US6162931A — Fluorinated xanthene derivatives

Claim 1

Independent Claim 926 words

A compound having the formula ##STR10## or the formula ##STR11## wherein R 1 and R 6 are independently H, F, Cl, Br, I, C 1 -C 18 alkyl or C 1 -C 18 alkoxy; R 2 , R 3 , R 4 and R 5 are independently H, F, Cl, Br, I, CN; or C 1 -C 18 alkyl, C 1 -C 18 alkoxy or C 1 -C 18 alkylthio, where each alkyl, alkoxy or alkylthio is optionally further substituted by F, Cl, Br, I, sulfonic acid, salt of sulfonic acid, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 where R 18 is a C 1 -C 4 alkyl; or amino, alkylamino, dialkylamino, or alkoxy, the alkyl portions of which independently have 1-6 carbons; or one or both of R 3 and R 4 are --CH 2 N(CH 2 COOR 17 ) 2 , where R 17 is H, a biologically compatible counterion, a linear or branched alkyl having 1-6 carbons, or --CH 2 --O--(C═O)--R 18 ; A is OR 7 or NR 8 R 9 , where each R 7 is independently H, C 1 -C 18 alkyl, a C 1 -C 18 acyl wherein each alkyl group independently has 1-6 carbons and is optionally substituted by amino, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or a trialkylsilyl wherein each alkyl group independently has 1-6 carbons; R 8 and R 9 are independently H, C 1 -C 6 alkyl, C 1 -C 6 carboxyalkyl, C 1 -C 6 sulfoalkyl, a salt of C 1 -C 6 carboxyalkyl, a salt of C 1 -C 6 sulfoalkyl, or C 1 -C 18 acyl wherein the alkyl portions are optionally substituted by amino, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or R 8 in combination with R 2 , or R 9 in combination with R 3 , or both, form a saturated 5- or 6-membered ring that is optionally substituted by one or more methyls; or R 8 in combination with R 9 forms a saturated 5- or 6-membered heterocycle that is a piperidine, a morpholine, a pyrrolidine or a piperazine, each of which is optionally substituted by methyl, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, or a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; R 10 is F, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, or a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or R 10 is C 1 -C 18 alkyl, alkenyl or alkynyl that is optionally substituted one or more times by F, Cl, Br, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , sulfonic acid, salt of sulfonic acid, amino, alkylamino, or dialkylamino, the alkyl groups of which have 1-6 carbons; or R 10 has the formula ##STR12## where R 12 , R 13 , R 14 , R 15 and R 16 are independently H, F, Cl, Br, I; or sulfonic acid, salt of sulfonic acid, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , CN, nitro, hydroxy, azido, amino, hydrazino; or C 1 -C 18 alkyl, C 1 -C 18 alkoxy, C 1 -C 18 alkylthio, C 1 -C 18 alkylamino, C 1 -C 18 alkylester, C 1 -C 18 alkylamido or C 1 -C 18 arylamido, the alkyl or aryl portions of which are optionally substituted one or more times by F, Cl, Br, I, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , sulfonic acid, salt of sulfonic acid, amino, alkylamino, dialkylamino or alkoxy, the alkyl portions of each having 1-6 carbons; or one pair of adjacent substituents R 13 and R 14 , R 14 and R 15 or R 15 and R 16 , when taken in combination, form a fused 6-membered aromatic ring that is optionally further substituted by carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; and R 11 is H, hydroxy, CN or a C 1 -C 6 alkoxy; or R 10 in combination with R 11 forms a 5-membered spirolactone ring or a 5-membered spirosultone ring; or R 11 in combination with R 12 forms a 5- or 6-membered spirolactone ring or a 5- or 6-membered spirosultone ring that is optionally and independently substituted by H, F or CH 3 ; or R 10 when taken in combination with R 11 is a carbonyl oxygen; provided that at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 10 is F, or at least three of R 12 , R 13 , R 14 , R 15 and R 16 are F.

Claim 2

Dependent Claim 926 words

A compound having the formula ##STR10## or the formula ##STR11## wherein R 1 and R 6 are independently H, F, Cl, Br, I, C 1 -C 18 alkyl or C 1 -C 18 alkoxy; R 2 , R 3 , R 4 and R 5 are independently H, F, Cl, Br, I, CN; or C 1 -C 18 alkyl, C 1 -C 18 alkoxy or C 1 -C 18 alkylthio, where each alkyl, alkoxy or alkylthio is optionally further substituted by F, Cl, Br, I, sulfonic acid, salt of sulfonic acid, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 where R 18 is a C 1 -C 4 alkyl; or amino, alkylamino, dialkylamino, or alkoxy, the alkyl portions of which independently have 1-6 carbons; or one or both of R 3 and R 4 are --CH 2 N(CH 2 COOR 17 ) 2 , where R 17 is H, a biologically compatible counterion, a linear or branched alkyl having 1-6 carbons, or --CH 2 --O--(C═O)--R 18 ; A is OR 7 or NR 8 R 9 , where each R 7 is independently H, C 1 -C 18 alkyl, a C 1 -C 18 acyl wherein each alkyl group independently has 1-6 carbons and is optionally substituted by amino, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or a trialkylsilyl wherein each alkyl group independently has 1-6 carbons; R 8 and R 9 are independently H, C 1 -C 6 alkyl, C 1 -C 6 carboxyalkyl, C 1 -C 6 sulfoalkyl, a salt of C 1 -C 6 carboxyalkyl, a salt of C 1 -C 6 sulfoalkyl, or C 1 -C 18 acyl wherein the alkyl portions are optionally substituted by amino, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or R 8 in combination with R 2 , or R 9 in combination with R 3 , or both, form a saturated 5- or 6-membered ring that is optionally substituted by one or more methyls; or R 8 in combination with R 9 forms a saturated 5- or 6-membered heterocycle that is a piperidine, a morpholine, a pyrrolidine or a piperazine, each of which is optionally substituted by methyl, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, or a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; R 10 is F, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, or a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or R 10 is C 1 -C 18 alkyl, alkenyl or alkynyl that is optionally substituted one or more times by F, Cl, Br, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , sulfonic acid, salt of sulfonic acid, amino, alkylamino, or dialkylamino, the alkyl groups of which have 1-6 carbons; or R 10 has the formula ##STR12## where R 12 , R 13 , R 14 , R 15 and R 16 are independently H, F, Cl, Br, I; or sulfonic acid, salt of sulfonic acid, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , CN, nitro, hydroxy, azido, amino, hydrazino; or C 1 -C 18 alkyl, C 1 -C 18 alkoxy, C 1 -C 18 alkylthio, C 1 -C 18 alkylamino, C 1 -C 18 alkylester, C 1 -C 18 alkylamido or C 1 -C 18 arylamido, the alkyl or aryl portions of which are optionally substituted one or more times by F, Cl, Br, I, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , sulfonic acid, salt of sulfonic acid, amino, alkylamino, dialkylamino or alkoxy, the alkyl portions of each having 1-6 carbons; or one pair of adjacent substituents R 13 and R 14 , R 14 and R 15 or R 15 and R 16 , when taken in combination, form a fused 6-membered aromatic ring that is optionally further substituted by carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; and R 11 is H, hydroxy, CN or a C 1 -C 6 alkoxy; or R 10 in combination with R 11 forms a 5-membered spirolactone ring or a 5-membered spirosultone ring; or R 11 in combination with R 12 forms a 5- or 6-membered spirolactone ring or a 5- or 6-membered spirosultone ring that is optionally and independently substituted by H, F or CH 3 ; or R 10 when taken in combination with R 11 is a carbonyl oxygen; provided that at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 10 is F, or at least three of R 12 , R 13 , R 14 , R 15 and R 16 are F.

Claim 3

Dependent Claim 25 words

A compound, as claimed in claim 1, wherein at least one of R 2 , R 3 , R 4 or R 5 is F.

Claim 4

Dependent Claim 15 words

A compound, as claimed in claim 2, wherein R 2 and R 5 are F.

Claim 5

Dependent Claim 29 words

A compound, as claimed in claim 2, wherein at least one of R 12 , R 13 , R 14 , R 15 , or R 16 is F.

Claim 6

Dependent Claim 27 words

A compound, as claimed in claim 2, wherein none of R 12 , R 13 , R 14 , R 15 , or R 16 is F.

Claim 7

Dependent Claim 29 words

A compound, as claimed in claim 1, wherein at least one of R 12 , R 13 , R 14 , R 15 , or R 16 is F.

Claim 8

Dependent Claim 24 words

A compound, as claimed in claim 6, wherein each of R 13 , R 14 , R 15 , and R 16 is F.

Claim 9

Dependent Claim 29 words

A compound, as claimed in claim 6, wherein none of R 1 , R 2 , R 3 , R 4 , R 5 or R 6 is F.

Claim 10

Dependent Claim 13 words

A compound, as claimed in claim 1, wherein A is OR 7 .

Claim 11

Dependent Claim 13 words

A compound, as claimed in claim 9, wherein each R 7 is H.

Claim 12

Dependent Claim 36 words

A compound, as claimed in claim 10, wherein at least one of R 1 , R 2 , R 3 , R 4 , R 5 or R 6 is F; and R 11 is H.

Claim 13

Dependent Claim 33 words

A compound, as claimed in claim 10, wherein at least one of R 12 , R 13 , R 14 , R 15 or R 16 is F; and R 11 is H.

Claim 14

Dependent Claim 19 words

A compound, as claimed in claim 1, wherein R 12 is carboxylic acid or a salt of carboxylic acid.

Claim 15

Dependent Claim 15 words

A compound, as claimed in claim 1, wherein A is NR 8 R 9 .

Claim 16

Dependent Claim 18 words

A compound, as claimed in claim 1, wherein R 1 and R 6 are independently H or F.

Claim 17

Dependent Claim 19 words

A compound, as claimed in claim 1, wherein R 12 is sulfonic acid or a salt of sulfonic acid.

Claim 18

Dependent Claim 81 words

A compound, as claimed in claim 1, wherein each of substituents R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 13 , R 14 , R 15 and R 16 are either F or H and at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 13 , R 14 , R 15 and R 16 is F.

Claim 19

Dependent Claim 35 words

A compound, as claimed in claim 1, wherein R 1 and R 6 are H and R 2 , R 3 , R 4 , R 5 are independently H, F, Cl, Br or I.

Claim 20

Dependent Claim 23 words

A compound, as claimed in claim 1, wherein R 10 , when taken in combination with R 11 , is a carbonyl oxygen.

Claim 21

Dependent Claim 31 words

A compound, as claimed in claim 1, wherein A is OR 7 , and one or both of R 3 and R 4 are --CH 2 N(CH 2 COOR 17 ).

Claim 22

Dependent Claim 156 words

A compound, as claimed in claim 1, having the formula ##STR13## wherein R 2 , R 3 , R 4 and R 5 are independently H or F; R 12 is carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , sulfonic acid or a salt of sulfonic acid,; R 13 , R 14 , R 15 and R 16 are independently H, F, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , sulfonic acid, salt of sulfonic acid, or C 1 -C 6 alkylthio that is optionally substituted by carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, or a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 .

