Lung function impairment in chronic obstructive pulmonary disease (COPD) treated with 1-phenyl-4-oxo-3,4,6,7-tetrahydro-1,4-diazepinoindoles as phosphodiesterase 4 (PDE4) inhibitors

摘要

Described is the use of diazepinoindoles of formula (I) for the manufacture of a medicament for the treatment of chronic obstructive pulmonary disease, in which: - A is aryl or nitrogen-containing heteroaryl, each optionally being substituted with one to three groups chosen independently from halogen, lower alkyl, lower haloalkyl, lower alkoxy, cycloalkyloxy, amino or lower alkylcarbonyl-amino or alkyloxycarbonylamino; - B is: 1) -OR1, R1 being -H or R4, 2) -NR2R3, R2 being -C(NH)NH2 and R3 being -H, 3) -NR2R3, R2 being R4 and R3 being -H, 4) -NR2R3, R2 and R3 independently being -H or lower alkyl, or 5) -NR2R3, R2 and R3 forming, together with the nitrogen atom to which they are attached, a saturated five- to seven-membered heterocycle which may comprise, as second heteroatom not attached directly to the nitrogen atom, an oxygen, a sulphur or a nitrogen; - R4 is: 1) -CH2 -CO2H, 2) -CO-(CH2)p-CO2H, 3) -CO-A, where A has the definition indicated above, 4) -CO-CH=CH-CO2H, 5) -CO-(CH2)n-CH3, n being an integer equal to or greater than 0 and less than or equal to 18, 6) -CO-(CH2-O-CH2)p-CH2-O-CH3, 7) -CO-(CH2-O-CH2)p-CO2H, 8) -(CH2)p-NR5R6, R5 and R6 independently being -H or lower alkyl, or 9) -(CH2)p-NR5R6, R5 and R6 forming, together with the nitrogen atom to which they are attached, a saturated five- to seven-membered heterocycle which may comprise, as second heteroatom not attached directly to the nitrogen atom, an oxygen, a sulphur or a nitrogen; - p is an integer equal to 2, 3 or 4; the racemic forms and isomers thereof, in particular those of a configuration determined by carbon 3 of the diazepinoindol-4-one ring, in addition to the pharmaceutically acceptable derivatives thereof.