Patent ID: 6168776
Filing Date: 2001-01-02
Classification: A61K,C07B,C07C,C07D,C07F,C09B,G01N

Abstract:
An amyloid binding compound of Formula I or a water soluble, non-toxic salt thereof: ##STR19## X is C(R"").sub.2, wherein each R"" independently is H, F, Cl, Br, I, a lower alkyl group, (CH.sub.2).sub.n OR' wherein n=1, 2, or 3, CF.sub.3, CH.sub.2 --CH.sub.2 F, O--CH.sub.2 --CH.sub.2 F, CH.sub.2 --CH.sub.2 --CH.sub.2 F, O--CH.sub.2 --CH.sub.2 --CH.sub.2 F, CN, (C.dbd.O)--R', N(R').sub.2, NO.sub.2, (C.dbd.O)N(R').sub.2, O(CO)R', OR', SR', COOR', R.sub.ph, CR'.dbd.CR'--R.sub.ph, CR.sub.2 '--CR.sub.2 '--R.sub.ph, wherein R.sub.ph represents an unsubstituted or substituted phenyl group with the phenyl substituents being chosen from any of the non-phenyl substituents defined for R"", a tetrazole or oxadiazole of the form: ##STR20## wherein R' is H or a lower alkyl group, or X is CR'.dbd.CR', N.dbd.N, C.dbd.O, O, NR', where R' represents H or a lower alkyl group, S, or SO.sub.2 ; each R.sub.1 and R.sub.2 independently is selected from the group consisting of H, F, Cl, Br, I, a lower alkyl group, (CH.sub.2).sub.n OR', wherein n=1, 2, or 3, CF.sub.3, CH.sub.2 --CH.sub.2 F, O--CH.sub.2 --CH.sub.2 F, CH.sub.2 --CH.sub.2 --CH.sub.2 F, O--CH.sub.2 --CH.sub.2 --CH.sub.2 F, CN, (C.dbd.O)--R', N(R').sub.2, NO.sub.2, (C.dbd.O)N(R').sub.2, O(CO)R', OR', SR', COOR', tri-alkyl tin, R.sub.ph, CR'.dbd.CR'--R.sub.ph, CR.sub.2 '--CR.sub.2 '--R.sub.ph, wherein R.sub.ph represents an unsubstituted or substituted phenyl group with the phenyl substituents being chosen from any of the non-phenyl substituents defined from R.sub.1 and R.sub.2, tetrazole and oxadiazole of the form: ##STR21## wherein R' is H or a lower alykl group, or a triazene of the form: ##STR22## each Q is independently selected from one or the following structures: IA, IB, IC, ID, IE, IF, and IG, wherein IA has the following structure: ##STR23## wherein: each of R.sub.3, R.sub.4, R.sub.5, R.sub.6, or R.sub.7 independently is defined the same as R.sub.1 above, provided that: i) if the compound of Formula I is: ##STR24## then at least one of R.sub.1 -R.sub.4 or R.sub.6 -R.sub.7 is independently selected from the group consisting of F, Cl, Br, I, a lower alkyl group, (CH.sub.2).sub.n OR', wherein n=1, 2, or 3, CF.sub.3, CH.sub.2 --CH.sub.2 F, O--CH.sub.2 --CH.sub.2 F, CH.sub.2 --CH.sub.2 --CH.sub.2 F, O--CH.sub.2 --CH.sub.2 --CH.sub.2 F, CN, (C.dbd.O)--R', N(R').sub.2, NO.sub.2, (C.dbd.O)N(R').sub.2, O(CO)R', OR', SR', COOR', tri-alkyl tin, R.sub.ph , CR'.dbd.CR'--R.sub.ph, CR.sub.2 '--CR.sub.2 '--R.sub.ph, wherein R' is H or a lower alkyl group and wherein R.sub.ph represents an unsubstituted or substituted phenyl group with the phenyl substituents being chosen from any of the non-phenyl substituents defined from R.sub.1 and R.sub.2 above, tetrazole and oxadiazole of the form: ##STR25## or a triazene of the form: ##STR26## ii) if the compound of Formula I is: ##STR27## wherein R.sub.2 is a lower alkyl group, OR' (wherein R' is a lower alkyl group) or Cl, then at least one other of R.sub.1 -R.sub.7 is independently selected from the group consisting of F, Br, I, (CH.sub.2).sub.n OR', wherein n=1, 2, or 3, CF.sub.3, CH.sub.2 --CH.sub.2 F, O--CH.sub.2 --CH.sub.2 F, CH.sub.2 --CH.sub.2 --CH.sub.2 F, O--CH.sub.2 --CH.sub.2 --CH.sub.2 F, (C.dbd.O) --R', N(R').sub.2, (C.dbd.O)N(R').sub.2, O(CO)R', OR', SR', COOR', tri-alkyl