Claim 23

Dependent Claim 85 words

A compound, as claimed in claim 1, that is 6-amino-9-(2-carboxy-3,4,5,6-tetrafluorophenyl)-3H-xanthene-3-one, 6-amino-9-(2,4-dicarboxyphenyl)-2-fluoro-3H-xanthene-3-one, 6-amino-9-(2,4-dicarboxyphenyl)-7-fluoro-3H-xanthene-3-one, 4',5'-bis((di(carboxymethyl)amino)methyl)-2',7'-difluorofluorescein (2',7'-difluorocalcein), 4',5'-bis((di(carboxymethyl)amino)methyl)-2',7'-difluorofluorescein, acetoxymethyl ester (2',7'-difluorocalcein AM), 6-carboxy-2',7'-difluorodihydrofluorescein, di(acetoxymethyl ester), 4-(carboxymethyl)thio-5,6,7-trifluorofluorescein, 6-(carboxymethyl)thio-4,5,7-trifluorofluorescein, 4-(carboxymethyl)thio-2',5,6,7,7'-pentafluorofluorescein, 6-(carboxymethyl)thio-2',4,5,7,7'-pentafluorofluorescein, 9-(2-carboxyphenyl)-2',7'-difluorodihydrofluorescein, 9-(2-carboxyphenyl)-2',7'-difluorodihydrofluorescein diacetate, 9-(2-carboxyphenyl)-2',4',5',7'-tetrafluorodihydrofluorescein, 9-(4-carboxy-2-sulfophenyl)-2',7'-difluorofluorescein, 4',5'-dichloro-2',7'-dimethoxy-4,5,6,7-tetrafluorofluorescein-5-carboxylic acid, 2',7'-dichloro-4,5,6,7-tetrafluorofluorescein, 1',8'-difluorofluorescein, 2',7'-difluorofluorescein, 2',7'-difluorofluorescein diacetate, 4',5'-difluorofluorescein, 2',7'-difluoro-6-hydroxy-3H-xanthene-3-one, 2',7'-difluorofluorescein-5-carboxylic acid, 2',7'-difluorofluorescein-5-carboxylic acid diacetate, 2',7'-difluorofluorescein-5-carboxylic acid diacetate, acetoxymethyl ester, 2',7'-difluorofluorescein-6-carboxylic acid, 2',7'-difluorofluorescein-5-sulfonic acid, 2',7'-difluorofluorescein-6-sulfonic acid, 2',7'-dimethoxy-4,5,6,7-tetrafluorofluorescein, 2',7'-dimethoxy-4,5,6,7-tetrafluorofluorescein-5-carboxylic acid, 5-dodecanoylamino-2',7'-difluorofluorescein, 2'-fluorofluorescein, 4'-fluorofluorescein, 2',4,5,6,7,7'-hexafluorofluorescein, 2',4,5,6,7,7'-hexafluorofluorescein diacetate, 1,2,4,5,7,8-hexafluoro-6-hydroxy-9-(pentafluorophenyl)-3H-xanthene-3-one, 9-(2-sulfophenyl)-2,7-difluoro-dihydro-9H-xanthene-3,6-diol, 6-hydroxy-9-(2-sulfo-3,4,5,6-tetrafluorophenyl)-3H-xanthene-3-one, 2',4',5',7'-tetrabromo-4,5,6,7-tetrafluorofluorescein, 2',4',5',7'-tetrafluorofluorescein, 2',4',5',7'-tetrafluorofluorescein-5-carboxylic acid, 2',4',5',7'-tetrafluorofluorescein diacetate, 4,5,6,7-tetrafluorofluorescein, 4,5,6,7-tetrafluorofluorescein diacetate, 4,5,6,7-tetrafluorofluorescein-2',7'-dipropionic acid, 4,5,6,7-tetrafluorofluorescein-2',7'-dipropionic acid, acetoxymethyl ester, or 2',4',5',7'-tetraiodo-4,5,6,7-tetrafluorofluorescein.

Claim 24

Dependent Claim 1072 words

A compound having the formula ##STR14## or the formula ##STR15## wherein R 1 and R 6 are independently H, F, Cl, Br, I, C 1 -C 18 alkyl or C 1 -C 18 alkoxy; R 2 , R 3 , R 4 and R 5 are independently H, F, Cl, Br, I, CN; or C 1 -C 18 alkyl, C 1 -C 18 alkoxy or C 1 -C 18 alkylthio, where each alkyl, alkoxy or alkylthio is optionally further substituted by F, Cl, Br, I, sulfonic acid, salt of sulfonic acid, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 where R 18 is a C 1 -C 4 alkyl; or amino, alkylamino, dialkylamino, or alkoxy, the alkyl portions of which independently have 1-6 carbons; or one or more of R 2 , R 3 , R 4 , and R 5 is --L--R x ; A is OR 7 or NR 8 R 9 , where each R 7 is independently H, C 1 -C 18 alkyl, a C 1 -C 18 acyl wherein each alkyl group independently has 1-6 carbons and is optionally substituted by amino, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or a trialkylsilyl wherein each alkyl group independently has 1-6 carbons; or R 7 is an --L--R x ; R 8 and R 9 are independently H, C 1 -C 6 alkyl, C 1 -C 6 carboxyalkyl, C 1 -C 6 sulfoalkyl, a salt of C 1-C 6 carboxyalkyl, a salt of C 1 -C 6 sulfoalkyl, or C 1 -C 18 acyl wherein the alkyl portions are optionally substituted by amino, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or R 8 in combination with R 2 , or R 9 in combination with R 8 , or both, form a saturated 5- or 6-membered ring that is optionally substituted by one or more methyls; or R 8 in combination with R 9 forms a saturated 5- or 6-membered heterocycle that is a piperidine, a morpholine, a pyrrolidine or a piperazine, each of which is optionally substituted by methyl, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, or a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or one of R 8 and R 9 is --L--R x ; and R 10 is F, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, or a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or R 10 is C 1 -C 18 alkyl, alkenyl or alkynyl that is optionally substituted one or more times by F, Cl, Br, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , sulfonic acid, salt of sulfonic acid, amino, alkylamino, or dialkylamino, the alkyl groups of which have 1-6 carbons; or R 10 is an --L--R x ; or R 10 has the formula ##STR16## where R 12 , R 13 , R 14 , R 15 and R 16 are independently H, F, Cl, Br, I; or sulfonic acid, salt of sulfonic acid, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , CN, nitro, hydroxy, azido, amino, hydrazino; or C 1 -C 18 alkyl, C 1 -C 18 alkoxy, C 1 -C 18 alkylthio, C 1 -C 18 alkylamino, C 1 -C 18 alkylester, C 1 -C 18 alkylamido or C 1 -C 18 arylamido, the alkyl or aryl portions of which are optionally substituted one or more times by F, Cl, Br, I, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , sulfonic acid, salt of sulfonic acid, amino, alkylamino, dialkylamino or alkoxy, the alkyl portions of each having 1-6 carbons; or one pair of adjacent substituents R 13 and R 14 , R 14 and R 15 or R 15 and R 16 , when taken in combination, form a fused 6-membered aromatic ring that is optionally further substituted by carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or one or more of R 12 , R 13 , R 14 , R 15 and R 16 is --L--R x ; R 11 is H, hydroxy, CN or a C 1 -C 6 alkoxy; or R 10 in combination with R 11 forms a 5-membered spirolactone ring or a 5-membered spirosultone ring; or R 11 in combination with R 12 forms a 5- or 6-membered spirolactone ring or a 5- or 6-membered spirosultone ring that is optionally and independently substituted by H, F or CH 3 ; or R 10 when taken in combination with R 11 is a carbonyl oxygen; provided that at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 10 is F, or at least three of R 12 , R 13 , R 14 , R 15 and R 16 are F; and further provided that at least one of R 2 , R 3 , R 4 , R 5 , R 7 , R 8 , R 9 , R 10 , R 12 , R 13 , R 14 , R 15 and R 16 is --L--R x , where each --L--R x is optionally the same or different; wherein L is a single covalent bond, or L is a covalent linkage having 1-24 nonhydrogen atoms selected from the group consisting of C, N, O and S and is composed of any combination of single, double, triple or aromatic carbon-carbon bonds, carbon-nitrogen bonds, nitrogen-nitrogen bonds, carbon-oxygen bonds and carbon-sulfur bonds; and R x is a reactive site.

Claim 25

Dependent Claim 1072 words

A compound having the formula ##STR14## or the formula ##STR15## wherein R 1 and R 6 are independently H, F, Cl, Br, I, C 1 -C 18 alkyl or C 1 -C 18 alkoxy; R 2 , R 3 , R 4 and R 5 are independently H, F, Cl, Br, I, CN; or C 1 -C 18 alkyl, C 1 -C 18 alkoxy or C 1 -C 18 alkylthio, where each alkyl, alkoxy or alkylthio is optionally further substituted by F, Cl, Br, I, sulfonic acid, salt of sulfonic acid, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 where R 18 is a C 1 -C 4 alkyl; or amino, alkylamino, dialkylamino, or alkoxy, the alkyl portions of which independently have 1-6 carbons; or one or more of R 2 , R 3 , R 4 , and R 5 is --L--R x ; A is OR 7 or NR 8 R 9 , where each R 7 is independently H, C 1 -C 18 alkyl, a C 1 -C 18 acyl wherein each alkyl group independently has 1-6 carbons and is optionally substituted by amino, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or a trialkylsilyl wherein each alkyl group independently has 1-6 carbons; or R 7 is an --L--R x ; R 8 and R 9 are independently H, C 1 -C 6 alkyl, C 1 -C 6 carboxyalkyl, C 1 -C 6 sulfoalkyl, a salt of C 1-C 6 carboxyalkyl, a salt of C 1 -C 6 sulfoalkyl, or C 1 -C 18 acyl wherein the alkyl portions are optionally substituted by amino, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or R 8 in combination with R 2 , or R 9 in combination with R 8 , or both, form a saturated 5- or 6-membered ring that is optionally substituted by one or more methyls; or R 8 in combination with R 9 forms a saturated 5- or 6-membered heterocycle that is a piperidine, a morpholine, a pyrrolidine or a piperazine, each of which is optionally substituted by methyl, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, or a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or one of R 8 and R 9 is --L--R x ; and R 10 is F, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, or a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or R 10 is C 1 -C 18 alkyl, alkenyl or alkynyl that is optionally substituted one or more times by F, Cl, Br, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , sulfonic acid, salt of sulfonic acid, amino, alkylamino, or dialkylamino, the alkyl groups of which have 1-6 carbons; or R 10 is an --L--R x ; or R 10 has the formula ##STR16## where R 12 , R 13 , R 14 , R 15 and R 16 are independently H, F, Cl, Br, I; or sulfonic acid, salt of sulfonic acid, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , CN, nitro, hydroxy, azido, amino, hydrazino; or C 1 -C 18 alkyl, C 1 -C 18 alkoxy, C 1 -C 18 alkylthio, C 1 -C 18 alkylamino, C 1 -C 18 alkylester, C 1 -C 18 alkylamido or C 1 -C 18 arylamido, the alkyl or aryl portions of which are optionally substituted one or more times by F, Cl, Br, I, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , sulfonic acid, salt of sulfonic acid, amino, alkylamino, dialkylamino or alkoxy, the alkyl portions of each having 1-6 carbons; or one pair of adjacent substituents R 13 and R 14 , R 14 and R 15 or R 15 and R 16 , when taken in combination, form a fused 6-membered aromatic ring that is optionally further substituted by carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or one or more of R 12 , R 13 , R 14 , R 15 and R 16 is --L--R x ; R 11 is H, hydroxy, CN or a C 1 -C 6 alkoxy; or R 10 in combination with R 11 forms a 5-membered spirolactone ring or a 5-membered spirosultone ring; or R 11 in combination with R 12 forms a 5- or 6-membered spirolactone ring or a 5- or 6-membered spirosultone ring that is optionally and independently substituted by H, F or CH 3 ; or R 10 when taken in combination with R 11 is a carbonyl oxygen; provided that at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 10 is F, or at least three of R 12 , R 13 , R 14 , R 15 and R 16 are F; and further provided that at least one of R 2 , R 3 , R 4 , R 5 , R 7 , R 8 , R 9 , R 10 , R 12 , R 13 , R 14 , R 15 and R 16 is --L--R x , where each --L--R x is optionally the same or different; wherein L is a single covalent bond, or L is a covalent linkage having 1-24 nonhydrogen atoms selected from the group consisting of C, N, O and S and is composed of any combination of single, double, triple or aromatic carbon-carbon bonds, carbon-nitrogen bonds, nitrogen-nitrogen bonds, carbon-oxygen bonds and carbon-sulfur bonds; and R x is a reactive site.

