1.-30. (canceled)
31. A compound according to formula I
wherein
R1 is selected from H and methyl;
R2 is selected from H and methyl;
R3 is selected from H, fluoro, chloro, bromo, C1-3 alkyl and CH2 phenyl;
R4 is selected from H, fluoro, chloro, bromo, C1-3 alkyl and CH2 phenyl;
G is selected from G1 and G2;
in G1 the stereochemistry of the double-bond of G1, onto which the substituents R5 and R6 are attached, is such that R5 and R6 are oriented in a cis-fashion, or in a trans-fashion, relative to each other;
R5 is selected from H, C1-5 alkyl, CH2 phenyl and C1-5 fluoroalkyl;
R6 is selected from H, C1-5 alkyl, CH2 phenyl and C1-5 fluoroalkyl;
X1, X2, X3, X4 and X5 are, independently of each other, selected from N and C; 0 (zero), 1 or 2 of X1, X2, X3, X4 and X5 is N; Q is optionally substituted with a maximum of \u201cn\u201d independently selected substituent(s) R7 at any substitutable ring carbon atom, wherein \u201cn\u201d represents an integer number;
the integer number \u201cn\u201d is 0 to 2;
R7 is selected from C1-5 alkyl, C1-5 fluoroalkyl, halo, hydroxy, C0-3 alkyleneOC0-5 alkyl, C0-3 alkyleneOC1-5 fluoroalkyl, C0-3 alkyleneNH2, C0-3 alkyleneNHC1-3 alkyl, C0-3 alkyleneN(C1-5 alkyl)2, in which the C1-5 alkyl may be the same or different, N(C4-5 alkylene), C1-5 alkylthio, S(O)C1-5 alkyl, SO2C1-5 alkyl, C1-5 fluoroalkylthio, NH(CO)C1-5 alkyl, NH(CO)C1-5 alkoxy, NHSO2C1-5 alkyl, (CO)C1-5 alkyl, COOH, (CO)C1-5 alkoxy, (CO)NH2, (CO)NHC1-5 alkyl, (CO)N(C1-5 alkyl)2, in which the C1-5 alkyl may be the same or different, cyano, SO2NHC0-5 alkyl, nitro, aryl, heteroaryl, azido (N3), and morpholinyl;
in G2 the stereochemistry of the double-bond of G2, onto which the substituents R8 and R9 are attached, is such that R8 and R9 are oriented in a cis-fashion, or in a trans-fashion, relative to each other;
R8 is selected from H, C1-5 alkyl, CH2 phenyl and C1-5 fluoroalkyl;
R9 is selected from H, C1-5 alkyl, CH2 phenyl and C1-5 fluoroalkyl;
the condensed rings W1 and W2 together represent a bicyclic aromatic system, in which X6, X7 and X8, independently of each other, are selected from N and C; none or one of X6, X7 and X8 is N; said bicyclic aromatic system is optionally substituted with a maximum of \u201cp\u201d independently selected substituent(s) R10, at any substitutable ring carbon atom of any of the rings W1 and W2, wherein \u201cp\u201d represents an integer number;
The integer number \u201cp\u201d is 0 to 2;
R10 is selected from C1-5 alkyl, C1-5 fluoroalkyl, halo, hydroxy, C0-3 alkyleneOC0-5 alkyl, C0-3 alkyleneOC1-5 fluoroalkyl, C0-3 alkyleneNH2, C0-3 alkyleneNHC1-3 alkyl, C0-3 alkyleneN(C1-5 alkyl)2, in which the C1-5 alkyl may be the same or different, N(C4-5 alkylene), C1-5 alkylthio, S(O)C1-5 alkyl, SO2C1-5 alkyl, C1-5 fluoroalkylthio, NH(CO)C1-5 alkyl, NH(CO)C1-5 alkoxy, NHSO2C1-5 alkyl, (CO)C1-5 alkyl, COOH, (CO)C1-5 alkoxy, (CO)NH2, (CO)NHC1-5 alkyl, (CO)N(C1-5 alkyl)2, in which the C1-5 alkyl may be the same or different, cyano, SO2NHC0-5 alkyl, nitro, aryl, heteroaryl, azido (N3), and morpholinyl;
as a free base, an acid in its non-charged protonated form or a pharmaceutically acceptable salt, solvate or solvate of a salt thereof and as a pure stereoisomer, a racemic-, diastereomeric- or scalemic mixture;
with the proviso
that not both of R1 and R2 is methyl.
32. The compound according to claim 31, wherein R1 and R2 is H.
33. The compound according to claim 32, wherein R3 and R4, independent of each other, are selected from H, fluoro, chloro, bromo, and methyl.
34. The compound according to claim 33, wherein R3 and R4 are chloro.
35. The compound according to claim 31, wherein G is G1 and the stereochemistry of the double-bond of G1, onto which the substituents R5 and R6 are attached, is such that R5 and R6 are oriented in a trans-fashion relative to each other.
36. The compound according to claim 31, wherein G is G1 and at least one of X1 to X5 is N.
37. The compound according to claim 36, wherein G is G1, X1 or X2 is N and only one of X1 to X5 is N.
38. The compound according to claim 31, wherein G is G1, \u201cn\u201d is 1 or 2, and R7 is selected from C1-C3 alkyl, trifluoromethyl, halo, hydroxy, N(C4-5 alkylene), methoxy, SO2Me, cyano, thienyl, nitro, phenyl, morpholinyl and NMe2.
