Method of imaging amyloid deposits

Claim 3

The method of claim 1 wherein X═Y is C═C or N═N; R 1 and R 2 are each independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, nitro, C 1 -C 6 thioalkoxy, or R 1 and R 2 combined form a benzene, cyclopentane or cyclohexane ring that is fused to the phenyl ring; R 3 is C 1 -C 10 alkyl, C 2 -C 10 alkenyl, arylalkyl, (cycloalkyl)alkyl, arylalkenyl, diarylalkenyl, or --(CH 2 ) m --A--(CH 2 ) n --Q; m is 1 to 5 and n is 0 to 4; A is --O--, --S--, or a single bond; Q is phenyl substituted with R 7 or naphthyl substituted with R 7 ; R 7 is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, hydroxy, halogen, amino, di(C 1 -C 6 alkyl)amino, nitro, C 1 -C 6 thioalkoxy, aryl, aryloxy, --CO-aryl, or arylthio; R 4 and R 5 are each independently hydrogen or C 1 -C 6 alkyl; and R 6 is hydrogen, C 1 -C 6 alkyl, or halogen.

Claim 4

The method of claim 1 wherein X═Y is C═C or N═N; R 1 and R 2 are each independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, nitro, or R 1 and R 2 combined form a (4,5), (5,6), or (6,7) benzene ring that is fused to the phenyl ring; R 3 is C 1 -C 10 alkyl, C 2 -C 10 alkenyl, arylalkyl, arylalkenyl, diarylalkyl, or --(CH 2 ) m --A--(CH 2 ) n --Q; m is 2 to 4 and n is 0 to 3; A is --O--, or a single bond; Q is phenyl substituted with R 7 or naphthyl substituted with R 7 ; R 7 is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, hydroxy, halogen, aryl, aryloxy, or --CO-aryl; R 4 and R 5 are each independently hydrogen, methyl, ethyl, n-propyl or n-butyl; and R 6 is hydrogen or halogen.