Claim 26

Dependent Claim 94 words

A compound, as claimed in claim 23, wherein R x is an acrylamide, an activated ester of a carboxylic acid, an acyl azide, an acyl halide, an acyl nitrile, hydroxy, an aldehyde, an alkyl halide, a sulfonate, an amine, an anhydride, an aniline, an aryl halide, an azide, an aziridine, a boronate, a carboxylic acid, a carbodiimide, a diazoalkane, an epoxide, a glycol, a haloacetamide, a halotriazine, a hydrazine, a hydroxylamine, an imido ester, an isocyanate, an isothiocyanate, a ketone, a maleimide, a phosphoramidite, a silyl halide, a sulfonyl halide, or a thiol group.

Claim 27

Dependent Claim 53 words

A compound, as claimed in claim 23, wherein exactly one of R 2 , R 3 , R 4 , R 5 , R 7 , R 8 , R 9 , R 10 , R 12 , R 13 , R 14 , R 15 or R 16 is --L--R x .

Claim 28

Dependent Claim 12 words

A compound, as claimed in claim 23, wherein R 11 is H.

Claim 29

Dependent Claim 13 words

A compound, as claimed in claim 23, wherein L contains 1-6 carbon atoms.

Claim 30

Dependent Claim 14 words

A compound, as claimed in claim 25, wherein L is a single covalent bond.

Claim 31

Dependent Claim 38 words

A compound, as claimed in claim 25, wherein exactly one of R 2 , R 3 , R 4 , R 5 , R 7 , R 8 , R 9 or R 10 is --L--R x .

Claim 32

Dependent Claim 26 words

A compound, as claimed in claim 25, wherein exactly one of R 13 , R 14 , R 15 and R 16 is --L--R x .

Claim 33

Dependent Claim 94 words

A compound, as claimed in claim 30, wherein R x is an acrylamide, an activated ester of a carboxylic acid, an acyl azide, an acyl halide, an acyl nitrile, hydroxy, an aldehyde, an alkyl halide, a sulfonate, an amine, an anhydride, an aniline, an aryl halide, an azide, an aziridine, a boronate, a carboxylic acid, a carbodiimide, a diazoalkane, an epoxide, a glycol, a haloacetamide, a halotriazine, a hydrazine, a hydroxylamine, an imido ester, an isocyanate, an isothiocyanate, a ketone, a maleimide, a phosphoramidite, a silyl halide, a sulfonyl halide, or a thiol group.

Claim 34

Dependent Claim 14 words

A compound, as claimed in claim 31, wherein L is a single covalent bond.

Claim 35

Dependent Claim 31 words

A compound, as claimed in claim 30, wherein at least one of R 1 , R 2 , R 3 , R 4 , R 5 or R 6 is F.

Claim 36

Dependent Claim 15 words

A compound, as claimed in claim 30, wherein R 2 and R 5 are F.

Claim 37

Dependent Claim 34 words

A compound, as claimed in claim 30, wherein R 1 and R 6 are H and R 2 , R 3 , R 4 , R 5 are H, F, Cl, Br or I.

Claim 38

Dependent Claim 28 words

A compound, as claimed in claim 30, wherein at least one of R 12 , R 13 , R 14 , R 15 or R 16 is F.

Claim 39

Dependent Claim 13 words

A compound, as claimed in claim 36, wherein L incorporates a thioether bond.

Claim 40

Dependent Claim 46 words

A compound, as claimed in claim 30, wherein L is a single covalent bond and R x is a carboxylic acid, an activated ester of a carboxylic acid, an amine, an azide, a haloacetamide, an alkyl halide, a sulfonyl halide, an isothiocyanate, or a maleimide group.

Claim 41

Dependent Claim 13 words

A compound, as claimed in claim 31, wherein A is OR 7 .

Claim 42

Dependent Claim 15 words

A compound, as claimed in claim 31, wherein A is NR 8 R 9 .

Claim 43

Dependent Claim 78 words

A compound, as claimed in claim 23, wherein one or both of R 7 and R 8 are independently C 1 -C 18 acyl, the alkyl portions of which are optionally substituted one or more times by amino, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, or a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , where R 18 is a C 1 -C 4 alkyl.

Claim 44

Dependent Claim 120 words

A compound, as claimed in claim 30, wherein each of R 1 , R 3 , R 4 , R 6 and R 7 are H; R 2 and R 5 are F; R 12 is selected from the group consisting of carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , sulfonic acid, and salt of sulfonic acid; and exactly one of R 13 , R 14 , R 15 or R 16 is --L--R x , where L is a single covalent bond, and the remaining of R 13 , R 14 , R 15 or R 16 are H.

Claim 45

Dependent Claim 103 words

A compound, as claimed in claim 30, wherein each of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are H; R 12 is carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , sulfonic acid, salt of sulfonic acid; one of R 13 , R 14 , R 15 or R 16 is --L--R x , and the remaining of R 13 , R 14 , R 15 and R 16 are F.

Claim 46

Dependent Claim 106 words

A compound, as claimed in claim 30, wherein each of R 1 , R 3 , R 4 , R 6 and R 7 are H; R 2 and R 5 are F; R 12 is carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , sulfonic acid, or salt of sulfonic acid; exactly one of R 13 , R 14 , R 15 or R 16 is --L--R x and the remaining of R 13 , R 14 , R 15 or R 16 are all F.

Claim 47

Dependent Claim 120 words

A compound, as claimed in claim 23, that is 5-(acryloylamino)fluorescein, 4'-(((acryloyl)amino)methyl)fluorescein, 6-amino-9-(2,4-dicarboxyphenyl)-3H-xanthene-3-one, succinimidyl ester, 5-amino-2',7'-difluorofluorescein, 6-amino-2',7'-difluorofluorescein, 5-amino-2',4',5',7'-tetrafluorofluorescein, 5-azido-2',7'-difluorofluorescein, 4'-aminomethyl-2',7'-difluorofluorescein, 5-aminomethyl-2',7'-difluorofluorescein, 4',5'-bis(aminomethyl)-2',7'-difluorofluorescein, 5-bromomethyl-2',7'-difluorofluorescein, 9-(4-carboxy-2-sulfophenyl)-2',7'-difluorofluorescein, 9-(4-carboxy-2-sulfophenyl)2',7'-difluorofluorescein, succinimidyl ester, 6-(carboxymethyl)thio-2',4,5,7,7'-pentafluorofluorescein, succinimidyl ester, 6-(carboxymethyl)thio-2',4,5,7,7'-pentafluorofluorescein diacetate, succinimidyl ester, 6-carboxymethyl)thio-4,5,7-trifluorofluorescein diacetate, succinimidyl ester, 4-(carboxymethyl)thio-5,6,7-trifluorofluorescein diacetate, succinimidyl ester, 6-(carboxymethyl)thio-4,5,7-trifluorofluorescein, succinimidyl ester, 4-(carboxymethyl)thio-5,6,7-trifluorofluorescein, succinimidyl ester, 6-(carboxymethyl)thio-4,5,6,7-tetrafluoro-2',4',5',7'-tribromo-fluorescein, succinimidyl ester, 9-(2-carboxyphenyl)-2',7'-difluorodihydrofluorescein, succinimidyl ester, 9-(2-carboxyphenyl)-2',7'-difluorodihydrofluorescein diacetate, succinimidyl ester, 5-((4-(chloromethyl)benzoyl)amino)-2',7-difluorofluorescein, 5-((4-(chloromethyl)benzoyl)amino)-2',7-difluorofluorescein diacetate, 5-chloromethyl-2',7'-difluorofluorescein, 5-chloromethyl-2',7'-difluorofluorescein diacetate, 5-(4,6-dichlorotriazinyl)amino-2',7'-difluorofluorescein, 2-((((2',7'-difluorofluorescein-5-amino)carbonyl)methyi)thio)acetic acid, succinimidyl ester, 6-(2',7'-difluorofluorescein-5-carbonyl)aminohexanoic acid, succinimidyl ester, 2',7'-difluorofluorescein-5-carboxylic acid, succinimidyl ester, 2',7'-difluorofluorescein-5-carboxylic acid, sulfosuccinimidyl ester, sodium salt, 2',7'-difluorofluorescein-5-carboxylic acid, pentafluorophenyl ester, 2',7'-difluorofluorescein-5-carboxylic acid, p-nitrophenyl ester, 2',7'-difluorofluorescein-6-carboxylic acid, succinimidyl ester, 2',7'-difluorofluorescein-5-carboxylic acid diacetate, succinimidyl ester, 2',7'-difluorofluorescein-6-carboxylic acid diacetate, succinimidyl ester, 2',7'-difluorofluorescein-5-iodoacetamide, 2',7'-difluorofluorescein-6-iodoacetamide, 2',7'-difluorofluorescein-5-isothiocyanate, 2',7'-difluorofluorescein-6-isothiocyanate, 2',7'-difluorofluorescein-5-maleimide, 2',7'-difluorofluorescein-5-thiosemicarbazide, 2',7'-difluoro-5-((pentafluorobenzoyl)amino)fluorescein, 2',7'-difluoro-5-((pentafluorobenzoyl)amino)fluorescein diacetate, 6-(((hydrazino)carbonyl)methyl)thio-4,5,7-trifluorofluorescein, 4'-((iodoacetyl)arnino)methyl-2',7'-difluorofluorescein or 2',4',5',7'-tetrafluorofluorescein-5-carboxylic acid, succinimidyl ester.

