Patent ID: 6191159
Filing Date: 2001-02-20
Classification: A61P,C07D

Abstract:
A compound of formula I: ##STR147##or a steroisomer or pharmaceutically acceptable salt thereof, wherein;M.sup.1 is CR.sup.1c ;M.sup.2 is CR.sup.1a R.sup.1a ;D is selected from C(.dbd.NR.sup.8)NR.sup.7 R.sup.9, NHC(.dbd.NR.sup.8)NR.sup.7 R.sup.9, NR.sup.8 CH(.dbd.NR.sup.7), C(O)NR.sup.7 R.sup.8, and CR.sup.8 R.sup.9 NR.sup.7 R.sup.8 ;E is selected from phenyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, and piperidinyl substituted with 1 R;alternatively, D--E--G together represent pyridyl substituted with 1 R;R is selected from H, Cl, F, Br, I, (CH.sub.2).sub.t OR.sup.3, C.sub.1-4 alkyl, OCF.sub.3, CF.sub.3, C(O)NR.sup.7 R.sup.8, and (CR.sup.8 R.sup.9).sub.t NR.sup.7 R.sup.8 ;G is selected from NHCH.sub.2, OCH.sub.2, and SCH.sub.2, provided that when s is 0, then G is absent;Z is selected from a C.sub.1-4 alkylene, (CH.sub.2).sub.r O(CH.sub.2).sub.r, (CH.sub.2).sub.r NR.sup.3 (CH.sub.2).sub.r, (CH.sub.2).sub.r C(O)(CH.sub.2).sub.r, (CH.sub.2).sub.r C(O)O(CH.sub.2).sub.r, (CH.sub.2).sub.r OC(O)(CH.sub.2).sub.r, (CH.sub.2).sub.r C(O)NR.sup.3 (CH.sub.2).sub.r, (CH.sub.2).sub.r NR.sup.3 C(O)(CH.sub.2).sub.r, (CH.sub.2).sub.r OC(O)O(CH.sub.2).sub.r, (CH.sub.2).sub.r OC(O)NR.sup.3 (CH.sub.2).sub.r, (CH.sub.2).sub.r NR.sup.3 C(O)O(CH.sub.2).sub.r, (CH.sub.2).sub.r NR.sup.3 C(O)NR.sup.3 (CH.sub.2).sub.r, (CH.sub.2).sub.r S(O).sub.p (CH.sub.2).sub.r, (CH.sub.2).sub.r SO.sub.2 NR.sup.3 (CH.sub.2).sub.r, (CH.sub.2).sub.r NR.sup.3 SO.sub.2 (CH.sub.2).sub.r, and (CH.sub.2).sub.r NR.sup.3 SO.sub.2 NR.sup.3 (CH.sub.2).sub.r, provided that Z does not form a N--N, N--O, N--S, NCH.sub.2 N, NCH.sub.2 O, or NCH.sub.2 S bond with group A;R.sup.1a and R.sup.1b are, at each occurrence, independently selected from H, --(CH.sub.2).sub.r --R.sup.1', NCH.sub.2 R.sup.1"", OCH.sub.2 R.sup.1"", SCH.sub.2 R.sup.1"", N(CH.sub.2).sub.2 (CH.sub.2).sub.t R.sup.1', O(CH.sub.2).sub.2 (CH.sub.2).sub.t R.sup.1', and S(CH.sub.2).sub.2 (CH.sub.2).sub.t R.sup.1' ;R.sup.1c is selected from H, --(CH.sub.2).sub.q --R.sup.1', C.sub.1-3 alkyl, C(O)R.sup.2c, (CF.sub.2).sub.r CO.sub.2 R.sup.2c, C(O)NR.sup.2 R.sup.2a, C.sub.3-6 carbocyclic residue substituted 0-2 R.sup.4, and 5-10 membered heterocyclic system comprising carbon atoms and from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted 0-2 R.sup.4 ;R.sup.1' is selected from H, C.sub.1-3 alkyl, halo, (CF.sub.2).sub.r CF.sub.3, OR.sup.2, NR.sup.2 R.sup.2a, C(O)R.sup.2c, OC(O)R.sup.2, (CF.sub.2).sub.r CO.sub.2 R.sup.2c, S(O).sub.p R.sup.2b, NR.sup.2 (CH.sub.2).sub.r