A compound of the general formula (I):
- 172
- wherein
- 173
- represents a bicyclic ring system, of 9 ring members, in which the ring
- 174
- is an oxazole, and the ring
- 175
- is a benzene ring;
- R1 represents hydrogen or a straight- or branched-chain alkyl group of 1 to about 4 carbon atoms, optionally substituted by hydroxy or one or more halogen atoms, or when Z1 represents a direct bond R1 may also represent a lower alkenyl or lower alkynyl group, or a formyl group;
- R2 represents hydrogen, alkenyl, alkoxy, alkyl, alkylsulphinyl, alkylsulphonyl, alkylthio, aryl, arylalkyloxy, arylalkylsulphinyl, arylalkylsulphonyl, arylalkylthio, aryloxy, arylsulphinyl, arylsulphonyl, arylthio, cyano, cycloalkenyl, cycloalkenyloxy, cycloalkyl, cycloalkyloxy, hydroxy, —SO2NR4R5, —NR4SO2R5, —NR4R5, —C(═O)R5, —C(═O)C(═O)R5, —C(═O)NR4R5, —C(═O)OR5, —O(C═O)NR4R5, or —NR4C(═O)R5;
- R3 is:
- —C(═Z)—N(R7)R6
- R4 and R5, which may be the same or different, each represent a hydrogen atom, or an alkyl, aryl, arylalkyl, cycloalkyl, heteroaryl, or heteroarylalkyl group;
- R6 is optionally substituted pyridyl;
- R7 is a hydrogen atom or an alkyl or amino group;
- R8 and R9, which may be the same or different, is each a hydrogen atom or alkyl, —CO2R5, —C(═Z)NR26R27 (where R26 and R27 may be the same or different and each is as described for R5), —CN or —CH2CN;
- R10 and R11, which may be the same or different, is each a group —(CH2)pR6;
- R12 is a hydrogen atom or an alkyl group;
- R13 is a hydrogen or halogen atom or an —OR28 group (where R28 is a hydrogen atom or an alkyl, alkenyl, alkoxyalkyl, acyl, carboxamido or thiocarboxamido group);
- R14 is a hydrogen atom or an alkyl group;
- R15 is a hydrogen atom or a hydroxyl group;
- R16 is a hydrogen atom or an alkyl, amino, aryl, arylalkyl or hydroxy group;
- R17 is a hydrogen atom or a C1-4alkyl or arylC1-4alkyl group;
- R18 is an amino, alkylamino, arylamino, alkoxy or aryloxy group;
- R19 is an alkyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl group;
- R20 is R5, (CH2)pCO2R5 or (CH2)pCOR5;
- R21 is a group L1—R29, or R21 is an optionally substituted cycloalkyl, cycloalkenyl or heterocycloalkyl group which may optionally be fused to an additional optionally substituted aromatic, heteroaromatic, carbocyclic or heterocycloalkyl ring (where the one or more optional substituents, for either or both rings, may be represented by -L1—R29);
- L1 is a straight or branched C16alkylene chain, a straight or branched C2-6alkenylene chain, a straight or branched C2-6alkynylene chain or a straight or branched C1-6alkylene chain containing an oxygen or sulphur atom, a phenylene, imino (—NH—) or alkylimino linkage, or a sulphinyl or sulphonyl group, in which each of the alkylene, alkenylene and alkynylene chains may be optionally substituted, the substituents chosen from alkoxy, aryl, carboxy, cyano, cycloalkyl, halogen, heteroaryl, hydroxyl or oxo;
- and R29 is hydrogen, or arylalkoxycarbonyl, carboxy or an acid bioisostere, cyano, —NY1Y2;
- Y1 and Y2 are independently hydrogen, alkyl, aryl, arylalkyl, heterocycloalkyl, heteroaryl or heteroarylalkyl, or the group —NY1Y2 may form a 4-6 membered cyclic amine (which may optionally contain a further heteroatom selected from O, S, or NY1, or which may be fused to an additional aromatic or heteroaromatic ring);
- R22 is a hydrogen atom, a group -L1—R29, or an optionally substituted aryl, heteroaryl, cycloalkyl, cycloalkenyl or heterocycloalkyl group which may optionally be fused to an additional optionally substituted aromatic, heteroaromatic, carbocyclic or heterocycloalkyl ring (where the one or more optional substituents, for either or both rings, may be represented by -L1—R29);