Claim 48

Dependent Claim 1047 words

A compound having the formula ##STR17## or the formula ##STR18## wherein R 1 and R 6 are independently H, F, Cl, Br, I, C 1 -C 18 alkyl or C 1 -C 18 alkoxy; R 2 , R 3 , R 4 and R 5 are independently H, F, Cl, Br, I, CN; or C 1 -C 18 alkyl, C 1 -C 18 alkoxy or C 1 -C 18 alkylthio, where each alkyl, alkoxy or alkylthio is optionally further substituted by F, Cl, Br, I, sulfonic acid, salt of sulfonic acid, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 where R 18 is a C 1 -C 4 alkyl; or amino, alkylamino, dialkylamino, or alkoxy, the alkyl portions of which independently have 1-6 carbons; or one or more of R 2 , R 3 , R 4 , and R 5 is --L--S c ; A is OR 7 or NR 8 R 9 , where each R 7 is independently H, C 1 -C 18 alkyl, a C 1 -C 18 acyl wherein each alkyl group independently has 1-6 carbons and is optionally substituted by amino, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or R 7 is --L--S c ; R 8 and R 9 are independently H, C 1 -C 6 alkyl, C 1 -C 6 carboxyalkyl, C 1 -C 6 sulfoalkyl, a salt of C 1 -C 6 carboxyalkyl, a salt of C 1 -C 6 sulfoalkyl, or C 1 -C 18 acyl wherein the alkyl portions are optionally substituted by amino, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or R 8 in combination with R 2 , or R 9 in combination with R 3 , or both, form a saturated 5- or 6-membered ring that is optionally substituted by one or more methyls; or R 8 in combination with R 9 forms a saturated 5- or 6-membered heterocycle that is a piperidine, a morpholine, a pyrrolidine or a piperazine, each of which is optionally substituted by methyl, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, or a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or one of R 8 and R 9 is --L--S c ; and R 10 is F, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, or a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or R 10 is C 1 -C 18 alkyl, alkenyl or alkynyl that is optionally substituted one or more times by F, Cl, Br, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , sulfonic acid, salt of sulfonic acid, amino, alkylamino, or dialkylamino, the alkyl groups of which have 1-6 carbons; or R 10 is --L--S c ; or R 10 has the formula ##STR19## where R 12 , R 13 , R 14 , R 15 and R 16 are independently H, F, Cl, Br, I; or sulfonic acid, salt of sulfonic acid, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , CN, nitro, hydroxy, azido, amino, hydrazino; or C 1 -C 18 alkyl, C 1 -C 18 alkoxy, C 1 -C 18 alkylthio, C 1 -C 18 alkylamino, C 1 -C 18 alkylester, C 1 -C 18 alkylamido or C 1 -C 18 arylamido, the alkyl or aryl portions of which are optionally substituted one or more times by F, Cl, Br, I, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , sulfonic acid, salt of sulfonic acid, amino, alkylamino, dialkylamino or alkoxy, the alkyl portions of each having 1-6 carbons; or one pair of adjacent substituents R 13 and R 14 , R 14 and R 15 or R 15 and R 16 , when taken in combination, form a fused 6-membered aromatic ring that is optionally further substituted by carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or one or more of R 12 , R 13 , R 14 , R 15 and R 16 is --L--S c ; R 11 is H, hydroxy, CN or a C 1 -C 6 alkoxy; or R 10 in combination with R 11 forms a 5-membered spirolactone ring or a 5-membered spirosultone ring; or R 11 in combination with R 12 forms a 5- or 6-membered spirolactone ring or a 5- or 6-membered spirosultone ring that is optionally and independently substituted by H, F or CH 3 ; or R 10 in combination with R 11 is a carbonyl oxygen; provided that at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 10 is F, or at least three of R 12 , R 13 , R 14 , R 15 and R 16 are F; and further provided that at least one of R 2 , R 3 , R 4 , R 5 , R 7 , R 8 , R 9 , R 10 , R 12 , R 13 , R 14 , R 15 and R 16 is an --L--S c ; L is a single covalent bond, or L is a covalent linkage having 1-24 nonhydrogen atoms selected from the group consisting of C, N, O and S and is composed of any combination of single, double, triple or aromatic carbon-carbon bonds, carbon-nitrogen bonds, nitrogen-nitrogen bonds, carbon-oxygen bonds and carbon-sulfur bonds; and S c is a conjugated substance.

Claim 49

Dependent Claim 1047 words

A compound having the formula ##STR17## or the formula ##STR18## wherein R 1 and R 6 are independently H, F, Cl, Br, I, C 1 -C 18 alkyl or C 1 -C 18 alkoxy; R 2 , R 3 , R 4 and R 5 are independently H, F, Cl, Br, I, CN; or C 1 -C 18 alkyl, C 1 -C 18 alkoxy or C 1 -C 18 alkylthio, where each alkyl, alkoxy or alkylthio is optionally further substituted by F, Cl, Br, I, sulfonic acid, salt of sulfonic acid, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 where R 18 is a C 1 -C 4 alkyl; or amino, alkylamino, dialkylamino, or alkoxy, the alkyl portions of which independently have 1-6 carbons; or one or more of R 2 , R 3 , R 4 , and R 5 is --L--S c ; A is OR 7 or NR 8 R 9 , where each R 7 is independently H, C 1 -C 18 alkyl, a C 1 -C 18 acyl wherein each alkyl group independently has 1-6 carbons and is optionally substituted by amino, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or R 7 is --L--S c ; R 8 and R 9 are independently H, C 1 -C 6 alkyl, C 1 -C 6 carboxyalkyl, C 1 -C 6 sulfoalkyl, a salt of C 1 -C 6 carboxyalkyl, a salt of C 1 -C 6 sulfoalkyl, or C 1 -C 18 acyl wherein the alkyl portions are optionally substituted by amino, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or R 8 in combination with R 2 , or R 9 in combination with R 3 , or both, form a saturated 5- or 6-membered ring that is optionally substituted by one or more methyls; or R 8 in combination with R 9 forms a saturated 5- or 6-membered heterocycle that is a piperidine, a morpholine, a pyrrolidine or a piperazine, each of which is optionally substituted by methyl, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, or a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or one of R 8 and R 9 is --L--S c ; and R 10 is F, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, or a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or R 10 is C 1 -C 18 alkyl, alkenyl or alkynyl that is optionally substituted one or more times by F, Cl, Br, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , sulfonic acid, salt of sulfonic acid, amino, alkylamino, or dialkylamino, the alkyl groups of which have 1-6 carbons; or R 10 is --L--S c ; or R 10 has the formula ##STR19## where R 12 , R 13 , R 14 , R 15 and R 16 are independently H, F, Cl, Br, I; or sulfonic acid, salt of sulfonic acid, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , CN, nitro, hydroxy, azido, amino, hydrazino; or C 1 -C 18 alkyl, C 1 -C 18 alkoxy, C 1 -C 18 alkylthio, C 1 -C 18 alkylamino, C 1 -C 18 alkylester, C 1 -C 18 alkylamido or C 1 -C 18 arylamido, the alkyl or aryl portions of which are optionally substituted one or more times by F, Cl, Br, I, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , sulfonic acid, salt of sulfonic acid, amino, alkylamino, dialkylamino or alkoxy, the alkyl portions of each having 1-6 carbons; or one pair of adjacent substituents R 13 and R 14 , R 14 and R 15 or R 15 and R 16 , when taken in combination, form a fused 6-membered aromatic ring that is optionally further substituted by carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or one or more of R 12 , R 13 , R 14 , R 15 and R 16 is --L--S c ; R 11 is H, hydroxy, CN or a C 1 -C 6 alkoxy; or R 10 in combination with R 11 forms a 5-membered spirolactone ring or a 5-membered spirosultone ring; or R 11 in combination with R 12 forms a 5- or 6-membered spirolactone ring or a 5- or 6-membered spirosultone ring that is optionally and independently substituted by H, F or CH 3 ; or R 10 in combination with R 11 is a carbonyl oxygen; provided that at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 10 is F, or at least three of R 12 , R 13 , R 14 , R 15 and R 16 are F; and further provided that at least one of R 2 , R 3 , R 4 , R 5 , R 7 , R 8 , R 9 , R 10 , R 12 , R 13 , R 14 , R 15 and R 16 is an --L--S c ; L is a single covalent bond, or L is a covalent linkage having 1-24 nonhydrogen atoms selected from the group consisting of C, N, O and S and is composed of any combination of single, double, triple or aromatic carbon-carbon bonds, carbon-nitrogen bonds, nitrogen-nitrogen bonds, carbon-oxygen bonds and carbon-sulfur bonds; and S c is a conjugated substance.

Claim 50

Dependent Claim 55 words

A compound, as claimed in claim 46, wherein exactly one of R 2 , R 3 , R 4 , R 5 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 R 13 , R 14 , R 15 and R 16 is --L--S c .

Claim 51

Dependent Claim 26 words

A compound, as claimed in claim 47, wherein one of R 13 , R 14 , R 15 or R 16 is an L--S c .

Claim 52

Dependent Claim 53 words

A compound, as claimed in claim 48, wherein R 7 is H; R 12 is H, F, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , sulfonic acid or a salt of sulfonic acid.

Claim 53

Dependent Claim 22 words

A compound, as claimed in claim 49, wherein R 13 , R 14 , R 15 and R 16 are all F.

Claim 54

Dependent Claim 22 words

A compound, as claimed in claim 49, wherein R 13 , R 14 , R 15 and R 16 are all H.

Claim 55

Dependent Claim 15 words

A compound, as claimed in claim 49, wherein A is NR 8 R 9 .

Claim 56

Dependent Claim 38 words

A compound, as claimed in claim 47, wherein one of R 2 , R 3 , R 4 , R 5 , R 7 , R 8 , R 9 or R 10 is an L--S c .

Claim 57

Dependent Claim 45 words

A compound, as claimed in claim 49, wherein S c is an amino acid, peptide, protein, polysaccharide, ion-complexing moiety, nucleotide, oligonucleotide, nucleic acid, hapten, drug, lipid, phospholipid, lipoprotein, lipopolysaccharide, liposome, lipophilic polymer, non-biological organic polymer, polymeric microparticle, animal cell, plant cell, bacterium, yeast, or virus.

Claim 58

Dependent Claim 29 words

A compound, as claimed in claim 54, wherein one of R 12 , R 13 , R 14 , R 15 or R 16 is an L--S c .

Claim 59

Dependent Claim 17 words

A compound, as claimed in claim 55, wherein S c is an amino acid, peptide or protein.

