Pyrrolopyrrolone derivatives for the treatment or prophylaxis of inflammatory disease such as chronic bronchitis, obstructive pulmonary disease and asthma

摘要

Pyrrolopyrrolone derivatives of the above formula, wherein: R1 represents C1-6alkyl, C2-6alkenyl, aryl, aryl-C1-4alkyl, aryl-C2-4alkenyl, heteroaryl, heteroaryl-C1-4alkyl, or heteroaryl-C2-4alkenyl, or the aryl or heteroaryl moiety is substituted by one or more C1-4alkyl, halo, tetrazolyl, trifluoromethyl-sulphonamide, NR9CO-C1-8alkyl, -(CH2)m-NR4R5 and as further defined in the specification; X represents a ketone group, a sulphonyl group or an ester group, where the carbonyl is bound to the ring nitrogen; R2 represents C2-4alkyl, C2-4alkenyl, C1-3alkoxy or C1-3alkylthio; R3 represents C1-6alkyl, -CH2(CF2)0-4CF3, aryl or heteroaryl as defined in the specification; R4 and R5 independently represent hydrogen, C1-4alkyl, C1-4alkoxy, -(CH2)1-4CONR11R12, -CO-C1-4alkyl or phenyl optionally substituted by one or more C1-4alkyl or halogen groups or R4 and R5 may be joined such that NR4R5 represents a mono, bi- or tri-cyclic ring system containing 4-15 ring carbon atoms, wherein one or more rings may be optionally interrupted by one or more heteroatoms selected from O, N and S and wherein one or more ring carbon atoms may have carbonyl functionality or -(CH2)n-NR4R5 is as defined in the specification. R7, R8, R9, R10, R11 and R12 represent hydrogen or C1-4alkyl; m represents an integer of 0 to 8; n represents an integer of 1 to 9 The use of formula I in a pharmaceutical preparation for the treatment or prophylaxis of chronic bronchitis, obstructive pulmonary disease and asthma as well as the process for its manufacture is also described.