US5453517A
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Reactive derivatives of bapta used to make ion-selective chelators
Assignee: Molecular Probes Inc
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Filing: 1992-02-25
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Granted: 1995-09-26
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Expires: 2012-02-25
Abstract
Abstract The invention relates to fluorescent and/or reactive derivatives of 1,2-bis-(2-aminophenoxyethane)-N,N,N',N'-tetraacetic acid (BAPTA) according to the formula: ##STR1## where at least one of W and X is a functional group, with or without a spacer, that terminates in an alcohol or phenol, a thiol, a haloacetamide, an alkyl halide, an amine or aniline, a carboxylic acid, an anhydride, an isocyanate, an isothiocyanate, a maleimide, or an activated ester. The BAPTA-like molecule may be further substituted, one or more times, by additional functional groups with or without spacers or by CH 3 , NO 2 , CF 3 , F, Cl, Br, I, or carboxylic acid derivatives or pharmaceutically acceptable salts thereof, or by indolyl or benzofuran fluorophores. The functional groups allow for subsequent covalent attachment of one or more oxygen heterocycle fluorophores (e.g. fluorescein, coumarin, rhodamine); or polymolecular assemblies (e.g. gel and resin polymers, polysaccharides, polypeptides, nucleic acids, and liposomes); or combinations thereof.
Inventors
- 👤 Michael A. Kuhn
- 👤 Richard P. Haugland
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-29 12:12
CPC Classifications
C; C07; C07D; C07D311/00; C07D311/02; C07D311/78; C07D311/80; C07D311/82; C07D209/00; C07D209/02; C07D209/04; C07D209/10; C07D209/14; C07D311/90; C07D413/00; C07D413/02; C07D413/04; C09; C09K; C09K11/00; C09K11/06
Claims Analysis
Total Claims: 71
Claim 1
Independent Claim
714 words
A compound of the formula: ##STR8## where both of W and X, which may be the same or different, are functional groups of the formula (R 1 ) n (R 2 ), wherein n=0 or 1; R 1 is a spacer that is --OCH 2 R 3 --, --OR 3 --, --SR 3 --, --SR 3' --, --NHCOCH 2 R 3 --, --NHCOR 3' --, --CONHCH 2 R 3 --, --CONHR 3 --, --NHSO 2 R 3 --, --NHSO 2 R 3' --, --NHCONHCH 2 R 3 --, --NHCONHR 3' --, --NHCSNHCH 2 R 3 --, or --NHCSNHR 3 --, where R 3 is (CH 2 ) m and m=1-18, and R 3' is phenylene (--C 6 H 4 --); and R 2 is a reactive terminus that is an alcohol or phenol, a thiol, a haloacetamide, an alkyl halide, an alkyl sulfonate, an amine or aniline, a carboxylic acid, an anhydride, an isocyanate, an isothiocyanate, a maleimide, or an activated ester; or one of W and X is a functional group of the formula (R 1 ) n (R 2 ) in any of its described variations, and the other of W and X is H, CH 3 , NO 2 , CF 3 , F, Cl, Br, I, or contains a fluorophore according to the formula: (R a ) n (R b ) n ,-FLUOR, wherein n"=O or 1; R a is --OCH 2 R 3 --, --OR 3' --, --SR 3 --, --SR 3' --, --NHCOCH 2 R 3 --, --NHCOR 3' --, --CONHCH 2 R 3 --, --CONHR 3 --, --NHSO 2 R 3 --, --NHSO 2 R 3' --, --NHCONHCH 2 R 3 --, --NHCONHR 3' --, --NHCSNHCH 2 R 3 --, or --NHCSNHR 3' --, where R 3 is (CH 2 ) m and m=1-18, and R 3' is phenylene (--C 6 H 4 --); R b is --NH--, --NHCO--, --NHCS--, --S--, --O--, --CO--; or --CH 2 -- or --COCH 2 --, or succinimidyl, and n'=0 or 1; and -FLUOR is an aromatic oxygen heterocycle fluorophore, or a 2-indolyl or carboxy substituted 2-indolyl, provided that when -FLUOR is a 2-indolyl or a carboxy substituted 2-indolyl fluorophore, n" and n' are 0; or --OR 5 , --CO 2 R 5 , or --OCH 2 CO 2 R 5 , where R 5 is an alkyl group with 1-5 carbons, a benzyl (C 6 H 5 CH 2 --), an alpha-acyloxyalkyl or a pharmaceutically acceptable esterifying group, or a pharmaceutically acceptable salt; and Y and Z, which may be the same or different, are independently H, CH 3 , NO 2 , CF 3 , F, Cl, Br, I, --OR 5 , --CO 2 R 5 , or --OCH 2 CO 2 R 5 , where R 5 is an alkyl group with 1-5 carbons, a benzyl, an alpha-acyloxyalkyl or a pharmaceutically acceptable esterifying group, or a pharmaceutically acceptable salt; a functional group of the formula (R 1 ) n (R 2 ), in any of its described variations; or contains a fluorophore according to the formula: (R a ) n" (R b ) n' -FLUOR, wherein n"=0 or 1; R a is --OCH 2 R 3 --, --OR 3' --, --SR 3 --, --SR 3' --, --NHCOCH 2 R 3 --, --NHCOR 3' --, --CONHCH 2 R 3 --, --CONHR 3' --, --NHSO 2 R 3 --, --NHSO 2 R 3' --, --NHCONHCH 2 R 3 --, --NHCONHR 3' --, --NHCSNHCH 2 R 3 --, or --NHCSNHR 3' --, where R 3 is (CH 2 ) m and m=1-18, and R 3' is phenylene (--C 6 H 4 --); R b is --NH--, --NHCO--, --NHCS--, --S--, --O--, --CO--; or --CH 2 -- or --COCH 2 --, or succinimidyl, and n'=0 or 1; and -FLUOR is an aromatic oxygen heterocycle fluorophore, or a 2-indolyl or carboxy substituted 2-indolyl, provided that when -FLUOR is a 2-indolyl or a carboxy substituted 2-indolyl fluorophore, n" and n' are 0; or combinations thereof; or Y taken together with Z and the aromatic carbons at the 4' and 5' positions form a benzofuran or oxazolyl-substituted or carboxy-oxazolyl substituted benzofuran fluorophore; and R 6 is an alkyl group with 1-5 carbons, a benzyl, an alpha-acyloxyalkyl or a pharmaceutically acceptable esterifying group, or a pharmaceutically acceptable salt.
