# US 9,518,050 B2 · Cyclohexyl and quinuclidinyl carbamate derivatives having β2 adrenergic agonist and M3 muscarinic antagonist activity

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- Number: US 9,518,050 B2
- Document ID: US9518050B2
- Status: Granted
- Kind: B2
- Application number: 14/653,048
- Filed: 2013-12-17
- Published: 2015-11-19
- Granted: 2016-12-13
- Earliest claimed: 2012-12-18
- Assignees: Almirall, S.A.
- Applicants: Almirall, S.A.
- Inventors: Laia Sole Feu; Ines Carranco Moruno; Jose Aiguade Bosch; Carlos Puig Duran; Silvia Fonquerna Pou
- Web page: https://patentgrep.com/patent/US9518050B2

## CPC

- C07D 453/04: having a quinolyl-4, a substituted quinolyl-4 or a alkylenedioxy-quinolyl-4 radical linked through only one carbon atom, attached in position 2, e.g. quinine
- A61K 31/13: Amines {(A61K31/04 takes precedence)}
- A61K 31/4184: condensed with carbocyclic rings, e.g. benzimidazoles
- A61K 31/439: the ring forming part of a bridged ring system, e.g. quinuclidine (8-azabicyclo [3.2.1] octanes A61K31/46)
- A61K 31/4704: 2-Quinolinones, e.g. carbostyril
- A61K 31/4709: Non-condensed quinolines and containing further heterocyclic rings
- A61K 31/475: having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine (vincamine A61K31/4375)
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/55: the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/06: Antiasthmatics
- A61P 11/08: Bronchodilators
- A61P 13/00: Drugs for disorders of the urinary system
- A61P 15/06: Antiabortive agents; Labour repressants
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 27/06: Antiglaucoma agents or miotics
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- 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
- C07C 271/38: with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring
- C07D 213/75: Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
- C07D 215/26: Alcohols; Ethers thereof
- C07D 249/18: Benzotriazoles
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 413/12: linked by a chain containing hetero atoms as chain links
- C07D 453/02: containing not further condensed quinuclidine ring systems
- C07C 2601/14: The ring being saturated
- 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
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## Abstract

The present invention relates to novel compounds having β2 adrenergic agonist and M3 muscarinic antagonist dual activity, to pharmaceutical compositions containing them, to the process for their preparation and to their use in respiratory therapies.

## Claims

### Claim 1

A compound of Formula (A), or a pharmaceutically acceptable salt or deuterated derivative thereof:
wherein:
R is chosen from the group consisting of a hydrogen atom, a halogen atom, a hydroxyl group, a linear or branched C1-4 alkyl group, a linear or branched C1-4 hydroxyalkyl group, and a linear or branched C1-4 alkoxy group,
n is lor 2,
R1 is:
wherein:
R2 and R3 are independently chosen from a hydrogen atom, a linear or branched C1-4 alkyl group, a (C5-6 aryl)-(C1-4)alkyl group, and a linear or branched C1-4 alkoxy group,
R′ is chosen from a hydrogen atom or a linear or branched C1-4 alkyl group,
* is a point of attachment of R1 to the remainder of the molecule of Formula (A),
Lx is a suitable covalent linker, and
B represents a group of Formula (IB):
wherein:
R4 is chosen from the group consisting of a hydrogen atom, a linear or branched C1-4 alkyl group, and a linear or branched C1-4 alkoxy group,
Ar is chosen from the group consisting of a C3-10 saturated or unsaturated, mono- or bicyclic cycloalkyl group; a C5-C14 mono- or bicyclic aryl group; a 3 to 14-membered saturated or unsaturated mono- or bicyclic heterocyclyl group having one or more heteroatoms chosen from N, S, and O; and a 5- to 14-membered mono- or bicyclic heteroaryl group having one or more heteroatoms chosen from N, S, and O; and wherein the cyclic groups independently are optionally substituted with one or more substituents chosen from a halogen atom, a cyano group, a nitro group, an oxo group, a carboxy group, a C1-4 alkyl group, a C1-4 alkoxy group, —CF3, —OCF3, —NReRf, —(CH2)p—OH, —NRe(CO)Rf, —NRe—SO2—Rg, —SO2NReRf, —OC(O)Rh, and —NRe(CH2)(0-2)—Ri, wherein p is 0, 1 or 2 and wherein:
Re and Rf are independently chosen from a hydrogen atom and a linear or branched C1-4 alkyl group,
Rg is chosen from the group consisting of a linear or branched C1-4 alkyl group, a C5-6 aryl group, and a saturated or unsaturated C3-8 cycloalkyl, wherein the cyclic groups independently are optionally substituted with one or more substituents chosen from a halogen atom, a C1-4 alkyl group, and a C1-4 alkoxy group, Rh is chosen from a hydrogen atom, —NReRf, and a C5-6 aryl group, which is optionally substituted with one or more substituents chosen from a C1-4 alkyl group and a C1-4 alkoxy group,
Ri is chosen from the group consisting of a C5-6 aryl group, a C3-8 cycloalkyl group, and a 3 to 8 membered saturated or unsaturated heterocyclyl group, which groups independently are optionally substituted with one or more substituents chosen from a halogen atom, a C1-4 alkyl group, and a C1-4 alkoxy group.