tin, CR'.dbd.CR'--R.sub.ph, CR.sub.2, CR.sub.2 '--R.sub.ph, wherein R' is H or a lower alkyl group, unless indicated and whrein R.sub.ph represents an unsubstitutd or substituted phenyl group with the phenyl substituents being chosen from any of the non-phenyl substituents defined from R.sub.1 and R.sub.2 above, tetrazole and oxadiazole of the form: ##STR28## wherein R' is H or a lower alkyl group, or a traizene of the form: ##STR29## iii) if the compound of Formula I is ##STR30## wherein R.sub.3 or R.sub.7 is a lower alkyl group, CN, F, Cl, or Br, then at least one other of R.sub.1 -R.sub.7 is independendtly selected from the group consisting of F, Br, I, (CH.sub.2).sub.n OR', wherein n=1, 2, or 3, CF.sub.3, CH.sub.2 --CH.sub.2 F, O--CH.sub.2 --CH.sub.2 F, CH.sub.2 --CH.sub.2 --CH.sub.2 F, O--CH.sub.2 --CH.sub.2 --CH.sub.2 F, CN, (C.dbd.O)R', N(R').sub.2, NO.sub.2, (C.dbd.O)N(R').sub.2, O(CO)R', OR', SR', COOR', tri-alkyl tin, R.sub.ph, CR'.dbd.CR'--R.sub.ph, CR.sub.2 '--CR.sub.2 '--R.sub.ph, wherein R' is H or a lower alkyl group and wherein R.sub.ph represents an unsubstituted or substituted phenyl group with the phenyl substituents being chosen from any of the non-phenyl substituents defined from R.sub.1 and R.sub.2 above, tetrazole and oxadiazole of the form: ##STR31## wherein R' is H or a lower alkyl group, or a triazene of the form: ##STR32## iv) if the compound of Formula I is ##STR33## wherein R.sub.5 is H, a lower alkyl group, CN, COOR', (C.dbd.O)N(R').sub.2, F, Cl, or Br, then at least one other of R.sub.1 -R.sub.7 is independently selected from the group consisting of I, (CH.sub.2).sub.n OR', wherein n=1, 2, or 3, CF.sub.3, CH.sub.2 --CH.sub.2 F, O--CH.sub.2 --CH.sub.2 F, CH.sub.2 CH.sub.2 --CH.sub.2 F, O--CH.sub.2 --CH.sub.2 --CH.sub.2 F, (C.dbd.O)--R', N(R').sub.2, NO.sub.2, O(CO)R', OR', SR', tri-alkyl tin, R.sub.ph, CR'.dbd.CR'--R.sub.ph, CR.sub.2 '--CR.sub.2 '--R.sub.ph, wherein R' is H or a lower alkyl group and wherein R.sub.ph represents an unsubstituted or substituted phenyl group with the phenyl substituents being chosen from any of the non-pheny substituents defined from R.sub.1 and R.sub.2 above, tetrazole and oxadiazole of the form: ##STR34## wherin R' is H or a lower alkyl group, or a triazene of the form: ##STR35## v) if the compound of Formula I is ##STR36## wherein R.sub.5 is N(R').sub.2 (wherein R' is a lower alkyl group) and R.sub.1, R.sub.2, R.sub.4, and R.sub.6 are all H, then R.sub.3 and R.sub.7 are independently selected from the group consisting of F, Cl, Br, I, (CH.sub.2).sub.n OR', wherein n=1, 2, or 3, CF.sub.3, CH.sub.2 --CH.sub.2 F, O--CH.sub.2 --CH.sub.2 F, CH.sub.2 --CH.sub.2 CH.sub.2 F, O--CH.sub.2 --CH.sub.2 --CH.sub.2 F, CN, (C.dbd.O)--R', N(R').sub.2, NO.sub.2, (C.dbd.O)N(R').sub.2, O(CO)R', OR' (wherein R' is H), SR', COOR' (wherein R' is H), tri-alkyl tin, R.sub.ph, CR'.dbd.CR'--R.sub.ph, CR'.dbd.CR'--R.sub.ph, CR.sub.2 '--CR.sub.2 '--R.sub.ph, wherein R' is H or a lower alkyl group, unless indicated, and wherein R.sub.ph represents an unsubstituted or substituted phenyl group with the phenyl substituents being chosen from any of the non-phenyl substituents defined from R.sub.1 and R.sub.2 above, tetrazole and oxadiazole of the form: ##STR37## or a triazene of the form: ##STR38## vi) if the compound of Formula I is: ##STR39## wherein R.sub.5 is H, (CH.sub.2).sub.n OR' (wherein n is 1 and R' is H) or COOR' (wherein R' is a lower alkyl group), then at least one of R.sub.1 -R.sub.4, R.sub.6 or R.sub.7 is independently selected from the group consisting of F, Cl, Br, I, a lower alkyl group, (CH.sub.2).sub.n OR', wherein n=1, 2, or 3, CF.sub.3, CH.sub.2 --CH.sub.2 F, O--CH.sub.2 --CH.sub.2 F, CH.sub.2 --CH.sub.2 CH.sub.2 F, O--CH.sub.2 --CH.sub.2 --CH.sub.2 F, CN, (C.dbd.O)--R', N(R').sub.2, NO.sub.2, (C.dbd.O)N(R').sub.2, O(CO)R', OR', SR', COOR' (wherein R' is H), tri-alkyl tin, R.sub.ph, CR'.dbd.CR'--R.sub.ph, CR.sub.2 '--CR.sub.2 '--R.sub.ph, wherein R' is H or a lower alkyl group, unless indicated, and wherein R.sub.ph represents an unsubstituted or substituted phenyl group with phenyl substituents being chosen from any of the non-phenyl substituents defined from R.sub.1 and R.sub.2 above, tetrazole and oxadiazole of the form: ##STR40## or a triazene of the form: ##STR41## vii) if the compound of Formula I is: ##STR42## wherein at least one of R.sub.3, R.sub.5 or R.sub.7 is a H, CN, COOR', or (C.dbd.O)N(R').sub.2, then at least one other of R.sub.1 -R.sub.7 is independently selected from the group consisting of F, Cl, Br, I, (CH.sub.2).sub.n OR', wherein n=1, 2, or 3, CF.sub.3, CH.sub.2 --CH.sub.2 F, O--CH.sub.2 --CH.sub.2 F, CH.sub.2 --CH.sub.2 --CH.sub.2 F, O--CH.sub.2 --CH.sub.2 --CH.sub.2 F, (C.dbd.O)R', N(R').sub.2, NO.sub.2, (C.dbd.O)N(R').sub.2, O(CO)R', OR', SR', tri-alkyl tin, R.sub.ph, CR'.dbd.CR'--R.sub.ph, CR.sub.2 '--CR.sub.2 '--R.sub.ph, wherein R' is H or a lower alkyl group and wherein R.sub.ph represents an unsubstituted or substituted phenyl group with the phenyl substituents being chosen from any of the non-phenyl substituents defined from R.sub.1 and R.sub.2 above, tetrazole and oxadiazole of the form: ##STR43## wherein R' is H or a lower alkyl group, or a triazene of the form: ##STR44## viii) if the compound of Formula I is: ##STR45## wherein R.sub.5 is COOR' (wherein R' is H or lower alkyl), then at least one of R.sub.1 -R.sub.4, R.sub.6 or R.sub.7 is independently selected from the group consisting of F, Cl, Br, I, a lower alkyl group, (CH.sub.2).sub.n OR', wherein n=1, 2, or 3, CF.sub.3, CH.sub.2 --CH.sub.2 F, O--CH.sub.2 --CH.sub.2 F, CH.sub.2 --CH.sub.2 CH.sub.2 F, O--CH.sub.2 --CH.sub.2 --CH.sub.2 F, CN, (C.dbd.O)--R', N(R').sub.2, NO.sub.2, (C.dbd.O)N(R').sub.2, O(CO)R', OR', SR', COOR', tri-alkyl tin, R.sub.ph, CR'.dbd.CR'--R.sub.ph, CR'.dbd.CR'--R.sub.ph, CR.sub.2 '--CR.sub.2 '--R.sub.ph, wherein R' H or a lower alkyl group, unless indicated, and wherein R.sub.ph represents an unsubstituted or substituted phenyl group with phenyl substituents being chosen from any of the non-penyl substituents defined from R.sub.1 and R.sub.2 above, tetrazole and oxadiazole of the form: ##STR46## or a triazene of the form: ##STR47## ix) if the compound of Formula I is: ##STR48## wherein both R.sub.5 are N(R').sub.2 (wherein R' is a lower alkyl group), then at least one of R.sub.1 -R.sub.4, R.sub.6 or R.sub.7 is independently selected from the group consisting of F, Cl, Br, I, a lower alkyl group, (CH.sub.2).sub.n OR', wherein n=1, 2, or 3, CF.sub.3, CH.sub.2 --CH.sub.2 F, O--CH.sub.2 --CH.sub.2 F, CH.sub.2 --CH.sub.2 --CH.sub.2 F, O--CH.sub.2 --CH.sub.2 --CH.sub.2 F, CN, (C.dbd.O)--R', N(R').sub.2, NO.sub.2, (C.dbd.O)N(R').sub.2, O(CO)R', OR', SR', COOR', tri-alkyl