Claim 2
Dependent Claim
714 words
A compound of the formula: ##STR8## where both of W and X, which may be the same or different, are functional groups of the formula (R 1 ) n (R 2 ), wherein n=0 or 1; R 1 is a spacer that is --OCH 2 R 3 --, --OR 3 --, --SR 3 --, --SR 3' --, --NHCOCH 2 R 3 --, --NHCOR 3' --, --CONHCH 2 R 3 --, --CONHR 3 --, --NHSO 2 R 3 --, --NHSO 2 R 3' --, --NHCONHCH 2 R 3 --, --NHCONHR 3' --, --NHCSNHCH 2 R 3 --, or --NHCSNHR 3 --, where R 3 is (CH 2 ) m and m=1-18, and R 3' is phenylene (--C 6 H 4 --); and R 2 is a reactive terminus that is an alcohol or phenol, a thiol, a haloacetamide, an alkyl halide, an alkyl sulfonate, an amine or aniline, a carboxylic acid, an anhydride, an isocyanate, an isothiocyanate, a maleimide, or an activated ester; or one of W and X is a functional group of the formula (R 1 ) n (R 2 ) in any of its described variations, and the other of W and X is H, CH 3 , NO 2 , CF 3 , F, Cl, Br, I, or contains a fluorophore according to the formula: (R a ) n (R b ) n ,-FLUOR, wherein n"=O or 1; R a is --OCH 2 R 3 --, --OR 3' --, --SR 3 --, --SR 3' --, --NHCOCH 2 R 3 --, --NHCOR 3' --, --CONHCH 2 R 3 --, --CONHR 3 --, --NHSO 2 R 3 --, --NHSO 2 R 3' --, --NHCONHCH 2 R 3 --, --NHCONHR 3' --, --NHCSNHCH 2 R 3 --, or --NHCSNHR 3' --, where R 3 is (CH 2 ) m and m=1-18, and R 3' is phenylene (--C 6 H 4 --); R b is --NH--, --NHCO--, --NHCS--, --S--, --O--, --CO--; or --CH 2 -- or --COCH 2 --, or succinimidyl, and n'=0 or 1; and -FLUOR is an aromatic oxygen heterocycle fluorophore, or a 2-indolyl or carboxy substituted 2-indolyl, provided that when -FLUOR is a 2-indolyl or a carboxy substituted 2-indolyl fluorophore, n" and n' are 0; or --OR 5 , --CO 2 R 5 , or --OCH 2 CO 2 R 5 , where R 5 is an alkyl group with 1-5 carbons, a benzyl (C 6 H 5 CH 2 --), an alpha-acyloxyalkyl or a pharmaceutically acceptable esterifying group, or a pharmaceutically acceptable salt; and Y and Z, which may be the same or different, are independently H, CH 3 , NO 2 , CF 3 , F, Cl, Br, I, --OR 5 , --CO 2 R 5 , or --OCH 2 CO 2 R 5 , where R 5 is an alkyl group with 1-5 carbons, a benzyl, an alpha-acyloxyalkyl or a pharmaceutically acceptable esterifying group, or a pharmaceutically acceptable salt; a functional group of the formula (R 1 ) n (R 2 ), in any of its described variations; or contains a fluorophore according to the formula: (R a ) n" (R b ) n' -FLUOR, wherein n"=0 or 1; R a is --OCH 2 R 3 --, --OR 3' --, --SR 3 --, --SR 3' --, --NHCOCH 2 R 3 --, --NHCOR 3' --, --CONHCH 2 R 3 --, --CONHR 3' --, --NHSO 2 R 3 --, --NHSO 2 R 3' --, --NHCONHCH 2 R 3 --, --NHCONHR 3' --, --NHCSNHCH 2 R 3 --, or --NHCSNHR 3' --, where R 3 is (CH 2 ) m and m=1-18, and R 3' is phenylene (--C 6 H 4 --); R b is --NH--, --NHCO--, --NHCS--, --S--, --O--, --CO--; or --CH 2 -- or --COCH 2 --, or succinimidyl, and n'=0 or 1; and -FLUOR is an aromatic oxygen heterocycle fluorophore, or a 2-indolyl or carboxy substituted 2-indolyl, provided that when -FLUOR is a 2-indolyl or a carboxy substituted 2-indolyl fluorophore, n" and n' are 0; or combinations thereof; or Y taken together with Z and the aromatic carbons at the 4' and 5' positions form a benzofuran or oxazolyl-substituted or carboxy-oxazolyl substituted benzofuran fluorophore; and R 6 is an alkyl group with 1-5 carbons, a benzyl, an alpha-acyloxyalkyl or a pharmaceutically acceptable esterifying group, or a pharmaceutically acceptable salt.
Claim 3
Dependent Claim
151 words
A compound as claimed in claim 1, wherein the reactive terminus (R 2 ) of any functional group, which may be the same or different, is optionally --NH 2 , --NCO, --NCS, --SH, --OH, maleimidyl (--NC 4 H 2 O 2 ); --CH 2 Q or --NHCOCH 2 Q, where Q is Cl, Br, I, methane sulfonyloxy, p-toluenesulfonyloxy, or trifluoromethanesulfonyloxy; or --COR 7 or --O(CH 2 )COR 7 , where R 7 is Cl, --OH, oxysuccinimidyl (--ONC 4 H 4 O 2 ), -1-oxybenzotriazolyl (--OC 6 H 4 N 3 ); or a phenoxy or phenoxy substituted one or more times by substituents that are nitro, fluoro, chloro, cyano, or trifluoromethyl, or combinations thereof; or --OCOR 8 or --OC(═NR 8 )--NHR 9 , where R 8 and R 9 , which may be the same or different, are C 1 --C 6 alkyl, perfluoroalkyl, or alkoxy; or cyclohexyl, 3-dimethylaminopropyl, or N-morpholinoethyl.