### Claim 2 (depends on 1)

The compound according to claim 1, wherein Lx is Formula (La) or Formula (Lb):
wherein k1, k2, s1, s2, l2, t1, and t2 are independently 0 or 1;
A1, A2, A3, A4 and A5 are independently chosen from the group consisting of a direct bond, a C1-10 alkylene group, a C2-10 alkenylene group, and a C2-10 alkynylene group, wherein said groups are optionally substituted with one or more substituents chosen from a halogen atom, a hydroxy group, a linear or branched C1-4 alkyl group, a linear or branched C1-4 alkoxy group, a C5-6 aryl group, and a C3-7 cycloalkyl group,
L, L1 and L2 are independently chosen from a direct bond, —O—, —NRc—, —S—, —S(O)—, —SO2—, —NRc(CO)—, —(CO)NRc—, —NRc(CO)(CH2)qO—, —O(CH2)q(CO)NRc—, —NRc(CO)(CH2)qNRc(CO)—, —O(CH2)qNRc—, —NRc(CH2)qO—, —NRc(CO)NRd—, —C(O)—, —C(O)O—, —OC(O)—, —S(O)2NRc—, —NRcS(O)2—, —NRcS(O)2NRd—, —C(O)NRcS(O)2—, and —S(O)2NRcC(O)—, wherein Rc and Rd are independently chosen from a hydrogen atom and a linear or branched C1-4 alkyl group and q is 0, 1, 2, 3 or 4,
G and G2 are independently chosen from the group consisting of a direct bond; a C3-10 mono- or bicyclic cycloalkyl group; a C5-C14 mono- or bicyclic aryl group; a 3 to 14-membered saturated or unsaturated mono- or bicyclic heterocyclyl group having one or more heteroatoms chosen from N, S, and O; a 5- to 14-membered mono- or bicyclic heteroaryl group having one or more heteroatoms chosen from N, S, and O; and a bicyclic ring system comprising two monocyclic ring systems which are linked between each other by a covalent bond or by a —O— or —NH— group; wherein said monocyclic ring systems are independently chosen from a C cydcloalkyl group; a C5-6 aryl group; a 3 to 8-membered saturated or unsaturated heterocyclyl group having one or more heteroatoms chosen from N, S, and O; and a 5- to 6-membered heteroaryl group having one or more heteroatoms chosen from N, S, and O; wherein the cyclic groups independently are optionally substituted with one or more substituents chosen from a halogen atom, a C1-4 alkyl group, a C1-4 alkoxy group, a carboxy group, a cyano group, a nitro group, a hydroxy group, an oxo group, a trifluoromethyl group, and a trifluoromethoxy group.

### Claim 3 (depends on 2)

The compound according to claim 2, wherein k1, k2, s1, s2, l2, t1 and t2 are 0.

### Claim 4 (depends on 3)

The compound according to claim 3, wherein Lx is Formula (Lb1):

### Claim 5 (depends on 1)

The compound according to claim 1, wherein Lx is -A1-G-L-A2-.

### Claim 6 (depends on 1)

The compound according to claim 1, wherein Ar is formula (a), (b), (c), or (d):
wherein
Ga and Gb are independently chosen from a nitrogen atom and a carbon atom,
r is 0, 1, 2 or 3 and
Ra is chosen from the group consisting of a halogen atom, an amino group, a cyano group, a nitro group, an oxo group, a carboxy group, a C1-4 alkyl group, a C1-4 alkoxy group, —CF3, —OCF3, —(CH2)p—OH, —NH(CO)H, —NH—SO2—Rg, —SO2NH2, —OC(O)H, —O(CO)-(4-methyl)phenyl, —O(CO)—N(CH3)2, —OC(O)NH2, or —NH(CH2)(1-2)—Ri, wherein p is as defined above and Rg and Ri are independently chosen from a phenyl group optionally substituted with a one substituent chosen from a methyl group and a methoxy group,
Rj is a halogen atom,
T is chosen from the group consisting of —CH2— and —NH—,
Both X and Y are a hydrogen atom or X together with Y forms —CH2—CH2—, —CH═CH—, —CH2—O—, or —S—, wherein in the case of —CH2—O— the methylene group is bound to the carbonyl group holding X and the oxygen atom is bound to the carbon atom in the phenyl ring holding Y.

