Patent ID: 6306883
Filing Date: 2001-10-23
Classification: A61P,C07D

Abstract:
A compound of the formula: ##STR5##whereinone of R.sub.1 and R.sub.2 is a 4-pyridyl ring, which ring is optionally substituted with one or two substituents each of which is independently selected from C.sub.1-4 alykl, halo, C.sub.1-4 alkoxy, C.sub.1-4 alkylthio, CH.sub.2 OR.sub.8, NH.sub.2, mono- or di-C.sub.1-6 -alkylamino or N-heterocyclyl ring selected from pyrrolidine, piperidine, piperazine, morpholine, imidazolidine, and pyrazolidine;the other of R.sub.1 and R.sub.2 is selected from an optionally substituted phenyl ring, or naphthyl ring, which ring is 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)NR.sub.7 R.sub.17, C(Z)OR.sub.23, (CR.sub.10 R.sub.20).sub.n COR.sub.36, SR.sub.5, S(O)R.sub.5, OR.sub.36, halo-substituted C.sub.1-4 alkyl, C.sub.1-4 alkyl, ZC(Z)R.sub.36, NR.sub.10 C(Z)R.sub.23, or (CR.sub.10 R.sub.20).sub.n NR.sub.10 R.sub.20 and which, for other positions of substitution, is halo, (CR.sub.10 R.sub.20).sub.n nitro, (CR.sub.10 R.sub.20).sub.n cyano, (CR.sub.10 R.sub.20).sub.n C(Z)NR.sub.16 R.sub.26, (CR.sub.10 R.sub.20).sub.n C(Z)OR.sub.18, (CR.sub.10 R.sub.20).sub.n COR.sub.25, (CR.sub.10 R.sub.20).sub.n --S(O).sub.m R.sub.8, (CR.sub.10 R.sub.20).sub.n OH, (CR.sub.10 R.sub.20).sub.n OR.sub.25, halo-substituted-C.sub.1-4 alkyl, C.sub.1-4 alkyl, (CR.sub.10 R.sub.20).sub.n NR.sub.10 C(Z)R.sub.25, (CR.sub.10 R.sub.20).sub.n NHS(O).sub.m R.sub.6, (CR.sub.10 R.sub.20).sub.n NHS(O).sub.m NR.sub.7 R.sub.17, (CR.sub.10 R.sub.20).sub.n NR.sub.6 S(O).sub.m R.sub.6, (CR.sub.10 R.sub.20).sub.n NR.sub.6 S(O).sub.m 'NR.sub.7 R.sub.17 ; (CR.sub.10 R.sub.20).sub.n ZC(Z)R.sub.18 or (CR.sub.10 R.sub.20).sub.n NR.sub.7 R.sub.17 ;n is 0 or an integer of 1 or 2;m is 0 or an integer of 1 or 2;m' is an integer of 1 or 2;R.sub.3 is Q-(Y.sub.1).sub.t ;Q is a pyridyl group;t is an integer having a value of 1 to 3;R.sub.4 is hydrogen, C.sub.1-10 alkyl, halo-substituted C.sub.1-10 alkyl, C.sub.2-10 alkenyl, C.sub.2-10 alkynyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkylC.sub.1-10 alkyl, C.sub.5-7 cycloalkenyl, C.sub.5-7 cycloalkenyl-C.sub.1-10 alykl, aryl, arylC.sub.1-10 alkyl, (CR.sub.10 R.sub.20).sub.n 'OR.sub.12, (CR.sub.10 R.sub.20).sub.n OR.sub.13, (CR.sub.10 R.sub.20).sub.n S(O).sub.m R.sub.18, (CR.sub.10 R.sub.20).sub.n NHS(O).sub.2 R.sub.18, (CR.sub.10 R.sub.20).sub.n NR.sub.16 R.sub.26, (CR.sub.10 R.sub.20).sub.n NO.sub.2, (CR.sub.10 R.sub.20).sub.n CN, (CR.sub.10 R.sub.20).sub.n 'SO.sub.2 R.sub.18, (CR.sub.10 