Patent ID: 6329380
Filing Date: 2001-12-11
Classification: A61P,C07D,C07F

Abstract:
A compound of Formula I ##STR117##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.2g) R.sup.8,h) OR.sup.8,i) O(C.dbd.O)R.sup.8,j) O(C.dbd.O)OR.sup.8,k) O(C.dbd.O)NHR.sup.8,l) O(C.dbd.O)NR.sup.8 R.sup.9,m) SR.sup.8,n) S(O)R.sup.8,o) S(O).sub.2 R.sup.8,p) C(.dbd.O)R.sup.8,q) C(.dbd.O)OR.sup.8,r) C(.dbd.O)NHR.sup.8,s) C(.dbd.O)NR.sup.8 R.sup.9,t) NH.sub.2,u) NHR.sup.8,v) NR.sup.8 R.sup.9,w) NHC(.dbd.O)R.sup.8,x) NHC(.dbd.O)OR.sup.8,y) NR.sup.8 C(.dbd.O)R.sup.9,z) NR.sup.8 C(.dbd.O)NHR.sup.9,aa) NR.sup.8 C(.dbd.O)NR.sup.9 R.sup.10,ab) SO.sub.2 NHR.sup.8,ac) SO.sub.2 NR.sup.8 R.sup.9,ad) NHSO.sub.2 R.sup.8,ae) NR.sup.8 SO.sub.2 R.sup.9, 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 independently are: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, orc) C.sub.1 -C.sub.6 -alkoxyl;--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--;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.8,j) OR.sup.8,k) O(C.dbd.O)R.sup.8,l) O(C.dbd.O)OR.sup.8,m) O(C.dbd.O)NHR.sup.8,n) O(C.dbd.O)NR.sup.8 R.sup.9,o) SR.sup.8,P) S(O)R.sup.8,q) S(O).sub.2 R.sup.8,r) C.sub.1 -C.sub.6 -alkyl, unsubstituted or substituted with one, two, or three substituents selected from R.sup.8, R.sup.9, and R.sup.10,s) C(.dbd.O)R.sup.8,t) C(.dbd.O)OR.sup.8,u) C(.dbd.O)NHR.sup.8,v) C(.dbd.O)NR.sup.8 R.sup.9,w) C(.dbd.O)N(OR.sup.8)R.sup.9,x) NH.sub.2,y) NHR.sup.8,z) NHC.sub.1 -C.sub.6 -alkyl, unsubstituted or substituted with one, two, or three substituents selected from R.sup.8, R.sup.9, and R.sup.10,aa) NR.sup.8 R.sup.9,ab) NHC(.dbd.O)R.sup.8,ac) NR.sup.8 C(.dbd.O)R.sup.9,ad) NHC(.dbd.O)NHR.sup.8,ae) NR.sup.8 C(.dbd.O)NHR.sup.9,af) NR.sup.8 C(.dbd.O)NR.sup.9 R10,ag) SO.sub.2 NH.sub.2,ah) SO.sub.2 NHR.sup.8,ai) SO.sub.2 NR.sup.8 R.sup.9,aj) NHSO.sub.2 R.sup.8,ak) NR.sup.8 SO.sub.2 R.sup.9, oral) NHP(.dbd.O)(OC.sub.1 -C.sub.6 -alkyl).sub.2,am) 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) --N.dbd.CHNR.sup.9 --,xiii) ##STR118##xiv) ##STR119##orxv)R.sup.7 is:a) H,b) R.sup.8,c) OR.sup.8,d) NH.sub.2,e) NHR.sup.8, orf) NR.sup.8 R.sup.9 ;Y is O, N or CH;n and m are independently: 0, 1, 2, 3 or 4, such that n and m total no more than 6;Z is C.dbd.O, SO.sub.2, P(.dbd.O)(OR.sup.8), a single bond, or absent when Y is O;R.sup.8, R.sup.9 and R.sup.10 independently are selected from: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.2 -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, 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), 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), 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, and NH(C.dbd.O)(C.sub.1 -C.sub.6 -alkyl),p) NHeterocyclyl, 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, and 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 defined as 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 in o and heterocyclyl is as defined above in p,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; orx is 0, 1 or 2.