### Claim 7 (depends on 6)

The compound according to claim 6, wherein Ar is formula (a) or (b) wherein:
Both Ga and Gb are a carbon atom,
Ra is chosen from the group consisting of halogen atom, amino group, cyano group, nitro group, —(CH2)p—OH, —NH(CO)H, —NH—SO2—CH3, —SO2NH2, —OC(O)H, —O(CO)-(4-methyl)phenyl, —O(CO)—N(CH3)2, —OC(O)NH2, or —CF3, wherein p is 0, 1 or 2,
T is —NH—,
Both X and Y are a hydrogen atom or X together with Y forms —CH═CH—, —CH2—CH2—, —CH2—O—, or —S—, wherein in the case of —CH2—O— the methylene group is bound to the carbon atom in the amido substituent holding X and the oxygen atom is bound to the carbon atom in the phenyl ring holding Y.

### Claim 8 (depends on 6, 7)

The compound according to claim 6 or 7, wherein Ar is chosen from the group consisting of 3-bromoisoxazol-5-yl, 3,4-dihydroxyphenyl, 4-hydroxy-3-(methylsulfonamido)phenyl, 3,4-bis(4-methylbenzoyloxy)phenyl, 3,5-bis(dimethylcarbamoyloxy)phenyl, (5-hydroxy-6-hydroxymethyl)pyrid-2-yl, (4-amino-3,5-dichloro)phenyl, 4-hydroxyphenyl, 4-hydroxy-3-(2-hydroxyethyl)phenyl, 4-hydroxy-3-(hydroxymethyl)phenyl, [4-amino-3-chloro-5-(trifluoromethyl)]phenyl, (3-formamido-4-hydroxy)phenyl, 8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl, 8-hydroxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-yl, 5-hydroxy-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl, or 4-hydroxy-2-oxo-2,3-dihydrobenzo[d]thiazol-7-yl.

### Claim 9 (depends on 7)

The compound according to claim 7, wherein Ar is the compound of formula (b) wherein T is —NH.

### Claim 10 (depends on 1)

The compound according to claim 1, wherein Formula (I) is:
wherein:
R is chosen from the group consisting of a hydrogen atom, a halogen atom, a hydroxyl group, a linear or branched C1-4 alkyl group, a linear or branched C1-4 hydroxyalkyl group, and a linear or branched C1-4 alkoxy group,
n is 1 or 2,
X and Y are both a hydrogen atom or X together with Y forms —CH═CH—, —CH2—O—, or —S—, wherein in the case of —CH2—O— the methylene group is bound to the carbon atom in the amido substituent holding X and the oxygen atom is bound to the carbon atom in the phenyl ring holding Y,
A1 and A2 are independently chosen from the group consisting of a direct bond, a C1-10 alkylene group, a C2-10 alkenylene group, and a C2-10 alkynylene group, wherein said groups are optionally substituted with one or more substituents chosen from a halogen atom, a hydroxy group, a linear or branched C1-4 alkyl group, a linear or branched a C1-4 alkoxy group, a C5-6 aryl group, and a C3-7 cycloalkyl group,
G is chosen from the group consisting of a direct bond; a C3-10 mono- or bicyclic cycloalkyl group; a C5-14 mono- or bicyclic aryl group; a 3- to 14-membered saturated or unsaturated mono- or bicyclic heterocyclyl group having one or more heteroatoms chosen from N, S, and O; a 5- to 14-membered mono- or bicyclic heteroaryl group having one or more heteroatoms chosen from N, S, and O; and a bicyclic ring system consisting of two monocyclic ring systems which are linked between each other by a covalent bond or by a —O— group, wherein said monocyclic ring systems are independently chosen from a C3-8 cycloalkyl group; a C5-6 aryl group; a 3- to 8-membered saturated or unsaturated heterocyclyl group having one or more heteroatoms chosen from N, S, and O; and a 5- to 6-membered heteroaryl group having one or more heteroatoms chosen from N, S, and O; wherein the cyclic groups independently are optionally substituted with one or more substituents chosen from a halogen atom, a C1-4 alkyl group, a C1-4 alkoxy group, a carboxy, group, a cyano group, a nitro group, a hydroxy group, an oxo group, a trifluoromethyl group, and a trifluoromethoxy group,
L is chosen from a direct bond, —O—, —NRc—, —S—, —S(O)—, —SO2—, —NRc(CO)—, —(CO)NRc—, —NRc(CO)(CH2)qO—, —O(CH2)q(CO)NRc—, —NRc(CO)(CH2)qNRc(CO)—, —O(CH2)qNRc—, —NRc(CH2)qO—, —NRc(CO)NRd—, —C(O)—, —C(O)O—, —OC(O)—, —S(O)2NRc—, —NRcS(O)2—, —NRcS(O)2NRd—, —C(O)NRcS(O)2—, or —S(O)2NRcC(O)—, wherein Rc and Rd are independently chosen from a hydrogen atom and a linear or branched C1-4 alkyl group and q is 0, 1, 2, 3 or 4,
R1 is:
wherein:
R2 and R3 are independently chosen from a hydrogen atom, a linear or branched C1-4 alkyl group, and a (C5-6 aryl)-(C1-4) alkyl group and R′ is chosen from a hydrogen atom and a linear or branched C1-4 alkyl group.

