Patent ID: 6156767
Filing Date: 2000-12-05
Classification: C07D

Abstract:
A compound of the formula ##STR49## wherein A is C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.7 cycloalkyl, substituted C.sub.3 -C.sub.7 cycloalkyl, C.sub.3 -C.sub.6 alkenyl, substituted C.sub.3 -C.sub.6 alkenyl, C.sub.3 -C.sub.6 alkynyl, substituted C.sub.3 -C.sub.6 alkynyl, C.sub.1 -C.sub.6 alkoxy, or C.sub.0 -C.sub.5 alkyl-S(O).sub.n -C.sub.0 -C.sub.5 alkyl, C.sub.0 -C.sub.5 alkyl-O-C.sub.0 -C.sub.5 alkyl, C.sub.0 -C.sub.5 alkyl-NR.sub.18 --C.sub.0 -C.sub.5 alkyl where R.sub.18 and the C.sub.0 -C.sub.5 alkyl can be joined to form a ring, ##STR50## or a single bond; R.sub.0 is hydrogen, C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl, wherein the substituents are as defined below; aryl, substituted aryl, aralkyl or substituted aralkyl, wherein the substituents are as defined for R.sub.3, R.sub.4 and R.sub.5 ; ##STR51## the nitrogen atoms contained in the R.sub.1 heteroaromatic rings may exist either as drawn or, when chemically allowed, in their oxidized (N.fwdarw.O) state;R.sub.2 is heteroaryl, substituted heteroaryl, C.sub.1 -C.sub.6 heteroaralkyl, C.sub.1 -C.sub.6 substituted heteroaralkyl;R.sub.3, R.sub.4 and R.sub.5 are independently hydrogen, C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, substituted C.sub.2 -C.sub.6 alkenyl, CN, nitro, C.sub.1 -C.sub.3 perfluoroalkyl, C.sub.1 -C.sub.3 perfluoroalkoxy, aryl, substituted aryl, aralkyl, substituted aralkyl, R.sub.11 O(CH.sub.2).sub.p --, --CH.sub.2).sub.p S(O).sub.n R.sub.17 or halogen; wherein R.sub.17 is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.3 perfluoroalkyl, aryl or substituted aryl; orR.sub.3 and R.sub.4 taken together form a carbocyclic ring of 3-7 carbon atoms or a heterocyclic ring containing 1-3 heteroatoms selected from N, O and S;R.sub.6 is hydrogen, C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl, aryl, substituted aryl, C.sub.1 -C.sub.3 perfluoroalkyl, CN, NO.sub.2, halogen, R.sub.16 O(CH.sub.2).sub.p --;R.sub.7 is hydrogen, C.sub.1 -C.sub.6 alkyl, or substituted C.sub.1 -C.sub.6 alkyl, unless X is hydrogen or halogen, then R.sub.7 is absent;R.sub.8 is hydrogen, C(O)OR.sub.9, C(O)NR.sub.11 R.sub.12, NR.sub.11 R.sub.12, C(O)R.sub.11, NR.sub.12 C(O)R.sub.11, NR.sub.12 C(O)NR.sub.11 R.sub.12, NR.sub.12 S(O).sub.2 R.sub.11, NR.sub.12 S(O).sub.2 NR.sub.11 R.sub.12, OC(O)R.sub.11, OC(O)NR.sub.11 R.sub.12, OR.sub.11, SO.sub.n R.sub.11, S(O).sub.n NR.sub.11 R.sub.12, a heterocyclic ring or bicyclic heterocyclic ring with from 1 to 4 heteroatoms selected from N, O or S which can be optionally substituted by R.sub.3, R.sub.4 and R.sub.5, C.sub.1 -C.sub.6 alkyl or substituted C.sub.1 -C.sub.6 alkyl, unless X is hydrogen or halogen, then R.sub.8 is absent; orR.sub.7 and R.sub.8 taken together form a heterocyclic ring containing one or more heteroatoms selected from N, O or S which can be optionally substituted by R.sub.3, R.sub.4 and R.sub.5 ; orR.sub.7 and R.sub.8 taken together form a carbocyclic ring of 3-7 atoms or ##STR52## when m.noteq.0; R.sub.9 and R.sub.9a are independently hydrogen, C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl; aryl or substituted aryl, aralkyl or substituted aralkyl when m.noteq.0; orR.sub.9 and R.sub.9a taken together for a carbocyclic ring of 3-7 atoms or ##STR53## when m.noteq.0; R.sub.10 and R.sub.10a are independently hydrogen, C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl, aryl, substituted aryl, aralkyl or substituted aralkyl; orR.sub.10 and R.sub.10a taken together form a carbocyclic ring of 3-7 atoms or ##STR54## R.sub.9 and R.sub.10 when taken together form a carbocyclic ring of 3-7 carbon atoms or a heterocyclic ring containing one or more heteroatoms when m.noteq.0; orR.sub.9 and R.sub.2 taken together form a heterocyclic ring containing 