Claim 4
Dependent Claim
393 words
A fluorescent ion-selective conjugate with a carrier having the formula: ##STR9## where at least one of W' and X' contains -POLY that is attached by a covalent linkage that is an ether, a thioether, a carboxamide, a sulfonamide, an alkyl amide, a urea or a thiourea linkage, where -POLY is a biologically compatible polymolecular assembly with a molecular weight greater than about 750 Daltons; and at least one of X' and Z' contains a fluorophore according to the formula: (R a ) n (R b ) n' -FLUOR, wherein n=0 or 1; R a is --OCH 2 R 3 --, --OR 3 --, --SR 3 --, --SR 3' --, --NHCOCH 2 R 3 --, --NHCOR 3' --, --CONHCH 2 R 3 --, --CONHR 3' --, --NHSO 2 R 3 --, --NHSO 2 R 3' --, --NHCONHCH 2 R 3 --, --NHCONHR 3' --, --NHCSNHCH 2 R 3 --, or --NHCSNHR 3' --, where R 3 is (CH 2 ) m and m=1-6, and R 3' is phenylene (--C 6 H 4 --); R b is --NH--, --NHCO--, --NHCS--, --S--, --O--, --CO--; or --CH 2 -- or --COCH 2 --, or succinimidyl, and n'=0 or 1; and -FLUOR is an aromatic oxygen heterocycle fluorophore, or a 2-indolyl or a carboxy substituted 2-indolyl fluorophore, provided that when -FLUOR is a 2-indolyl or a carboxy substituted 2-indolyl fluorophore, n and n' are 0; or Z' taken together with Y' and the aromatic carbons at the 4' and 5' positions form a benzofuran or oxazolyl-substituted or carboxy-oxazolyl substituted benzofuran fluorophore; the remainder of substituents W', X', Y', and Z', which may be the same or different, are independently H, CH 3 , NO 2 , CF 3 , F, Cl, Br, I, --OR 5 , --CO 2 R 5 , or --OCH 2 CO 2 R 5 , where R 5 is an alkyl group with 1-5 carbons, a benzyl (C 6 H 5 CH 2 --), an alpha-acyloxyalkyl or a pharmaceutically acceptable esterifying group, or a pharmaceutically acceptable salt; (R a ) n (R b )-POLY, in any of its described variations; or (R a ) n (R b ) n' -FLUOR, in any of its described variations; or combinations thereof; and R 6 is an alkyl group with 1-5 carbons, a benzyl, an alpha-acyloxyalkyl or a pharmaceutically acceptable esterifying group, or a pharmaceutically acceptable salt.
Claim 5
Dependent Claim
393 words
A fluorescent ion-selective conjugate with a carrier having the formula: ##STR9## where at least one of W' and X' contains -POLY that is attached by a covalent linkage that is an ether, a thioether, a carboxamide, a sulfonamide, an alkyl amide, a urea or a thiourea linkage, where -POLY is a biologically compatible polymolecular assembly with a molecular weight greater than about 750 Daltons; and at least one of X' and Z' contains a fluorophore according to the formula: (R a ) n (R b ) n' -FLUOR, wherein n=0 or 1; R a is --OCH 2 R 3 --, --OR 3 --, --SR 3 --, --SR 3' --, --NHCOCH 2 R 3 --, --NHCOR 3' --, --CONHCH 2 R 3 --, --CONHR 3' --, --NHSO 2 R 3 --, --NHSO 2 R 3' --, --NHCONHCH 2 R 3 --, --NHCONHR 3' --, --NHCSNHCH 2 R 3 --, or --NHCSNHR 3' --, where R 3 is (CH 2 ) m and m=1-6, and R 3' is phenylene (--C 6 H 4 --); R b is --NH--, --NHCO--, --NHCS--, --S--, --O--, --CO--; or --CH 2 -- or --COCH 2 --, or succinimidyl, and n'=0 or 1; and -FLUOR is an aromatic oxygen heterocycle fluorophore, or a 2-indolyl or a carboxy substituted 2-indolyl fluorophore, provided that when -FLUOR is a 2-indolyl or a carboxy substituted 2-indolyl fluorophore, n and n' are 0; or Z' taken together with Y' and the aromatic carbons at the 4' and 5' positions form a benzofuran or oxazolyl-substituted or carboxy-oxazolyl substituted benzofuran fluorophore; the remainder of substituents W', X', Y', and Z', which may be the same or different, are independently H, CH 3 , NO 2 , CF 3 , F, Cl, Br, I, --OR 5 , --CO 2 R 5 , or --OCH 2 CO 2 R 5 , where R 5 is an alkyl group with 1-5 carbons, a benzyl (C 6 H 5 CH 2 --), an alpha-acyloxyalkyl or a pharmaceutically acceptable esterifying group, or a pharmaceutically acceptable salt; (R a ) n (R b )-POLY, in any of its described variations; or (R a ) n (R b ) n' -FLUOR, in any of its described variations; or combinations thereof; and R 6 is an alkyl group with 1-5 carbons, a benzyl, an alpha-acyloxyalkyl or a pharmaceutically acceptable esterifying group, or a pharmaceutically acceptable salt.
Claim 6
Dependent Claim
25 words
A conjugate, as claimed in claim 3, wherein -FLUOR is a fluorescein, a rhodamine, a coumarin, or a 2-indolyl or a carboxy substituted 2-indolyl fluorophore.
Claim 7
Dependent Claim
500 words
A fluorescent ion-selective compound having the formula: ##STR10## where at least one of W', X', Y' and Z' contains a fluorophore conjugate -FLUOR' that is attached to the compound by a covalent linkage that is an ether, thioether, sulfonamide, carboxamide, alkyl amine, urea, or thiourea linkage, according to the formula: (R a ) n (R b )-FLUOR', wherein n=0 or 1; R a is --OCH 2 R 3 --, --OR 3' --, --SR 3 --, --SR 3' --, NHCOCH 2 R 3 --, --NHCOR 3' --, --CONHCH 2 R 3 --, --CONHR 3' --, NHSO 2 R 3 --, --NHSO 2 R 3' --, --NHCONHCH 2 R 3 --, --NHCONHR 3' --, --NHCSNHCH 2 R 3 --, or --NHCSNHR 3' --, where R 3 is (CH 2 ) m and m=1-6, and R 3' is phenylene (--C 6 H 4 --); R b is --NH--, --NHCO--, --NHCS--, --S--, --O--, --CO--; or --CH 2 -- or --COCH 2 --, or succinimidyl; and -FLUOR' is a fluorescein, rhodamine or coumarin fluorophore; and the remainder of substituents W', X', Y', and Z', which may be the same or different, are independently H, CH 3 , NO 2 , CF 3 , F, Cl, Br, I, --OR 5 , --CO 2 R 5 , or --OCH 2 CO 2 R 5 , where R 5 is an alkyl group with 1-5 carbons, a benzyl (C 6 H 5 CH 2 --), an alpha-acyloxyalkyl or a pharmaceutically acceptable esterifying group, or a pharmaceutically acceptable salt; or contains an additional fluorophore -FLUOR that is attached to the compound by a covalent linkage that is an ether, thioether, sulfonamide, carboxamide, alkylamine, urea, or thiourea linkage or a single covalent bond, according to the formula: (R a ) n (R b ) n' -FLUOR, wherein n=0 or 1; R a is --OCH 2 R 3 --, --OR 3' --, --SR 3 --, --SR 3' --, NHCOCH 2 R 3 --, --NHCOR 3' --, --CONHCH 2 R 3 --, --CONHR 3' --, --NHSO 2 R 3 --, --NHSO 2 R 3' --, --NHCONHCH 2 R 3 --, --NHCONHR 3' --, --NHCSNHCH 2 R 3 --, or --NHCSNHR 3' --, where R 3 is (CH 2 ) m and m=1-6, and R 3' is phenylene (--C 6 H 4 --); R b is --NH--, --NHCO--, --NHCONH--, --NHCS--, --NHCSNH-- , --NHSO 2 --, --S--, --O--, --CO--; or --CH 2 -- or --COCH 2 --, or succinimidyl, and n'=0 or 1; and -FLUOR is a fluorescein rhodamine or coumarin fluorophore, a 2-indolyl or a carboxy substituted 2-indolyl fluorophore, provided that when -FLUOR is a 2-indolyl or a carboxy, substituted 2-indolyl fluorophore, the linkage is a single covalent bond; or Z' taken together with Y' and the aromatic carbons at the 4' and 5' positions form a benzofuran or oxazolyl-substituted or carboxy-oxazolyl substituted benzofuran fluorophore; or combinations thereof; and R 6 is an alkyl group with 1-5 carbons, a benzyl, an alpha-acyloxyalkyl or a pharmaceutically acceptable esterifying group, or a pharmaceutically acceptable salt.