tin, R.sub.ph, CR'.dbd.CR'--R.sub.ph, CR.sub.2 '--CR.sub.2 '--R.sub.ph, wherein R' is H or a lower alkyl group, unless indicated, and wherein R.sub.ph represents an unsubstituted or substituted phenyl group with the phenyl substituents being chosen from any of the non-phenyl substituents defined from R.sub.1 and R.sub.2 above, tetrazole and oxadiazole of the form: ##STR49## or a triazene of the form: ##STR50## x) if the compound of Formula I is: ##STR51## wherein at least one of R.sub.3, R.sub.5 or R.sub.7 is a lower alkyl group, Cl, or OR' (wherein R' is a lower alkyl group), then at least one other of R.sub.2 -R.sub.7 is independently selected from the other of R.sub.1 -R.sub.7 is independently selected from the group consisting of F, Cl, Br, I, (CH.sub.2).sub.n OR', wherein n=1, 2, or 3, CF.sub.3, CH.sub.2 --CH.sub.2 F, O--CH.sub.2 --CH.sub.2 F, CH.sub.2 --CH.sub.2 --CH.sub.2 F, O--CH.sub.2 --CH.sub.2 --CH.sub.2 F, CN, C(.dbd.O)--R', N(R').sub.2, NO.sub.2, O(CO)R', OR' (wherein R' is H), SR', a tri-alkyl tin, R.sub.ph, CR'.dbd.CR'R.sub.ph, CR.sub.2 '--CR.sub.2 'R.sub.ph, wherein R' is H or a lower alkyl group, unless indicated, and wherein R.sub.ph represents an unsubstituted or substituted phenyl group with the phenyl substituents being chosen from any of the non-phenyl substituents defined from R.sub.1 and R.sub.2 above, tetrazole and oxadiazole of the form: ##STR52## wherein R' is H or a lower alkyl group, or a triazene of the form: ##STR53## xi) if the compound of Formula I is ##STR54## wherein exactly two to R.sub.2 are OR' (wherein R' is a lower alkyl group), then R.sub.5 is selected from the group consisting of H, F, Cl, Br, I, or a lower alkyl group, (CH.sub.2).sub.n OR', wherein n=1, 2, or 3, CF.sub.3, CH.sub.2 --CH.sub.2 F, O--CH.sub.2 --CH.sub.2 F, CH.sub.2 --CH.sub.2 --CH.sub.2 F, O--CH.sub.2 --CH.sub.2 --CH.sub.2 F, CN, (C.dbd.O)--R', N(R').sub.2, NO.sub.2, (C.dbd.O)N(R').sub.2, O(CO)R', OR', SR', tri-alkyl tin, R.sub.ph, CR'.dbd.CR'--R.sub.ph, CR.sub.2 '--CR.sub.2 '--R.sub.ph, wherein R' is H or a lower alkyl group, unless indicated, and wherein R.sub.ph represents an unsubstituted or substituted phenyl group with the phenyl substituents being chosen from any of the non-phenyl substituents defined from R.sub.1 and R.sub.2 above, tetrazole and oxadiazole of the form: ##STR55## or a triazene of the form: ##STR56## xii) if the compound of Formula I is: ##STR57## wherein R.sub.5 is N(R').sub.2 (wherein R' is a lower alkyl group) and R.sub.2, R.sub.4, R.sub.6, and R.sub.7 are all H, then R.sub.3 and R.sub.7 are independently selected from the group consisting of F, Cl, Br, I, (CH.sub.2).sub.n OR', wherein n=1, 2, or 3, CF.sub.3, CH.sub.2 --CH.sub.2 F, O--CH.sub.2 --CH.sub.2 F, CH.sub.2 --CH.sub.2 CH.sub.2 F, O--CH.sub.2 --CH.sub.2 --CH.sub.2 F, CN, (C.dbd.O)--R', N(R').sub.2, NO.sub.2, (C.dbd.O)N(R').sub.2, O(CO)R', OR' SR', COOR', tri-alkyl tin, R.sub.ph, R.sub.ph, CR'.dbd.CR'--R.sub.ph, CR'.dbd.CR'--R.sub.ph, CR.sub.2 '--CR.sub.2 '--R.sub.ph, wherein R' is H or a lower alkyl group, unless indicated, and wherein R.sub.ph represents an unsubstituted or substituted phenyl group with the phenyl substituents being chosen from any of the non-phenyl substituents defined from R.sub.1 and R.sub.2 above, tetrazole and oxadiazole of the form: ##STR58## or a triazene of