Patent ID: 6316444
Filing Date: 2001-11-13
Classification: A61P,C07D

Abstract:
A compound of Formula I ##STR91##or pharmaceutically acceptable salts, hydrates, solvates, crystal forms and individual diastereomers thereof, whereinR.sup.1 and R.sup.2 are independently:a) H,b) halo(Br, Cl, I, or F),c) OH,d) SH,e) CN,f) NO.sub.2,g) R.sup.9,h) OR.sup.9,i) O(C.dbd.O)R.sup.9,j) O(C.dbd.O)OR.sup.9,k) O(C.dbd.O)NHR.sup.9,l) O(C.dbd.O)NR.sup.9 R.sup.10,m) SR.sup.9,n) S(O)R.sup.9,o) S(O).sub.2 R.sup.9,p) C(.dbd.O)R.sup.9,q) C(.dbd.O)OR.sup.9,r) C(.dbd.O)NHR.sup.9,s) C(.dbd.O)NR.sup.9 R.sup.10,t) NH.sub.2,u) NHR.sup.9,v) NR.sup.9 R.sup.10,w) NHC(.dbd.O)R.sup.9,x) NHC(.dbd.O)OR.sup.9,y) NR.sup.9 C(.dbd.O)R.sup.10,z) NR.sup.9 C(.dbd.O)NHR.sup.10,aa) NR.sup.9 C(.dbd.O)NR.sup.10 R.sup.11,ab) SO.sub.2 NHR.sup.9,ac) SO.sub.2 NR.sup.9 R.sup.10,ad) NHSO.sub.2 R.sup.9,ae) NR.sup.9 SO.sub.2 R.sup.10, oraf) R.sup.1 and R.sup.2 can join together to form a fused methylenedioxy ring or a fused 6-membered aromatic ring;R.sup.3 and R.sup.5 are independently:a) H,b) C.sub.1 -C.sub.6 -alkyl, unsubstituted or substituted with one, two, or three substituents selected from oxo, X', Y' and Z',c) aryl, wherein aryl is defined as phenyl or naphthyl unsubstituted or substituted with one, two or three substituents selected from: X', Y' and Z', ord) R.sup.3 and R.sup.5 taken together can represent .dbd.O;R.sup.4 is:a) H, orb) C.sub.1 -C.sub.6 -alkyl,c) C.sub.1 -C.sub.6 -alkoxyl, ord) R.sup.4 and R.sup.8 can join together to form a 5- or 6-membered ring with --CHR.sup.9 --, --CH.sub.2 CHR.sup.9 --, or --CHR.sup.9 CH.sub.2 --;--X.sup.1 --X.sup.2 --X.sup.3 --X.sup.4 -- is:a) --CR.sup.6.dbd.CR.sup.6 --CR.sup.6a.dbd.CR.sup.6 --,b) --CR.sup.6a.dbd.CR.sup.6 --CR.sup.6.dbd.CR.sup.6 --,c) --CR.sup.6.dbd.CR.sup.6a --CR.sup.6.dbd.CR.sup.6 --,d) --CR.sup.6.dbd.CR.sup.6 --CR.sup.6.dbd.CR.sup.6a --,e) --N.dbd.CR.sup.6 --CR.sup.6.dbd.CR.sup.6 --,f) --CR.sup.6.dbd.N--CR.sup.6.dbd.CR.sup.6 --,g) --CR.sup.6.dbd.CR.sup.6 --N.dbd.CR.sup.6 --,h) --CR.sup.6.dbd.CR.sup.6 --CR.sup.6.dbd.N--,i) --N.dbd.CR.sup.6 --N.dbd.CR.sup.6 --,j) --CR.sup.6.dbd.N--CR.sup.6.dbd.N-,k) --CR.sup.6.dbd.N--N.dbd.CR.sup.6 --, orl) --N.dbd.CR.sup.6 --CR.sup.6.dbd.N--;X.sup.5 is N or CH;R.sup.6 and R.sup.6a are independently:a) H,b) halo(Br, Cl, I, or F),c) OH,d) SH,e) CN,f) NO.sub.2,g) N.sub.3,h) N.sub.2 +BF.sub.4 --,i) R.sup.9,j) OR.sup.9,k) O(C.dbd.O)R.sup.9,l) O(C.dbd.O)OR.sup.9,m) O(C.dbd.O)NHR.sup.9,n) O(C.dbd.O)NR.sup.9 R.sup.10,o) SR.sup.9,p) S(O)R.sup.9,q) S(O).sub.2 R.sup.9,r) C.sub.1 -C.sub.6 -alkyl, unsubstituted or substituted with one, two, or three substituents selected from R.sup.9, R.sup.10, and