OR.sup.2, NR.sup.2 C(O)R.sup.2b, NR.sup.2 C(O)NHR.sup.2b, NR.sup.2 C(O).sub.2 R.sup.2a, OC(O)NR.sup.2b, C(O)NR.sup.2 R.sup.2a, SO.sub.2 NR.sup.2 R.sup.2a, NR.sup.2 SO.sub.2 R.sup.2b, C.sub.3-6 carbocyclic residue substituted 0-2 R.sup.4, and 5-10 membered heterocyclic system comprising carbon atoms and from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted 0-2 R.sup.4 ;R.sup.1"" is selected from H, C(O)R.sup.2b, C(O)NR.sup.2 R.sup.2a, S(O)R.sup.2b, S(O).sub.2 R.sup.2b, and SO.sub.2 NR.sup.2 R.sup.2a ;R.sup.2, at each occurrence, is selected from H, CF.sub.3, C.sub.1-6 alkyl, benzyl, C.sub.3-6 carbocyclic residue substituted 0-2 R.sup.4b, and 5-6 membered heterocyclic system comprising carbon atoms and from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R.sup.4b ;R.sup.2a, at each occurrence, is selected from H, CF.sub.3, C.sub.1-6 alkyl, benzyl, C.sub.3-6 carbocyclic residue substituted 0-2 R.sup.4b, and 5-6 membered heterocyclic system comprising carbon atoms and from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R.sup.4b ;R.sup.2b, at each occurrence, is selected from CF.sub.3, C.sub.1-4 alkoxy, C.sub.1-6 alkyl, benzyl, C.sub.3-6 carbocyclic residue substituted with 0-2 R.sup.4b, and 5-6 membered heterocyclic system comprising carbon atoms and from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R.sup.4b ;R.sup.2c, at each occurrence, is selected from CF.sub.3, OH, C.sub.1-4 alkoxy, C.sub.1-6 alkyl, benzyl, C.sub.3-6 carbocyclic residue substituted 0-2 R.sup.4b, and 5-6 membered heterocyclic system comprising carbon atoms and from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted 0-2 R.sup.4b ;alternatively, R.sup.2 and R.sup.2a combine to form a 5 or 6 membered saturated, partially saturated or unsaturated ring substituted 0-2 R.sup.4b which comprises from 0-1 additional heteroatoms selected from the group consisting of N, O, and S;R.sup.3, at each occurrence, is selected from H, C.sub.1-4 alkyl, and phenyl;R.sup.3a, at each occurrence, is selected from H, C.sub.1-4 alkyl, and phenyl;A is selected from:C.sub.3-10 carbocyclic residue substituted 0-2 R.sup.4, and5-10 membered heterocyclic system comprising carbon atoms and from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted 0-2 R.sup.4 ;B is selected from:X--Y, NR.sup.2 R.sup.2a, C(.dbd.NR.sup.2)NR.sup.2 R.sup.2a, NR.sup.2 C(.dbd.NR.sup.2)NR.sup.2 R.sup.2a,C.sub.3-10 carbocyclic residue substituted with 0-2 R.sup.4a, and5-10 membered heterocyclic system comprising carbon atoms and from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted 0-2 R.sup.4a ;X is selected