3-7 carbon atoms and one or more heteroatoms when m.noteq.0; orR.sub.10 and R.sub.2 taken together form a heterocyclic ring containing 3-7 carbon atoms and one or more heteroatoms;R.sub.11 and R.sub.12 are independently a bond, hydrogen, C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl, aryl, substituted aryl, aralkyl, substituted aralkyl, a carbocyclic ring of 3-7 atoms, a substituted carbocyclic ring containing 3-7 atoms, a heterocyclic ring or bicyclic heterocyclic ring with from 1 to 4 heteroatoms selected from N, O or S which can be optionally substituted by R.sub.3, R.sub.4 and R.sub.5, C.sub.1 -C.sub.6 -alkyl substituted by a heterocyclic ring or bicyclic heterocyclic ring with from 1 to 4 heteroatoms selected from N, O or S which can be optionally substituted by R.sub.3, R.sub.4 and R.sub.5 ;R.sub.11 and R.sub.12 when taken together can form an optionally substituted ring of 3-9 atoms;R.sub.13 is hydrogen, OH, NR.sub.7 R.sub.8, NR.sub.16 SO.sub.2 (C.sub.1 -C.sub.6 alkyl), NR.sub.16 SO.sub.2 (substituted C.sub.1 -C.sub.6 alkyl), NR.sub.16 SO.sub.2 (aryl), NR.sub.16 SO.sub.2 (substituted aryl), NR.sub.16 SO.sub.2 (C.sub.1 -C.sub.3 perfluoroalkyl); SO.sub.2 NR.sub.16 (C.sub.1 -C.sub.6 alkyl), SO.sub.2 NR.sub.11 (subsituted C.sub.1 -C.sub.6 alkyl), SO.sub.2 NR.sub.11 (aryl), SO.sub.2 NR.sub.16 (substituted aryl), SO.sub.2 NR.sub.16 (C.sub.1 -C.sub.3 perfluoroalkyl); SO.sub.2 NR.sub.16 (C(O)C.sub.1 -C.sub.6 alkyl); SO.sub.2 NR.sub.16 (C(O)-substituted C.sub.1 -C.sub.6 alkyl); SO.sub.2 NR.sub.16 (C(O)-aryl); SO.sub.2 NR.sub.16 (C(O)-substituted aryl); S(O).sub.n (C.sub.1 -C.sub.6 alkyl); S(O).sub.n (substituted C.sub.1 -C.sub.6 alkyl), S(O).sub.n (aryl), S(O).sub.n (substituted aryl), C.sub.1 -C.sub.3 perfluoroalkyl, C.sub.1 -C.sub.3 perfluoroalkoxy, C.sub.1 -C.sub.6 alkoxy, substituted C.sub.1 -C.sub.6 alkoxy, COOH, halogen, NO.sub.2 ; or CN;R.sub.14 and R.sub.15 are independently hydrogen, C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, substituted C.sub.2 -C.sub.6 alkenyl, CN, nitro, C.sub.1 -C.sub.3 perfluoroalkyl, C.sub.1 -C.sub.3 perfluoroalkoxy, aryl, substituted aryl, aralkyl, substituted aralkyl, R.sub.16 O(CH.sub.2).sub.p --, R.sub.16 C(O)O(CH.sub.2).sub.p --, R.sub.16 OC(O)(CH.sub.2).sub.p --, --(CH.sub.2).sub.p S(O).sub.n R.sub.17, --(CH.sub.2).sub.p C(O) N(R.sub.16).sub.2 or halogen;wherein R.sub.17 is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.3 perfluoroalkyl, aryl or substituted aryl;R.sub.16 is hydrogen, C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl, aryl, substituted aryl, aralkyl, substituted aralkyl, a carbocyclic ring of 3-7 atoms or a substituted carbocyclic ring containing 3-7 atoms;R.sub.18 is hydrogen, C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl, C(O)OR.sub.16, C(O)N(R.sub.16).sub.2, C(O)R.sub.16, S(O).sub.n R.sub.16 ;R.sub.19 is either the definition of R.sub.13 or R.sub.14 ;X is N, O, S(O).sub.n, C(O), (CR.sub.11 R.sub.12).sub.p, a single bond to R.sub.8, C.sub.2 -C.sub.6 alkenyl, substituted C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, or substituted C.sub.2 -C.sub.6 alkynyl; when X is O, S(O).sub.n, C(O), or CR.sub.11 R.sub.12 only R.sub.8 is possible;Z is O, S or NR.sub.11 ;m is 0, 1, 2 or 3;n is 0, 1 or 2;p is 0, 1, 2, 3 or 4; andthe alkyl, cycloalkyl, alkenyl and alkynyl substituents are selected from C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.7 cycloalkyl, aryl, substituted aryl, aralkyl, substituted aralkyl, hydroxy, oxo, cyano, C.sub.1 -C.sub.6 alkoxy, fluoro, C(O)OR.sub.11, aryl C.sub.1 -C.sub.3 alkoxy, substituted aryl C.sub.1 -C.sub.3 alkoxy, and thearyl substituents are as defined for R.sub.3, R.sub.4 and R.sub.5 ;or a pharmaceutically acceptable addition salt and/or hydrate thereof, or where applicable, a geometric or optical isomer or racemic mixture thereof.