1461024513-7a905876-1e2a-4316-8f29-1ab284c88d75

1. A multilayer structure comprising, in this order:
a) a first layer (1) comprising a polyamide (A) or a polyamide (A)polyolefin (B) blend having a polyamide matrix;
b) optionally, a tie layer (2a);
c) a polymeric layer (2) wherein the polymer comprises a graft copolymer having polyamide blocks, said graft copolymer comprising a polyolefin backbone and at least one polyamide graft from a polyamide having an amine end group, wherein:
the grafts are attached to the polyolefin backbone by the residues of an unsaturated monomer (X) having a functional group capable of reacting with said polyamide having an amine end group;
the residues of said unsaturated monomer (X) being attached to the backbone by grafting or copolymerization via its double bond; and
the average number of moles of unsaturated monomer X attached to the polyolefin backbone is 1.3 to 7 moles per mole of chain;

layer (1), optionally layer (2a), and layer (2) being successive and adhering to one another in their respective contact region,
wherein the proportion by weight of the polyolefin backbone to the polyamide having an amine end group is 8020 to 9010, and
wherein said multilayer structure is in the form of a tube.
2. A structure according to claim 1, further comprising a polyamide or a polyolefin layer (3), superposed on layer (2), and optionally further comprising a tie layer (3a) placed between layer (2) and layer (3).
3. A structure according to claim 1, wherein said polyolefin backbone comprises an ethylenealkyl(meth)acrylate copolymer.
4. A structure according to claim 1, in which X is an unsaturated carboxylic acid anhydride.
5. A structure according to claim 1, wherein said polyolefin backbone is chosen from ethylenemaleic anhydride copolymers and ethylenealkyl(meth)acrylatemaleic anhydride copolymers.
6. A structure according to claim 1, wherein layer (2) forms the inner layer intended to be in contact with the stored or transported fluid.
7. A structure according to claim 1, wherein said structure is in the form of a tube for use in a cooling circuit for an internal combustion engine in which the layer (2) forms the inner layer of said tube, said inner layer intended to be in contact with the transported fluid.
8. A multilayer structure according to claim 1, comprising said tie layer (2a).
9. A structure according to claim 2, comprising said tie layer (3a).
10. A structure according to claim 8, further comprising a polyamide or a polyolefin layer (3) superposed on layer (2) and a tie layer (3a) placed between layer (2) and layer (3).
11. A structure according to claim 1, wherein said polyolefin backbone is a polyolefin homopolymer or copolymer.
12. A structure according to claim 1, wherein Xis an unsaturated epoxide, an unsaturated carboxylic acid anhydride, an aliphatic glycidyl ester, an aliphatic glycidyl ether, an alicylic glycidyl ester or an alicylic glycidyl ether.
13. A structure according to claim 1, wherein the first layer (1) is formed from a polyamide (A)polyolefin (B) blend having a polyamide matrix.
14. A structure according to claim 1, wherein said first layer is formed from PA-612, PA-66,6, PA-6, PA-6,6, PA-11 or PA-12.
15. A structure according to claim 8, wherein said tie layer comprises a functionalized polyolefin or a copolyamide.
16. A structure according to claim 9, wherein said tie layer between layer (2) and layer (3) comprises a functionalized polyolefin or a copolyamide.
17. A method comprising fabricating a tube, said method comprising shaping a multilayer structure according to claim 2 such that layer (3) forms the inner layer.
18. A method of fabricating a tube for use in a cooling circuit of an internal combustion engine, said method comprising shaping a multilayer structure according to claim 2 such that layer (2) comprises graft copolymers having amide blocks, and either said layer (2) or layer (3) forms the inner layer of the tube.
19. A structure according to claim 1, wherein said first layer (1) comprises a blend of a polyamide (A) and at least one copolymer having polyamide blocks and polyether blocks.
20. A structure according to claim 13, wherein the proportion of polyamide in the polyamide (A)polyolefin (B) blend is between 40 and 75% by weight.
