Patent US5672333A successfully refreshed from Google Patents.
US5672333A
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Delta1,6 bicyclo 4,4,0! functional dyes for contrast enhancement in optical imaging
Assignee: Mallinckrodt Inc
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Filing: 1996-05-13
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Granted: 1997-09-30
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Expires: 2016-05-13
Abstract
Abstract This invention provides functional dyes of the general formula: ##STR1## wherein R1, R2, and R 5 may be the same or different and are selected from the group consisting of hydrogen, C 1 -C 10 alkyl, C 1 -C 10 alkoxyl, hydroxyl, C 1 -C 10 hydroxyalkyl, C 1 -C 10 alkoxyalkyl, C 1 -C 10 aryl, carboxyl, C 1 -C 10 carboxylalkyl, halogen, nitro, C 1 -C 10 alkoxycarbonyl, mercapto, C 1 -C 10 mercaptoalkyl, C 1 -C 10 alkylthio, sulfonate, and --(CH 2 ) m --N(R 6 )(R 7 ) wherein R 6 and R 7 are independently hydrogen or C 1 -C 10 alkyl, C 1 -C 10 acyl, and R 6 and R 7 are capable of forming 5, 6, or 7 membered rings which may optionally be substituted with --O--, --NR 8 , or --S--; R 3 and R 4 may be the same or different and are selected from the group consisting of C 1 -C 10 alkyl, C 1 -C 10 hydroxyalkyl, C 1 -C 10 alkoxyalkyl, C 1 -C 10 aryl, C 1 -C 10 carboxylalkyl, C 1 -C 10 alkyl sulfonate, mercapto alkyl and --(CH 2 ) m N(R 6 )(R 7 ); W 1 and W 2 may be the same or different and are selected from the group consisting of --S--, --O--, --Se--, --Te--, --NR 8 and C(R 9 )(R 10 ); and m is about 0-10; R 8 , R 9 , and R 10 are independently hydrogen, C 1 -C 10 alkyl, C 1 -C 10 alkoxy, C 1 -C 10 mercaptoalkyl, hydroxyl, C 1 -C 10 hydroxyalkyl, C 1 -C 10 alkoxyalkyl, C 1 -C 10 aryl, C 1 -C 10 carboxylalkyl, C 1 -C 10 alkoxycarbonyl, C 1 -C 10 alkylthio, and --(CH 2 ) m --N(R 6 )(R 7 ); and A is selected from the group consisting of --(CH 2 )--, --O--, --S--, or --NR 8 . Also provided are methods of using dyes of the invention comprising administering a diagnostically effective amount of the dye to a patient and visualizing the dye.
Inventors
- 👤 Raghavan Rajagopalan
- 👤 Ella Y. Fung
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-07 17:57
CPC Classifications
A; A61; A61K; A61K49/00; A61K49/001; A61K49/0013; A61K49/0017; A61K49/0019; A61K49/0021; A61K49/0032; G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/52
Claims Analysis
Total Claims: 12
Claim 1
Independent Claim
324 words
A diagnostic composition comprising a compound of the formula: ##STR6## wherein R1, R2, and R 5 may be the same or different and are selected from the group consisting of hydrogen, C 1 -C 10 alkyl, C 1 -C 10 alkoxyl, hydroxyl, C 1 -C 10 hydroxyalkyl, C 1 -C 10 alkoxyalkyl, C 1 -C 10 aryl, carboxyl, C 1 -C 10 carboxylalkyl, halogen, nitro, C 1 -C 10 alkoxycarbonyl, mercapto, C 1 -C 10 mercaptoalkyl, C 1 -C 10 alkylthio, sulfonate, and --(CH 2 ) m --N(R 6 )(R 7 ) wherein R 6 and R 7 are independently hydrogen or C 1 -C 10 alkyl, C 1 -C 10 acyl, and R 6 and R 7 are capable of forming 5, 6, or 7 membered rings which may optionally be substituted with --O--, --NR 8 , or --S--; R 3 and R 4 may be the same or different and are selected from the group consisting of C 1 -C 10 alkyl, C 1 -C 10 hydroxyalkyl, C 1 -C 10 alkoxyalkyl, C 1 -C 10 aryl, C 1 -C 10 carboxylalkyl, C 1 -C 10 alkyl sulfonate, mercapto alkyl and --(CH 2 ) m N(R 6 )(R 7 ); W 1 and W 2 may be the same or different and are selected from the group consisting of --S--, --O--, --Se--, --Te--, --NR 8 and C(R 9 )(R 10 ); and m is about 0-10; R 8 , R 9 , and R 10 are independently hydrogen, C 1 -C 10 alkyl, C 1 -C 10 alkoxy, C 1 -C 10 mercaptoalkyl, hydroxyl, C 1 -C 10 hydroxyalkyl, C 1 -C 10 alkoxyalkyl, C 1 -C 10 aryl, C 1 -C 10 carboxylalkyl, C 1 -C 10 alkoxycarbonyl, C 1 -C 10 alkylthio, and --(CH 2 ) m --N(R 6 )(R 7 ); and A is selected from the group consisting of --(CH 2 )--, --O--, --S--, or --NR 8 .