Claim 8
Dependent Claim
500 words
A fluorescent ion-selective compound having the formula: ##STR10## where at least one of W', X', Y' and Z' contains a fluorophore conjugate -FLUOR' that is attached to the compound by a covalent linkage that is an ether, thioether, sulfonamide, carboxamide, alkyl amine, urea, or thiourea linkage, according to the formula: (R a ) n (R b )-FLUOR', wherein n=0 or 1; R a is --OCH 2 R 3 --, --OR 3' --, --SR 3 --, --SR 3' --, NHCOCH 2 R 3 --, --NHCOR 3' --, --CONHCH 2 R 3 --, --CONHR 3' --, NHSO 2 R 3 --, --NHSO 2 R 3' --, --NHCONHCH 2 R 3 --, --NHCONHR 3' --, --NHCSNHCH 2 R 3 --, or --NHCSNHR 3' --, where R 3 is (CH 2 ) m and m=1-6, and R 3' is phenylene (--C 6 H 4 --); R b is --NH--, --NHCO--, --NHCS--, --S--, --O--, --CO--; or --CH 2 -- or --COCH 2 --, or succinimidyl; and -FLUOR' is a fluorescein, rhodamine or coumarin fluorophore; and the remainder of substituents W', X', Y', and Z', which may be the same or different, are independently H, CH 3 , NO 2 , CF 3 , F, Cl, Br, I, --OR 5 , --CO 2 R 5 , or --OCH 2 CO 2 R 5 , where R 5 is an alkyl group with 1-5 carbons, a benzyl (C 6 H 5 CH 2 --), an alpha-acyloxyalkyl or a pharmaceutically acceptable esterifying group, or a pharmaceutically acceptable salt; or contains an additional fluorophore -FLUOR that is attached to the compound by a covalent linkage that is an ether, thioether, sulfonamide, carboxamide, alkylamine, urea, or thiourea linkage or a single covalent bond, according to the formula: (R a ) n (R b ) n' -FLUOR, wherein n=0 or 1; R a is --OCH 2 R 3 --, --OR 3' --, --SR 3 --, --SR 3' --, NHCOCH 2 R 3 --, --NHCOR 3' --, --CONHCH 2 R 3 --, --CONHR 3' --, --NHSO 2 R 3 --, --NHSO 2 R 3' --, --NHCONHCH 2 R 3 --, --NHCONHR 3' --, --NHCSNHCH 2 R 3 --, or --NHCSNHR 3' --, where R 3 is (CH 2 ) m and m=1-6, and R 3' is phenylene (--C 6 H 4 --); R b is --NH--, --NHCO--, --NHCONH--, --NHCS--, --NHCSNH-- , --NHSO 2 --, --S--, --O--, --CO--; or --CH 2 -- or --COCH 2 --, or succinimidyl, and n'=0 or 1; and -FLUOR is a fluorescein rhodamine or coumarin fluorophore, a 2-indolyl or a carboxy substituted 2-indolyl fluorophore, provided that when -FLUOR is a 2-indolyl or a carboxy, substituted 2-indolyl fluorophore, the linkage is a single covalent bond; or Z' taken together with Y' and the aromatic carbons at the 4' and 5' positions form a benzofuran or oxazolyl-substituted or carboxy-oxazolyl substituted benzofuran fluorophore; or combinations thereof; and R 6 is an alkyl group with 1-5 carbons, a benzyl, an alpha-acyloxyalkyl or a pharmaceutically acceptable esterifying group, or a pharmaceutically acceptable salt.
Claim 9
Dependent Claim
186 words
A non-fluorescent ion-selective conjugate with a carrier having the formula: ##STR11## where at least one of W', X', Y', and Z' contains -POLY that is attached by a covalent linkage that is an ether, a thioether, a carboxamide, a sulfonamide, an alkyl amide, a urea or a thiourea linkage, where -POLY is a polymolecular assembly with a molecular weight greater than about 750 Daltons; the remainder of substituents W', X', Y', and Z', which may be the same or different, are independently H, CH 3 , NO 2 , CF 3 , F, Cl, Br, I, --OR 5 , --CO 2 R 5 , or --OCH 2 CO 2 R 5 , where R 5 is an alkyl group with 1-5 carbons, a benzyl (C 6 H 5 CH 2 --), an alpha-acyloxyalkyl or a pharmaceutically acceptable esterifying group, or a pharmaceutically acceptable salt; or (R a ) n (R b )-POLY, in any of its described variations; or combinations thereof; and R 6 is an alkyl group with 1-5 carbons, a benzyl, an alpha-acyloxyalkyl or a pharmaceutically acceptable esterifying group, or a pharmaceutically acceptable salt.