39. The compound according to claim 38, wherein R7 is selected from methyl, trifluoromethyl, fluoro, chloro and NMe2.
40. The compound according to claim 31 wherein G is G1 and R5 is H.
41. The compound according to claim 31, wherein G is G1 and R6 is H or methyl.
42. The compound according to claim 31, wherein G is G2 and the stereochemistry of the double-bond of G2, onto which the substituents R8 and R9 are attached, is such that R8 and R9 are oriented in a trans-fashion relative to each other.
43. The compound according to claim 42, wherein G is G2, at least one of X6 to X8 is N.
44. The compound according to claim 42, wherein G is G2 and R8 and R9 are, independently or each other, selected from H and methyl.
45. The compound according to claim 31, wherein said compound is selected from the group consisting of:
46. The compound according to claim 31, wherein said compound is selected from the group consisting of:
47. A pharmaceutical composition comprising a compound according to claim 1 and at least one pharmaceutically acceptable carrier.
48. The pharmaceutical composition according to claim 47, comprising an anti-asthmatic.
49. The pharmaceutical composition according to claim 48, wherein the principal mechanism of action of the anti-asthmatic is selected from the group consisting of \u03b22-agonist, anticholinergic and calcium antagonist, or wherein the anti-asthmatic is a corticosteroid.
50. A method of prevention andor treatment of a disease or condition characterized by bronchoconstriction andor inflammatory conditions of the respiratory apparatus, such as asthma, chronic obstructive pulmonary disease, chronic bronchitis, emphysema, bronchiectasis, cystic fibrosis, bronchiolitis andor bronchopulmonary dysplasia, comprising administering to a mammal, including man in need of such prevention andor treatment, a therapeutically effective amount of a compound according to claim 31.
51. The method according to claim 50 further comprising the simultaneous or consecutive administration of a therapeutically effective amount an anti-asthmatic.
52. The method according to claim 51, wherein the administered dose of the anti-asthmatic is 1 to 10 times less than the established therapeutically effective dose when administered alone for prevention or treatment of the same disease or condition.
53. The method according to claim 51, wherein the administered dose of a compound is 1 to 10 times less than the established therapeutically effective dose when administered alone for prevention or treatment of the same disease or condition.
54. The method according to any of the claims 51, wherein the principal mechanism of action of the anti-asthmatic is selected from the group consisting of \u03b22-agonist, anticholinergic and calcium antagonist, or wherein the anti-asthmatic is a corticosteroid.
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 cellular core structure able to be used in an acoustic panel for a turbojet engine nacelle comprising at least one cellular unit, each cellular unit comprising at least one intermediate sheet and two end sheets, wherein said cellular core structure includes a surface that is substantially of revolution, said surface being made by joining together edge to edge end sheets of a cellular unit or several cellular units by joining pads positioned in such a way as to form alveolar cells.
2. The structure as claimed in claim 1, wherein the joining pads are made of a material comprising at least one of metals, alloys, polymers, and an epoxy-based resin.
3. An acoustic panel for a nacelle, comprising at least one cellular core structure as claimed in claim 1.
4. The acoustic panel as claimed in claim 3, wherein it comprises several cellular core structures arranged in layers between which a multi-perforated or porous skin is located.
5. A turbojet engine nacelle comprising an acoustic panel, wherein the acoustic panel is as claimed in claim 3.
6. A method of preparing a cellular core structure as claimed in claim 1, comprising at least one cellular unit, comprising:
A\u2014selecting at least one cellular unit in a substantially compacted and substantially flat form, each cellular unit comprising at least one intermediate sheet and two end sheets, wherein said cellular core structure includes a surface that is substantially of revolution;
B\u2014joining the end sheets of a cellular unit or several cellular units edge to edge and positioned the end sheets to face one another using bonding means positioned on one end sheet in such a way as to form substantially compacted alveolar cells;
C\u2014stretching the structure obtained at the outcome of step (B) using expansion means in order to form the substantially expanded alveolar cells.
7. The method as claimed in claim 6, further comprising a step (D) in which at least one of a perforated acoustic skin and a non-perforated skin are attached to at least one face of the cellular core structure obtained at the outcome of step (C).
8. The method as claimed in claim 6, wherein the bonding means comprise a polymer, of metal or of alloy used for welding.
9. The method as claimed in claim 6, wherein the bonding means comprise a material the position and thickness of which are such that the bonding means create a non-negligible air-filled space between two end sheets.
10. The method as claimed in claim 6, wherein the expansion means are mechanical means able to stretch the structure obtained at the outcome of step (B) in a direction that is substantially perpendicular or radial to internal and external faces.
11. An acoustic panel for a nacelle, comprising at least one cellular core structure obtained by the method as claimed in claim 6.
12. The acoustic panel as claimed in claim 11, wherein it comprises several cellular core structures arranged in layers between which a multi-perforated or porous skin is located.
13. A turbojet engine nacelle comprising an acoustic panel, wherein the acoustic panel is as claimed in claim 11.