R.sup.11,s) C(.dbd.O)R.sup.9,t) C(.dbd.O)OR.sup.9,u) C(.dbd.O)NHR.sup.9,v) C(.dbd.O)NR.sup.9 R.sup.10,w) C(.dbd.O)N(OR.sup.9)R.sup.10,x) NH.sub.2,y) NHR.sup.9,z) NHC.sub.1 -C.sub.6 -alkyl, unsubstituted or substituted with one, two, or three substituents selected from R.sup.9, R.sup.10, and R.sup.11,aa) NR.sup.9 R.sup.10,ab) NHC(.dbd.O)R.sup.9,ac) NR.sup.9 C(.dbd.O)R.sup.10,ad) NHC(.dbd.O)NHR.sup.9,ae) NR.sup.9 C(.dbd.O)NHR.sup.10,af) NR.sup.9 C(.dbd.O)NR.sup.10 R.sup.11,ag) SO.sub.2 NH.sub.2,ah) SO.sub.2 NHR.sup.9,al) SO.sub.2 NR.sup.9 R.sup.10,aj) NHSO.sub.2 R.sup.9,ak) NR.sup.9 SO.sub.2 R.sup.10,al) NHP(.dbd.O)(OC.sub.1 -C.sub.6 -alkyl).sub.2, oram) R.sup.6 and R.sup.6a when on adjacent carbons can be joined to form a 5- or 6-membered ring having the following bridging atoms, when read from right to left, or left to right:i) --CH.dbd.CH--CH.dbd.CH--,ii) --OCH.sub.2 O--,iii) --C(O)N(R.sup.9)C(O)--,iv) --CH.sub.2 N(R.sup.9)CH.sub.2 --,v) --N.dbd.CHNHC(O)--,vi) --C(O)NHCH.dbd.N--,vii) --C(O)OC(O)--,viii) --NHC(O)NHC(O)--,ix) --C(O)NHC(O)NH--,x) --N.dbd.CHNH--,xi) --NHCH.dbd.N--,xii) --NR.sup.9 CH.dbd.N--,xiii) --N.dbd.CHNR.sup.9 --, orxiv) ##STR92##xv)R.sup.7 is:a) Hb) R.sup.9,c) OR.sup.9 ;d) NH.sub.2,e) NHR.sup.9, orf) NR.sup.9 R .sup.10 ;X is O, S, SO, SO.sub.2, NR.sup.8 ;Z is C.dbd.O, SO.sub.2, P(.dbd.O)(OR.sup.9) or a single bond; andR.sup.8 is:a) H,b) R.sup.9,c) SO.sub.2 R.sup.9,d) C(.dbd.O)R.sup.9,e) C(.dbd.O)OR.sup.9,f) C(.dbd.O)NHR.sup.9,g) C(.dbd.O)NR.sup.9 R.sup.10, orh) R.sup.8 and R.sup.4 can be joined to represent --C(R.sup.16).sub.2 --;R.sup.9, R.sup.10 and R.sup.11 are independently:a) C.sub.1 -C.sub.6 -perfluoroalkyl,b) C.sub.1 -C.sub.6 -alkyl, unsubstituted or substituted with one, two, or three substituents selected from oxo, X', Y' and Z',c) C.sub.1 -C.sub.6 -alkenyl, unsubstituted or substituted with one, two, or three substituents selected from oxo, X', Y' and Z',d) C.sub.2 -C.sub.6 -alkynyl, unsubstituted or substituted with one, two, or three substituents selected from oxo, X', Y' and Z',e) aryl, wherein aryl is defined as phenyl or naphthyl, unsubstituted or substituted with one, two, or three substituents selected from X', Y' and Z',f) heterocyclyl, wherein the heterocyclyl is unsubstituted or substituted with one, two, three or four substituents selected from oxo, X', Y', and Z', org) C.sub.3 -C.sub.6 -cycloalkyl, unsubstituted or substituted with one, two, or three substituents selected from oxo, X', Y' and Z';X'Y' and Z' independently are selected from:a) H,b) halo,c) CN,d) NO.sub.2,e) hydroxy,f) C.sub.1 -C.sub.6 -perfluoroalkyl,g) C.sub.1 -C.sub.6 -alkoxyl, unsubstituted or substituted with