Claim 2
Dependent Claim
324 words
A diagnostic composition comprising a compound of the formula: ##STR6## wherein R1, R2, and R 5 may be the same or different and are selected from the group consisting of hydrogen, C 1 -C 10 alkyl, C 1 -C 10 alkoxyl, hydroxyl, C 1 -C 10 hydroxyalkyl, C 1 -C 10 alkoxyalkyl, C 1 -C 10 aryl, carboxyl, C 1 -C 10 carboxylalkyl, halogen, nitro, C 1 -C 10 alkoxycarbonyl, mercapto, C 1 -C 10 mercaptoalkyl, C 1 -C 10 alkylthio, sulfonate, and --(CH 2 ) m --N(R 6 )(R 7 ) wherein R 6 and R 7 are independently hydrogen or C 1 -C 10 alkyl, C 1 -C 10 acyl, and R 6 and R 7 are capable of forming 5, 6, or 7 membered rings which may optionally be substituted with --O--, --NR 8 , or --S--; R 3 and R 4 may be the same or different and are selected from the group consisting of C 1 -C 10 alkyl, C 1 -C 10 hydroxyalkyl, C 1 -C 10 alkoxyalkyl, C 1 -C 10 aryl, C 1 -C 10 carboxylalkyl, C 1 -C 10 alkyl sulfonate, mercapto alkyl and --(CH 2 ) m N(R 6 )(R 7 ); W 1 and W 2 may be the same or different and are selected from the group consisting of --S--, --O--, --Se--, --Te--, --NR 8 and C(R 9 )(R 10 ); and m is about 0-10; R 8 , R 9 , and R 10 are independently hydrogen, C 1 -C 10 alkyl, C 1 -C 10 alkoxy, C 1 -C 10 mercaptoalkyl, hydroxyl, C 1 -C 10 hydroxyalkyl, C 1 -C 10 alkoxyalkyl, C 1 -C 10 aryl, C 1 -C 10 carboxylalkyl, C 1 -C 10 alkoxycarbonyl, C 1 -C 10 alkylthio, and --(CH 2 ) m --N(R 6 )(R 7 ); and A is selected from the group consisting of --(CH 2 )--, --O--, --S--, or --NR 8 .
Claim 3
Dependent Claim
198 words
The composition of claim 1 wherein R 1 , R 2 and R 5 are independently hydrogen, C 1 -C 10 alkyl, hydroxyl, C 1 -C 10 alkoxyl, carboxyl, halogen, nitro, sulfonate, or --(CH 2 ) m --N(R 6 )(R 7 ) wherein m is about 0-10; R 3 and R 4 are independently C 1 -C 10 alkyl, C 1 -C 10 hydroxyalkyl, C 1 -C 10 carboxyalkyl, or --(CH 2 ) m --N(R 6 )(R 7 ); R 6 and R 7 are independently hydrogen, C 1 -C 10 alkyl, C 1 -C 10 acyl, and hydroxyalkyl; W 1 and W 2 are independently --S-- or C(R 9 )(R 10 ) wherein R 9 and R 10 are independently hydrogen, C 1 -C 10 alkyl, C 1 -C 10 hydroxyalkyl, C 1 -C 10 carboxyalkyl or --(CH 2 ) m --N(R 6 )(R 7 ); m is about 1-10; R 8 is hydrogen, C 1 -C 10 alkyl, C 1 -C 10 hydroxyalkyl, C 1 -C 10 carboxyalkyl or --(CH 2 ) m --N(R 6 )(R 7 ); and A may be --(CH 2 ) m or --(CH 2 ) m N(R 6 )(R 7 ).
