6 alkyl substituted by OH.

### Claim 78 (depends on 77)

A compound of formula (I) according to claim 77, wherein R22 represents —CH2OH.

### Claim 79 (depends on 61)

A compound of formula (I) according to claim 61, wherein R2a is in the para position.

### Claim 80 (depends on 61)

A compound of formula (I) according to claim 61, wherein X represents O.

### Claim 81 (depends on 61)

A compound of formula (I) according to claim 61, wherein X represents —OCH2—.

### Claim 82 (depends on 61)

A compound of formula (I) according to claim 61, wherein R2 and R3 together with the phenyl ring to which they are attached form a naphthyl ring.

### Claim 83 (depends on 61)

A compound of formula (I) according to claim 61 selected from:
1-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)-3-(4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yloxy)naphthalen-1-yl)urea;
1-(3-tert-butyl-1-(4-methoxyphenyl)-1H-pyrazol-5-yl)-3-(4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yloxy)naphthalen-1-yl)urea;
1-(3-tert-butyl-1-phenyl-1H-pyrazol-5-yl)-3-(4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yloxy)naphthalen-1-yl)urea;
1-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)-3-(4-(1-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yloxy)naphthalen-1-yl)urea;
1-(3-tert-butyl-1-(4-methoxyphenyl)-1H-pyrazol-5-yl)-3-(4-(1-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yloxy)naphthalen-1-yl)urea;
1-(3-tert-butyl-1-phenyl-1H-pyrazol-5-yl)-3-(8-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yloxy)quinolin-5-yl)urea;
1-(3-tert-butyl-1-(4-methoxyphenyl)-1H-pyrazol-5-yl)-3-(8-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yloxy)quinolin-5-yl)urea;
1-(3-(tert-butyl)-1-phenyl-1H-pyrazol-5-yl)-3-(4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-butyl)-1-(p-tolyl)-1H-pyrazol-5-yl)-3-(4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-butyl)-1-phenyl-1H-pyrazol-5-yl)-3-(4-((2-methyl-3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-butyl)-1-(p-tolyl)-1H-pyrazol-5-yl)-3-(4-((2-methyl-3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-Butyl)-1-(4-methoxyphenyl)-1H-pyrazol-5-yl)-3-(4-((2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-Butyl)-1-(4-methoxyphenyl)-1H-pyrazol-5-yl)-3-(4-((1-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-Butyl)-1-(4-methoxyphenyl)-1H-pyrazol-5-yl)-3-(4-((1-ethyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-Butyl)-1-(4-methoxyphenyl)-1H-pyrazol-5-yl)-3-(4-((1-isopropyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-Butyl)-1-(4-methoxyphenyl)-1H-pyrazol-5-yl)-3-(2,3-dichloro-4-((1-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)urea;
1-(3-(tert-Butyl)-1-(4-methoxyphenyl)-1H-pyrazol-5-yl)-3-(8-((2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yl)oxy)quinolin-5-yl)urea;
1-(3-(tert-Butyl)-1-(p-tolyl)-1H-pyrazol-5-yl)-3-(4-((8-oxo-8,9-dihydro-7H-purin-6-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-Butyl)-1-(4-hydroxyphenyl)-1H-pyrazol-5-yl)-3-(4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-Butyl)-1-(4-(hydroxymethyl)phenyl)-1H-pyrazol-5-yl)-3-(4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-Butyl)-1-(4-(hydroxymethyl)-3-methoxyphenyl)-1H-pyrazol-5-yl)-3-(4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yloxy)naphthalen-1-yl)urea;
1-(3-(tert-Butyl)-1-(4-methoxyphenyl)-1H-pyrazol-5-yl)-3-(2,3-dichloro-4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yloxy)phenyl)urea;
1-(3-(tert-Butyl)-1-(6-methoxypyridin-3-yl)-1H-pyrazol-5-yl)-3-(4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-Butyl)-1-(5-methylthiophen-2-yl)-1H-pyrazol-5-yl)-3-(4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-Butyl)-1-(4-methoxyphenyl)-1H-pyrazol-5-yl)-3-(4-((7-oxo-7,8-dihydropteridin-4-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-butyl)-1-(6-methoxypyridin-3-yl)-1H-pyrazol-5-yl)-3-(4-((1-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-butyl)-1-(4-methoxyphenyl)-1H-pyrazol-5-yl)-3-(4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)naphthalen-1-yl)urea;
1-(4-(3-(tert-butyl)-5-(3-(4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)naphthalen-1-yl)ureido)-1H-pyrazol-1-yl)phenyl)-N-methylmethanesulfonamide;
1-(3-(tert-butyl)-1-(4-chlorophenyl)-1H-pyrazol-5-yl)-3-(4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)naphthalen-1-yl)urea;
1-(3-cyclopropyl-1-(p-tolyl)-1H-pyrazol-5-yl)-3-(4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)naphthalen-1-yl)urea;
1-(3-(1-methylcyclopropyl)-1-(p-tolyl)-1H-pyrazol-5-yl)-3-(4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)naphthalen-1-ylurea;
1-(3-isopropyl-1-(p-tolyl)-1H-pyrazol-5-yl)-3-(4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-butyl)-1-(4-(methylsulfonyl)phenyl)-1H-pyrazol-5-yl)-3-(4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-butyl)-1-(3,4-dichlorophenyl)-1H-pyrazol-5-yl)-3-(4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-butyl)-1-(4-(methylthio)phenyl)-1H-pyrazol-5-yl)-3-(4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)naphthalen-1-yl)urea;
and pharmaceutically acceptable salts of any one thereof, including all stereoisomers, tautomers and isotopic derivatives thereof.

