Aryloxy substituted pyrimidine imidazole compounds

A compound of formula (I):

• wherein:
• R1 is 4-pyrimidinyl ring which ring is substituted by Y, or NHRa, and is optionally substituted independently one to three times with Y, NHRa′, optionally substituted C1-4 alkyl, halogen, hydroxyl, optionally substituted C1-4 alkoxy, optionally substituted C1-4 alkylthio, optionally substituted C1-4 alkylsulfinyl, CH2OR12, amino, mono and di- C1-6 alkyl substituted amino, N(R10)C(O)Rb, N(R10)S(O)2Rd, or an N-heterocyclyl ring which ring has from 5 to 7 members and optionally contains an additional heteroatom selected from oxygen, sulfur or NR15;
• Y is X1-Ra;
• X1 is sulfur or oxygen;
• Ra is aryl, arylC1-6 alkyl, heterocyclic, heterocyclylC1-6 alkyl, heteroaryl, or heteroarylC1-6alkyl, wherein each of these moieties may be optionally substituted;
• Ra′ is C1-6alkyl, aryl, arylC1-6alkyl, heterocyclic, heterocyclylC1-6 alkyl, heteroaryl, or heteroarylC1-6alkyl, wherein each of these moieties may be optionally substituted;
• Rb is hydrogen, C1-6 alkyl, C3-7 cycloalkyl, aryl, arylC1-4 alkyl, heteroaryl, heteroarylC1-4 alkyl, heterocyclyl, or heterocyclylC1-4 alkyl;
• Rd is C1-6 alkyl, C3-7 cycloalkyl, aryl, arylC1-4 alkyl, heteroaryl, heteroarylC1-4alkyl, heterocyclyl, or heterocyclylC1-4 alkyl;
• R2 is hydrogen, C1-10 alkyl, halo-substituted C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-7 cycloalkyl, C3-7 cycloalkylC1-10 alkyl, C5-7 cycloalkenyl, aryl, arylC1-10 alkyl, heteroaryl, heteroarylC1-10 alkyl, heterocyclyl, heterocyclylC1-10 alkyl, (CR10R28)nOR12, (CR10R28)n′OR13, (CR10R28)n′S(O)mR25, (CR10R28)n S(O)2R25, (CR10R28)n′NHS(O)2R25, (CR10R28)n′NR8R9, (CR10R28)n′NO2, (CR10R28)n′CN, (CR10R28)n′S(O)mNR8R9, (CR10R28)n′C(Z)R13, (CR10R28)n′C(Z)OR13, (CR10R28)n′C(Z)NR8R9, (CR10R28)n′C(Z)NR13OR12, (CR10R28)n′NR10C(Z)R13, (CR10R28)n′NR10C(Z)NR8R9, (CR10R28)n′N(OR21)C(Z)NR8R9, (CR10R28)n′N(OR21)C(Z)R13, (CR10R28)n′C(═NOR21)R13, (CR10R28)n′NR10C(═NR27)NR8R9, (CR10R28)n′OC(Z)NR8R9, (CR10R28)n′NR10C(Z)OR10, (CR10R28)n′NR10C(Z)OR10, 5-(R25)-1,2,4-oxadizaol-3-yl or 4-(R12)-5-(R18R19)-4,5-dihydro-1,2,4-oxadiazol-3-yl;
• wherein the cyclcoalkyl, cycloalkyl alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, or heterocyclylalkyl moieties may be optionally substituted;
• n is 0 or an integer from 1 to 10;
• n′ is an integer having a value of 1 to 10;
• m is 0, or the integer 1 or 2;
• m′ is an integer having a value of 1 or 2,
• m″ is 0, or an integer having a value of 1 to 5;
• t is a number having a value of 1, 2 or 3;
• v is 0, or an integer having a value of 1 or 2;
• R3 is Q—(Y1)t;
• Q is an aryl or heteroaryl group;
• Z is oxygen or sulfur;
• Y1 is independently selected from hydrogen, C1-5 alkyl, halo-substituted C1-5 alkyl, halogen, or (CR10R20)nY2;
• Y2 is OR8, NO2, S(O)m″R11, SR8, S(O)m″OR8, S(O)mNR8R9, NR8R9, O(CR10R20)n′NR8R9, C(O)R8, CO2R8, CO2(CR10R20)n′CONR8R9, ZC(O)R8, CN, C(Z)NR8R9, NR10C(Z)R8, C(Z)NR8OR9, NR10C(Z)NR8R9, NR10S(O)m″R11, N(OR21)C(Z)NR8R9, N(OR21)C(Z)R8, C(═NOR21)R8, NR10C(═NR15)SR11, NR10C(═NR15)NR8R9, NR10C(═CR14R24)SR11, NR10C(═CR14R24)NR8R9, NR10C(O)C(O)NR8R9, NR10C(O)C(O)OR10, C(═NR13)NR8R9, C(═NOR13)NR8R9, C(═NR13)ZR11, OC(Z)NR8R9, NR10S(O)m″CF3, NR10C(Z)OR10, 5-(R18)-1,2,4-oxadizaol-3-yl or 4-(R12)-5-(R18R19)-4,5-dihydro-1,2,4-oxadiazol-3-yl;