21. A structure according to claim 2, wherein layer (3) forms the inner layer of said structure, said inner layer intended to be in contact with the stored or transported fluid.
22. A structure according to claim 2, wherein said structure is in the form of a tube for use in a cooling circuit for an internal combustion engine, and wherein layer (3) forms the inner layer of said tube, said inner layer intended to be in contact with the stored or transported fluid.
23. A structure according to claim 1, wherein the tie layer (2a) is selected from functionalized polyolefins and copolyamides.
24. A structure according to claim 1, wherein said polyamide having an amine end group has a molar mass of between 1,000 and 5,000 gmol.
25. A structure according to claim 1, wherein said graft copolymer having polyamide blocks has a nanostructured organization with polyamide lamellae having a thickness of between 10 and 50 nanometers.
26. A structure according to claim 24, wherein said graft copolymer having polyamide blocks has a nanostructured organization with polyamide lamellae having a thickness of between 10 and 50 nanometers.
27. A multilayer structure comprising, in this order:
a) a first layer (1) comprising a polyamide (A) or a polyamide (A)polyolefin (B) blend having a polyamide matrix;
b) optionally, a tie layer (2a);
c) a polymeric layer (2) wherein the polymer comprises a graft copolymer having polyamide blocks, said graft copolymer comprising a polyolefin backbone and at least one polyamide graft from a polyamide having an amine end group, wherein:
the grafts are attached to the polyolefin backbone by the residues of an unsaturated monomer (X) having a functional group capable of reacting with said polyamide having an amine end group;
the residues of said unsaturated monomer (X) being attached to the backbone by grafting or copolymerization via its double bond; and
said polyamide having an amine end group has a molar mass of between 1,000 and 5,000 gmol;

The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.

1. A compound of formula (I):
wherein
R1 is phenyl optionally substituted by cyano, S(O)2(C1-6 alkyl), S(O)2(C1-6 haloalkyl), halogen, C1-6 alkyl, C1-6 haloalkyl or C1-6 alkoxy;
n is 1, 2, 3 or 4; m is 0; q is 0;
wherein R2 and R3 are, independently, hydrogen or C1-6 alkyl, and R4 is hydrogen, then R5 is phenyl substituted at least once with a substituent selected from the group consisting of: C1-6 alkyl substituted with at least one of NH2, CO2(C1-6 alkyl), S(O)2(C1-6 alkyl), NHS(O)2(C1-6 alkyl) and S(O)2NR13R14, S(O)2(C1-6 alkyl), S(O)2(C1-6 hydroxyalkyl), S(O)2NH(C1-6 alkyl), NHC(O)(C1-6 alkyl), NHS(O)2(C1-6 alkyl), C1-6 alkoxy substituted with at least one of C1-6 alkoxy, hydroxy, CO2(C1-6 alkyl), NHC(O)O(C1-6 alkyl) and NH2, C2-6 alkenyl, pyrrolyl and \u03943-pyrrolinyl; and optionally further substituted with a substituent selected from the group consisting of: halogen, cyano, nitro, hydroxy, C1-6 alkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 alkoxycarbonyl, C1-6 haloalkyl, C1-6 haloalkoxy, NR6R7, C3-6 cycloalkylamino, C1-6 alkylthio, C1-6 alkylthio(C1-6 alkyl), C1-6 alkylcarbonylamino, C(O)NR8R9, sulphonamido (S(O)2NH2), (di)C1-6 alkylsulphonamido, phenyl, phenylamino, nitrophenyl, pyridyl, pyridylthio, benzodioxanyl, thienyl, furanyl, and C(O)R10-substituted C1-6 alkyl or C1-6 alkoxy groups; and
