TRI-SUBSTITUTED PHENYL DERIVATIVES USEFUL AS PDE IV INHIBITORS

摘要

Compounds of general formula (1) are described wherein =W- is (1) =C(Y)- where Y is a halogen atom, or an alkyl or -XR group where X is -O-, -S(O)m-[where m is zero or an integer of value 1 or 2], or -N(R)- where R is a hydrogen atom or an optionally substituted alkyl group or, (2) =N; L is a -XR, [where R is an optionally substituted alkyl, alkenyl, cycloalkyl or cycloalkenyl group], -C(R<11>)=C(R<1>)(R<2>) or [-CH(R<11>)]nCH(R<1>)(R<2>) group where R<11> is a hydrogen or a fluorine atom or a methyl group, and R<1> and R<2>, which may be the same or different, is each a hydrogen or fluorine atom or an optionally substituted alkyl, alkenyl, alkynyl, alkoxy, alkylthio, -CO2 R<8>, [where R<8> is a hydrogen atom or an optionally substituted alkyl, aralkyl, or aryl group], -CONR<9>R<10> [where R<9> and R<10>, which may be the same or different are as defined for R<8>], -CSNR<9>R<10>, -CN or -NO2group, or R<1> and R<2> together with the C atom to which they are attached are linked to form an optionally substituted cycloalkyl or cycloalkenyl group and n is zero or the integer 1; Z is (1) a group -C(R<3>)(R<4>)C(R<5>)(R<6>)(R<7) or -C(R?4>)=C(R<5>)(R<6>) where R<3> is a hydrogen or a fluorine atom or an optionally substituted straight or branched alkyl group; R<4> is a group selected from -XL<1>R<12> [where X is as defined above for X, L<1> is a linker group and R<12> is a hydrogen atom or a cycloaliphatic, heterocycloaliphatic, or monocyclic or bicyclic aryl group optionally containing one or more heteroatoms selected from oxygen, sulphur or nitrogen atoms], -Alk<1>R<12> [where Alk<1> is an optionally substituted straight or branched alkenyl or alkynyl chain optionally containing one or more -O- or -S- atoms or -N(R)-, carbocyclic or heteroatom-containing groups], -CH2L<1>R<12a> [where R<12a> is as defined for R<12> but is not a hydrogen atom]; -XR<12a>; or -C(X)R<12a> [where X is an oxygen or sulphur atom]; R<5> is a -(CH2)pAr group where p is zero or an integer 1, 2 or 3 and Ar is a monocyclic or bicyclic aryl group optionally containing one or more heteroatoms selected from oxygen, sulphur or nitrogen atoms; R<6> is a hydrogen or a fluorine atom or an optionally substituted alkyl group; R<7> is a hydrogen or a fluorine atom or an OR group where R is a hydrogen atom or an optionally substituted alkyl or alkenyl group, or an alkoxyalkyl, alkanoyl, formyl, carboxamido or thiocarboxamido group; or Z is (2) a group -C(R<4>)C(R<5>)(R<6>)(R<7>) where R<4> is a group =CH2, or =CH(L<1>)n-R<12>; and the salts, solvates, hydrates, prodrugs and N-oxides thereof. Compounds according to the invention are phosphodiesterase type IV inhibitors and are useful in the prophylaxis and treatment of disease such as asthma where an unwanted inflammatory response or muscular spasm is present.