• R4 is phenyl, naphth-1-yl or naphth-2-yl which is optionally substituted by one or two substituents, each of which is independently selected, and which, for a 4-phenyl, 4-naphth-1-yl or 5-naphth-2-yl substituent, is halo,nitro, cyano, C(Z)NR7R17, C(Z)OR23, (CR10R20)vCOR36, SR5, SOR5, OR36, halo-substituted-C1-4 alkyl, C1-4 alkyl, ZC(Z)R36, NR10C(Z)R23, or (CR10R20)vNR10R20 and which, for other positions of substitution, is halo, nitro, cyano, C(Z)NR16R26, C(Z)OR8, (CR10R20)m″COR8, S(O)mR8, OR8, halo-substituted-C1-4 alkyl, C1-4 alkyl, CR10R20)m″NR10C(Z)R8, NR10S(O)m′R11, NR10S(O)m′NR7R17, ZC(Z)R8 or (CR10R20)m″NR16R26;
• R5 is hydrogen, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl or NR7R17, excluding the moieties SR5 being SNR7R17 and SOR5 being SOH;
• R7 and R17 is each independently selected from hydrogen or C1-4 alkyl or R7 and R17 together with the nitrogen to which they are attached form a heterocyclic ring of 5 to 7 members which ring optionally contains an additional heteroatom selected from oxygen, sulfur or NR22;
• R8 is hydrogen, heterocyclyl, heterocyclylalkyl or R11;
• R9 is hydrogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-7 cycloalkyl, C5-7 cycloalkenyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl or R8 and R9 may together with the nitrogen to which they are attached form a heterocyclic ring of 5 to 7 members which ring optionally contains an additional heteroatom selected from oxygen, sulfur or NR12;
• R10 and R20 is each independently selected from hydrogen or C1-4 alkyl;
• R11 is C1-10 alkyl, halo-substituted C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-7 cycloalkyl, C5-7 cycloalkenyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl;
• R12 is hydrogen, C(Z)R13 or optionally substituted C1-4 alkyl, optionally substituted aryl, optionally substituted arylC1-4 alkyl, or S(O)2R25;
• R13is hydrogen, C1-10 alkyl, C3-7 cycloalkyl, heterocyclyl, heterocyclylC1-10 alkyl, aryl, arylC1-10 alkyl, heteroaryl or heteroaryl C1-10 alkyl, wherein all of these moieties may be optionally substituted;
• R14 and R24 is each independently selected from hydrogen, alkyl, nitro or cyano;
• R15 is hydrogen, cyano, C1-4 alkyl, C3-7 cycloalkyl or aryl;
• R16 and R26 is each independently selected from hydrogen or optionally substituted C1-4 alkyl, optionally substituted aryl or optionally substituted aryl-C1-4 alkyl, or together with the nitrogen which they are attached form a heterocyclic ring of 5 to 7 members which ring optionally contains an additional heteroatom selected from oxygen, sulfur or NR12;
• R18 and R19 is each independently selected from hydrogen, C1-4 alkyl, substituted alkyl, optionally substituted aryl, optionally substituted arylalkyl or together denote a oxygen or sulfur;
• R21 is hydrogen, a pharmaceutically acceptable cation, C10 alkyl, C3-7 cycloalkyl, aryl, aryl C1-4 alkyl, heteroaryl, heteroarylalkyl, heterocyclyl, aroyl, or C1-10 alkanoyl;
• R22 is R10 or C(Z)-C1-4 alkyl;
• R23 is C1-4 alkyl, halo-substituted-C1-4 alkyl, or C3-5 cycloalkyl;
• R36 is hydrogen or R23;
• R25 is C1-10 alkyl, C3-7 cycloalkyl, heterocyclyl, aryl, arylalkyl, heterocyclyl, heterocyclyl-C1-10-alkyl, heteroaryl or heteroarylalkyl;
• R27 is hydrogen, cyano, C1-4 alkyl, C3-7 cycloalkyl, or aryl;
• R28 is hydrogen, C1-6 alkyl, C3-7 cycloalkyl, aryl, arylC1-4 alkyl, heteroaryl, heteroarylC1-4alkyl, heterocyclyl, or heterocyclylC1-4 alkyl moiety, all of which may be optionally substituted;
• or a pharmaceutically acceptable salt thereof.