aryl, wherein aryl is defined as phenyl or naphthyl,h) (C.dbd.O)(C.sub.1 -C.sub.6 -alkyl), unsubstituted or substituted with aryl, wherein aryl is defined as phenyl or naphthyl,i) (C.dbd.O)O(C.sub.1 -C.sub.6 -alkyl), unsubstituted or substituted with aryl, wherein aryl is defined as phenyl or naphthyl,j) (C.dbd.O)NH(C.sub.1 -C.sub.6 -alkyl),k) (C.dbd.O)N(C.sub.1 -C.sub.6 alkyl).sub.2,l) NH.sub.2,m) NHC.sub.1 -C.sub.6 -alkyl, wherein alkyl is unsubstituted or substituted with aryl or NH.sub.2,n) N(C.sub.1 -C.sub.6 -alkyl).sub.2,o) NHaryl, wherein aryl is defined as phenyl or naphthyl, unsubstituted or substituted with one, two, or three substituents selected from halo, phenyl, CN, NO.sub.2, hydroxy, C.sub.1 -C.sub.6 -alkyl, C.sub.1 -C.sub.6 -alkoxyl, NH.sub.2, NHC.sub.1 -C.sub.6 -alkyl, N(C.sub.1 -C.sub.6 -alkyl).sub.2, (C.dbd.O)(C.sub.1 -C.sub.6 -alkyl), (C.dbd.O)O(C.sub.1 -C.sub.6 -alkyl), (C.dbd.O)NH(C.sub.1 -C.sub.6 -alkyl), (C.dbd.O)N(C.sub.1 -C.sub.6 -alkyl).sub.2, NH(C.dbd.O)(C.sub.1 -C.sub.6 -alkyl),p) NHheterocyclyl, wherein heterocyclyl is unsubstituted or substituted with one, two or three substituents selected from halo, phenyl, oxo, CN, NO.sub.2, hydroxy, C.sub.1 -C.sub.6 -alkyl, C.sub.1 -C.sub.6 -alkyl substituted with C.sub.3 -C.sub.7 -cycloalkyl, C.sub.1 -C.sub.6 -alkoxyl, NH.sub.2, NHC.sub.1 -C.sub.6 -alkyl, N(C.sub.1 -C.sub.6 -alkyl).sub.2, (C.dbd.O)(C.sub.1 -C.sub.6 -alkyl), (C.dbd.O)O(C.sub.1 -C.sub.6 -alkyl), (C.dbd.O)OCH.sub.2 phenyl, (C.dbd.O)NH(C.sub.1 -C.sub.6 -alkyl), (C.dbd.O)N(C.sub.1 -C.sub.6 -alkyl).sub.2, NH(C.dbd.O)(C.sub.1 -C.sub.6 -alkyl),q) NHCHO,r) NH(C.dbd.O)(C.sub.1 -C.sub.6 -alkyl),s) NH(C.dbd.O)(OC.sub.1 -C.sub.6 -alkyl),t) aryl, wherein aryl is as defined above in o,u) C.sub.1 -C.sub.6 -alkyl, wherein alkyl is unsubstituted or substituted with hydroxy, C.sub.3 -C.sub.7 -cycloalkyl, aryl or heterocyclyl, wherein aryl is defined as above and heterocyclyl is as defined below,v) heterocyclyl, wherein heterocyclyl is as defined above in p,w) when two of X', Y' and Z' are on adjacent carbons they can join to form a methylenedioxy bridge,x) NH(C.dbd.O)aryl,y)--NR.sup.14 NHR.sup.15,z) --S(O)x C.sub.1 -C.sub.6 -alkyl,aa) SO.sub.2 NH C.sub.1 -C.sub.6 -alkyl, orab) CO.sub.2 H;R.sup.14 and R.sup.15 are independently: H, C.sub.1 -C.sub.6 -alkyl, aryl or C.sub.1 -C.sub.6 -alkylaryl; orR.sup.16 is:a) H,b) (CH.sub.2).sub.x aryl, wherein the aryl is unsubstituted or substituted with one or two substituents selected from X', Y', and Z';c) (CH.sub.2).sub.x heterocyclyl, wherein the heterocyclyl is unsubstituted or substituted with one or two substituents selected from X', Y', and Z'; orx is 0, 1 or 2.