### Claim 11 (depends on 1)

The compound according to claim 1, wherein A1 and A2 are independently chosen from the group consisting of C1-6 alkylene group, C1-6 alkenylene group, and C1-6alkynylene group, wherein said groups are optionally substituted with one or more substituents chosen from a halogen atom, a hydroxy group, a C1-2 alkyl group, a C1-2 alkoxy group, a C5-6 aryl group, and a C3-6 cycloalkyl group.

### Claim 12 (depends on 1)

The compound according to claim 1, wherein X together with Y forms —CH═CH— or —CH2—O—.

### Claim 13 (depends on 1)

The compound according to claim 1, wherein L is chosen from the group consisting of a direct bond, —O—, —NRc—, —S—, —S(O)—, —SO2—, —NRc(CO)—, —(CO)NRc—, —NRc(CO)(CH2)qO—, —O(CH2)q(CO)NRc—, —NRc(CO)(CH2)qNRc(CO)—, —O(CH2)qNRc—, —NRc(CH2)qO—, —NRc(CO)NRd—, —C(O)—, —C(O)O—, —OC(O)—, —S(O)2NRc—, —NRcS(O)2—, —NRcS(O)2NRd—, —C(O)NRcS(O)2—, or —S(O)2NRcC(O)—, wherein Rc and Rd are independently chosen from a hydrogen atom and a linear or branched C1-4 alkyl group and q has a value of 0, 1, 2, 3 or 4.

### Claim 14 (depends on 13)

The compound according to claim 13, wherein L is chosen from a direct bond, —NRc(CO)—, —(CO)NRc—, —O(CH2)q(CO)NRc— or —C(O)—.

### Claim 15 (depends on 1)

The compound according to claim 1, wherein G is chosen from the group consisting of a direct bond; a C3-7 cycloalkyl group; a C5-14 mono- or bicyclic aryl group; a 3- to 14-membered saturated or unsaturated mono- or bicyclic heterocyclyl group having one or more heteroatoms selected from N, S, and O; a 5- to 14-membered mono- or bicyclic heteroaryl group having one or more heteroatoms chosen from N, S, and O; or a bicyclic ring system comprising two monocyclic ring systems which are linked between each other by a covalent bond or by a —O— group, wherein said monocyclic ring system are independently chosen from the group consisting of a C3-8 cycloalkyl group and a C5-6 aryl group, wherein the cyclic groups independently are optionally substituted with one or more substituents chosen from a halogen atom, a C1-4 alkyl group, a C1-4 alkoxy group, a carboxy group, a cyano group, a nitro group, a hydroxy group, an oxo group, a trifluoromethyl group, and a trifluoromethoxy group.

### Claim 16 (depends on 15)

The compound according to claim 15, wherein, G is chosen from the group consisting of a C3-7 cycloalkyl group, a C5-C6 aryl group, or a group of Formula (Iwa):
wherein
V, W and Z are independently chosen from —N—, —NH—, —C—, —CH—, —S—, —O—, and —C(O)—,
wherein the cyclic groups independently are optionally substituted with one or more substituents chosen from a halogen atom, a C1-4 alkyl group and a C1-4 alkoxy group.

### Claim 17 (depends on 16)

The compound according to claim 16, wherein W is chosen from —N—, —NH—, or a —C(O)— group.

### Claim 18 (depends on 16)

The compound according to claim 16, wherein V is chosen from —N—, —NH—, —S—, or —O—.

### Claim 19 (depends on 16)

The compound according to claim 16, wherein G is chosen from a phenylene group, a cyclohexyl group, or a group of Formula (Iwb):
wherein V is chosen from —N—, —NH—, or —O— and W is a —C(O)— group, and wherein the cyclic groups are independently optionally substituted with one or two substituents chosen from a chlorine atom, methyl group, and methoxy group.

### Claim 20 (depends on 1)

The compound according to claim 1, wherein R1 is formula:
wherein R′, R2 and R3 are independently chosen from a hydrogen atom and a C1-2 alkyl group.

### Claim 21 (depends on 20)

A compound according to claim 20, wherein R1 is formula:

### Claim 22 (depends on 1)

The compound according to claim 1, wherein R is chosen from the group consisting of a hydrogen atom, a halogen atom, or a hydroxy group.

### Claim 23 (depends on 1)

The compound according to claim 1, wherein n is 1 or 2.

### Claim 24 (depends on 1)

The compound according to claim 1, wherein A1 and A2 independently are a C1-4 alkylene group optionally substituted with one or two methyl groups, X together with Y forms —CH═CH—, L is chosen from the group consisting of a direct bond, —NRc(CO)—, or —(CO)NRc—, wherein Rc is chosen from a hydrogen atom and a methyl group, G is chosen from a phenylene group, a cyclohexyl group, or a group of Formula (Iwb):
wherein V is chosen from —N—, —NH—, or —O— and W is a —C(O) group, and wherein the cyclic groups are independently optionally substituted with one or two substituents chosen from a chlorine atom, a methyl group, and a methoxy group, and R1 has formula:
wherein both R2 and R3 are a hydrogen atom and R′ is chosen from a hydrogen atom or a methyl group, R is a hydrogen atom and n is 1.