Claim 10
Dependent Claim
186 words
A non-fluorescent ion-selective conjugate with a carrier having the formula: ##STR11## where at least one of W', X', Y', and Z' contains -POLY that is attached by a covalent linkage that is an ether, a thioether, a carboxamide, a sulfonamide, an alkyl amide, a urea or a thiourea linkage, where -POLY is a polymolecular assembly with a molecular weight greater than about 750 Daltons; the remainder of substituents W', X', Y', and Z', which may be the same or different, are independently H, CH 3 , NO 2 , CF 3 , F, Cl, Br, I, --OR 5 , --CO 2 R 5 , or --OCH 2 CO 2 R 5 , where R 5 is an alkyl group with 1-5 carbons, a benzyl (C 6 H 5 CH 2 --), an alpha-acyloxyalkyl or a pharmaceutically acceptable esterifying group, or a pharmaceutically acceptable salt; or (R a ) n (R b )-POLY, in any of its described variations; or combinations thereof; and R 6 is an alkyl group with 1-5 carbons, a benzyl, an alpha-acyloxyalkyl or a pharmaceutically acceptable esterifying group, or a pharmaceutically acceptable salt.
Claim 11
Dependent Claim
27 words
A compound, as claimed in claim 2, wherein one of W and X is a functional group of the formula (R 1 ) n (R 2 ).
Claim 12
Dependent Claim
81 words
A compound, as claimed in claim 7, wherein one of W and X is a functional group of the formula (R 1 ) n (R 2 ), where n=0 or 1, and R 1 is --O(CH 2 ) m --, m=1-18; R 2 is --NH 2 , --NCS, --CH 2 Q, --NHCOCH 2 Q, or --COR 7 , where Q is Cl, Br or I and where R 7 is Cl, --OH, or oxysuccinimidyl (--ONC 4 H 4 O 2 ).
Claim 13
Dependent Claim
13 words
A compound, as claimed in claim 8, wherein X is --NH 2 .
Claim 14
Dependent Claim
11 words
A compound, as claimed in claim 8, wherein X is --NCS.
Claim 15
Dependent Claim
17 words
A compound as claimed in claim 8, wherein X is --CH 2 Q or --NHCOCH 2 Q.
Claim 16
Dependent Claim
47 words
A compound, as claimed in claim 8, wherein W is (R 1 ) n (R 2 ), R 1 is --O(CH 2 ) m -- and R 2 is --COR 7 , where R 7 is Cl, --OH, or oxysuccinimidyl (--ONC 4 H 4 O 2 ).
Claim 17
Dependent Claim
73 words
A compound, as claimed in claim 12, wherein one of Y and Z is H, CH 3 , NO 2 , CF 3 , F, Cl, Br, I, --OR 5 , --CO 2 R 5 , or --OCH 2 CO 2 R 5 , where R 5 is an alkyl group with 1-5 carbons or a benzyl (C 6 H 5 CH 2 --); and the other of Y and Z is H.
Claim 18
Dependent Claim
18 words
A compound, as claimed in claim 9, wherein Z is --NH 2 and W and Y are H.
Claim 19
Dependent Claim
18 words
A compound, as claimed in claim 10, wherein Z is --NH 2 and W and Y are H.
Claim 20
Dependent Claim
107 words
A compound, as claimed in claim 7, wherein the other of W or X contains a fluorophore according to the formula: (R a ) n" (R b ) n' -FLUOR, where n"=0; or Z contains a fluorophore according to the formula: (R a ) n" (R b ) n' -FLUOR, where n"=0; and remaining substituents are independently H, CH 3 , NO 2 , CF 3 , F, Cl, Br, I, --OR 5 , --CO 2 R 5 , or --OCH 2 CO 2 R 5 , where R 5 is an alkyl group with 1-5 carbons or a benzyl (C 6 H 5 CH 2 --).
Claim 21
Dependent Claim
32 words
A compound, as claimed in claim 16, wherein -FLUOR is an aromatic oxygen heterocycle fluorophore that is a fluorescein, a naphthofluorescein, a seminaphthofluorescein, a rhodol, a rhodamine, a rosamine or a coumarin.
Claim 22
Dependent Claim
37 words
A compound, as claimed in claim 16, wherein one of X or Z contains a fluorophore according to the formula: (R a ) n" (R b ) n' -FLUOR, wherein R b is --NH--, --NHCO--, or --NHCS--.
Claim 23
Dependent Claim
54 words
A compound, as claimed in claim 18, wherein -FLUOR is a naphthofluorescein, a semi-naphthofluorescein, a rhodol, an eosin, an erythrosin, a tetrachlorofluorescein, a dichlorofluorescein, a tetramethylrhodamine, a rhodamine -B, -6G, -101, -110, -123, or -X, a sulfonamide of sulfo rhodamine 101, a rosamine, a hydroxycoumarin, an alkoxy coumarin, a dialkylaminocoumarin or a trifluoromethyl coumarin.
Claim 24
Dependent Claim
55 words
A compound, as claimed in claim 17, where W is a functional group of the formula (R 1 ) n (R 2 ), wherein R 1 is --O(CH 2 ) m , m=1-18, and R 2 is --COR 7 , where R 7 is Cl, --OH, or oxysuccinimidyl (--ONC 4 H 4 O 2 ).
Claim 25
Dependent Claim
92 words
A compound, as claimed in claim 20, where W is --OCH 2 COR 7 , where R 7 is oxysuccinimidyl (--ONC 4 H 4 O 2 ); X or Z contains a fluorophore according to the formula: (R a ) n" (R b ) n' -FLUOR, wherein R b is --NH--, --NHCO--, or --NHCS--; and -FLUOR is a 2',7'-dichlorofluorescein, a tetramethylrhodamine, or a sulfonamide of sulforhodamine 101; such that when Z contains a fluorophore, X is H and when X contains a fluorophore, Z is CH 3 ; and Y is H.
Claim 26
Dependent Claim
81 words
A compound, as claimed in claim 19, wherein X is a functional group of the formula (R 1 ) n (R 2 ), wherein n=0 or 1, R 1 is --O(CH 2 ) m --, m=1-18; R 2 is --NH 2 , --NCS, --CH 2 Q, --NHCOCH 2 Q, or --COR 7 ; where Q is Cl, Br or I and R 7 is Cl, --OH, or oxysuccinimidyl (--ONC 4 H 4 O 2 ) and where Z contains a fluorophore.
Claim 27
Dependent Claim
38 words
A compound, as claimed in claim 22, wherein X is --NH 2 , --NCS, --NHCOCH 2 Q or CH 2 Q; and Z contains a fluorophore that is a 2',7'-dichlorofluorescein, a tetramethylrhodamine, or a sulfonamide of sulforhodamine 101.
Claim 28
Dependent Claim
17 words
A compound, as claimed in claim 16, wherein -FLUOR is a 2-indolyl or carboxy substituted 2-indolyl fluorophore.