Claim 5

The method of claim 1 wherein the compound is (E)-{4-[2-(5-Chlorobenzothiazol-2-yl)vinyl]phenyl}dimethylamine; (E)-{4-[2-Benzothiazol-2-yl)vinyl])phenyl}dimethylamine; (E)-Dimethyl-{4-[2-(5-methylbenzothiazol-2-yl)vinyl]phenyl}amine; (E)-Dimethyl-{4-[2-(6-methylbenzothiazol-2-yl)vinyl]phenyl}amine; (E)-{2-[2-(4-Dimethylaminophenyl)vinyl]benzothiazol-6-yl}dimethylamine; (E)-3-Benzyl-2-[2-(4-dimethylaminophenyl)vinyl]benzothiazol-3-ium bromide; (E)-2-[2-(4-Dimethylaminophenyl)vinyl]-3-ethylbenzothiazol-3-ium iodide; (E)-2-[2-(4-Dimethylaminophenyl)vinyl]-1-methylnaphtho[1,2-d]thiazol-3-ium iodide; (E)-2-[2-(4-Dimethylaminophenyl)vinyl]-3-methylbenzothiazol-3-ium iodide; (E)-2-[2-(4-Dimethylaminophenyl)vinyl]-3-allylbenzothiazol-3-ium bromide; (E)-2-[2-(4-Dimethylaminophenyl)vinyl]-3-butylbenzothiazol-3-ium iodide; (E)-2-[2-(4-Dimethylaminophenyl)vinyl]-3-heptylbenzothiazol-3-ium iodide; (E)-5-Chloro-2-[2-(4-dimethylaminophenyl)vinyl]-3-methylbenzothiazol-3-ium iodide; (E)-2-[2-(4-Dimethylaminophenyl)vinyl]-5-fluoro-3-methylbenzothiazol-3-ium iodide; (E)-2-[2-(4-Dimethylaminophenyl)vinyl]-3-benzyl-5-fluorobenzothiazol-3-ium bromide; (E)-2-[2-(4-Dimethylaminophenyl)vinyl]-3,5-dimethylbenzothiazol-3-ium iodide; (E)-2-[2-(4-Dimethylaminophenyl)vinyl]-3,6-dimethylbenzothiazol-3-ium iodide; (E)-3-Benzyl-2-[2-(4-dimethylaminophenyl)vinyl]-6-methylbenzothiazol-3-ium bromide; (E)-2-[2-(4-Dimethylaminophenyl)vinyl]-6-methoxy-3-methylbenzothiazol-3-ium iodide; (E)-2-[2-(4-Dimethylaminophenyl)vinyl]-3-heptyl-6-methoxybenzothiazol-3-ium iodide; (E)-2-[2-(4-Dimethylaminophenyl)vinyl]-3-methyl-6-nitrobenzothiazol-3-ium toluene-4-sulfonate; (E)-2-[2-(4-Dimethylaminophenyl)vinyl]-1-ethylnaphtho[1,2-d]thiazol-1-ium toluene-4-sulfonate; (E)-2-[2-(4-Dimethylaminophenyl)vinyl]-3-methylnaphtho[2,3-d]thiazol-3-ium iodide; (E)-2-[2-(4-Dimethylaminophenyl)vinyl]-3-methylnaphtho[2,l-d]thiazol-3-ium iodide; (E)-2-[2-(4-Dimethylaminophenyl)vinyl]-3-(4-fluorobenzyl)benzothiazol-3-ium bromide; (E)-3-Biphenyl-4-ylmethyl-2-[2-(4-dimethylaminophenyl)vinyl]benzothiazol-3-ium iodide; (E)-2-[2-(4-Dimethylaminophenyl)vinyl]-3-naphthalen-2-ylmethylbenzothiazol-3-ium bromide; (E)-3-Biphenyl-2-ylmethyl-2-[2-(4-dimethylaminophenyl)vinyl]benzothiazol-3-ium bromide; (E)-3-(3-Benzoylbenzyl)-2-[2-(4-dimethylaminophenyl)vinyl]benzothiazol-3-ium bromide; (E)-2-[2-(4-Dimethylaminophenyl)vinyl]-3-(3-phenoxybenzyl)benzothiazol-3-ium bromide (E)-2-[2-(4-Dimethylaminophenyl)vinyl]-3-(3-phenylpropyl)benzothiazol-3-ium iodide; (E,E)-2-[2-(4-Dimethylaminophenyl)vinyl]-3-(3-phenylallyl)benzothiazol-3-ium bromide; (E)-2-[2-(4-Dimethylaminophenyl)vinyl]-3-(4,4-diphenylbutyl)benzothiazol-3-ium iodide; (E)-3-(3-Benzyloxypropyl)-2-[2-(4-dimethylaminophenyl)vinyl]benzothiazol-3-ium iodide; (E)-2-[2-(4-Dimethylaminophenyl)vinyl]-3-(4-phenoxybutyl)benzothiazol-3-ium iodide; (E)-2-[2-(4-Dimethylaminophenyl)vinyl]-3-(5-phenylpentyl)benzothiazol-3-ium iodide; (E)-2-[2-(4-Dimethylaminophenyl)vinyl]-3-(5-phenoxypentyl)benzothiazol-3-ium iodide; (E)-3-(2-Cyclohexylethyl)-2-[2-(4-dimethylaminophenyl)vinyl]benzothiazol-3-ium iodide; (E)-2-[2-(4-Dimethylaminonaphthalen-1-yl)vinyl]-3-heptylbenzothiazol-3-ium iodide; (E)-2-[2-(4-Dimethylaminophenyl)vinyl]-3-(2-hydroxyethyl)benzothiazol-3-ium bromide; (E)-2-[2-(4-Dimethylaminonaphthalen-1-yl)vinyl]-6-methoxy-3-methylbenzothiazol-3-ium iodide; (E)-2-[2-(4-Dimethylaminonaphthalen-1-yl)vinyl]-1-methylnaphtho[1,2-d]thiazol-1-ium toluene-4-sulfonate; (E)-2-[2-(4-Diethylaminophenyl)vinyl]-3-methylbenzothiazol-3-ium chlordide; (E)-2-[2-(4-Dibethylaminophenyl)vinyl]-3-heptylbenzothiazol-3-ium iodide; (E)-2-[2-(4-Dibutylaminophenyl)vinyl]-3-heptylbenzothiazol-3-ium iodide; (E)-3-Heptyl-2-[2-[(4-pyrrolidin-1-yl)phenyl]vinyl]benzothiazol-3-ium iodide; [4-(Dimethylamino)phenylazo]benzothiazole; 4-(Benzothiazol-2-ylazo)naphthalen-1-ylamine; 2-[[4-(Dimethylamino)phenyl]azo]-6-methoxybenzothiazole; 6-Chloro-2-[[4-(dimethylamino)phenyl]azo]benzothiazole; [4-(6-Methoxybenzothiazol-2-ylazo)naphthalen-1-yl]dimethylamine; Dimethyl[4-(naphtho[1,2-d]thiazol-2-ylazo)naphthalen-1-yl]amine; 2-[[(4-Dimethylamino)phenyl]azo]-6-methoxy-3-methylbenzothiazol-3-ium methylsulfate; and 2-[[(4-Dimethylamino)phenyl]azo]-3-methylbenzothiazolium methylsulfate.

