Patent ID: 6251914
Filing Date: 2001-06-26
Classification: A61P,C07D

Abstract:
A compound of the formula: ##STR30##whereinR.sub.1 is a 4-pyridyl, pyrimidinyl, quinolyl, isoquinolinyl, quinazolin-4-yl, 4-pyridazinyl or 1,2,4-triazin-5-yl ring which ring is optionally substituted one or more times independently by C.sub.1-4 alkyl, halogen, hydroxyl, C.sub.1-4 alkoxy, C.sub.1-4 alkylthio, C.sub.1-4 alkylsulfinyl, CH.sub.2 OR.sub.12, amino, mono and di-C.sub.1-6 alkyl substituted amino, N(R.sub.10)C(O)R.sub.c or an N-heterocyclyl ring which ring has from 5 to 7 members and optionally contains an additional heteroatom selected from oxygen, sulfur or NR.sub.15 ;R.sub.4 is phenyl, naphth-1-yl or naphth-2-yl, or a heteroaryl, 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, 5-naphth-2-yl or 6-naphth-2-yl substituent, is halogen, cyano, nitro, C(Z)NR.sub.7 R.sub.17, C(Z)OR.sub.16, (CR.sub.10 R.sub.20).sub.v COR.sub.12, SR.sub.5, SOR.sub.5, OR.sub.12, halo-substituted-C.sub.1-4 alkyl, C.sub.1-4 alkyl, ZC(Z)R.sub.12, NR.sub.10 C(Z)R.sub.16, or (CR.sub.10 R.sub.20).sub.v NR.sub.10 R.sub.20 and which, for other positions of substitution, is halogen, cyano, C(Z)NR.sub.13 R.sub.14, C(Z)OR.sub.3, (CR.sub.10 R.sub.20).sub.m"" COR.sub.3, S(O).sub.m R.sub.3, OR.sub.3, halo-substituted-C.sub.1-4 alkyl, C.sub.1-4 alkyl, (CR.sub.10 R.sub.20).sub.m"" NR.sub.10 C(Z)R.sub.3, NR.sub.10 S(O).sub.m' R.sub.8, NR.sub.10 S(O).sub.m' NR.sub.7 R.sub.17, ZC(Z)R.sub.3 or (CR.sub.10 R.sub.20).sub.m"" NR.sub.13 R.sub.14 ;v is 0, or an integer having a value of 1 or 2;m is 0, or the integer 1 to 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;R.sub.c is hydrogen, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, aryl, arylC.sub.1-4 alkyl, heteroaryl, heteroarylC.sub.1-4 alkyl, heterocyclyl, or heterocyclylC.sub.1-4 alkyl C.sub.1-4 alkyl, all of which may be optionally substituted;R.sub.2 is a C.sub.3-7 cycloalkyl ring substituted by R.sub.22, or R.sub.2 a C.sub.3-7 cycloalkylC.sub.1-10 alkyl ring substituted by R.sub.22 ;R.sub.22 is --X.sub.2 C.sub.1-10 alkyl, and wherein the C.sub.1-10 alkyl is substituted one to three times independently by halogen, hydroxy, OR.sub.11, nitro, cyano, NR.sub.7 R.sub.17, optionally substituted aryl, S(O).sub.m alkyl or S(O).sub.m aryl;X.sub.2 is oxygen, sulfur, or N(R.sub.10)--;R.sub.3 is heterocyclyl, heterocyclylC.sub.1-10 alkyl or R.sub.8,R.sub.5 is hydrogen, C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.2-4 alkylnyl 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 SOII;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 of 5 to 7 members which ring optionally contains an additional heteroatom selected from oxygen, sulfur or NR.sub.15 ;R.sub.8 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, heteroaryl, heteroarylC.sub.1-10 alkyl, (CR.sub.10 R.sub.20).sub.n OR.sub.11, (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.13 R.sub.14 ; wherein the aryl, arylalkyl, heteroaryl, heteroaryl alkyl may be optionally substituted;n is an integer having a value of 1 to 10;R.sub.9 is hydrogen, C(Z)R.sub.11 or optionally substituted C.sub.1-10 alkyl, S(O).sub.2 R.sub.18, optionally substituted aryl or optionally substituted aryl-C.sub.1-4 alkyl;R.sub.10 and R.sub.20 is each independently selected from hydrogen or C.sub.1-4 alkyl;R.sub.11 is hydrogen, or R.sub.18 ;R.sub.12 is hydrogen or R.sub.16 ;R.sub.13 and R.sub.14 is each independently selected from hydrogen or optionally substituted C.sub.1-4 alkyl, optionally substituted aryl or optionally substituted aryl-C.sub.1-4 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 NR.sub.9 ;R.sub.15 is hydrogen, C.sub.1-4 alkyl or C(Z)--C.sub.1-4 alkyl;R.sub.16 is C.sub.1-4 alkyl, halo-substituted-C.sub.1-4 alkyl, or C.sub.3-7 cycloalkyl;R.sub.18 is C.sub.1-10 alkyl, C.sub.3-7 cycloalkyl, heterocyclyl, aryl, arylC.sub.1-10 alkyl, heterocyclyl, heterocyclyl-C.sub.1-10 alkyl, heteroaryl or heteroarylalkyl;Z is oxygen or sulfur;or a pharmaceutically acceptable salt thereof.