when R2 and R3 are, independently, hydrogen or C1-6 alkyl, and R4 is C1-4 alkyl or C3-6 cycloalkyl(C1-4 alkyl), then R5 is a phenyl optionally substituted by halogen, cyano, nitro, hydroxy, C1-6 alkyl optionally substituted with one or more of halogen, C1-6 alkylthio, NH2, C(O)R10, CO2(C1-6 alkyl), S(O)2(C1-6 alkyl), NHS(O)2(C1-6 alkyl) and S(O)2NR13R14, C3-6 cycloalkyl, C1-6 alkoxy substituted with at least one of halogen, C1-6 alkoxy, hydroxy, C(O)R10, CO2(C1-6 alkyl), NHC(O)O(C1-6 alkyl) and NH2, C2-6 alkenyl, C1-6 alkoxycarbonyl, NR6R7, C3-6 cycloalkylamino, C1-6 alkylthio, C1-6 alkylcarbonylamino, C(O)NR8R9, sulphonamido (S(O)2NH2), (di)C1-6 alkylsulphonamido, S(O)2(C1-6 alkyl), S(O)2(C1-6 hydroxyalkyl), S(O)2NH(C1-6 alkyl), NHC(O)(C1-6 alkyl), NHS(O)2(C1-6 alkyl), phenyl, phenylamino, nitrophenyl, pyridyl, pyridylthio, benzodioxanyl, thienyl, furanyl, pyrrolyl or \u03943-pyrrolinyl;
R10 is hydroxy or NR11R12 group; and,
R6, R7 R8, R9, R11, R12, R13 and R14 are independently hydrogen or C1-6 alkyl;

or a pharmaceutically acceptable salt thereof; or a solvate thereof.
2. A compound of formula (I) as claimed in claim 1 wherein R1 is phenyl optionally substituted by cyano, S(O)2(C1-6 alkyl), S(O)2(C1-6 haloalkyl), halogen, C1-6 alkyl, C1-6 haloalkyl or C1-6 alkoxy; n is 1, 2, 3 or 4; m is 0; q is 0, R2 and R3 are, independently, hydrogen or C1-6 alkyl; R4 is hydrogen; R5 is phenyl substituted at least once with a substituent selected from the group consisting of: C1-6 alkyl substituted with at least one of NH2, CO2(C1-6 alkyl), S(O)2(C1-6 alkyl), NHS(O)2(C1-6 alkyl) and S(O)2NR13R14, S(O)2(C1-6 alkyl), S(O)2(C1-6 hydroxyalkyl), S(O)2NH(C1-6 alkyl), NHC(O)(C1-6 alkyl), NHS(O)2(C1-6 alkyl), C1-6 alkoxy substituted with at least one of C1-6 alkoxy, hydroxy, CO2(C1-6 alkyl), NHC(O)O(C1-6 alkyl) and NH2, C2-6 alkenyl, pyrrolyl and \u03943-pyrrolinyl; and optionally further substituted with a substituent selected from the group consisting of: halogen, cyano, nitro, hydroxy, C1-6 alkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 alkoxycarbonyl, C1-6 haloalkyl, C1-6 haloalkoxy, NR6R7, C3-6 cycloalkylamino, C1-6 alkylthio, C1-6 alkylthio(C1-6 alkyl), C1-6 alkylcarbonylamino, C(O)NR8R9, sulphonamido (S(O)2NH2), (di)C1-6 alkylsulphonamido, phenyl, phenylamino, nitrophenyl, pyridyl, pyridylthio, benzodioxanyl, thienyl, furanyl, and C(O)R10-substituted C1-6 alkyl or C1-6 alkoxy groups;
R10 is hydroxy or NR11R12 group; and, R6, R7 R8, R9, R11, R12, R13 and R14 are independently hydrogen or C1-6 alkyl.