Claim 60

Dependent Claim 23 words

A compound, as claimed in claim 56, wherein S c is an antibody, antibody fragment, avidin, streptavidin, lectin, protein A or protein G.

Claim 61

Dependent Claim 13 words

A compound, as claimed in claim 55, wherein S c is a polysaccharide.

Claim 62

Dependent Claim 14 words

A compound, as claimed in claim 55, wherein S c is an ion-complexing moiety.

Claim 63

Dependent Claim 19 words

A compound, as claimed in claim 59, wherein the ion-complexing moiety is a BAPTA or APTRA or a phenanthroline.

Claim 64

Dependent Claim 14 words

A compound, as claimed in claim 55, wherein S c is a crown ether.

Claim 65

Dependent Claim 19 words

A compound, as claimed in claim 55, wherein S c is a nucleotide, an oligonucleotide or a nucleic acid.

Claim 66

Dependent Claim 15 words

A compound, as claimed in claim 55, wherein S c is a hapten or drug.

Claim 67

Dependent Claim 20 words

A compound, as claimed in claim 55, wherein S c is a lipid, phospholipid, lipoprotein, lipopolysaccharide, liposome or lipophilic polymer.

Claim 68

Dependent Claim 18 words

A compound, as claimed in claim 55, wherein S c is a non-biological organic polymer or polymeric microparticle.

Claim 69

Dependent Claim 20 words

A compound, as claimed in claim 55, wherein S c is a animal cell, plant cell, bacterium, yeast or virus.

Claim 70

Dependent Claim 1197 words

A compound having the formula ##STR20## or the formula ##STR21## wherein R 1 and R 6 are independently H, F, Cl, Br, I, C 1 -C 18 alkyl or C 1 -C 18 alkoxy; R 2 , R 3 , R 4 and R 5 are independently H, F, Cl, Br, I, CN; or C 1 -C 18 alkyl, C 1 -C 18 alkoxy or C 1 -C 18 alkylthio, where each alkyl, alkoxy or alkylthio is optionally further substituted by F, Cl, Br, I, sulfonic acid, salt of sulfonic acid, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 where R 18 is a C 1 -C 4 alkyl; or amino, alkylamino, dialkylamino, or alkoxy, the alkyl portions of which independently have 1-6 carbons; or one or both of R 3 and R 4 are --CH 2 N(CH 2 COOR 17 ) 2 , where R 17 is H, a biologically compatible counterion, a linear or branched alkyl having 1-6 carbons, or --CH 2 --O--(C═O)--R 18 ; or one or more of R 2 , R 3 , R 4 , and R 5 is --L--R x ; or one or more of R 2 , R 3 , R 4 , and R 5 is --L--S c ; A is OR 7 or NR 8 R 9 , where each R 7 is independently a BLOCK, or R 7 is --L--R x , or R 7 is --L--S c ; R 8 and R 9 are independently H, C 1 -C 6 alkyl, C 1 -C 6 carboxyalkyl, C 1 -C 6 sulfoalkyl, a salt of C 1 -C 6 carboxyalkyl, a salt of C 1 -C 6 sulfoalkyl, or C 1 -C 18 acyl wherein the alkyl portions are optionally substituted by amino, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or R 8 in combination with R 2 , or R 9 in combination with R 3 , or both, form a saturated 5- or 6-membered ring that is optionally substituted by one or more methyls; or R 8 in combination with R 9 forms a saturated 5- or 6-membered heterocycle that is a piperidine, a morpholine, a pyrrolidine or a piperazine, each of which is optionally substituted by methyl, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, or a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or one of R 8 and R 9 is a BLOCK; or one of R 8 and R 9 is --L--R x ; or one of R 8 and R 9 is --L--S c ; and R 10 is F, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, or a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or R 10 is C 1 -C 18 alkyl, alkenyl or alkynyl that is optionally substituted one or more times by F, Cl, Br, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , sulfonic acid, salt of sulfonic acid, amino, alkylamino, or dialkylamino, the alkyl groups of which have 1-6 carbons; or R 10 is --L--R x ; or R 10 is --L--S c ; or R 10 has the formula ##STR22## where R 12 , R 13 , R 14 , R 15 and R 16 are independently H, F, Cl, Br, I; or sulfonic acid, salt of sulfonic acid, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , CN, nitro, hydroxy, azido, amino, hydrazino; or C 1 -C 18 alkyl, C 1 -C 18 alkoxy, C 1 -C 18 alkylthio, C 1 -C 18 alkylamino, C 1 -C 18 alkylester, C 1 -C 18 alkylamido or C 1 -C 18 arylamido, the alkyl or aryl portions of which are optionally substituted one or more times by F, Cl, Br, I, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , sulfonic acid, salt of sulfonic acid, amino, alkylamino, dialkylamino or alkoxy, the alkyl portions of each having 1-6 carbons; or one pair of adjacent substituents R 13 and R 14 , R 14 and R 15 or R 15 and R 16 , when taken in combination, form a fused 6-membered aromatic ring that is optionally further substituted by carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or one or more of R 12 , R 13 , R 14 , R 15 and R 16 is --L--R x ; or one or more of R 12 , R 13 , R 14 , R 15 and R 16 is --L--S c ; R 11 is H, hydroxy, CN or a C 1 -C 6 alkoxy; or R 10 in combination with R 11 forms a 5-membered spirolactone ring or a 5-membered spirosultone ring; or R 11 in combination with R 12 forms a 5- or 6-membered spirolactone ring or a 5- or 6-membered spirosultone ring that is optionally and independently substituted by H, F or CH 3 ; or R 10 in combination with R 11 is a carbonyl oxygen; provided that at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 10 is F, or at least three of R 12 , R 13 , R 14 , R 15 and R 16 are F; and further provided at least one of R 7 , R 8 or R 9 is a BLOCK; each L is a single covalent bond, or L is a covalent linkage having 1-24 nonhydrogen atoms selected from the group consisting of C, N, O and S and is composed of any combination of single, double, triple or aromatic carbon-carbon bonds, carbon-nitrogen bonds, nitrogen-nitrogen bonds, carbon-oxygen bonds and carbon-sulfur bonds; and R x is a reactive site; S c is a conjugated substance; and each BLOCK moiety is independently a monovalent moiety derived by removal of a hydroxy group from phosphate or from sulfate, or a biologically compatible salt thereof; or a monovalent moiety derived by removal of a hydroxy group from a carboxy group of an aliphatic or aromatic carboxylic acid or of an amino acid, protected amino acid, peptide, or protected peptide; or a monovalent moiety derived by removal of a hydroxy group from an alcohol or from a mono- or polysaccharide, where said BLOCK is selected to be removable from said compound by action of an enzyme; or BLOCK is a photolabile caging group.

Claim 71

Dependent Claim 1197 words

A compound having the formula ##STR20## or the formula ##STR21## wherein R 1 and R 6 are independently H, F, Cl, Br, I, C 1 -C 18 alkyl or C 1 -C 18 alkoxy; R 2 , R 3 , R 4 and R 5 are independently H, F, Cl, Br, I, CN; or C 1 -C 18 alkyl, C 1 -C 18 alkoxy or C 1 -C 18 alkylthio, where each alkyl, alkoxy or alkylthio is optionally further substituted by F, Cl, Br, I, sulfonic acid, salt of sulfonic acid, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 where R 18 is a C 1 -C 4 alkyl; or amino, alkylamino, dialkylamino, or alkoxy, the alkyl portions of which independently have 1-6 carbons; or one or both of R 3 and R 4 are --CH 2 N(CH 2 COOR 17 ) 2 , where R 17 is H, a biologically compatible counterion, a linear or branched alkyl having 1-6 carbons, or --CH 2 --O--(C═O)--R 18 ; or one or more of R 2 , R 3 , R 4 , and R 5 is --L--R x ; or one or more of R 2 , R 3 , R 4 , and R 5 is --L--S c ; A is OR 7 or NR 8 R 9 , where each R 7 is independently a BLOCK, or R 7 is --L--R x , or R 7 is --L--S c ; R 8 and R 9 are independently H, C 1 -C 6 alkyl, C 1 -C 6 carboxyalkyl, C 1 -C 6 sulfoalkyl, a salt of C 1 -C 6 carboxyalkyl, a salt of C 1 -C 6 sulfoalkyl, or C 1 -C 18 acyl wherein the alkyl portions are optionally substituted by amino, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or R 8 in combination with R 2 , or R 9 in combination with R 3 , or both, form a saturated 5- or 6-membered ring that is optionally substituted by one or more methyls; or R 8 in combination with R 9 forms a saturated 5- or 6-membered heterocycle that is a piperidine, a morpholine, a pyrrolidine or a piperazine, each of which is optionally substituted by methyl, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, or a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or one of R 8 and R 9 is a BLOCK; or one of R 8 and R 9 is --L--R x ; or one of R 8 and R 9 is --L--S c ; and R 10 is F, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, or a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or R 10 is C 1 -C 18 alkyl, alkenyl or alkynyl that is optionally substituted one or more times by F, Cl, Br, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , sulfonic acid, salt of sulfonic acid, amino, alkylamino, or dialkylamino, the alkyl groups of which have 1-6 carbons; or R 10 is --L--R x ; or R 10 is --L--S c ; or R 10 has the formula ##STR22## where R 12 , R 13 , R 14 , R 15 and R 16 are independently H, F, Cl, Br, I; or sulfonic acid, salt of sulfonic acid, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , CN, nitro, hydroxy, azido, amino, hydrazino; or C 1 -C 18 alkyl, C 1 -C 18 alkoxy, C 1 -C 18 alkylthio, C 1 -C 18 alkylamino, C 1 -C 18 alkylester, C 1 -C 18 alkylamido or C 1 -C 18 arylamido, the alkyl or aryl portions of which are optionally substituted one or more times by F, Cl, Br, I, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , sulfonic acid, salt of sulfonic acid, amino, alkylamino, dialkylamino or alkoxy, the alkyl portions of each having 1-6 carbons; or one pair of adjacent substituents R 13 and R 14 , R 14 and R 15 or R 15 and R 16 , when taken in combination, form a fused 6-membered aromatic ring that is optionally further substituted by carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or one or more of R 12 , R 13 , R 14 , R 15 and R 16 is --L--R x ; or one or more of R 12 , R 13 , R 14 , R 15 and R 16 is --L--S c ; R 11 is H, hydroxy, CN or a C 1 -C 6 alkoxy; or R 10 in combination with R 11 forms a 5-membered spirolactone ring or a 5-membered spirosultone ring; or R 11 in combination with R 12 forms a 5- or 6-membered spirolactone ring or a 5- or 6-membered spirosultone ring that is optionally and independently substituted by H, F or CH 3 ; or R 10 in combination with R 11 is a carbonyl oxygen; provided that at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 10 is F, or at least three of R 12 , R 13 , R 14 , R 15 and R 16 are F; and further provided at least one of R 7 , R 8 or R 9 is a BLOCK; each L is a single covalent bond, or L is a covalent linkage having 1-24 nonhydrogen atoms selected from the group consisting of C, N, O and S and is composed of any combination of single, double, triple or aromatic carbon-carbon bonds, carbon-nitrogen bonds, nitrogen-nitrogen bonds, carbon-oxygen bonds and carbon-sulfur bonds; and R x is a reactive site; S c is a conjugated substance; and each BLOCK moiety is independently a monovalent moiety derived by removal of a hydroxy group from phosphate or from sulfate, or a biologically compatible salt thereof; or a monovalent moiety derived by removal of a hydroxy group from a carboxy group of an aliphatic or aromatic carboxylic acid or of an amino acid, protected amino acid, peptide, or protected peptide; or a monovalent moiety derived by removal of a hydroxy group from an alcohol or from a mono- or polysaccharide, where said BLOCK is selected to be removable from said compound by action of an enzyme; or BLOCK is a photolabile caging group.