from C.sub.1-4 alkylene, --CR.sup.2 (CR.sup.2 R.sup.2b)(CH.sub.2).sub.t --, --C(O)--, --C(.dbd.NR)--, --CR.sup.2 (NR.sup.1"" R.sup.2)--, --CR.sup.2 (OR.sup.2)--, --CR.sup.2 (SR.sup.2)--, --C(O)CR.sup.2 R.sup.2a --, --CR.sup.2 R.sup.2a C(O), --S(O).sub.p --, --S(O).sub.p CR.sup.2 R.sup.2a --, --CR.sup.2 R.sup.2a S(O).sub.p --, --S(O).sub.2 NR.sup.2 --, --NR.sup.2 S(O).sub.2 --, --NR.sup.2 S(O).sub.2 CR.sup.2 R.sup.2a --, --CR.sup.2 R.sup.2a S(O).sub.2 NR.sup.2 --, --NR.sup.2 S(O).sub.2 NR.sup.2 --, --C(O)NR.sup.2 --, --NR.sup.2 C(O)--, --C(O)NR.sup.2 CR.sup.2 R.sup.2a --, --NR.sup.2 C(O)CR.sup.2 R.sup.2a --, --CR.sup.2 R.sup.2a C(O)NR.sup.2 --, --CR.sup.2 R.sup.2a NR.sup.2 C(O)--, --NR.sup.2 C(O)O--, --OC(O)NR.sup.2 --, --NR.sup.2 C(O)NR.sup.2 --, --NR.sup.2 --, --NR.sup.2 CR.sup.2 R.sup.2a --, --CR.sup.2 R.sup.2a NR.sup.2 --, O, --CR.sup.2 R.sup.2a O--, and OCR.sup.2 R.sup.2a --;Y is selected from:(CH.sub.2).sub.r NR.sup.2 R.sup.2a, provided that X--Y do not form a N--N, O--N, or S--N bond,C.sub.3-10 carbocyclic residue substituted 0-2 R.sup.4a, and5-10 membered heterocyclic system comprising carbon atoms and from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted 0-2 R.sup.4a ;R.sup.4, at each occurrence, is selected from .dbd.O, (CH.sub.2).sub.r OR.sup.2, halo, C.sub.1-4 alkyl, --CN, NO.sub.2, (CH.sub.2).sub.r NR.sup.2 R.sup.2a, (CH.sub.2).sub.r C(O)R.sup.2b, NR.sup.2 C(O)R.sup.2b, C(O)NR.sup.2 R.sup.2a, NR.sup.2 C(O)NR.sup.2 R.sup.2a, CH(.dbd.NR.sup.2)NR.sup.2 R.sup.2a, NHC(.dbd.NR.sup.2)NR.sup.2 R.sup.2a, SO.sub.2 NR.sup.2 R.sup.2a, NR.sup.2 SO.sub.2 NR.sup.2 R.sup.2a, NR.sup.2 SO.sub.2 -C.sub.1-4 NR.sup.2 SO.sub.2 R.sup.5, S(O).sub.p R.sup.5, (CF.sub.2).sub.r CF.sub.3, NCH.sub.2 R.sup.1"", OCH.sub.2 R.sup.1"", SCH.sub.2 R.sup.1"", N(CH.sub.2).sub.2 (CH.sub.2).sub.t R.sup.1', O(CH.sub.2).sub.2 (CH.sub.2).sub.t R.sup.1', and S(CH.sub.2).sub.2 (CH.sub.2).sub.t R.sup.1',alternatively, one R.sup.4 is a 5-6 membered aromatic heterocycle comprising carbon atoms and from 1-4 heteroatoms selected from the group consisting of N, O, and S;R.sup.4a, at each occurrence, is selected from .dbd.O, (CH.sub.2).sub.r OR.sup.2, halo, C.sub.1-4 alkyl, --CN, NO.sub.2, (CH.sub.2).sub.r NR.sup.2 R.sup.2a, (CH.sub.2).sub.r C(O)R.sup.2b, NR.sup.2 C(O)R.sup.2b, C(O)NR.sup.2 R.sup.2a, NR.sup.2 C(O)NR.sup.2 R.sup.2a, CH(.dbd.NR.sup.2)NR.sup.2 R.sup.2a, NHC(.dbd.NR.sup.2)NR.sup.2 R.sup.2a, SO.sub.2 NR.sup.2 R.sup.2a, NR.sup.2 SO.sub.2 NR.sup.2 R.sup.2a, NR.sup.2 SO.sub.2 -C.sub.1-4 alkyl, NR.sup.2 SO.sub.2 R.sup.5, S(O).sub.p R.sup.5, and (CF.sub.2).sub.r CF.sub.3 ;alternatively, one R.sup.4a is a 5-6 membered aromatic heterocycle comprising carbon atoms and from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-R.sup.5 ;R.sup.4b, at each occurrence, is selected from .dbd.O, (CH.sub.2).sub.r OR.sup.3, halo, C.sub.1-4 alkyl, --CN, NO.sub.2, (CH.sub.2).sub.r NR.sup.3 R.sup.3a, (CH.sub.2).sub.r C(O)R.sup.3, NR.sup.3 C(O)R.sup.3a, C(O)NR.sup.3 R.sup.3a, NR.sup.3 C(O)NR.sup.3 R.sup.3a, CH(.dbd.NR.sup.3)NR.sup.3 R.sup.3a, NH.sup.3 C(.dbd.NR.sup.3)NR.sup.3 R.sup.3a, SO.sub.2 NR.sup.3 R.sup.3a, NR.sup.3 SO.sub.2 NR.sup.3 R.sup.3a, NR.sup.3 SO.sub.2 -C.sub.1-4 alkyl, NR.sup.3 SO.sub.2 CF.sub.3, NR.sup.3 SO.sub.2 -phenyl, S(O).sub.p CF.sub.3, S(O).sub.p -C.sub.1-4 alkyl, S(O).sub.p -phenyl, and (CF.sub.2).sub.r CF.sub.3 ;R.sup.5, at each occurrence, is selected from CF.sub.3, C.sub.1-6 alkyl, phenyl substituted 0-2 R.sup.6, and benzyl substituted 0-2 R.sup.6 ;R.sup.6, at each occurrence, is selected from H, OH, (CH.sub.2).sub.r OR.sup.2, halo, C.sub.1-4 alkyl, CN, NO.sub.2, (CH.sub.2).sub.r NR.sup.2 R.sup.2a, (CH.sub.2).sub.r C(O)R.sup.2b, NR.sup.2 C(O)R.sup.2b, NR.sup.2 C(O)NR.sup.2 R.sup.2a, CH(.dbd.NH)NH.sub.2, NHC(.dbd.NH)NH.sub.2, SO.sub.2 NR.sup.2 R.sup.2a, NR.sup.2 SO.sub.2 NR.sup.2 R.sup.2a, and NR.sup.2 SO.sub.2 C.sub.1-4 alkyl;R.sup.7, at each occurrence, is selected from H, OH, C.sub.1-6 alkyl, C.sub.1-6 alkylcarbonyl, C.sub.1-6 alkoxy, C.sub.1-4 alkoxycarbonyl, (CH.sub.2).sub.n -phenyl, C.sub.6-10 aryloxy, C.sub.6-10 aryloxycarbonyl, C.sub.6-10 arylmethylcarbonyl, C.sub.1-4 alkylcarbonyloxy C.sub.1-4 alkoxycarbonyl, C.sub.6-10 arylcarbonyloxy C.sub.1-4 alkoxycarbonyl, C.sub.1-6 alkylaminocarbonyl, phenylaminocarbonyl, and phenyl C.sub.1-4 alkoxycarbonyl;R.sup.8, at each occurrence, is selected from H, C.sub.1-6 alkyl and (CH.sub.2).sub.n -phenyl;alternatively, R.sup.7 and R.sup.8 combine to form a 5 or 6 membered saturated, ring which comprises from 0-1 additional heteroatoms selected from the group consisting of N, O, and S;R.sup.9, at each occurrence, is selected from H, C.sub.1-6 alkyl and (CH.sub.2).sub.n -phenyl;n, at each occurrence, is selected from 0, 1, 2, and 3;m, at each occurrence, is selected from 0, 1, and 2;p, at each occurrence, is selected from 0, 1, and 2;q, at each occurrence is selected from 1 and 2;r, at each occurrence, is selected from 0, 1, 2, and 3;s, at each occurrence, is selected from 0, 1, and 2; and,t, at each occurrence, is selected from 0 and 1provided that when a heterocyclic group is present it is other than a morpholine, pyrazine, primidine, pyridazine, piperidine, pyridine or tetrazole.