TRIARYLETHANES USEFUL AS PDE IV INHIBITORS

摘要

Compounds of formula (1) are described wherein Y is a halogen atom, or a -XRa group where X is -O-, -S(O)¿m?- [where m is zero or an integer of value 1 or 2], or -N(R?b¿)- [where Rb is a hydrogen atom or an optionally substituted alkyl group] and Ra is a hydrogen atom or an optionally substituted alkyl group; Z is a group -XR5 [where R5 is an optionally substituted alkyl, alkenyl, cycloalkyl, cycloalkenyl or heterocycloalkyl group], -C(R?6)=C(R7)(R8¿) [where R6 is a hydrogen or fluorine atom or a methyl group, and R?7 and R8¿, which may be the same or different, is each a hydrogen or fluorine atom or an optionally substituted alkyl, alkenyl, alkoxy, alkylthio, -CO¿2R?9 [where R9 is a hydrogen atom or an optionally substituted alkyl, aralkyl or aryl group], -CONR10R11 [where R?10 and R11¿, which may be the same or different, is each as defined for R9], -CSNR10R11, -CN or -NO¿2? group, or R?7 and R8¿ together with the carbon atom to which they are attached are linked to form an optionally substituted cycloalkyl, cycloalkenyl or heterocycloalkyl group] or -[-CH(R6)]nCH(R7)(R8) where n is zero or the integer 1; R2 is a hydrogen or a fluorine atom, an optionally substituted alkyl group, or a hydroxyl group; R3 is a hydrogen or a fluorine atom, or an optionally substituted alkyl group; R4 is a hydrogen or a fluorine atom, an optionally substituted alkyl group or an ORc group where Rc is a hydrogen atom or an optionally substituted alkyl or alkenyl group, or an alkoxyalkyl, alkanoyl, formyl, carboxamido or thiocarboxamido group; Ar1 is an optionally substituted monocyclic or bicyclic aryl group, optionally containing one or more heteroatoms selected from oxygen, sulphur or nitrogen atoms; Ar is a monocyclic or bicyclic aryl group, optionally containing one or more heteroatoms selected from oxygen, sulphur or nitrogen atoms; R1 is a group -N(R12)C(=NCN)NHR13 [where R12 is a hydrogen atom or a C¿1-3?alkyl group and R?13¿ is a hydrogen atom, a C¿1-3?alkyl group or an optionally substituted phenyl or phenylC1-3alkyl group], -N(R?12¿)C(=NCN)SR?13, N(R12¿)C(=CHNO¿2)NHR?13 or -N(R12)C(=CHNO¿2)SR?13; and the salts, solvates, hydrates, prodrugs and N-oxides thereof. The compounds are metabolically stable phosphodiesterase type IV inhibitors and are of use in the prophylaxis and treatment of diseases such as asthma where an unwanted inflammatory response or muscular spasm is present.