Claim 8

The method of claim 5 wherein X═Y is C═C or N═N; R 1 and R 2 are each independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, nitro, C 1 -C 6 thioalkoxy, or R 1 and R 2 combined form a benzene, cyclopentane, or cyclohexane ring that is fused to the phenyl ring; R 3 is C 1 -C 10 alkyl, C 2 -C 10 alkenyl, arylalkyl, (cycloalkyl)alkyl, arylalkenyl, diarylalkyl, or --(CH 2 ) m --A--(CH 2 ) n --Q; m is 1 to 5 and n is 0 to 4; A is --O--, --S--, or a single bond; Q is phenyl substituted with R 7 or naphthyl substituted with R 7 ; R 7 is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, hydroxy, halogen, amino, di(C 1 -C 6 alkyl)amino, nitro, C 1 -C 6 thioalkoxy, aryl, aryloxy, --CO-aryl, or arylthio; R 4 and R 5 are each independently hydrogen or C 1 -C 6 alkyl; and R 6 is hydrogen, C 1 -C 6 alkyl, or halogen.

Claim 9

The method of claim 5 wherein X═Y is C═C or N═N; R 1 and R 2 are each independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, nitro, or R 1 and R 2 combined form a (4,5), (5,6), or (6,7) benzene ring that is fused to the phenyl ring; R 3 is C 1 -C 10 alkyl, C 2 -C 10 alkenyl, arylalkyl, arylalkenyl, diarylalkyl, or --(CH 2 ) m --A--(CH 2 ) n --Q; m is 2 to 4 and n is 0 to 3; A is --O--, or a single bond; Q is phenyl substituted with R 7 or naphthyl substituted with R 7 ; R 7 is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, hydroxy, halogen, aryl, aryloxy, or --CO-aryl; R 4 and R 5 are each independently hydrogen, methyl, ethyl, n-propyl or n-butyl; and R 6 is hydrogen or halogen.

Claim 10

The method of claim 5 wherein the patient has Alzheimer's disease or Down's syndrome.

Claim 11

The method of claim 5 wherein the linking moiety is a covalent bond, amino acids, peptide, alkyl chain, hydroxy acid, or diacid.

Claim 14

The method of claim 10 wherein X═Y is C═C or N═N; R 1 and R 2 are each independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, nitro, C 1 -C 6 thioalkoxy, or R 1 and R 2 combined form a benzene, cyclopentane, or cyclohexane ring that is fused to the phenyl ring; R 3 is C 1 -C 10 alkyl, C 2 -C 10 alkenyl, arylalkyl, (cycloalkyl)alkyl, arylalkenyl, diarylalkenyl, or --(CH 2 ) m --A--(CH 2 ) n --Q; m is 1 to 5 and n is 0 to 4; A is --O--, --S--, or a single bond; Q is phenyl substituted with R 7 or naphthyl substituted with R 7 ; R 7 is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, hydroxy, halogen, amino, di(C 1 -C 6 alkyl)amino, nitro, C 1 -C 6 thioalkoxy, aryl, aryloxy, --CO-aryl, or arylthio; R 4 and R 5 are each independently hydrogen or C 1 -C 6 alkyl; and R 6 is hydrogen, C 1 -C 6 alkyl, or halogen.

Claim 15

The method of claim 10 wherein X═Y is C═C or N═N; R 1 and R 2 are each independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, nitro, or R 1 and R 2 combined form a (4,5), (5,6), or (6,7) benzene ring that is fused to the phenyl ring; R 3 is C 1 -C 10 alkyl, C 2 -C 10 alkenyl, arylalkyl, arylalkenyl, diarylalkyl, or --(CH 2 ) m --A--(CH 2 ) n --Q; m is 2 to 4 and n is 0 to 3; A is --O--, or a single bond; Q is phenyl substituted with R 7 or naphthyl substituted with R 7 ; R 7 is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, hydroxy, halogen, aryl, aryloxy, or --CO-aryl; R 4 and R 5 are each independently hydrogen, methyl, ethyl, n-propyl or n-butyl; and R 6 is hydrogen or halogen.

Claim 18

The method of claim 13 wherein X═Y is C═C or N═N; R 1 and R 2 are each independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, nitro, C 1 -C 6 thioalkoxy, or R 1 and R 2 combined form a benzene, cyclopentane, or cyclohexane ring that is fused to the phenyl ring; R 3 is C 1 -C 10 alkyl, C 2 -C 10 alkenyl, arylalkyl, (cycloalkyl)alkyl, arylalkenyl, diarylalkenyl, or --(CH 2 ) m --A--(CH 2 ) n --Q; m is 1 to 5 and n is 0 to 4; A is --O--, --S--, or a single bond; Q is phenyl substituted with R 7 or naphthyl substituted with R 7 ; R 7 is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, hydroxy, halogen, amino, di(C 1 -C 6 alkyl)amino, nitro, C 1 -C 6 thioalkoxy, aryl, aryloxy, --CO-aryl, or arylthio; R 4 and R 5 are each independently hydrogen or C 1 -C 6 alkyl; and R 6 is hydrogen, C 1 -C 6 alkyl, or halogen.