Claim 72

Dependent Claim 53 words

A compound, as claimed in claim 67, wherein none of R 2 , R 3 , R 4 , R 5 , R 7 , R 8 , R 9 , R 10 , R 13 , R 14 , R 15 or R 6 is an --L--R x or --L--S c .

Claim 73

Dependent Claim 31 words

A compound, as claimed in claim 68, wherein at least one of R 1 , R 2 , R 3 , R 4 , R 5 or R 6 is F.

Claim 74

Dependent Claim 25 words

A compound, as claimed in claim 68, wherein at least one of R 13 , R 14 , R 15 or R 16 is F.

Claim 75

Dependent Claim 23 words

A compound, as claimed in claim 68, wherein each of R 13 , R 14 , R 15 and R 16 is F.

Claim 76

Dependent Claim 17 words

A compound, as claimed in claim 68, wherein A is OR 7 and R 7 is BLOCK.

Claim 77

Dependent Claim 16 words

A compound, as claimed in claim 72, wherein R 2 and R 5 are each F.

Claim 78

Dependent Claim 22 words

A compound, as claimed in claim 68, wherein BLOCK is an ester of phosphate, sulfate or an aliphatic or aromatic carboxylic acid.

Claim 79

Dependent Claim 22 words

A compound, as claimed in claim 72, wherein BLOCK is an ester of phosphate, sulfate or an aliphatic or aromatic carboxylic acid.

Claim 80

Dependent Claim 20 words

A compound, as claimed in claim 68, wherein BLOCK is an ether of an alcohol or a mono- or polysaccharide.

Claim 81

Dependent Claim 22 words

A compound, as claimed in claim 67, wherein R 7 and R 8 are BLOCK and BLOCK is a photolabile caging group.

Claim 82

Dependent Claim 21 words

A compound, as claimed in claim 77, wherein said photolabile caging group is an o-nitroarylmethine, a 2-methoxy-5-nitrophenyl or a desyl moiety.

Claim 83

Dependent Claim 38 words

A compound, as claimed in claim 67, wherein one of R 2 , R 3 , R 4 , R 5 , R 13 , R 14 , R 15 or R 16 is an --L--R x .

Claim 84

Dependent Claim 42 words

A compound, as claimed in claim 79, wherein R x is a carboxylic acid, an activated ester of a carboxylic acid, a succinimidyl ester, an amine, an azide, a haloacetamide, an alkyl halide, a sulfonyl halide, an isothiocyanate, or a maleimide group.

Claim 85

Dependent Claim 38 words

A compound, as claimed in claim 67, wherein one of R 2 , R 3 , R 4 , R 5 , R 13 , R 14 , R 15 or R 16 is an --L--S c .

Claim 86

Dependent Claim 45 words

A compound, as claimed in claim 81, wherein S c is an amino acid, peptide, protein, polysaccharide, ion-complexing moiety, nucleotide, oligonucleotide, nucleic acid, hapten, drug, lipid, phospholipid, lipoprotein, lipopolysaccharide, liposome, lipophilic polymer, non-biological organic polymer, polymeric microparticle, animal cell, plant cell, bacterium, yeast, or virus.

Claim 87

Dependent Claim 15 words

A compound, as claimed in claim 67, wherein A is NR 8 R 9 .

Claim 88

Dependent Claim 96 words

A compound, as claimed in claim 67, wherein R 9 is H; R 8 is BLOCK where BLOCK is an amino acid, a peptide or a protected peptide; or R 8 is a C 1 -C 18 aliphatic carboxylic acid, arylalkanoic carboxylic acid or alkylaromatic carboxylic acid, the alkyl and aryl portion of which are optionally substituted one or more times by F, Cl, Br, I, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, or a carboxylic acid ester of --CH 2 --O--(C═O)R 18 .

Claim 89

Dependent Claim 12 words

A compound, as claimed in claim 67 wherein R 11 is H.

Claim 90

Dependent Claim 76 words

A compound, as claimed in claim 67, that is 3'-acetoxy-6'-acetylamino-4,5,6,7-tetrafluorospiro(isobenzofuran)-1(3H),9'-(9H)xanthen-3-one, 6'-acetylamino-3'-phosphoryloxy-4,5,6,7-tetrafluorospiro(isobenzofuran)-1(3H),9'-(9H)xanthen-3-one, tetrasodium salt, 6'-amino-3'-methoxy-4,5,6,7-tetrafluorospiro(isobenzofuran)-1(3H),9'-(9H)xanthen-3-one, 5-chloromethyl-2',7'-difluorofluorescein diacetate, 5-chloromethyl-2',7'-difluorofluorescein di-β-D-galactopyranoside, 2',7'-difluoro-5-dodecanoylaminofluorescein di-β-D-galactopyranoside, 2',7'-difluorofluorescein diacetate, 2',7'-difluorofluorescein-5-carboxylic acid diacetate, 2',7'-difluorofluoreseein-5-carboxylic acid diacetate, succinimidyl ester, 2',7'-difluorofluorescein-5-carboxylic acid di(2-nitrobenzyl ether), 2',7'-difluorofluorescein dibutyrate, 2',7'-difluorofluorescein di(4,5-dimethoxy-2-nitrobenzyl ether), 2',7'-difluorofluorescein diethyl ether, 2',7'-difluorofluorescein dioctadecanoate, 2',7'-difluorofluorescein di-β-D-galactopyranoside, 2',7'-difluorofluorescein di-β-D-glucuronide, 2',7'-difluorofluorescein di(4-guanidinobenzoate), 2',7'-difluorofluorescein diphosphate, tetrasodium salt, 2',7'-difluorofluorescein mono(4-guanidinobenzoate), 2',7'-difluoro-3-O-methylfluorescein phosphate, 2',7 '-difluoro-5-((pentafluorobenzoyl)amino)fluorescein diacetate, 2',4,5,6,7,7'-hexafluorofluorescein diacetate, 6'-L-leucylamino-3'-methoxy-4,5,6,7-tetrafluorospiro(isobenzofuran)-1(3H),9'-(9H)xanthen-3 -one, 2',4',5',7'-tetrafluorofluorescein diacetate, 4,5,6,7-tetrafluorofluorescein diacetate, 4,5,6,7-tetrafluorofluorescein di-β-D-galactopyranoside or 4,5,6,7-tetrafluorofluorescein diphosphate, tetraammonium salt.

Claim 91

Independent Claim 1253 words

A method of staining a biological sample, comprising the steps of: a) preparing a dye solution comprising a dye compound of the formula: ##STR23## or the formula ##STR24## wherein R 1 and R 6 are independently H, F, Cl, Br, I, C 1 -C 18 alkyl or C 1 -C 18 alkoxy; R 2 , R 3 , R 4 and R 5 are independently H, F, Cl, Br, I, CN; or C 1 -C 18 alkyl, C 1 -C 18 alkoxy or C 1 -C 18 alkylthio, where each alkyl, alkoxy or alkylthio is optionally further substituted by F, Cl, Br, I, sulfonic acid, salt of sulfonic acid, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 where R 18 is a C 1 -C 4 alkyl; or amino, alkylamino, dialkylamino, or alkoxy, the alkyl portions of which independently have 1-6 carbons; or one or both of R 3 and R 4 are --CH 2 N(CH 2 COOR 17 ) 2 , where R 17 is H, a biologically compatible counterion, a linear or branched alkyl having 1-6 carbons, or --CH 2 --O--(C═O)--R 18 ; or one or more of R 2 , R 3 , R 4 , and R 5 is --L--R x ; or one or more of R 2 , R 3 , R 4 , and R 5 is --L--S c ; A is OR 7 or NR 8 R 9 , where each R 7 is independently a BLOCK, or R 7 is --L--R x , or R 7 is --L--S c ; R 8 and R 9 are independently H, C 1 -C 6 alkyl, C 1 -C 6 carboxyalkyl, C 1 -C 6 sulfoalkyl, a salt of C 1 -C 6 carboxyalkyl, a salt of C 1 -C 6 sulfoalkyl, or C 1 -C 18 acyl wherein the alkyl portions are optionally substituted by amino, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or R 8 in combination with R 2 , or R 9 in combination with R 3 , or both, form a saturated 5- or 6-membered ring that is optionally substituted by one or more methyls; or R 8 in combination with R 9 forms a saturated 5- or 6-membered heterocycle that is a piperidine, a morpholine, a pyrrolidine or a piperazine, each of which is optionally substituted by methyl, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, or a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or one of R 8 and R 9 is a BLOCK; or one of R 8 and R 9 is --L--R x ; or one of R 8 and R 9 is --L--S c ; and R 10 is F, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, or a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or R 10 is C 1 -C 18 alkyl, alkenyl or alkynyl that is optionally substituted one or more times by F, Cl, Br, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , sulfonic acid, salt of sulfonic acid, amino, alkylamino, or dialkylamino, the alkyl groups of which have 1-6 carbons; or R 10 is --L--R x ; or R 10 is --L--S c ; or R 10 has the formula ##STR25## where R 12 , R 13 , R 14 , R 15 and R 16 are independently H, F, Cl, Br, I; or sulfonic acid, salt of sulfonic acid, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , CN, nitro, hydroxy, azido, amino, hydrazino; or C 1 -C 18 alkyl, C 1 -C 18 alkoxy, C 1 -C 18 alkylthio, C 1 -C 18 alkylamino, C 1 -C 18 alkylester, C 1 -C 18 alkylamido or C 1 -C 18 arylamido, the alkyl or aryl portions of which are optionally substituted one or more times by F, Cl, Br, I, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , sulfonic acid, salt of sulfonic acid, amino, alkylamino, dialkylamino or alkoxy, the alkyl portions of each having 1-6 carbons; or one pair of adjacent substituents R 13 and R 14 , R 14 and R 15 or R 15 and R 16 , when taken in combination, form a fused 6-membered aromatic ring that is optionally further substituted by carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or one or more of R 12 , R 13 , R 14 , R 15 and R 16 is --L--R x ; or one or more of R 12 , R 13 , R 14 , R 15 and R 16 is --L--S c ; R 11 is H, hydroxy, CN or a C 1 -C 6 alkoxy; or R 10 in combination with R 11 forms a 5-membered spirolactone ring or a 5-membered spirosultone ring; or R 11 in combination with R 12 forms a 5- or 6-membered spirolactone ring or a 5- or 6-membered spirosultone ring that is optionally and independently substituted by H, F or CH 3 ; or R 10 in combination with R 11 is a carbonyl oxygen; provided that at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 10 is F, or at least three of R 12 , R 13 , R 4 , R 15 and R 16 are F; each L is a single covalent bond, or L is a covalent linkage having 1-24 nonhydrogen atoms selected from the group consisting of C, N, O and S and is composed of any combination of single, double, triple or aromatic carbon-carbon bonds, carbon-nitrogen bonds, nitrogen-nitrogen bonds, carbon-oxygen bonds and carbon-sulfur bonds; and R x is a reactive site; S c is a conjugated substance; and each BLOCK moiety is independently a monovalent moiety derived by removal of a hydroxy group from phosphate or from sulfate, or a biologically compatible salt thereof; or a monovalent moiety derived by removal of a hydroxy group from a carboxy group of an aliphatic or aromatic carboxylic acid or of an amino acid, protected amino acid, peptide, or protected peptide; or a monovalent moiety derived by removal of a hydroxy group from an alcohol or from a mono- or polysaccharide, where said BLOCK is selected to be removable from said compound by action of an enzyme; or BLOCK is a photolabile caging group; in a concentration sufficient to yield a detectable optical response under the desired conditions; b) combining the sample of interest with the dye solution for a period of time sufficient for the dye compound to yield a detectable optical response upon illumination; and c) illuminating said sample at a wavelength selected to elicit said optical response.

