US5364614A
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US
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Cascade polymer bound chelating compounds, their chelates and conjugates, processes for their production, and pharmaceutical agents containing them
Assignee: Bayer Pharma AG
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Filing: 1990-11-21
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Granted: 1994-11-15
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Expires: 2010-11-21
Abstract
Abstract Cascade polymers, containing complex-forming ligands, optionally at least five ions of an element of atomic numbers 21-29, 39, 42, 44 or 57-83, as well as, if desired, cations of inorganic and/or organic bases, amino acids or amino acid amides, are valuable complexing compounds and complexes for diagnostics and therapy.
Inventors
- 👤 Johannes Platzek
- 👤 Heribert Schmitt-Willich
- 👤 Heinz Gries
- 👤 Gabriele Schuhmann-Giampieri
- 👤 Hubert Vogler
- 👤 Hanns-Joachim Weinmann
- 👤 Hans Bauer
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-03 12:37
CPC Classifications
C; C08; C08G; C08G85/00; C08G83/00; A; A61; A61K; A61K49/00; A61K49/0002; A61K49/04; A61K49/06; A61K49/08; A61K49/085; A61K49/10; A61K49/12; A61K49/124; A61K51/00; A61K51/02; A61K51/04; A61K51/06; A61K51/065; C08G83/002; C08G83/003; Y; Y10; Y10T; Y10T436/00; Y10T436/24
Claims Analysis
Total Claims: 12
Claim 1
Independent Claim
949 words
A cascade polymer, being either a chelating agent capable of being chelated with at least five ions of an element of atomic numbers 21-29, 39, 42, 44 or 57-83 or a chelate --K, with at least give of said ions, of formula I ##STR15## wherein A is a nitrogen-containing cascade nucleus of basis multiplicity b of the formula: ##STR16## wherein R 2 , R 3 and R 4 are, in each case independently of one another, a covalent bond or --(CH.sub.2).sub.k --(C.sub.6 H.sub.4).sub.r --(CH.sub.2).sub.1 --N< g is the number 2, 3, 4 or 5, t is the number 1, 2, 3, 4, 5, 6, 7 or 8, l is the number 0, 1, 2, 3, 4 or 5, r is the number 0 or 1, n is the number 0, 1, 2, 3 or 4, m is the number 0, 1, 2, 3 or 4, k is the number 1, 2, 3, 4 or 5, a is the number 2, 3, 4 or 5, W is CH, CH 2 , NH or a nitrogen atom, C 1 is (CH 2 ) k --N<, C 2 , C 3 , C 4 and C 5 are, in each case independently, a hydrogen atom or (CH 2 ) f --N<, f is the number 1, 2, 3, 4 or 5, j is the number 6, 7 or 8, Y 1 and Y 2 are, in each case independently of each other, a hydrogen atom, CH 2 --CH(OH)--CH 2 N< or (CH 2 ) a --N<, and Y 3 is a nitrogen atom, O--CH 2 --CH(OH)--CH 2 N< or O--(CH 2 ) 9 --N<, a and g are as defined above, means a single or double bond, with the proviso that, if Y 3 is a nitrogen atom, Y 1 and Y 2 are hydrogen; S is a repeating unit of the formula: ##STR17## a is 2, 3, 4 or 5, α and β each independently is a hydrogen atom or (CH 2 ) o , `γ means (CH 2 ) f , each f independently is the number 1, 2, 3, 4 or 5, and r is the number 0 or 1, and k is 1, 2, 3, 4 or 5, l is 0, 1, 2, 3, 4 or 5, o is 0, 1, 2, 3, 4 or 5, with the proviso that l and o are not both zero at the same time; N is a nitrogen atom, Z 1 and Z 2 , for the first to penultimate generation, in each case are ##STR18## and, for the last generation, Z 1 is hydrogen, a C 1 -C 10 -alkyl, C 2 -C 10 -carboxylic acyl or C 1 -C 10 -alkylsulfonyl, each optionally containing 1-3 carboxy, 1-3 sulfonic acid, 1-5 hydroxy groups and/or 1-3 oxa atoms, or is the residue of a chelating agent or chelate K, and Z 2 is, to an extent of 96-100% of the total Z 2 content, the residue of an attached chelating agent or chelate k and, to an extent of 4-0%, V', wherein V' is V having at its end a functional group or, linked via this functional group, which is: --NH 2 ; --NHR; --NHNH 2 ; NRNH 2 ; SH; OH; --COCH 2 ; CH═CH--CO 2 R; --NCS; NCO; ##STR19## wherein R and R' are identical or different and in each case are hydrogen, a saturated or unsaturated C 1 -C 20 -hydrocarbyl residue optionally substituted by a phenyl group, or a phenyl