R.sub.20).sub.n S(O).sub.m 'NR.sub.16 R.sub.26, (CR.sub.10 R.sub.20).sub.n C(Z)R.sub.13, (CR.sub.10 R.sub.20).sub.n OC(Z)R.sub.13, (CR.sub.10 R.sub.20).sub.n C(Z)OR.sub.13, (CR.sub.10 R.sub.20).sub.n C(Z)NR.sub.16 R.sub.26, (CR.sub.10 R.sub.20).sub.n C(Z)NR.sub.13 OR.sub.9, (CR.sub.10 R.sub.20).sub.n NR.sub.10 C(Z)R.sub.11, (CR.sub.10 R.sub.20).sub.n NR.sub.10 C(Z)NR.sub.16 R.sub.26, (CR.sub.10 R.sub.20).sub.n N(OR.sub.6)C(Z)NR.sub.16 R.sub.26, (CR.sub.10 R.sub.20).sub.n N(OR.sub.6)C(Z)R.sub.13, (CR.sub.10 R.sub.20).sub.n C(.dbd.NOR.sub.6)R.sub.13, (CR.sub.10 R.sub.20).sub.n NR.sub.10 C(.dbd.NR.sub.19)NR.sub.16 R.sub.26, (CR.sub.10 R.sub.20).sub.n OC(Z)NR.sub.16 R.sub.26, (CR.sub.10 R.sub.20).sub.n NR.sub.10 C(Z)NR.sub.16 R.sub.26, (CR.sub.10 R.sub.20).sub.n NR.sub.10 C(Z)OR.sub.10, wherein the aryl, arylalkyl, cyclcoalkyl, cycloalkyl alkyl groups may be optionally substituted;R.sub.6 is C.sub.1-10 alkyl, C.sub.3-7 cycloalkyl, aryl, arylC.sub.1-10 alkyl;R.sub.5 is hydrogen, C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl or NR.sub.7 R.sub.17, excluding the moieties--SR.sub.5 being --SNR.sub.7 R.sub.17 and --SOR.sub.5 being --SOH;R.sub.16 and R.sub.26 are independently hydrogen, or C.sub.1-4 alkyl or R.sub.16 and R.sub.26 together with the nitrogen to which they are attached form a heterocyclic selected from pyrrolidine, piperidine, piperazine, morpholine, imidazolidine, and pyrazolidine;Y.sub.1 is independently selected from hydrogen, C.sub.1-5 alkyl, halo-substituted C.sub.1-5 alkyl, halogen, or --(CR.sub.10 R.sub.20).sub.n Y.sub.2 ;Y.sub.2 is hydrogen, halogen, OR.sub.8, NO.sub.2, S(O).sub.m 'R.sub.11, SR.sub.8, S(O).sub.m 'OR.sub.8, S(O).sub.m NR.sub.8 R.sub.9, NR.sub.8 R.sub.9, O(CR.sub.10 R.sub.20).sub.n 'NR.sub.8 R.sub.9, C(O)R.sub.8, CO.sub.2 R.sub.8, CO.sub.2 (CR.sub.10 R.sub.20).sub.m ""CONR.sub.8 R.sub.9, ZC(O)R.sub.8, CN, C(Z)NR.sub.8 R.sub.9, NR.sub.10 C(Z)R.sub.8, C(Z)NR.sub.8 OR.sub.9, NR.sub.10 C(Z)NR.sub.8 R.sub.9, NR.sub.10 S(O).sub.m 'R.sub.11, N(OR.sub.21)C(Z)NR.sub.8 R.sub.9, N(OR.sub.21)C(Z)R.sub.8, C(.dbd.NOR.sub.21)R.sub.8, NR.sub.10 C(.dbd.NR.sub.15)SR.sub.11, NR.sub.10 C(.dbd.NR.sub.15)NR.sub.8 R.sub.9, NR.sub.10 C(.dbd.CR.sub.14 R.sub.24)SR.sub.11, NR.sub.10 C(.dbd.CR.sub.14 R.sub.24)NR.sub.8 R.sub.9, NR.sub.10 C(O)C(O)NR.sub.8 R.sub.9, NR.sub.10 C(O)C(O)OR.sub.10, C(.dbd.NR.sub.13)NR.sub.8 R.sub.9, C(.dbd.NOR.sub.13)NR.sub.8 R.sub.9, C(.dbd.NR.sub.13)ZR.sub.11, OC(Z)NR.sub.8 R.sub.9, NR.sub.10 S(O).sub.m CF.sub.3, NR.sub.10 C(Z)OR.sub.10, 5-(R.sub.18)-1,2,4-oxadizaol-3-yl