Claim 4
Dependent Claim
40 words
The composition of claim 2 wherein R 1 is hydrogen; R 2 is hydrogen; R 3 is methyl; R 4 is methyl; R 5 is methoxycarbonyl; W 1 is --S--; W 2 is --S--; and A is --CH 2 --.
Claim 5
Dependent Claim
38 words
The composition of claim 2 wherein R 1 is hydrogen; R 2 is hydrogen; R 3 is methyl; R 4 is methyl; R 5 is methoxycarbonyl; W 1 is --S--; W 2 is --S--; and A is --O--.
Claim 6
Dependent Claim
41 words
The composition of claim 2 wherein R 1 is hydrogen; R 2 is hydrogen; R 3 is methyl; R 4 is methyl; W 1 is --S--; W 2 is --S--; and A is --NR 8 , wherein --R 8 is carboxymethyl.
Claim 7
Independent Claim
335 words
A method of imaging a patient comprising the administration of a diagnostically effective amount of a compound of the formula: ##STR7## wherein R1, R2, and R 5 may be the same or different and are selected from the group consisting of hydrogen, C 1 -C 10 alkyl, C 1 -C 10 alkoxyl, hydroxyl, C 1 -C 10 hydroxyalkyl, C 1 -C 10 alkoxyalkyl, C 1 -C 10 aryl, carboxyl, C 1 -C 10 carboxylalkyl, halogen, nitro, C 1 -C 10 alkoxycarbonyl, mercapto, C 1 -C 10 mercaptoalkyl, C 1 -C 10 alkylthio, sulfonate, and --(CH 2 ) m --N(R 6 )(R 7 ) wherein R 6 and R 7 are independently hydrogen or C 1 -C 10 alkyl, C 1 -C 10 acyl, and R 6 and R 7 are capable of forming 5, 6, or 7 membered rings which may optionally be substituted with --O--, --NR 8 , or --S--; R 3 and R 4 may be the same or different and are selected from the group consisting of C 1 -C 10 alkyl, C 1 -C 10 hydroxyalkyl, C 1 -C 10 alkoxyalkyl, C 1 -C 10 aryl, C 1 -C 10 carboxylalkyl, C 1 -C 10 alkyl sulfonate, mercapto alkyl and --(CH 2 ) m N(R 6 )(R 7 ); W 1 and W 2 may be the same or different and are selected from the group consisting of --S--, --O--, --Se--, --Te--, --NR 8 and C(R 9 )(R 10 ); and m is about 0-10; R 8 , R 9 , and R 10 are independently hydrogen, C 1 -C 10 alkyl, C 1 -C 10 alkoxy, C 1 -C 10 mercaptoalkyl, hydroxyl, C 1 -C 10 hydroxyalkyl, C 1 -C 10 alkoxyalkyl, C 1 -C 10 aryl, C 1 -C 10 carboxylalkyl, C 1 -C 10 alkoxycarbonyl, C 1 -C 10 alkylthio, and --(CH 2 ) m --N(R 6 )(R 7 ); and A is selected from the group consisting of --(CH 2 )--, --O--, --S--, or --NR 8 .
