Patent ID: 6610695
Filing Date: 2003-08-26
Classification: A61P,C07D

Abstract:
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, NHRaâ€², 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; Raâ€² 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)nâ€²OR13, (CR10R28)nâ€²S(O)mR25, (CR10R28)n S(O)2R25, (CR10R28)nâ€²NHS(O)2R25, (CR10R28)nâ€²NR8R9, (CR10R28)nâ€²NO2, (CR10R28)nâ€²CN, (CR10R28)nâ€²S(O)mNR8R9, (CR10R28)nâ€²C(Z)R13, (CR10R28)nâ€²C(Z)OR13, (CR10R28)nâ€²C(Z)NR8R9, (CR10R28)nâ€²C(Z)NR13OR12, (CR10R28)nâ€²NR10C(Z)R13, (CR10R28)nâ€²NR10C(Z)NR8R9, (CR10R28)nâ€²N(OR21)C(Z)NR8R9, (CR10R28)nâ€²N(OR21)C(Z)R13, (CR10R28)nâ€²C(&boxH;NOR21)R13, (CR10R28)nâ€²NR10C(&boxH;NR27)NR8R9, (CR10R28)nâ€²OC(Z)NR8R9, (CR10R28)nâ€²NR10C(Z)OR10, (CR10R28)nâ€²NR10C(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; nâ€² is an integer having a value of 1 to 10; m is 0, or the integer 1 or 2; mâ€² is an integer having a value of 1 or 2, mâ€³ 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 Qâ€”(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)mâ€³R11, SR8, S(O)mâ€³OR8, S(O)mNR8R9, NR8R9, O(CR10R20)nâ€²NR8R9, C(O)R8, CO2R8, CO2(CR10R20)nâ€²CONR8R9, ZC(O)R8, CN, C(Z)NR8R9, NR10C(Z)R8, C(Z)NR8OR9, NR10C(Z)NR8R9, NR10S(O)mâ€³R11, N(OR21)C(Z)NR8R9, N(OR21)C(Z)R8, C(&boxH;NOR21)R8, NR10C(&boxH;NR15)SR11, NR10C(&boxH;NR15)NR8R9, NR10C(&boxH;CR14R24)SR11, NR10C(&boxH;CR14R24)NR8R9, NR10C(O)C(O)NR8R9, NR10C(O)C(O)OR10, C(&boxH;NR13)NR8R9, C(&boxH;NOR13)NR8R9, C(&boxH;NR13)ZR11, OC(Z)NR8R9, NR10S(O)mâ€³CF3, 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)mâ€³COR8, S(O)mR8, OR8, halo-substituted-C1-4 alkyl, C1-4 alkyl, CR10R20)mâ€³NR10C(Z)R8, NR10S(O)mâ€²R11, NR10S(O)mâ€²NR7R17, ZC(Z)R8 or (CR10R20)mâ€³NR16R26; 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.