### Claim 25 (depends on 1)

The compound according to claim 1, having Formula (I):
wherein, R is a hydrogen atom and n is 1, A1 and A2 are independently chosen from a direct bond and a C1-6 alkylene group optionally substituted with a methyl group, X together with Y forms —CH═CH—, —CH2—CH2— or —CH2—O—, L is chosen from the group consisting of a direct bond, —O—, —NRc(CO)O—, —O(CH2)(CO)NRc—, —NRc(CO)— —(CH2)4NRc(CO)—, —(CH2)(0-1)NRc(CO)—, —(CO)NRc—, or —NH(CO)NH—, wherein Rc is chosen from a hydrogen atom or a methyl group, G is chosen from a direct bond, a phenylene group, a pyridyl group, a cyclobutyl group, a cyclohexyl group, or a group of Formula (Iwa):
wherein V and Z independently are chosen from the group consisting of —N—, —NH—, —C—, —O—, and —S—, and W is chosen from —N—, —NH—, —C—, and a —C(O)— group, and wherein the phenylene group, pyridyl group, cyclobutyl group, cyclohexyl group, and the group of Formula (Iwa) are independently optionally substituted with one or two substituents chosen from a chlorine atom, methyl group, and methoxy group, R1 has formula:
wherein both R2 and R3 are independently chosen from a hydrogen atom, a methyl group, a hexyl group, and a propyl group substituted with a phenyl group and R′ is a hydrogen atom or a methyl group.