### Claim 84 (depends on 83)

A compound of formula (I) according to claim 83 selected from:
1-(3-tert-butyl-1-(4-methoxyphenyl)-1H-pyrazol-5-yl)-3-(4-(1-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yloxy)naphthalen-1-yl)urea;
1-(3-tert-butyl-1-(4-methoxyphenyl)-1H-pyrazol-5-yl)-3-(8-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yloxy)quinolin-5-yl)urea;
1-(3-(tert-Butyl)-1-(4-methoxyphenyl)-1H-pyrazol-5-yl)-3-(4-((2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-Butyl)-1-(4-methoxyphenyl)-1H-pyrazol-5-yl)-3-(4-((1-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-Butyl)-1-(4-methoxyphenyl)-1H-pyrazol-5-yl)-3-(4-((1-ethyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-Butyl)-1-(4-methoxyphenyl)-1H-pyrazol-5-yl)-3-(4-((1-isopropyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-Butyl)-1-(4-methoxyphenyl)-1H-pyrazol-5-yl)-3-(2,3-dichloro-4-((1-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)urea;
1-(3-(tert-Butyl)-1-(4-methoxyphenyl)-1H-pyrazol-5-yl)-3-(8-((2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yl)oxy)quinolin-5-yl)urea;
1-(3-(tert-Butyl)-1-(p-tolyl)-1H-pyrazol-5-yl)-3-(4-((8-oxo-8,9-dihydro-7H-purin-6-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-Butyl)-1-(4-hydroxyphenyl)-1H-pyrazol-5-yl)-3-(4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-Butyl)-1-(4-(hydroxymethyl)phenyl)-1H-pyrazol-5-yl)-3-(4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-Butyl)-1-(4-(hydroxymethyl)-3-methoxyphenyl)-1H-pyrazol-5-yl)-3-(4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-Butyl)-1-(4-methoxyphenyl)-1H-pyrazol-5-yl)-3-(2,3-dichloro-4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)phenyl)urea;
1-(3-(tert-Butyl)-1-(6-methoxypyridin-3-yl)-1H-pyrazol-5-yl)-3-(4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-Butyl)-1-(5-methylthiophen-2-yl)-1H-pyrazol-5-yl)-3-(4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-Butyl)-1-(4-methoxyphenyl)-1H-pyrazol-5-yl)-3-(4-((7-oxo-7,8-dihydropteridin-4-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-butyl)-1-(6-methoxypyridin-3-yl)-1H-pyrazol-5-yl)-3-(4-((1-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-butyl)-1-(4-methoxyphenyl)-1H-pyrazol-5-yl)-3-(4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)naphthalen-1-yl)urea;
1-(4-(3-(tert-butyl)-5-(3-(4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)naphthalen-1-yl)ureido)-1H-pyrazol-1-yl)phenyl)-N-methylmethanesulfonamide;
1-(3-(tert-butyl)-1-(4-chlorophenyl)-1H-pyrazol-5-yl)-3-(4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)naphthalen-1-yl)urea;
1-(3-cyclopropyl-1-(p-tolyl)-1H-pyrazol-5-yl)-3-(4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)naphthalen-1-yl)urea;
1-(3-(1-methylcyclopropyl)-1-(p-tolyl)-1H-pyrazol-5-yl)-3-(4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)naphthalen-1-ylurea;
1-(3-isopropyl-1-(p-tolyl)-1H-pyrazol-5-yl)-3-(4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-butyl)-1-(4-(methylsulfonyl)phenyl)-1H-pyrazol-5-yl)-3-(4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-butyl)-1-(3,4-dichlorophenyl)-1H-pyrazol-5-yl)-3-(4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)naphthalen-1-yl)urea;
1-(3-(tert-butyl)-1-(4-(methylthio)phenyl)-1H-pyrazol-5-yl)-3-(4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)naphthalen-1-yl)urea;
and pharmaceutically acceptable salts of any one thereof, including all stereoisomers, tautomers and isotopic derivatives thereof.

### Claim 85 (depends on 61)

A method of a respiratory disorder, such as asthma and COPD comprising administering a therapeutically effective dose of a compound as defined in claim 61 to a patient in need thereof.

### Claim 86 (depends on 61)

A method of treating or preventing viral infection comprising administering a therapeutically effective dose of a compound as defined in claim 61 to a patient in need thereof.