Claim 19

The method of claim 13 wherein X═Y is C═C or N═N; R 1 and R 2 are each independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, nitro, or R 1 and R 2 combined form a (4,5), (5,6), or (6,7) benzene ring fused to the phenyl group; R 3 is C 1 -C 10 alkyl, C 2 -C 10 alkenyl, arylalkyl, arylalkenyl, diarylalkyl, or --(CH 2 ) m --A--(CH 2 ) n --Q; m is 2 to 4 and n is 0 to 3; A is --O--, or a single bond; Q is phenyl substituted with R 7 or naphthyl substituted with R 7 ; R 7 is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, hydroxy, halogen, aryl, aryloxy, or --CO-aryl; R 4 and R 5 are each independently hydrogen, methyl, ethyl, n-propyl, or n-butyl; and R 6 is hydrogen or halogen.

Claim 20

A compound of the Formula I or a pharmaceutically acceptable salt, ester, or amide thereof ##STR30## wherein X and Y are each independently C or N and the X═Y double bond has the trans configuration; Z is ##STR31## R 1 and R 2 are each independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, hydroxy, halogen, amino, di(C 1 -C 6 alkyl)amino, mono(C 1 -C 6 alkyl)amino, nitro, C 1 -C 6 thioalkoxy, or R 1 and R 2 combined form a benzene, cyclopentane, or cyclohexane ring that is fused to the phenyl ring; R 3 is a lone pair of electrons, C 1 -C 10 alkyl, C 2 -C 10 alkenyl, arylalkyl, (heteroaryl)alkyl, di(cycloalkyl)alkyl, arylalkenyl, diarylalkyl, or --(CH 2 ) m --A--(CH 2 ) n --Q; m is 1 to 6 and n is 0 to 6; A is --O--, --S--, --NR 4- , C═O, or a single bond; Q is phenyl substituted with R 7 or naphthyl substituted with R 7 ; R 7 is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, hydroxy, halogen, amino, di(C 1 -C 6 alkyl)amino, nitro, C 1 -C 6 thioalkoxy, aryl, heteroaryl, aryloxy, --CO-aryl, or arylthio; R 4 and R 5 are each independently hydrogen, C 1 -C 6 alkyl or --NR 4 R 5 represents a 5-, 6- or 7-membered ring containing nitrogen; and R 6 is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, hydroxy, halogen, amino, di(C 1 -C 6 alkyl)amino, nitro, or C 1 -C 6 thioalkoxy, and one or more atoms in the compound has been replaced with a radioisotope.

Claim 21

A compound of the Formula I or a pharmaceutically acceptable salt, ester, or amide thereof ##STR30## wherein X and Y are each independently C or N and the X═Y double bond has the trans configuration; Z is ##STR31## R 1 and R 2 are each independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, hydroxy, halogen, amino, di(C 1 -C 6 alkyl)amino, mono(C 1 -C 6 alkyl)amino, nitro, C 1 -C 6 thioalkoxy, or R 1 and R 2 combined form a benzene, cyclopentane, or cyclohexane ring that is fused to the phenyl ring; R 3 is a lone pair of electrons, C 1 -C 10 alkyl, C 2 -C 10 alkenyl, arylalkyl, (heteroaryl)alkyl, di(cycloalkyl)alkyl, arylalkenyl, diarylalkyl, or --(CH 2 ) m --A--(CH 2 ) n --Q; m is 1 to 6 and n is 0 to 6; A is --O--, --S--, --NR 4- , C═O, or a single bond; Q is phenyl substituted with R 7 or naphthyl substituted with R 7 ; R 7 is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, hydroxy, halogen, amino, di(C 1 -C 6 alkyl)amino, nitro, C 1 -C 6 thioalkoxy, aryl, heteroaryl, aryloxy, --CO-aryl, or arylthio; R 4 and R 5 are each independently hydrogen, C 1 -C 6 alkyl or --NR 4 R 5 represents a 5-, 6- or 7-membered ring containing nitrogen; and R 6 is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, hydroxy, halogen, amino, di(C 1 -C 6 alkyl)amino, nitro, or C 1 -C 6 thioalkoxy, and one or more atoms in the compound has been replaced with a radioisotope.

Claim 22

The compound of claim 16 wherein the radioisotope is 3 H, 123 I, 128 I, 131 I, 35 S, 11 C, 15 O, or 18 F.