3. A compound of formula (I) as claimed in claim 1 wherein R1 is phenyl optionally substituted by cyano, S(O)2(C1-6 alkyl), S(O)2(C1-6 haloalkyl), halogen, C1-6 alkyl, C1-6 haloalkyl or C1-6 alkoxy; n is 1, 2, 3 or 4; m is 0; q is 0, R2 and R3 are, independently, hydrogen or C1-6 alkyl; R4 is C1-4 alkyl or C3-6 cycloalkyl(C1-4 alkyl); R5 is phenyl optionally substituted by halogen, cyano, nitro, hydroxy, C1-6 alkyl optionally substituted with one or more of halogen, C1-6 alkylthio, NH2, C(O)R10, CO2(C1-6 alkyl), S(O)2(C1-6 alkyl), NHS(O)2(C1-6 alkyl) and S(O)2NR13R14, C3-6 cycloalkyl, C1-6 alkoxy substituted with at least one of halogen, C1-6 alkoxy, hydroxy, C(O)R10, CO2(C1-6 alkyl), NHC(O)O(C1-6 alkyl) and NH2, C2-6 alkenyl, C1-6 alkoxycarbonyl, NR6R7, C3-6 cycloalkylamino, C1-6 alkylthio, C1-6 alkylcarbonylamino, C(O)NR8R9, sulphonamido (S(O)2NH2), (di)C1-6 alkylsulphonamido, S(O)2(C1-6 alkyl), S(O)2(C1-6 hydroxyalkyl), S(O)2NH(C1-6 alkyl), NHC(O)(C1-6 alkyl), NHS(O)2(C1-6 alkyl), phenyl, phenylamino, nitrophenyl, pyridyl, pyridylthio, benzodioxanyl, thienyl, furanyl, pyrrolyl or \u03943-pyrrolinyl; R10 is hydroxy or NR11R12 group; and, R6, R7 R8, R9, R11, R12, R13 and R14 are independently hydrogen or C1-6 alkyl.
4. A compound of formula (I) as claimed in claim 1, wherein R1 is phenyl optionally substituted by halogen, C1-4 alkyl or C1-4 alkoxy.
5. A compound of formula (I) as claimed in claim 1, wherein n is 2.
6. A compound of formula (I) as claimed in claim 1, wherein R4 is hydrogen or C1-4 alkyl; and R5 is phenyl substituted by at least one of C1-6 alkyl substituted with at least one of S(O)2(C1-6 alkyl), NHS(O)2(C1-6 alkyl) and S(O)2NR13R14, S(O)2(C1-6 alkyl), S(O)2NH(C1-6 alkyl), NHC(O)(C1-6 alkyl) or NHS(O)2(C1-6 alkyl); and optionally further substituted with a substituent selected from the group consisting of: halogen, cyano, nitro, hydroxy, C1-6 alkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 alkoxycarbonyl, C1-6 haloalkyl, C1-6 haloalkoxy, NR6R7, C3-6 cycloalkylamino, C1-6 alkylthio, C1-6 alkylthio(C1-6 alkyl), C1-6 alkylcarbonylamino, C(O)NR8R9, sulphonamido (S(O)2NH2), (di)C1-6 alkylsulphonamido and C(O)R10-substituted C1-6 alkyl or C1-6 alkoxy groups; R10 is hydroxy or NR11R12 group; and, R6, R7 R8, R9, R11, R12, R13 and R14 are independently hydrogen or C1-6 alkyl.
7. A process for preparing a compound of formula (I) as claimed in claim 1 comprising reacting a compound of formula (III):
with a compound of formula (IV):
wherein L is a leaving group.
8. A pharmaceutical composition which comprises a compound of the formula (I), or a pharmaceutically acceptable salt thereof or a solvate thereof, and a pharmaceutically acceptable adjuvant, diluent or carrier.
9. A method of treating chronic obstructive pulmonary disease, asthma, bronchitis, respiratory tract allergy, rhinitis, sarcoidosis, farmer’s lung, nasal polyposis, fibroid lung, idiopathic interstitial pneumonia, chronic cough, iatrogenic induced cough, comprising administering to a patient in need of such treatment an effective amount of a compound of formula (I) as claimed in claim 1.