Claim 29
Dependent Claim
81 words
A compound, as claimed in claim 24, wherein one of W and X is a functional group of the formula (R 1 ) n (R 2 ), where n=0 or 1, and R 1 is --O(CH 2 ) m --, m=1-18; R 2 is --NH 2 , --NCS, --CH 2 Q, --NHCOCH 2 Q, or --COR 7 , where Q is Cl, Br or I and where R 7 is Cl, --OH, or oxysuccinimidyl (--ONC 4 H 4 O 2 ).
Claim 30
Dependent Claim
42 words
A compound, as claimed in claim 25, wherein W is --O(CH 2 )COR 7 , where R 7 is Cl, --OH, or oxysuccinimidyl (--ONC 4 H 4 O 2 ), and X or Z contains the 2-indolyl or carboxy substituted 2-indolyl fluorophore.
Claim 31
Dependent Claim
31 words
A compound, as claimed in claim 25, wherein X is --NH 2 , --NCS, --NHCOCH 2 Q or --CH 2 Q; and Z contains a 2-indolyl or carboxy substituted 2-indolyl fluorophore.
Claim 32
Dependent Claim
34 words
A compound, as claimed in claim 7, wherein Y taken together with Z and the aromatic carbons at the 4' and 5' positions form a benzofuran or an oxazolyl-substituted or carboxy-oxazolyl substituted benzofuran fluorophore.
Claim 33
Dependent Claim
139 words
A compound, as claimed in claim 28, wherein one of W and X is a functional group of the formula (R 1 ) n (R 2 ), where n=0 or 1, and R 1 is --O(CH 2 ) m --, m=1-18; R 2 is --NH 2 , --NCS, --CH 2 Q, --NHCOCH 2 Q, or --COR 7 , where Q is Cl, Br or I and where R 7 is Cl, --OH, or oxysuccinimidyl (--ONC 4 H 4 O 2 ); and the other of W and X is H, CH 3 , NO 2 , CF 3 , F, Cl, Br, I, --OR 5 , --CO 2 R 5 , or --OCH 2 CO 2 R 5 , where R 5 is an alkyl group with 1-5 carbons or a benzyl (C 6 H 5 CH 2 --).
Claim 34
Dependent Claim
21 words
A compound, as claimed in claim 29, wherein X is --NH 2 , --NCS, --NHCOCH 2 Q or --CH 2 Q.
Claim 35
Dependent Claim
30 words
A compound, as claimed in claim 29, wherein W is --O(CH 2 )COR 7 , where R 7 is Cl, --OH, or oxysuccinimidyl (--ONC 4 H 4 O 2 ).
Claim 36
Dependent Claim
27 words
A compound, as claimed in claim 7, wherein one of Y and Z is a functional group of the formula (R 1 ) n (R 2 ).
Claim 37
Dependent Claim
139 words
A compound, as claimed in claim 8, wherein one of Y and Z is a functional group of the formula (R 1 ) n (R 2 ), where n=0 or 1, and R 1 is --O(CH 2 ) m --, m=1-18; R 2 is --NH 2 , --NCS, --CH 2 Q, --NHCOCH 2 Q, or --COR 7 , where Q is Cl, Br or I and where R 7 is Cl, --OH, or oxysuccinimidyl (--ONC 4 H 4 O 2 ); and the other of Y and Z is H, CH 3 , NO 2 , CF 3 , F, Cl, Br, I, --OR 5 , --CO 2 R 5 , or --OCH 2 CO 2 R 5 , where R 5 is an alkyl group with 1-5 carbons or a benzyl (C 6 H 5 CH 2 --).
Claim 38
Dependent Claim
46 words
A compound, as claimed in claim 33, wherein W is --O(CH 2 )COR 7 , where R 7 is Cl, --OH, or oxysuccinimidyl (--ONC 4 H 4 O 2 ); and X or Z is --NH 2 , --NCS, --NHCOCH 2 Q or --CH 2 Q.
Claim 39
Dependent Claim
26 words
A conjugate, as claimed in claim 3, wherein -POLY is a biologically compatible polymolecular assembly with a molecular weight between about 1000 and about 10,000,000 Daltons.
Claim 40
Dependent Claim
42 words
A conjugate, as claimed in claim 3, wherein W' or X' contains -POLY that is a synthetic polymeric resin or gel; glass; polyol; polysaccharide; polypeptide or protein; or naturally or chemically cross-linked forms thereof; or a natural or synthetic liposome or micelle.
Claim 41
Dependent Claim
12 words
A conjugate, as claimed in claim 3, wherein -POLY is a polysaccharide.
Claim 42
Dependent Claim
12 words
A conjugate, as claimed in claim 35, wherein -POLY is a dextran.
Claim 43
Dependent Claim
76 words
A conjugate, as claimed in claim 3, wherein one of X' or Z' contains a fluorophore according to the formula: (R a ) n (R b ) n' -FLUOR, where -FLUOR is a naphthofluorescein, a semi-naphthofluorescein, a rhodol, an eosin, an erythrosin, a tetrachlorofluorescein, a dichlorofluorescein, a tetramethylrhodamine, a rhodamine -B, -6G, -101, -110, -123, or -X, a sulfonamide of sulfo rhodamine 101, a rosamine, a hydroxycoumarin, an alkoxy coumarin, a dialkylaminocoumarin or a trifluoromethyl coumarin.
Claim 44
Dependent Claim
39 words
A conjugate, as claimed in claim 3, wherein one of X' or Z' contains a fluorophore according to the formula: (R a ) n" (R b ) n' -FLUOR, wherein -FLUOR is a 2-indolyl or carboxy substituted 2-indolyl fluorophore.
Claim 45
Dependent Claim
33 words
A conjugate, as claimed in claim 3, wherein Z' taken together with Y' and the aromatic carbons at the 4' and 5' positions form a benzofuran or oxazolyl-substituted or carboxy-oxazolyl substituted benzofuran fluorophore.
Claim 46
Dependent Claim
29 words
A conjugate, as claimed in claim 3, wherein X' or Z' contains a fluorophore according to the formula: (R a ) n (R b ) n' -FLUOR, wherein n=0.
Claim 47
Dependent Claim
20 words
A conjugate, as claimed in claim 42, wherein -FLUOR is a 2',7'-dichlorofluorescein, a tetramethylrhodamine, or a sulfonamide of sulforhodamine 101.
Claim 48
Dependent Claim
15 words
A conjugate, as claimed in claim 43, wherein R b is --NH--, --NHCO--, or --NHCS--.