the form: ##STR59## IB has the following structure: ##STR60## wherein: each of R.sub.10, R.sub.11, R.sub.12, R.sub.13, R.sub.14, R.sub.15, or R.sub.16 independently is defined the same as R.sub.1 above, provided that: xiii) if the compound of Formula I is: ##STR61## wherein exactly two to R.sub.2 are a lower alkyl group, then at least one of R.sub.1, R.sub.10, R.sub.11, R.sub.12, R.sub.13, R.sub.14, R.sub.15 or R.sub.16 is independently selected from the group consisting of F, Cl, Br, I, a lower alkyl group, (CH.sub.2).sub.n OR', wherein n=1, 2, or 3, CF.sub.3, CH.sub.2 --CH.sub.2 F, O--CH.sub.2 --CH.sub.2 F, CH.sub.2 --CH.sub.2 --CH.sub.2 F, O--CH.sub.2 --CH.sub.2 --CH.sub.2 F, CN, (C.dbd.O)--R', N(R').sub.2, NO.sub.2, (C.dbd.O)N(R').sub.2, O(CO)R', OR', SR', COOR', tri-alkyl tin, R.sub.ph, CR'.dbd.CR'R.sub.ph, CR.sub.2 '--CR.sub.2 '--R.sub.ph, wherein R' is H or a lower alkyl group and wherein R.sub.ph represents an unsubstituted or substituted phenyl group with the phenyl substituents being chosen from any of the non-phenyl substituents defined from R.sub.1 and R.sub.2 above, tetrazole and oxadiazole of the form: ##STR62## or a triazene of the form: ##STR63## xiv) if the compound of Formula I is: ##STR64## wherein exactly two to R.sub.2 are a lower alkyl group, then at least one of R.sub.1, R.sub.10, R.sub.11, R.sub.12, R.sub.13, R.sub.14, R.sub.15 or R.sub.16 is independently selected from the group consisting of F, Cl, Br, I, a lower alkyl group, (CH.sub.2).sub.n OR', wherein n=1, 2, or 3, CF.sub.3, CH.sub.2 --CH.sub.2 F, O--CH.sub.2 --CH.sub.2 F, CH.sub.2 --CH.sub.2 --CH.sub.2 F, O--CH.sub.2 --CH.sub.2 --CH.sub.2 F, CN, (C.dbd.O)--R', N(R').sub.2, NO.sub.2, (C.dbd.O)N(R').sub.2, O(CO)R', OR', SR', COOR', tri-alkyl tin, R.sub.ph, CR'.dbd.CR'R.sub.ph, CR.sub.2 '--CR.sub.2 '--R.sub.ph, wherein R' is H or a lower alkyl group and wherein R.sub.ph represents an unsubstituted or substituted phenyl group with the phenyl substituents being chosen from any of the non-phenyl substituents defined from R.sub.1 and R.sub.2 above, tetrazole and oxadiazole of the form: ##STR65## or a triazene of the form: ##STR66## IC has the following structure: ##STR67## wherein: each of R.sub.17, R.sub.18, R.sub.19, R.sub.20, or R.sub.21 independently is defined the same as R.sub.1 above; ID has the following structure: ##STR68## wherein each of R.sub.22, R.sub.23, or R.sub.24 independently is defined the same as R.sub.1 above ##STR69## represents a heterocyclic ring of one of the six following formulas: ##STR70## IE has the following structure: ##STR71## wherein: each of R.sub.25, R.sub.26, or R.sub.27 independently is defined the same as R.sub.1 above ##STR72## represents a heterocyclic ring of one of the six following formulas: ##STR73## IF has the following structure: ##STR74## wherein: exactly one of R.sub.28, R.sub.29, R.sub.30, R.sub.31, or R.sub.32 is the ##STR75## link defined for Formula I above and each other R.sub.28, R.sub.29, R.sub.30, R.sub.31, or R.sub.32 independently is defined the same as R.sub.1 above; IG has the following structure: ##STR76## wherein: exactly one of R.sub.33, R.sub.34, R.sub.35, R.sub.36, R.sub.37, R.sub.38 or R.sub.39 is the ##STR77## link defined for Formula I above and each other R.sub.33, R.sub.34, R.sub.35, R.sub.36, R.sub.37, R.sub.38 or R.sub.39 independently is defined the same as R.sub.1 above.