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US 2004/0167153 A1Published application
Pharmaceutical combination
AssigneePfizer Inc.
InventorMichael Yeadon
Life of this patent
Estimating the term…
Abstract
The present invention relates to a combination of a selective PDE4 inhibitor, as defined herein, and an adrenergic β2 receptor agonist for simultaneous, sequential or separate administration by the inhaled route in the treatment of an obstructive airways or other inflammatory disease.
Claims17
An inhaled combination of (a) a selectiv PDE4 inhibitor of the formula (I)
- 3
- or a pharmaceutically acceptable salt or solvate thereof, wherein:
- R1 is H, (C1-C6) alkyl, (C1-C6) alkoxy, (C2-C4) alkenyl, phenyl, —N(CH3)2, (C3-C6) cycloalkyl, (C3-C6) cycloalkyl(C1-C3) alkyl or (C1-C6) acyl, wherein the alkyl, phenyl or alkenyl groups may be substituted with up to two —OH, (C1-C3) alkyl, or —CF3 groups or up to three halogens;
- R2 and R3 are each independently selected from the group consisting of H, (C1-C14) alkyl, (C1-C7) alkoxy(C1-C7) alkyl, (C2-C14) alkenyl, (C3-C7) cycloalkyl, (C3-C7) cycloalkyl(C1-C2) alkyl, a saturated or unsaturated (C4-C7) heterocyclic(CH2)n group wherein n is 0, 1 or 2, containing as the heteroatom one or two of the group consisting of oxygen, sulfur, sulfonyl, nitrogen and NR4 where R4 is H or (C1-C4) alkyl;
- or a group of the Formula (II):
- 4
- wherein a is an integer from 1 to 5;
- b and c are 0 or 1;
- R5 is H, —OH, (C1-C5) alkyl, (C2-C5) alkenyl, (C1-C5) alkoxy, (C3-C6) cycloalkoxy, halogen, —CF3, —CO2R6, —CONR6R7, —NR6R7, —NO2, or —SO2NR6R7 wherein R6 and R7 are each independently H, or (C1-C4) alkyl;
- Z is —O—, —S—, —SO2—, —CO— or —N(R8)— wherein R8 is H or (C1-C4) alkyl;
- and Y is (C1-C5) alkylene or (C2-C6) alkenylene optionally substituted with up to two (C1-C7) alkyl or (C3-C7) cycloalkyl groups;
- wherein each of the alkyl, alkenyl, cycloalkyl, alkoxyalkyl or heterocyclic groups may be substituted with 1 to 14, preferably 1 to 5, (C1-C2) alkyl, CF3, or halo groups;
- and
- R9 and R10 are each independently selected from the group consisting of H, (C1-C6) alkyl, (C1-C6) alkoxy, (C6-C10) aryl and (C6-C10) aryloxy;
- and (b) an adrenergic β2 receptor agonist.
12 more elements
A combination as claimed in any one of the preceding claims wherein the selective PDE4 inhibitor of the formula (I) is selected from:
- 9-cyclopentyl-5,6-dihydro-7-ethyl-3-phenyl-9H-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-α]pyridine;
- 9-cyclopenyl-5,6-dihydro-7-ethyl-3-(furan-2-yl)-9H-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-α]pyridine;
- 9-cyclopentyl-5,6-dihydro-7-ethyl-3-(2-pyridyl)-9H-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-α]pyridine;
- 9-cyclopentyl-5,6-dihydro-7-ethyl-3-(4-pyridyl)-9H-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-α]pyridine;
- 9-cyclopentyl-5,6-dihydro-7-ethyl-3-(3-thienyl)-9H-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-α]pyridine;
- 3-benzyl-9-cyclopentyl-5,6-dihydro-7-ethyl-9H-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-α]pyridine;
- 9-cyclopentyl-5,6-dihydro-7-ethyl-3-propyl-9H-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-α]pyridine;
- 3,9-dicyclopentyl-5,6-dihydro-7-ethyl-9H-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-α]pyridine;
- 9-cyclopentyl-5,6-dihydro-7-ethyl-3-(1-methylcyclohex-1-yl)-9H-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-α]pyridine;
- 3-(tert-butyl)-9-cyclopentyl-5,6-dihydro-7-ethyl-9H-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-α]pyridine;
- 9-cyclopentyl-5,6-dihydro-7-ethyl-3-(2-methylphenyl)-9H-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-α]pyridine;
- 9-cyclopentyl-5,6-dihydro-7-ethyl-3-(2-methoxyphenyl)-9H-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-α]pyridine;
- 9-cyclopentyl-5,6-dihydro-7-ethyl-3-(thien-2-yl)-9H-pyrazolo[3,4-c]1,2,4-triazolo[4,3-α]pyridine;
- 3-(2-chlorophenyl)-9-cyclopentyl-5,6-dihydro-7-ethyl-9H-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-α]pyridine;
- 9-cyclopentyl-5,6-dihydro-7-ethyl-3-(2-iodophenyl)-9 Hpyrazolo[3,4-c]-1,2,4-triazolo[4,3-α]pyridine;
- 9-cyclopentyl-5,6-dihydro-7-ethyl-3-(2-trifluoromethylphenyl)-9H-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-α]pyridine;
- and
- 5,6-dihydro-7-ethyl-9-(4-fluorophenyl)-3-(1-methylcyclohex-1-yl)-9H-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-α]pyridine;
- and the pharmaceutically acceptable salts and solvates thereof.
16 more elements
A combination as claimed in any one of the preceding claims wherein the adrenergic β2 receptor agonist is selected from salmeterol, formoterol and the pharmaceutically acceptable salts and solvates thereof.
A combination as claimed in any preceding claim for use as a medicament.
Dependencies are inferred from the claim text.