group, or, linked via this function group, a bio- or macromolecule, V being a straight-chain, C 1 -C 20 -alkylene group which optionally contains imino, phenylene, phenylenoxy, phenylenimino, amide, hydrazide, uredio, thioureido, carbonyl and/or ester group(s) and/or oxa, sulfur and/or nitrogen atom(s), and is optionally substituted by carboxyl carboxylalkyl, hydroxy, mercapto, imino, epoxy, oxo, thioxo, and/or amino, b is a number 1 through 50, and s is a number 1 to 3, wherein the reproduction units S need be identical only for a given generation, and the residue of the chelating agent or chelate is a residue of Formulae I A, I B or I C; ##STR20## bound to the terminal nitrogen atoms of the final generation by a --CH 2 CO-- or V group, n and m in each case independently is 0, 1, 2, 3 or 4, n and m adding up to no more than 4, k is the number 1, 2, 3, 4 or 5, l is the number 0, 1, 2, 3, 4 or 5, q is the number 0, 1 or 2, U is CH 2 X or V, X is in each case independently --COOH or V' wherein, if the molecule contains V', at least 0.1% of the substituents X stand for V', B, D and E, being identical or different, are in each case --(CH 2 ) a with a being the number 2, 3, 4 or 5, R 1 is V or a hydrogen atom, with the proviso that R 1 is V only if U is CH 2 X at the same time, and that U is V only if R 1 is a hydrogen atom at the same time, and wherein optionally, a portion of the COOH groups are present in the form of a corresponding ester of a C 1 -C 6 -alkyl group or amide of a saturated or unsaturated, linear, branched or cyclic hydrocarbon of 1-5 carbon atoms, optionally substituted with 1 to 3 hydroxy or C 1 -C 4 -alkyoxy or a 5- or 6-membered ring including the amide nitrogen; or a salt thereof with a cation of an in organic and/or organic base, an amino acid or an amino acid amide.
Claim 2
Dependent Claim
949 words
A cascade polymer, being either a chelating agent capable of being chelated with at least five ions of an element of atomic numbers 21-29, 39, 42, 44 or 57-83 or a chelate --K, with at least give of said ions, of formula I ##STR15## wherein A is a nitrogen-containing cascade nucleus of basis multiplicity b of the formula: ##STR16## wherein R 2 , R 3 and R 4 are, in each case independently of one another, a covalent bond or --(CH.sub.2).sub.k --(C.sub.6 H.sub.4).sub.r --(CH.sub.2).sub.1 --N< g is the number 2, 3, 4 or 5, t is the number 1, 2, 3, 4, 5, 6, 7 or 8, l is the number 0, 1, 2, 3, 4 or 5, r is the number 0 or 1, n is the number 0, 1, 2, 3 or 4, m is the number 0, 1, 2, 3 or 4, k is the number 1, 2, 3, 4 or 5, a is the number 2, 3, 4 or 5, W is CH, CH 2 , NH or a nitrogen atom, C 1 is (CH 2 ) k --N<, C 2 , C 3 , C 4 and C 5 are, in each case independently, a hydrogen atom or (CH 2 ) f --N<, f is the number 1, 2, 3, 4 or 5, j is the number 6, 7 or 8, Y 1 and Y 2 are, in each case independently of each other, a hydrogen atom, CH 2 --CH(OH)--CH 2 N< or (CH 2 ) a --N<, and Y 3 is a nitrogen atom, O--CH 2 --CH(OH)--CH 2 N< or O--(CH 2 ) 9 --N<, a and g are as defined above, means a single or double bond, with the proviso that, if Y 3 is a nitrogen atom, Y 1 and Y 2 are hydrogen; S is a repeating unit of the formula: ##STR17## a is 2, 3, 4 or 5, α and β each independently is a hydrogen atom or (CH 2 ) o , `γ means (CH 2 ) f , each f independently is the number 1, 2, 3, 4 or 5, and r is the number 0 or 1, and k is 1, 2, 3, 4 or 5, l is 0, 1, 2, 3, 4 or 5, o is 0, 1, 2, 3, 4 or 5, with the proviso that l and o are not both zero at the same time; N is a nitrogen atom, Z 1 and Z 2 , for the first to penultimate generation, in each case are ##STR18## and, for the last generation, Z 1 is hydrogen, a C 1 -C 10 -alkyl, C 2 -C 10 -carboxylic acyl or C 1 -C 10 -alkylsulfonyl, each optionally containing 1-3 carboxy, 1-3 sulfonic acid, 1-5 hydroxy groups and/or 1-3 oxa atoms, or is the residue of a chelating agent or chelate K, and Z 2 is, to an extent of 96-100% of the total Z 2 content, the residue of an attached chelating agent or chelate k and, to an extent of 