### Claim 26 (depends on 1)

The compound according to claim 1, wherein the compound is chosen from:
(3R)-1-azabicyclo[2.2.2]oct-3-yl(4-{3-[6-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-2-oxo-1,3-benzoxazol-3(2H)-yl]propyl}biphenyl-2-yl)carbamate,
(3R)-1-azabicyclo[2.2.2]oct-3-yl(4-{4-[4-(2-{[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}ethyl)phenoxy]butyl}biphenyl-2-yl)carbamate
trans-4-(methylamino)cyclohexyl(4-{3-[5-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-1H-1,2,3-benzotriazol-1-yl]propyl}biphenyl-2-yl)carbamate,
(3R)-1-azabicyclo[2.2.2]oct-3-yl(4-{3-[5-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-1H-1,2,3-benzotriazol-1-yl]propyl}biphenyl-2-yl)carbamate,
(3R)-1-azabicyclo[2.2.2]oct-3-yl(4-{3-[5-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl]propyl}biphenyl-2-yl)carbamate,
(3R)-1-azabicyclo[2.2.2]oct-3-yl(4-{3-[5-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-1H-indol-1-yl]propyl}biphenyl-2-yl)carbamate,
(3R)-1-azabicyclo[2.2.2]oct-3-yl(4-{4-[6-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-2-oxo-1,3-benzoxazol-3(2H)-yl]butyl}biphenyl-2-yl)carbamate,
trans-4-aminocyclohexyl(4-{3-[5-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydro-quinolin-5-yl)ethyl]amino}methyl)-1H-1,2,3-benzotriazol-1-yl]propyl}biphenyl-2-yl)carbamate,
(3R)-1-azabicyclo[2.2.2]oct-3-yl(4-{4-[3-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)phenoxy]butyl}biphenyl-2-yl)carbamate,
(3R)-1-azabicyclo[2.2.2]oct-3-yl(4-{4-[4-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)phenoxy]butyl}biphenyl-2-yl)carbamate,
trans-4-aminocyclohexyl(4-{4-[4-(2-{[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}ethyl)phenoxy]butyl}biphenyl-2-yl)carbamate,
(3R)-1-azabicyclo[2.2.2]oct-3-yl(4-{4-[5-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-yl)ethyl]amino}methyl)-1,3-benzoxazol-2-yl]butyl}biphenyl-2-yl)carbamate,
(3R)-1-azabicyclo[2.2.2]oct-3-yl(4-{3-[3-(2-{[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-ethyl]amino}ethyl)phenoxy]propyl}biphenyl-2-yl)carbamate,
(3R)-1-azabicyclo[2.2.2]oct-3-yl(4-{3-[({[2-chloro-4-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-5-methoxyphenyl]amino}carbonyl)oxy]-propyl}biphenyl-2-yl)carbamate,
(3R)-1-azabicyclo[2.2.2]oct-3-yl(4-{4-[5-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl-1H-indol-1-yl]butyl}biphenyl-2-yl)carbamate,
(3R)-1-azabicyclo[2.2.2]oct-3-yl(4-{4-[6-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-2-oxo-1,3-benzothiazol-3(2H)-yl]butyl}biphenyl-2-yl)carbamate,
(3R)-1-azabicyclo[2.2.2]oct-3-yl(4-{3-[4-(2-{[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}ethyl)phenoxy]propyl}biphenyl-2-yl)carbamate,
(3R)-1-azabicyclo[2.2.2]oct-3-yl(4-{4-[6-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-1,3-benzoxazol-2-y]butyl}biphenyl-2-yl)carbamate,
(3R)-1-azabicyclo[2.2.2]oct-3-yl(4-{4-[5-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-2H-1,2,3-benzotriazol-2-yl]butyl}biphenyl-2-yl)carbamate,
trans-4-aminocyclohexyl(4-{4-[6-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-2-oxo-1,3-benzoxazol-3(2H)-yl]butyl}biphenyl-2-yl)carbamate,
(3R)-1-azabicyclo[2.2.2]oct-3-yl(5-{4-[4-(2-{[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}ethyl)phenoxy]butyl}biphenyl-2-yl)carbamate,
(3R)-1-azabicyclo[2.2.2]oct-3-yl(5-{4-[6-({[(2R)-2-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-2-oxo-1,3-benzoxazol-3(2H)-yl]butyl}biphenyl-2-yl)carbamate,
trans-4-aminocyclohexyl[4-(4-{[4-({[(2R)-2-hydroxy-2-(8-hyroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)phenyl]amino}-4-oxobutyl)biphenyl-2-yl]carbamate,
(3R)-1-azabicyclo[2.2.2]oct-3-yl(4-{3-[5-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-2-oxo-1,3-benzoxazol-3(2H)-yl]propyl}biphenyl-2-y)carbamate,
(3R)-1-azabicyclo[2.2.2]oct-3-yl(4-{4-[6-({[(2R)-2-hydroxy-2-(5-hydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-8-yl)ethyl]amino}methyl)-2-oxo-1,3-benzoxazol-3(2H)-yl]butyl}biphenyl-2-yl)carbamate,
trans-4-aminocyclohexyl(4-{3-[5-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-2-oxo-1,3-benzoxazol-3(2H)-yl]propyl}biphenyl-2-yl)carbamate,
trans-4-aminocyclohexyl(4-{4-[5-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-1H-indol-1-yl]butyl}biphenyl-2-yl)carbamate,
(3R)-1-azabicyclo[2.2.2]oct-3-yl(4-{4-[6-(2-{[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}ethyl)-2-oxo-1,3-benzoxazol-3(2H)-yl]butyl}biphenyl-2-yl)carbamate,
trans-4-aminocyclohexyl(4-{5-[6-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-2-oxo-1,3-benzoxazol-3(2H)-yl]pentyl}biphenyl-2-yl)carbamate,
(3R)-1-azabicyclo[2.2.2]oct-3-yl(4-{3-[6-(2-{[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}ethyl)-2-oxo-1,3-benzoxazol-3(2H)-yl]propyl}biphenyl-2-yl)carbamate,
(3R)-1-azabicyclo[2.2.2]oct-3-yl(4-{5-[6-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-2-oxo-1,3-benzoxazol-3(2H)-yl]pentyl}biphenyl-2-yl)carbamate,
trans-4-aminocyclohexyl[4-(4-{[2-chloro-4-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-5-methoxyphenyl]amino}-4-oxobutyl)biphenyl-2-yl]carbamate,
trans-4-aminocyclohexyl {4-[(6-{[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}hexyl)oxy]biphenyl-2-yl}carbamate,
trans-4-aminocyclohexyl(5-{4-[6-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-2-oxo-1,3-benzoxazol-3(2H)-yl]butyl}biphenyl-2-yl)carbamate,
trans-4-aminocyclohexyl(4-{4-[5-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-1H-1,2,3-benzotriazol-1-yl]butyl}biphenyl-2-yl)carbamate,