- or both R21 and R22 represent aryl or heteroaryl each optionally substituted by
- -L1—R29;
- or the group —NR21R22 represents an optionally substituted, saturated or unsaturated 3 to 8 membered cyclic amine ring, which may optionally contain one or more heteroatoms selected from O, S or N, and may also be fused to an additional optionally substituted aromatic, heteroaromatic, carbocyclic or heterocycloalkyl ring (where the one or more optional substituents, for any of the rings, may be represented by -L1—R29);
- 176
- where:
- R30 is hydrogen atom or an alkyl, hydroxyalkyl or alkoxyalkl group;
- R31 is a hydrogen atom or an alkyl, carboxy, CONHOR14, N-alkylaminoalkyl, N,N-dialkylaminoalkyl or alkoxyalkyl group;
- or R30 and R31 together represent a —CH2—O—CH2—O—CH2— group;
- R32 is a hydrogen atom, or amino, alkyl, aminoalkyl, hydroxyalkyl, hydroxy, acyl, alkoxycarbonyl, methoxycarbonylalkyl, —(CH2)pCONY3Y4;
- Y3 and Y4 are each independently hydrogen or alkyl;
- —(CH2)pSO2NY3Y4, —(CH2)pPO3H2, —(CH2)pSO2NHCOalkyl, or —(CH2)pSO2NHCOR6;
- R33 is C1-4alkyl, CH2NHCOCONH2, CH═—C(R43)R44, cyclopropyl (optionally substituted by R43), CN, CH2OR44 or CH2NR44R45;
- R43 is R44 or fluorine and R44 is hydrogen or C1-4alkyl optionally substituted by 1 to 3 fluorine atoms;
- R45 is hydrogen, OR44, or C1-4alkyl optionally substituted by 1 to 3 fluorine atoms;
- NR44R45 represents a 5 to 7 membered cyclic amine optionally containing one or more additional heteroatoms selected from O, N, and S;
- R34 is methyl or ethyl optionally substituted by 1 or more halogen atoms;
- R35 is R14, —OR14, —C2R14, —COR14, —CN, —CONY3Y4 or —NY3Y4;
- R36 is —C(═Z)R14, —CO2R14, —CONY3Y4 or —CN;
- R37 and R39, which may be the same or different, is each a hydrogen atom, alkyl, acyl, arylalkyl, —(CH2)pCO2R5, —CONHR5, heteroarylalkyl, aryl, or heteroaryl;
- R38 is acyl, aroyl, —C(═O)cycloalkyl, alkoxycarbonyl, cycloalkoxycarbonyl, carboxy, alkoxyalkyl, —NO2, —CH2H, —CN, —NR14COR5, —NR14CONY5Y6, —NR14SO2R46, —SO2R46 or —CONY5Y6;
- R46 is alkyl, cycloalkyl, trifluoromethyl, aryl, arylalkyl or —NY5Y6;
- Y5 and Y6 are independently selected from hydrogen, alkyl, cycloalkyl, aryl or arylalkyl, or Y5 and Y6 together form a 4- to 7-membered heterocyclic or carbocyclic ring;
- R40 is hydrogen, alkyl, haloalkyl, cycloalkyl, aryl, acyl, aroyl, —C(═O)cycloalkyl, —CH2OH, alkoxyalkyl, alkoxycarbonyl, cycloalkoxycarbonyl, aryloxycarbonyl, —CN, —NO2, or —SO2R46;
- R41 is —CN, —C(Z)R47 (where R47 is hydrogen, alkyl, haloalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, C1-6alkoxy, arylalkoxy, aryloxy or —NY5Y6) or SO2R46;
- R42 is hydrogen, alkyl, cycloalkyl, acyl, aroyl, —C(═O)cycloalkyl, alkoxycarbonyl, cycloalkoxycarbonyl, carboxy, —CN, —SO2R46 or —CONY5Y6;
- W is (CH2)r or NR39;
- Z3 is an oxygen atom, NR14 or NOR14;
- s is zero or an integer 1 to 4;
- r is 1 to 4;
- and
- Y is an oxygen atom, C(═O), CH(OH) or C(OR14)(CH2)pR6;
- R24 is R5 or CONHR25;
- R25 is hydrogen, C1-3alkyl or (CH2)qR6;
- p is zero or an integer from 1 to 5;
- q is zero or 1;
- X1 and X2, which may be the same or different, is each a hydrogen or fluorine atom;
- X3 is a chlorine or fluorine atom, alkoxy, aryloxy, heteroaryloxy, arylalkyloxy or heteroarylalkyl;
- X4 is a halogen atom or hydroxy;
- Z represents an oxygen or sulphur atom;
- A1 is a straight or branched C1-6alkylene chain optionally substituted by hydroxyl, alkoxy, oxo, cycloalkyl, aryl or heteroaryl;
- Z1 represents a direct bond, an oxygen or sulphur atom or NH;
- n is zero;
- and
- m is 1;
- and N-oxides thereof, and their prodrugs, and pharmaceutically acceptable salts and solvates of the compounds of formula (I) and N-oxides thereof, and their prodrugs.