Claim 49
Dependent Claim
124 words
A conjugate, as claimed in claim 3, wherein W' or X' has the formula: (R a ) n (R b )-POLY, wherein n=0 or 1; R a is --OCH 2 R 3 --, --OR 3' --, --SR 3 --, --SR 3' --, --NHCOCH 2 R 3 --, --NHCOR 3' --, --CONHCH 2 R 3 --, --CONHR 3' --, --NHSO 2 R 3 --, --NHSO 2 R 3' --, --NHCONHCH 2 R 3 --, --NHCONHR 3' --, --NHCSNHCH 2 R 3 --, or --NHCSNHR 3' --, where R 3 is (CH 2 ) m and m=1-18, and R 3 ' is phenylene (--C 6 H 4 --); R b is --NH--, --NHCO--, --NHCS--, --S--, --O--, --CO--, --CH 2 --, --COCH 2 --, or a succinimidyl.
Claim 50
Dependent Claim
134 words
A conjugate, as claimed in claim 45, wherein -POLY is a polysaccharide and Z' contains a fluorophore according to the formula: (R a ) n (R b ) n' -FLUOR, wherein n=0, and -FLUOR is a naphthofluorescein, a semi-naphthofluorescein, a rhodol, an eosin, an erythrosin, a tetrachlorofluorescein, a dichlorofluorescein, a tetramethylrhodamine, a rhodamine -B, -6G, -101, -110, -123, or -X, a sulfonamide of sulfo rhodamine 101, a rosamine, a hydroxycoumarin, an alkoxy coumarin, a dialkylaminocoumarin or a trifluoromethyl coumarin; and the remaining substituents are H, CH 3 , NO 2 , CF 3 , F, Cl, Br, I, --OR 5 , --CO 2 R 5 , or --OCH 2 CO 2 R 5 , where R 5 is an alkyl group with 1-5 carbons or a benzyl (C 6 H 5 CH 2 --).
Claim 51
Dependent Claim
92 words
A conjugate, as claimed in claim 45, wherein -POLY is a polysaccharide; Z' contains a fluorophore according to the formula: (R a ) n (R b ) n' -FLUOR, wherein -FLUOR is 2-indolyl or carboxy substituted 2-indolyl fluorophore; and the remaining substituents are H, CH 3 , NO 2 , CF 3 F, Cl, Br, I, --OR 5 , --CO 2 R 5 , or --OCH 2 CO 2 R 5 , where R 5 is an alkyl group with 1-5 carbons or a benzyl (C 6 H 5 CH 2 --).
Claim 52
Dependent Claim
92 words
A conjugate, as claimed in claim 45, wherein -POLY is a polysaccharide; Z' taken together with Y' and the aromatic carbons at the 4' and 5' positions form a benzofuran or oxazolyl-substituted or carboxy-oxazolyl substituted benzofuran fluorophore; and the remaining substituents are H, CH 3 , NO 2 , CF 3 , F, Cl, Br, I, --OR 5 , --CO 2 R 5 , or --OCH 2 CO 2 R 5 , where R 5 is an alkyl group with 1-5 carbons or a benzyl (C 6 H 5 CH 2 --).
Claim 53
Dependent Claim
136 words
A conjugate, as claimed in claim 45, wherein W' contains -POLY that is a polysaccharide; X' contains a fluorophore according to the formula: (R a ) n (R b ) n' -FLUOR, wherein n=0 and -FLUOR is a naphthofluorescein, a semi-naphthofluorescein, a rhodol, an eosin, an erythrosin, a tetrachlorofluorescein, a dichlorofluorescein, a tetramethylrhodamine, a rhodamine -B, -6G, -101, -110, -123, or -X, a sulfonamide of sulfo rhodamine 101, a rosamine, a hydroxycoumarin, an alkoxy coumarin, a dialkylaminocoumarin or a trifluoromethyl coumarin; and the remaining substituents are H, CH 3 , NO 2 , CF 3 , F, Cl, Br, I, --OR 5 , --CO 2 R 5 , or --OCH 2 CO 2 R 5 , where R 5 is an alkyl group with 1-5 carbons or a benzyl (C 6 H 5 CH 2 --).
Claim 54
Dependent Claim
91 words
A conjugate, as claimed in claim 45, wherein Z' contains a fluorophore according to the formula: (R a ) n (R b ) n' -FLUOR, wherein -FLUOR is a 2-indolyl or a carboxy substituted 2-indolyl fluorophore; and the remaining substituents are H, CH 3 , NO 2 , CF 3 , F, Cl, Br, I, --OR 5 , --CO 2 R 5 , or --OCH 2 CO 2 R 5 , where R 5 is an alkyl group with 1-5 carbons or a benzyl (C 6 H 5 CH 2 --).
Claim 55
Dependent Claim
61 words
A compound, as claimed in claim 5, wherein X' contains a fluorophore -FLUOR' that is a naphthofluorescein, a semi-naphthofluorescein, a rhodol, an eosin, an erythrosin, a tetrachlorofluorescein, a dichlorofluorescein, a tetramethylrhodamine, a rhodamine -B, -6G, - 101,-110,-123, or -X, a sulfonamide of sulforhodamine 101, a rosamine, a hydroxycoumarin, an alkoxy coumarin, a dialkylaminocoumarin or a trifluoromethyl coumarin; and W' is H.
Claim 56
Dependent Claim
27 words
A compound, as claimed in claim 51, wherein FLUOR' is attached to the compound by a covalent linkage that is a carboxamide, sulfonamide, urea or thiourea linkage.
Claim 57
Dependent Claim
14 words
A compound, as claimed in claim 51, wherein Z' contains an additional fluorophore -FLUOR.
Claim 58
Dependent Claim
61 words
A compound as claimed in claim 53, wherein Z' contains an additional fluorophore -FLUOR, where -FLUOR is a naphthofluorescein, a semi-naphthofluorescein, a rhodol, an eosin, an erythrosin, a tetrachlorofluorescein, a dichlorofluorescein, a tetramethylrhodamine, a rhodamine -B, -6G, - 101, -110, -123, or -X, a sulfonamide of sulforhodamine 101, a rosamine, a hydroxycoumarin, an alkoxy coumarin, a dialkylaminocoumarin or a trifluoromethyl coumarin.
Claim 59
Dependent Claim
24 words
A compound, as claimed in claim 53, wherein Z' contains an additional fluorophore -FLUOR, wherein -FLUOR is a 2-indolyl or carboxy substituted 2-indolyl fluorophore.