4-0%, V', wherein V' is V having at its end a functional group or, linked via this functional group, which is: --NH 2 ; --NHR; --NHNH 2 ; NRNH 2 ; SH; OH; --COCH 2 ; CH═CH--CO 2 R; --NCS; NCO; ##STR19## wherein R and R' are identical or different and in each case are hydrogen, a saturated or unsaturated C 1 -C 20 -hydrocarbyl residue optionally substituted by a phenyl group, or a phenyl group, or, linked via this function group, a bio- or macromolecule, V being a straight-chain, C 1 -C 20 -alkylene group which optionally contains imino, phenylene, phenylenoxy, phenylenimino, amide, hydrazide, uredio, thioureido, carbonyl and/or ester group(s) and/or oxa, sulfur and/or nitrogen atom(s), and is optionally substituted by carboxyl carboxylalkyl, hydroxy, mercapto, imino, epoxy, oxo, thioxo, and/or amino, b is a number 1 through 50, and s is a number 1 to 3, wherein the reproduction units S need be identical only for a given generation, and the residue of the chelating agent or chelate is a residue of Formulae I A, I B or I C; ##STR20## bound to the terminal nitrogen atoms of the final generation by a --CH 2 CO-- or V group, n and m in each case independently is 0, 1, 2, 3 or 4, n and m adding up to no more than 4, k is the number 1, 2, 3, 4 or 5, l is the number 0, 1, 2, 3, 4 or 5, q is the number 0, 1 or 2, U is CH 2 X or V, X is in each case independently --COOH or V' wherein, if the molecule contains V', at least 0.1% of the substituents X stand for V', B, D and E, being identical or different, are in each case --(CH 2 ) a with a being the number 2, 3, 4 or 5, R 1 is V or a hydrogen atom, with the proviso that R 1 is V only if U is CH 2 X at the same time, and that U is V only if R 1 is a hydrogen atom at the same time, and wherein optionally, a portion of the COOH groups are present in the form of a corresponding ester of a C 1 -C 6 -alkyl group or amide of a saturated or unsaturated, linear, branched or cyclic hydrocarbon of 1-5 carbon atoms, optionally substituted with 1 to 3 hydroxy or C 1 -C 4 -alkyoxy or a 5- or 6-membered ring including the amide nitrogen; or a salt thereof with a cation of an in organic and/or organic base, an amino acid or an amino acid amide.
Claim 3
Dependent Claim
30 words
A cascade polymer according to claim 1, containing at least five ions of an element of atomic numbers 21-29, 39, 42, 44 or 57-83 bound to a chelating agent K.
Claim 4
Dependent Claim
26 words
A cascade polymer according to claim 1, wherein the bio- or macromolecule(s) optionally contained in V' is/are an antibody or antibodies or antibody fragment of fragments.
Claim 5
Dependent Claim
21 words
A cascade polymer according to claim 1, wherein the bio- or macromolecule(s) optionally contained in V' is/are a protein or proteins.
Claim 6
Dependent Claim
14 words
A cascade polymer of claim 4, wherein the protein is albumin, globulin or lectin.
Claim 7
Dependent Claim
21 words
A cascade polymer according to claim 1, wherein the bio- or macromolecule(s) optionally contained in V' is/are a polysaccharide or polysaccharides.
Claim 8
Dependent Claim
14 words
A cascade polymer of claim 6, wherein the polysaccharide is starch, dextran or dextrin.
Claim 9
Dependent Claim
11 words
A cascade polymer according to claim 1, wherein V is ##STR21##
Claim 10
Dependent Claim
14 words
A cascade polymer according to claim 1 which has 2-6 generations of reproduction units.
Claim 11
Dependent Claim
18 words
A pharmaceutical agent comprising at least one cascade polymer according to claim 1 and a pharmaceutically acceptable carrier.
Claim 12
Dependent Claim
18 words
A pharmaceutical agent comprising at least one cascade polymer according to claim 2 and a pharmaceutically acceptable carrier.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1997-11-14 | 1998-05-16 | 1998-11-15 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2001-11-14 | 2002-05-16 | 2002-11-15 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2005-11-14 | 2006-05-16 | 2006-11-15 | $7700.00 | Window Closed / Lapsed |