Claim 92

Independent Claim 1253 words

A method of staining a biological sample, comprising the steps of: a) preparing a dye solution comprising a dye compound of the formula: ##STR23## or the formula ##STR24## wherein R 1 and R 6 are independently H, F, Cl, Br, I, C 1 -C 18 alkyl or C 1 -C 18 alkoxy; R 2 , R 3 , R 4 and R 5 are independently H, F, Cl, Br, I, CN; or C 1 -C 18 alkyl, C 1 -C 18 alkoxy or C 1 -C 18 alkylthio, where each alkyl, alkoxy or alkylthio is optionally further substituted by F, Cl, Br, I, sulfonic acid, salt of sulfonic acid, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 where R 18 is a C 1 -C 4 alkyl; or amino, alkylamino, dialkylamino, or alkoxy, the alkyl portions of which independently have 1-6 carbons; or one or both of R 3 and R 4 are --CH 2 N(CH 2 COOR 17 ) 2 , where R 17 is H, a biologically compatible counterion, a linear or branched alkyl having 1-6 carbons, or --CH 2 --O--(C═O)--R 18 ; or one or more of R 2 , R 3 , R 4 , and R 5 is --L--R x ; or one or more of R 2 , R 3 , R 4 , and R 5 is --L--S c ; A is OR 7 or NR 8 R 9 , where each R 7 is independently a BLOCK, or R 7 is --L--R x , or R 7 is --L--S c ; R 8 and R 9 are independently H, C 1 -C 6 alkyl, C 1 -C 6 carboxyalkyl, C 1 -C 6 sulfoalkyl, a salt of C 1 -C 6 carboxyalkyl, a salt of C 1 -C 6 sulfoalkyl, or C 1 -C 18 acyl wherein the alkyl portions are optionally substituted by amino, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or R 8 in combination with R 2 , or R 9 in combination with R 3 , or both, form a saturated 5- or 6-membered ring that is optionally substituted by one or more methyls; or R 8 in combination with R 9 forms a saturated 5- or 6-membered heterocycle that is a piperidine, a morpholine, a pyrrolidine or a piperazine, each of which is optionally substituted by methyl, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, or a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or one of R 8 and R 9 is a BLOCK; or one of R 8 and R 9 is --L--R x ; or one of R 8 and R 9 is --L--S c ; and R 10 is F, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, or a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or R 10 is C 1 -C 18 alkyl, alkenyl or alkynyl that is optionally substituted one or more times by F, Cl, Br, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , sulfonic acid, salt of sulfonic acid, amino, alkylamino, or dialkylamino, the alkyl groups of which have 1-6 carbons; or R 10 is --L--R x ; or R 10 is --L--S c ; or R 10 has the formula ##STR25## where R 12 , R 13 , R 14 , R 15 and R 16 are independently H, F, Cl, Br, I; or sulfonic acid, salt of sulfonic acid, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , CN, nitro, hydroxy, azido, amino, hydrazino; or C 1 -C 18 alkyl, C 1 -C 18 alkoxy, C 1 -C 18 alkylthio, C 1 -C 18 alkylamino, C 1 -C 18 alkylester, C 1 -C 18 alkylamido or C 1 -C 18 arylamido, the alkyl or aryl portions of which are optionally substituted one or more times by F, Cl, Br, I, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , sulfonic acid, salt of sulfonic acid, amino, alkylamino, dialkylamino or alkoxy, the alkyl portions of each having 1-6 carbons; or one pair of adjacent substituents R 13 and R 14 , R 14 and R 15 or R 15 and R 16 , when taken in combination, form a fused 6-membered aromatic ring that is optionally further substituted by carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or one or more of R 12 , R 13 , R 14 , R 15 and R 16 is --L--R x ; or one or more of R 12 , R 13 , R 14 , R 15 and R 16 is --L--S c ; R 11 is H, hydroxy, CN or a C 1 -C 6 alkoxy; or R 10 in combination with R 11 forms a 5-membered spirolactone ring or a 5-membered spirosultone ring; or R 11 in combination with R 12 forms a 5- or 6-membered spirolactone ring or a 5- or 6-membered spirosultone ring that is optionally and independently substituted by H, F or CH 3 ; or R 10 in combination with R 11 is a carbonyl oxygen; provided that at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 10 is F, or at least three of R 12 , R 13 , R 4 , R 15 and R 16 are F; each L is a single covalent bond, or L is a covalent linkage having 1-24 nonhydrogen atoms selected from the group consisting of C, N, O and S and is composed of any combination of single, double, triple or aromatic carbon-carbon bonds, carbon-nitrogen bonds, nitrogen-nitrogen bonds, carbon-oxygen bonds and carbon-sulfur bonds; and R x is a reactive site; S c is a conjugated substance; and each BLOCK moiety is independently a monovalent moiety derived by removal of a hydroxy group from phosphate or from sulfate, or a biologically compatible salt thereof; or a monovalent moiety derived by removal of a hydroxy group from a carboxy group of an aliphatic or aromatic carboxylic acid or of an amino acid, protected amino acid, peptide, or protected peptide; or a monovalent moiety derived by removal of a hydroxy group from an alcohol or from a mono- or polysaccharide, where said BLOCK is selected to be removable from said compound by action of an enzyme; or BLOCK is a photolabile caging group; in a concentration sufficient to yield a detectable optical response under the desired conditions; b) combining the sample of interest with the dye solution for a period of time sufficient for the dye compound to yield a detectable optical response upon illumination; and c) illuminating said sample at a wavelength selected to elicit said optical response.

Claim 93

Dependent Claim 22 words

A method of staining, as claimed in claim 87, further comprising washing the sample after combining the sample with the dye solution.

Claim 94

Dependent Claim 31 words

A method of staining, as claimed in claim 88, further comprising combining the sample with an additional detection reagent that has spectral properties that are detectably different from said optical response.

Claim 95

Dependent Claim 30 words

A method of staining, as claimed in claim 88, further comprising the step of determining a characteristic of the sample by comparing the optical response with a standard response parameter.

Claim 96

Dependent Claim 37 words

A method of staining, as claimed in claim 90, wherein the characteristic of the sample being determined is the activity of an oxidative enzyme in a sample, and where for said dye compound R 11 is H.

Claim 97

Dependent Claim 167 words

A method of staining, as claimed in claim 90, wherein said sample comprises cells, and the characteristic of the sample being determined is the retention efficiency of said cells, and wherein the dye solution comprises a dye of the formula ##STR26## wherein R 2 , R 3 , R 4 and R 5 are independently H, F, Cl, Br, I, CN, C 1 -C 18 alkyl, C 1 -C 18 alkoxy or C 1 -C 18 alkylthio, where each alkyl, alkoxy or alkylthio is optionally further substituted by F, Cl, Br, I, amino, alkylamino, dialkylamino, or alkoxy, the alkyl portions of which independently have 1-6 carbons; or one or both of R 3 and R 4 are --CH 2 N(CH 2 COOR 17 ) 2 , where R 17 is a linear or branched alkyl having 1-6 carbons, or --CH 2 --O--(C═O)--R 18 where R 18 is a C 1 -C 4 alkyl; in the minimum concentration that gives a detectable optical response that is fluorescence emission.

Claim 98

Dependent Claim 116 words

A method of staining, as claimed in claim 92, wherein comparing comprises comparing the fluorescence emission within the cells in the sample with the fluorescence within in cells having a known cellular efflux pump efficiency, and where for said dye compound BLOCK is a monovalent moiety derived by removal of a hydroxy group from phosphate or from sulfate, or a biologically compatible salt thereof; or a monovalent moiety derived by removal of a hydroxy group from a carboxy group of an aliphatic or aromatic carboxylic acid; or a monovalent moiety derived by removal of a hydroxy group from an alcohol, where said BLOCK is selected to be removable from said compound by action of an enzyme.

Claim 99

Dependent Claim 13 words

A method of staining, as claimed in claim 92, wherein BLOCK is acetate.

Claim 100

Dependent Claim 26 words

A method of staining, as claimed in claim 90, wherein comparing comprises tracing the temporal or spatial location of the optical response within the biological sample.

Claim 101

Dependent Claim 158 words

A method of staining, as claimed in claim 95, wherein for said dye compound R 2 , R 3 , R 4 and R 5 are independently H or F; R 12 is carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , sulfonic acid or a salt of sulfonic acid,; R 13 , R 14 , R 15 and R 16 are independently H, F, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , sulfonic acid, salt of sulfonic acid, or C 1 -C 6 alkylthio that is optionally substituted by carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, or a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 .

Claim 102

Dependent Claim 152 words

A method of staining, as claimed in claim 95, wherein for said dye compound one or both of R 3 and R 4 are --CH 2 N(CH 2 COOR 17 ) 2 , where R 17 is H, a biologically compatible counterion, a linear or branched alkyl having 1-carbons, or --CH 2 --O--(C═O)--R 18 where R 18 is a C 1 -C 4 alkyl; or one or R 13 , R 14 , R 15 and R 16 is carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 where R 18 is a C 1 -C 4 alkyl, sulfonic acid, salt of sulfonic acid, C 1 -C 18 alkyl, C 1 -Cls alkoxy, C 1 -C 18 alkylthio, C 1 -C 18 alkylamino, C 1 -C 18 alkylamido or C 1 -C 18 arylamido.