trans-4-aminocyclohexyl[5-(4-{[4-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)phenyl]amino}-4-oxobutyl)biphenyl-2-yl]carbamate,
trans-4-aminocyclohexyl[4-(5-{[4-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)phenyl]amino}5-oxopentyl)biphenyl-2-yl]carbamate,
trans-4-aminocyclohexyl[4-(4-({[4-(2-{[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}ethyl)phenyl]amino}-4-oxobutyl)biphenyl-2-yl]carbamate,
trans-4-aminocyclohexyl(4-{4-[6-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-5-methoxy-2-oxo-1,3-benzoxazol-3(2H)-yl]butyl}biphenyl-2-yl)carbamate,
trans-4-[methyl(3-phenylpropyl)amino]cyclohexyl[4-(4-{[4-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)phenyl]amino}-4-oxobutyl)biphenyl-2-yl]carbamate,
trans-4-aminocyclohexyl[4-(3-{[4-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)phenyl]amino}-3-oxopropyl)biphenyl-2-yl]carbamate,
(3R)-1-azabicyclo[2.2.2]oct-3-yl[4-(4-{[4-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)phenyl]amino}-4-oxobutyl)biphenyl-2-yl]carbamate,
trans-4-aminocyclohexyl(4-{4-[[4-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)phenyl](methyl)amino]-4-oxobutyl}biphenyl-2-yl)carbamate,
trans-4-aminocyclohexyl[4-(4-(4-{[trans-4-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)cyclohexyl]amino}-4-oxobutyl)biphenyl-2-yl]carbamate,
trans-4-aminocyclohexyl[4-(4-{[4-(2-{[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}propyl)phenyl]amino}-4-oxobutyl)biphenyl-2-yl]carbamate,
trans-4-aminocyclohexyl(4-{4-[(5-{[4-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)phenyl]amino}-5-oxopentyl)(methyl)amino]-4-oxobutyl}biphenyl-2-yl)carbamate,
trans-4-aminocyclohexyl(4-{3-[{[2-chloro-4-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-5-methoxyphenoxy]acetyl}(methyl)amino]-propyl}biphenyl-2-yl)carbamate,
trans-4-amino-1-methylcyclohexyl[4-(3-{[2-chloro-4-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-5-methoxyphenyl]amino}-3-oxopropyl)biphenyl-2-yl]carbamate,
trans-4-amino-1-methylcyclohexyl[4-(3-{[trans-4-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)cyclohexyl]amino}-3-oxopropyl)biphenyl-2-yl]carbamate,
1-azabicyclo[2.2.2]oct-4-yl[4-(3-{[2-chloro-4-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-5-methoxyphenyl]amino}-3-oxopropyl)biphenyl-2-yl]carbamate,
trans-4-aminocyclohexyl(4-{2-[{[2-chloro-4-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-5-methoxyphenoxy]acetyl}(methyl)amino]ethyl}biphenyl-2-yl)carbamate,
trans-4-aminocyclohexyl(4-{2-[({[2-chloro-4-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-5-methoxyphenyl]amino}carbonyl)oxy]ethyl}biphenyl-2-yl)carbamate,
trans-4-aminocyclohexyl(4-{4-[4-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)phenoxy]butyl}biphenyl-2-yl)carbamate,
trans-4-aminocyclohexyl[4-(4-{[trans-3-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)cyclobutyl]amino}-4-oxobutyl)biphenyl-2-yl]carbamate,
trans-4-aminocyclohexyl[4-(3-{[2-chloro-4-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-5-methoxybenzoyl]amino}propyl)biphenyl-2-yl]carbamate,
trans-4-aminocyclohexyl[4-(3-{4-[4-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)phenoxy]phenyl}propyl)biphenyl-2-yl]carbamate,
trans-4-aminocyclohexyl[4-(4-{[4-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)benzyl]amino}-4-oxobutyl)biphenyl-2-yl]carbamate,
trans-4-aminocyclohexyl[4-(4-{[5-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)pyridin-2-yl]amino}-4-oxobutyl)biphenyl-2-yl]carbamate,
trans-4-[hexyl(methyl)amino]cyclohexyl[4-(4-{[2-chloro-4-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-5-methoxyphenyl]amino}-4-oxobutyl)biphenyl-2-yl]carbamate,
trans-4-aminocyclohexyl[4-(4-{[6-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)pyridin-3-yl]amino}-4-oxobutyl)biphenyl-2-yl]carbamate,
Trans-4-aminocyclohexyl(4-(3-(Trans-4-((((2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl)amino)methyl)cyclohexanecarboxamido)propyl)-biphenyl-2-yl)carbamate,
trans-4-aminocyclohexyl(4-{3-[({[2-chloro-4-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-5-methoxyphenyl]amino}carbonyl)amino]propyl}biphenyl-2-yl)carbamate,
trans-4-aminocyclohexyl[4-(4-{[2-chloro-4-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-5-methoxybenzoyl]amino}butyl)biphenyl-2-yl]carbamate,
1-azabicyclo[2.2.2]oct-4-yl[4-(4-{[4-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)phenyl]amino}-4-oxobutyl)biphenyl-2-yl]carbamate,
trans-4-aminocyclohexyl(4-{3-[({[trans-4-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)cyclohexyl]oxy}acetyl)methyl)amino]propyl}biphenyl-2-yl)carbamate,
1-azabicyclo[2.2.2]oct-4-yl[4-(4-{[2-chloro-4-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-5-methoxyphenyl]amino}-4-oxobutyl)biphenyl-2-yl]carbamate
trans-4-aminocyclohexyl(4-{4-[5-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-1H-benzimidazol-1-yl]butyl}biphenyl-2-yl)carbamate,
trans-4-amino-1-methylcyclohexyl[4-(4-{[2-chloro-4-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-5-methoxyphenyl]amino}-4-oxobutyl)biphenyl-2-yl]carbamate,
1-azabicyclo[2.2.2]oct-4-yl(4-{3-[{[2-chloro-4-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-5-methoxyphenoxy]acetyl}(methyl)amino propyl}biphenyl-2-yl)carbamate,
1-azabicyclo[2.2.2]oct-4-yl[4-(4-{[2-chloro-4-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-5-methoxybenzoyl]amino}butyl)biphenyl-2-yl]carbamate and
1-azabicyclo[2.2.2]oct-4-yl[4-(4-{[6-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)pyridin-3-yl]amino}-4-oxobutyl)biphenyl-2-yl]carbamate,
or pharmaceutically acceptable salts or deuterated derivates thereof.