or 4-(R.sub.12)-5-(R.sub.18 R.sub.19)-4,5-dihydro-1,2,4-oxadiazol-3-yl;n' is 0 or an integer having a value of 1 to 10;m"" is an integer having a value of 1 to 10;R.sub.7 and R.sub.17 is each independently selected from hydrogen or C.sub.1-4 alkyl or R.sub.7 and R.sub.17 together with the nitrogen to which they are attached form a heterocyclic ring selected from pyrrolidine, piperidine, piperazine, morpholine, imidazolidine, and pyrazolidine;R.sub.8 is hydrogen, C.sub.1-10 alkyl, C.sub.3-7 cycloalkyl, aryl, arylC.sub.1-10 alkyl;R.sub.9 is hydrogen, C.sub.1-10 alkyl, C.sub.2-10 alkenyl, C.sub.2-10 alkynyl, C.sub.3-7 cycloalkyl, C.sub.5-7 cycloalkenyl, aryl, arylalkyl, or R.sub.8 and R.sub.9 may together with the nitrogen to which they are attached form a heterocyclic selected from pyrrolidine, piperidine, piperazine, morpholine, imidazolidine, and pyrazolidine;R.sub.10 and R.sub.20 is each independently selected from hydrogen or C.sub.1-4 alkyl;R.sub.11 is C.sub.1-10 alkyl, halo-substituted C.sub.1-10 alkyl, C.sub.2-10 alkenyl, C.sub.2-10 alkynyl, C.sub.3-7 cycloalkyl, C.sub.5-7, aryl, aryl C.sub.1-10 alkyl;R.sub.12 is hydrogen, --C(Z)R.sub.13, optionally substituted C.sub.1-4 alkyl, optionally substituted aryl, optionally substituted aryl-C.sub.1-4 alkyl, or S(O).sub.2 R.sub.18 ;R.sub.13 is hydrogen, C.sub.1-10 alkyl, C.sub.3-7 cycloalkyl, aryl, arylC.sub.1-10 alkyl;R.sub.14 and R.sub.24 is each independently selected from hydrogen, alkyl, nitro or cyano;R.sub.15 is hydrogen, cyano, C.sub.1-4 alkyl, C.sub.3-7 cycloalkyl or aryl;R.sub.18 is C.sub.1-10 alkyl, C.sub.3-7 cycloalkyl, aryl, arylC.sub.1-10 alkyl;R.sub.19 is hydrogen, cyano, C.sub.1-4 alkyl, C.sub.3-7 cycloalkyl or aryl;R.sub.21 is hydrogen, a pharmaceutically acceptable cation, C.sub.1-10 alkyl, C.sub.3-7 cycloalkyl, aryl, aryl C.sub.1-4 alkyl, aroyl, or C.sub.1-10 alkanoyl;R.sub.22 is R.sub.10 or C(Z)-C.sub.1-4 alkyl;R.sub.23 is C.sub.1-4 alkyl, halo-substituted-C.sub.1-4 alkyl, or C.sub.3-7 cycloalkyl;R.sub.25 is C.sub.1-10 alkyl, halo-substituted C.sub.1-10 alkyl, C.sub.2-10 alkenyl, C.sub.2-10 alkynyl, C.sub.3-7 cycloalkyl, C.sub.5-7 cycloalkenyl, aryl, arylC.sub.1-10 alkyl, (CR.sub.10 R.sub.20).sub.n OR.sub.8, (CR.sub.10 R.sub.20).sub.n S(O).sub.m R.sub.18, (CR.sub.10 R.sub.20).sub.n NHS(O).sub.2 R.sub.18, (CR.sub.10 R.sub.20).sub.n NR.sub.7 R.sub.17 ; wherein the aryl, or arylalkyl may be optionally substituted;R.sub.36 is hydrogen or R.sub.23 ;Z is oxygen;Aryl is phenyl or naphthyl;or a pharmaceutically acceptable salt thereof.