Claim 103

Dependent Claim 55 words

A method of staining, as claimed in claim 97, wherein one of R 13 , R 14 , R 15 and R 16 is C 1 -C 18 alkyl, C 1 -C 18 alkoxy, C 1 -C 18 alkylthio, C 1 -C 18 alkylamino, C 1 -C 18 alkylamido or C 1 -C 18 arylamido.

Claim 104

Dependent Claim 45 words

A method of staining, as claimed in claim 95, wherein for said dye compound at least one of R 13 , R 14 , R 15 and R 16 is --L--R x ; where R x is a haloacetamide, an alkyl halide, halomethylbenzamido or perfluorobenzamido.

Claim 105

Dependent Claim 70 words

A method of staining, as claimed in claim 95, wherein for said dye compound at least one of R 13 , R 14 , R 15 and R 16 is --L--S c ; where S c is a protein, a polysaccharide, an ion-complexing moiety, a lipid, or a non-biological organic polymer or polymeric microparticle, that is optionally bound to one or more additional fluorophores that are the same or different.

Claim 106

Dependent Claim 49 words

A method of staining, as claimed in claim 95, wherein for said dye compound at least one R 7 is a BLOCK that is a monovalent moiety derived by removal of a hydroxy group from a carboxy group of a carboxylic acid, or BLOCK is a photolabile caging group.

Claim 107

Dependent Claim 85 words

A method of staining, as claimed in claim 87, wherein said sample further comprises cells, and wherein for said dye compound at least one R 7 is a BLOCK or H; R 11 in combination with R 12 forms a 5- or 6-membered spirolactone ring or a 5- or 6-membered spirosultone ring; and each of R 13 -R 16 is F; further comprising optionally washing the cells, after combining the sample with the dye compound, to remove residual dye compound that is outside said cells.

Claim 108

Dependent Claim 992 words

One or more dye compounds of the formula ##STR27## or the formula ##STR28## wherein R 1 and R 6 are independently H, F, Cl, Br, I, C 1 -C 18 alkyl or C 1 -C 18 alkoxy; R 2 , R 3 , R 4 and R 5 are independently H, F, Cl, Br, I, CN; or C 1 -C 18 alkyl, C 1 -C 18 alkoxy or C 1 -C 18 alkylthio, where each alkyl, alkoxy or alkylthio is optionally further substituted by F, Cl, Br, I, sulfonic acid, salt of sulfonic acid, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 where R 18 is a C 1 -C 4 alkyl; or amino, alkylamino, dialkylamino, or alkoxy, the alkyl portions of which independently have 1-6 carbons; A is OR 7 or NR 8 R 9 , where each R 7 is independently H, C 1 -C 18 alkyl, a C 1 -C 18 acyl wherein each alkyl group independently has 1-6 carbons and is optionally substituted by amino, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; R 8 and R 9 are independently H, C 1 -C 6 alkyl, C 1 -C 6 carboxyalkyl, C 1 -C 6 sulfoalkyl, a salt of C 1 -C 6 carboxyalkyl, a salt of C 1 -C 6 sulfoalkyl, or C 1 -C 18 acyl wherein the alkyl portions are optionally substituted by amino, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or R 8 in combination with R 2 , or R 9 in combination with R 3 , or both, form a saturated 5- or 6-membered ring that is optionally substituted by one or more methyls; or R 8 in combination with R 9 forms a saturated 5- or 6-membered heterocycle that is a piperidine, a morpholine, a pyrrolidine or a piperazine, each of which is optionally substituted by methyl, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, or a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; R 10 is F, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, or a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or R 10 is C 1 -C 18 alkyl, alkenyl or alkynyl that is optionally substituted one or more times by F, Cl, Br, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , sulfonic acid, salt of sulfonic acid, amino, alkylamino, or dialkylamino, the alkyl groups of which have 1-6 carbons; or R 10 is --L--; or R 10 has the formula ##STR29## where R 12 , R 13 , R 14 , R 15 and R 16 are independently H, F, Cl, Br, I; or sulfonic acid, salt of sulfonic acid, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , CN, nitro, hydroxy, azido, amino, hydrazino; or C 1 -C 18 alkyl, C 1 -C 18 alkoxy, C 1 -C 18 alkylthio, C 1 -C 18 alkylamino, C 1 -C 18 alkylester, C 1 -C 18 alkylamido or C 1 -C 18 arylamido, the alkyl or aryl portions of which are optionally substituted one or more times by F, Cl, Br, I, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , sulfonic acid, salt of sulfonic acid, amino, alkylamino, dialkylamino or alkoxy, the alkyl portions of each having 1-6 carbons; or one pair of adjacent substituents R 13 and R 14 , R 14 and R 15 or R 15 and R 16 , when taken in combination, form a fused 6-membered aromatic ring that is optionally further substituted by carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; R 11 is H, hydroxy, CN or a C 1 -C 6 alkoxy; or R 10 in combination with R 11 forms a 5-membered spirolactone ring or a 5-membered spirosultone ring; or R 11 in combination with R 12 forms a 5- or 6-membered spirolactone ring or a 5- or 6-membered spirosultone ring that is optionally and independently substituted by H, F or CH 3 ; or R 10 in combination with R 11 is a carbonyl oxygen; provided that at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 10 is F, or at least three of R 12 , R 13 , R 14 , R 15 and R 16 are F; and further provided that one of R 2 , R 3 , R 4 , R 5 , R 7 , R 8 , R 9 , R 10 , R 12 , R 13 , R 14 , R 15 or R 16 on each dye is --L--; where each L is a single covalent bond, or L is a covalent linkage having 1-24 nonhydrogen atoms selected from the group consisting of C, N, O and S and is composed of any combination of single, double, triple or aromatic carbon-carbon bonds, carbon-nitrogen bonds, nitrogen-nitrogen bonds, carbon-oxygen bonds and carbon-sulfur bonds; and each --L-- is bound to a S c that is a conjugated substance.

Claim 109

Dependent Claim 992 words

One or more dye compounds of the formula ##STR27## or the formula ##STR28## wherein R 1 and R 6 are independently H, F, Cl, Br, I, C 1 -C 18 alkyl or C 1 -C 18 alkoxy; R 2 , R 3 , R 4 and R 5 are independently H, F, Cl, Br, I, CN; or C 1 -C 18 alkyl, C 1 -C 18 alkoxy or C 1 -C 18 alkylthio, where each alkyl, alkoxy or alkylthio is optionally further substituted by F, Cl, Br, I, sulfonic acid, salt of sulfonic acid, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 where R 18 is a C 1 -C 4 alkyl; or amino, alkylamino, dialkylamino, or alkoxy, the alkyl portions of which independently have 1-6 carbons; A is OR 7 or NR 8 R 9 , where each R 7 is independently H, C 1 -C 18 alkyl, a C 1 -C 18 acyl wherein each alkyl group independently has 1-6 carbons and is optionally substituted by amino, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; R 8 and R 9 are independently H, C 1 -C 6 alkyl, C 1 -C 6 carboxyalkyl, C 1 -C 6 sulfoalkyl, a salt of C 1 -C 6 carboxyalkyl, a salt of C 1 -C 6 sulfoalkyl, or C 1 -C 18 acyl wherein the alkyl portions are optionally substituted by amino, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or R 8 in combination with R 2 , or R 9 in combination with R 3 , or both, form a saturated 5- or 6-membered ring that is optionally substituted by one or more methyls; or R 8 in combination with R 9 forms a saturated 5- or 6-membered heterocycle that is a piperidine, a morpholine, a pyrrolidine or a piperazine, each of which is optionally substituted by methyl, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, or a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; R 10 is F, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, or a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; or R 10 is C 1 -C 18 alkyl, alkenyl or alkynyl that is optionally substituted one or more times by F, Cl, Br, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , sulfonic acid, salt of sulfonic acid, amino, alkylamino, or dialkylamino, the alkyl groups of which have 1-6 carbons; or R 10 is --L--; or R 10 has the formula ##STR29## where R 12 , R 13 , R 14 , R 15 and R 16 are independently H, F, Cl, Br, I; or sulfonic acid, salt of sulfonic acid, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , CN, nitro, hydroxy, azido, amino, hydrazino; or C 1 -C 18 alkyl, C 1 -C 18 alkoxy, C 1 -C 18 alkylthio, C 1 -C 18 alkylamino, C 1 -C 18 alkylester, C 1 -C 18 alkylamido or C 1 -C 18 arylamido, the alkyl or aryl portions of which are optionally substituted one or more times by F, Cl, Br, I, hydroxy, carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 , sulfonic acid, salt of sulfonic acid, amino, alkylamino, dialkylamino or alkoxy, the alkyl portions of each having 1-6 carbons; or one pair of adjacent substituents R 13 and R 14 , R 14 and R 15 or R 15 and R 16 , when taken in combination, form a fused 6-membered aromatic ring that is optionally further substituted by carboxylic acid, a salt of carboxylic acid, a carboxylic acid ester of a C 1 -C 6 alkyl, a carboxylic acid ester of --CH 2 --O--(C═O)--R 18 ; R 11 is H, hydroxy, CN or a C 1 -C 6 alkoxy; or R 10 in combination with R 11 forms a 5-membered spirolactone ring or a 5-membered spirosultone ring; or R 11 in combination with R 12 forms a 5- or 6-membered spirolactone ring or a 5- or 6-membered spirosultone ring that is optionally and independently substituted by H, F or CH 3 ; or R 10 in combination with R 11 is a carbonyl oxygen; provided that at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 10 is F, or at least three of R 12 , R 13 , R 14 , R 15 and R 16 are F; and further provided that one of R 2 , R 3 , R 4 , R 5 , R 7 , R 8 , R 9 , R 10 , R 12 , R 13 , R 14 , R 15 or R 16 on each dye is --L--; where each L is a single covalent bond, or L is a covalent linkage having 1-24 nonhydrogen atoms selected from the group consisting of C, N, O and S and is composed of any combination of single, double, triple or aromatic carbon-carbon bonds, carbon-nitrogen bonds, nitrogen-nitrogen bonds, carbon-oxygen bonds and carbon-sulfur bonds; and each --L-- is bound to a S c that is a conjugated substance.

Claim 110

Dependent Claim 14 words

A compound, as claimed in claim 54, wherein S c is an ion-complexing moiety.

Claim 111

Dependent Claim 19 words

A compound, as claimed in claim 104, wherein the ion-complexing moiety is a BAPTA or APTRA or a phenanthroline.

Claim 112

Dependent Claim 39 words

A compound, as claimed in claim 105, wherein A is OR 7 ; R 2 and R 5 are each F; R 10 is --L--S c ; and the conjugated substance is an ion-complexing moiety that is a BAPTA.

Claim 113

Dependent Claim 14 words

A compound, as claimed in claim 106, wherein L is a single covalent bond.

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	2003-12-19	2004-06-19	2004-12-19	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	2007-12-19	2008-06-19	2008-12-19	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	2011-12-19	2012-06-19	2012-12-19	$7700.00	Window Closed / Lapsed

Fluorinated xanthene derivatives

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