Claim 8
Independent Claim
335 words
A method of imaging a patient comprising the administration of a diagnostically effective amount of a compound of the formula: ##STR7## wherein R1, R2, and R 5 may be the same or different and are selected from the group consisting of hydrogen, C 1 -C 10 alkyl, C 1 -C 10 alkoxyl, hydroxyl, C 1 -C 10 hydroxyalkyl, C 1 -C 10 alkoxyalkyl, C 1 -C 10 aryl, carboxyl, C 1 -C 10 carboxylalkyl, halogen, nitro, C 1 -C 10 alkoxycarbonyl, mercapto, C 1 -C 10 mercaptoalkyl, C 1 -C 10 alkylthio, sulfonate, and --(CH 2 ) m --N(R 6 )(R 7 ) wherein R 6 and R 7 are independently hydrogen or C 1 -C 10 alkyl, C 1 -C 10 acyl, and R 6 and R 7 are capable of forming 5, 6, or 7 membered rings which may optionally be substituted with --O--, --NR 8 , or --S--; R 3 and R 4 may be the same or different and are selected from the group consisting of C 1 -C 10 alkyl, C 1 -C 10 hydroxyalkyl, C 1 -C 10 alkoxyalkyl, C 1 -C 10 aryl, C 1 -C 10 carboxylalkyl, C 1 -C 10 alkyl sulfonate, mercapto alkyl and --(CH 2 ) m N(R 6 )(R 7 ); W 1 and W 2 may be the same or different and are selected from the group consisting of --S--, --O--, --Se--, --Te--, --NR 8 and C(R 9 )(R 10 ); and m is about 0-10; R 8 , R 9 , and R 10 are independently hydrogen, C 1 -C 10 alkyl, C 1 -C 10 alkoxy, C 1 -C 10 mercaptoalkyl, hydroxyl, C 1 -C 10 hydroxyalkyl, C 1 -C 10 alkoxyalkyl, C 1 -C 10 aryl, C 1 -C 10 carboxylalkyl, C 1 -C 10 alkoxycarbonyl, C 1 -C 10 alkylthio, and --(CH 2 ) m --N(R 6 )(R 7 ); and A is selected from the group consisting of --(CH 2 )--, --O--, --S--, or --NR 8 .
Claim 9
Dependent Claim
206 words
The method of claim 6 wherein R 1 , R 2 and R 5 and are independently hydrogen, C 1 -C 10 alkyl, hydroxyl, C 1 -C 10 alkoxyl, carboxyl, halogen, nitro, sulfonate, or --(CH 2 ) m --N(R 6 )(R 7 ) wherein m is about 0-10; R 3 and R 4 are independently C 1 -C 10 alkyl, C 1 -C 10 hydroxyalkyl, C 1 -C 10 carboxyalkyl or --(CH 2 ) m --N(R 6 )(R 7 ); R 6 and R 7 are independently hydrogen, C 1 -C 10 alkyl, C 1 -C 10 acyl, and hydroxyalkyl; X is --O--, --NR 8 or --S--; W 1 and W 2 are independently --S-- or --C(R 9 )(R 10 ) wherein R 9 and R 10 are independently hydrogen, C 1 -C 10 alkyl, C 1 -C 10 hydroxyalkyl, C 1 -C 10 carboxyalkyl, or --(CH 2 ) m --N(R 6 )(R 7 ); m is about 1-10; R 8 is hydrogen, C 1 -C 10 alkyl, C 1 -C 10 hydroxyalkyl, C 1 -C 10 carboxyalkyl, or --(CH 2 ) m --N(R 6 )(R 7 ); and A may be --(CH 2 ) m or --(CH 2 ) m N(R 6 )(R 7 ).
Claim 10
Dependent Claim
40 words
The method of claim 7 wherein R 1 is hydrogen; R 2 is hydrogen; R 3 is methyl; R 4 is methyl; R 5 is methoxycarbonyl; W 1 is --S--; W 2 is --S--; and A is --CH 2 --.
Claim 11
Dependent Claim
38 words
The method of claim 7 wherein R 1 is hydrogen; R 2 is hydrogen; R 3 is methyl; R 4 is methyl; R 5 is methoxycarbonyl; W 1 is --S--; W 2 is --S--; and A is --O--.
Claim 12
Dependent Claim
41 words
The method of claim 7 wherein R 1 is hydrogen; R 2 is hydrogen; R 3 is methyl; R 4 is methyl; W 1 is --S--; W 2 is --S--; and A is --NR 8 , wherein R 8 is carboxymethyl.
References Cited (Backward Citations)
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