### Claim 27 (depends on 1)

A pharmaceutical composition comprising the compound according to claim 1 and a pharmaceutically acceptable diluent or carrier.

### Claim 28 (depends on 1)

A combination product comprising (i) the compound according to claim 1; and (ii) at least one additional compound chosen from a corticosteroid and a PDE4 inhibitor, for simultaneous, separate or sequential use in the treatment of the human or animal body.

### Claim 29 (depends on 8)

The compound according to claim 8, wherein Ar is chosen from the group consisting of 4-hydroxy-3-(hydroxymethyl)phenyl, (3-formamido-4-hydroxy)phenyl, 8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl, 8-hydroxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-yl, or 5-hydroxy-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl.

### Claim 30 (depends on 11)

The compound according to claim 11, wherein A1 and A2 independently are a C1-6 alkylene group optionally substituted with one or more substituents selected from a C1-2 alkyl group, a C1-2 alkoxy group, and a phenyl group.

### Claim 31 (depends on 30)

The compound according to claim 30, wherein A1 and A2 independently are a C1-4 alkylene group optionally substituted with one or two substituents selected from a methyl group and a methoxy group.

### Claim 32 (depends on 31)

The compound according to claim 31, wherein A1 and A2 independently are a C1-4 alkylene group optionally substituted with one or two methyl groups.

### Claim 33 (depends on 12)

The compound according to claim 12, wherein X together with Y forms —CH═CH—.

### Claim 34 (depends on 13)

The compound according to claim 13, wherein L is chosen from the group consisting of direct bond, —O—, —NRc—, —NRc(CO)—, —(CO)NRc—, —NRc(CO)(CH2)qO—, —O(CH2)q(CO)NRc—, —NRc(CO)(CH2)qNRc(CO)—, —O(CH2)qNRc—, —NRc(CH2)qO—, —NRc(CO)NRd—, —C(O)—, —C(O)O—, or —OC(O)— wherein Rc and Rd are independently selected from a hydrogen atom and a methyl group and q has a value of 0, 1, 2, 3 or 4.

### Claim 35 (depends on 34)

The compound according to claim 34, wherein, L is selected from a direct bond, —O—, —NRc(CO)—, —(CO)NRc—, —NRc(CO)(CH2)qO—, —O(CH2)q(CO)NRc— or —C(O)—, wherein Rc and Rd independently are selected from a hydrogen atom and a methyl group and q has a value of 0, 1, 2, 3 or 4.

### Claim 36 (depends on 14)

The compound according to claim 14, wherein L is chosen from a direct bond, —NRc(CO)— or —(CO)NRc—, wherein Rc is chosen from a hydrogen atom or a methyl group.

### Claim 37 (depends on 15)

The compound according to claim 15, wherein G is chosen from the group consisting of a direct bond; a C3-7 cycloalkyl group; a C5-C6 aryl group; a 8- to 10-membered saturated or unsaturated bicyclic heterocyclyl group having one or more heteroatoms selected from N, S, and O; and a 8- to 10-membered bicyclic heteroaryl group having one or more heteroatoms chosen from N, S, and O, wherein the cyclic groups independently are optionally substituted with one or more substituents chosen from a halogen atom, a C1-4 alkyl group, a C1-4 alkoxy group, a cyano group, a nitro group, a hydroxy group and an oxo group.

### Claim 38 (depends on 17)

The compound according to claim 17, wherein W is a —C(O)— group.

### Claim 39 (depends on 18)

The compound according to claim 18, wherein V is chosen from —N—, —NH—, or —O.

### Claim 40 (depends on 16)

The compound according to claim 16, wherein W is a —C(O)— group and Z is a —N— or —NH— group.

### Claim 41 (depends on 21)

A compound accordingly to claim 21, wherein R′, R2 and R3 are independently chosen from a hydrogen atom and a methyl group.

### Claim 42 (depends on 41)

A compound accordingly to claim 41, wherein R2 and R3 are a hydrogen atom and R′ is a hydrogen atom or a methyl group.

### Claim 43 (depends on 22)

The compound according to claim 22, wherein R is chosen from a hydrogen atom or a hydroxy group.

### Claim 44 (depends on 43)

The compound according to claim 43, wherein R is a hydrogen atom.

### Claim 45 (depends on 23)

The compound according to claim 23, wherein n is 1.

### Claim 46 (depends on 1)

A method for treating a subject afflicted with a pathological condition or disease, wherein the pathological condition or disease is chosen from asthma and/or chronic obstructive pulmonary disease, the method comprising administering to said subject an effective amount of a compound according to claim 1.