Claim 60
Dependent Claim
33 words
A compound, as claimed in claim 51, wherein Z' taken together with Y' and the aromatic carbons at the 4' and 5' positions form a benzofuran or oxazolyl-substituted or carboxy-oxazolyl substituted benzofuran fluorophore.
Claim 61
Dependent Claim
37 words
A conjugate, as claimed in claim 6, wherein -POLY is a synthetic polymeric resin or gel; glass; polyol; polysaccharide; polypeptide or protein; or naturally or chemically cross-linked forms thereof; or a natural or synthetic liposome or micelle.
Claim 62
Dependent Claim
111 words
A compound, as claimed in claim 5, wherein R 6 is an alpha-acyloxyalkyl or a pharmaceutically acceptable salt; W' is H, X' contains a fluorophore conjugate FLUOR' that is a fluorescein, rhodamine, or coumarin derivative and that is attached to the compound by a covalent linkage that is a carboxamide, sulfonamide, urea or thiourea linkage, and Y' and Z' are independently H, CH 3 , NO 2 , CF 3 , F, Cl, Br, or I, or Z' contains an additional fluorophore FLUOR that is a fluorescein, rhodamine, or coumarin derivative and that is attached to the compound by a covalent linkage that is a carboxamide, sulfonamide, urea or thiourea linkage.
Claim 63
Dependent Claim
25 words
A compound, as claimed in claim 5, wherein X' contains a fluorophore conjugate according to the formula (R a ) n (R b )-FLUOR',wherein n=0.
Claim 64
Dependent Claim
31 words
A compound, as claimed in claim 59, wherein R b is --NHCO--, NHCONH--, NHCSNH-- or --NHSO 2 --; and -FLUOR' is a 2',7'-dichlorofluorescein, a tetramethylrhodamine, or a sulfonamide of sulforhodamine 101.
Claim 65
Dependent Claim
142 words
A compound, as claimed in claim 5, wherein R 6 is an alpha-acyloxyalkyl or a pharmaceutically acceptable salt; W' is H, X' contains a fluorophore conjugate according to the formula (R a ) n (R b )-FLUOR', wherein n=0, R b is --NHCO--, --NHCONH--, --NHCS--, --NHCSNH--, NHSO 2 --, and FLUOR' is a naphthofluorescein, a semi-naphthofluorescein, a rhodol, an eosin, an erythrosin, a tetrachlorofluorescein, a dichlorofluorescein, a tetramethylrhodamine, a rhodamine -B, -6G, - 101, -110,-123, or -X, a sulfonamide of sulforhodamine 101, a rosamine, and Y' and Z' are independently H, CH 3 , NO 2 , CF 3 , F, Cl, Br, or I, or Z' contains an additional fluorophore according to the formula (R a ) n (R b )-FLUOR, wherein n=0, R b is --NHCO--, --NHCONH--, --NHCS--, --NHCSNH--, or NHSO 2 --, and FLUOR is the same as FLUOR'.
Claim 66
Dependent Claim
71 words
A compound, as claimed in claim 61, wherein X' contains a fluorophore conjugate FLUOR' that is attached to the compound according to the formula (R a ) n (R b )-FLUOR', wherein n=0 and R b is --NHCO--, --NHCSNH--, or NHSO 2 --, and FLUOR' is a 2',7'-dichlorofluorescein; W' and Y' are H; and Z' is H, CH 3 , NO 2 , CF 3 , F, Cl, Br, or I.
Claim 67
Dependent Claim
89 words
A compound, as claimed in claim 61, wherein X' contains a fluorophore conjugate FLUOR' that is attached to the compound according to the formula (R a ) n (R b )-FLUOR', wherein n=0 and R b is --NHCO--, --NHCSNH--, or NHSO 2 --, and FLUOR' is a 2',7'-dichlorofluorescein; W' and Y' are H; and Z' contains an additional fluorophore according to the formula (R a ) n (R b )-FLUOR, wherein n=0 and R b is --NHCO--, --NHCSNH--, or NHSO 2 --, and FLUOR is the same as FLUOR'.
Claim 68
Dependent Claim
71 words
A compound, as claimed in claim 61, wherein X' contains a fluorophore conjugate FLUOR' that is attached to the compound according to the formula (R a ) n (R b )-FLUOR', wherein n=0 and R b is --NHCO--, --NHCSNH--, or NHSO 2 --, and FLUOR' is a tetramethylrhodamine; W' and Y' are H; and Z' is H, CH 3 , NO 2 , CF 3 , F, Cl, Br, or I.
Claim 69
Dependent Claim
89 words
A compound, as claimed in claim 61, wherein X' contains a fluorophore conjugate FLUOR' that is attached to the compound according to the formula (R a ) n (R b )-FLUOR', wherein n=0 and R b is --NHCO--, --NHCSNH--, or NHSO 2 --, and FLUOR' is a tetramethylrhodamine; W' and Y' are H; and Z' contains an additional fluorophore according to the formula (R a ) n (R b )-FLUOR, wherein n=0 and R b is --NHCO--, --NHCSNH--, or NHSO 2 --, and FLUOR is the same as FLUOR'.
Claim 70
Dependent Claim
74 words
A compound, as claimed in claim 61, wherein X' contains a fluorophore conjugate FLUOR' that is attached to the compound according to the formula (R a ) n (R b )-FLUOR', wherein n=0 and R b is --NHCO--, --NHCSNH--, or NHSO 2 --, and FLUOR' is a sulfonamide of sulforhodamine 101; W' and Y' are H; and Z' is H, CH 3 , NO 2 , CF 3 , F, Cl, Br, or I.
Claim 71
Dependent Claim
93 words
A compound, as claimed in claim 61, wherein X' contains a fluorophore conjugate FLUOR' that is attached to the compound according to the formula (R a ) n (R b )-FLUOR', wherein n=0 and R b is --NHCO--, --NHCSNH--, or NHSO 2 --, and FLUOR' is a sulfonamide of sulforhodamine 101; W' and Y' are H; and Z' contains an additional fluorophore according to the formula (R a ) n (R b )-FLUOR, wherein n=0 and R b is --NHCO--, --NHCSNH--, or NHS 2 O --, and FLUOR is the same as FLUOR'.
References Cited (Backward Citations)
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| 3.5 Years (Year 4) | 1998-09-25 | 1999-03-27 | 1999-09-26 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2002-09-25 | 2003-03-27 | 2003-09-26 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2006-09-25 | 2007-03-27 | 2007-09-26 | $7700.00 | Window Closed / Lapsed |