US4933456A
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Dipyridoxyl phosphate NMRI contrast agents
Assignee: Amersham Health Salutar Inc
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Filing: 1987-05-08
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Granted: 1990-06-12
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Expires: 2007-05-08
Abstract
Abstract N,N'-bis-(pyridoxal-5-phosphate)-alkylenediamine-N,N'-diacetic acids, N,N'-bis-(pyridoxal-5-phosphate)-1,2-cycloalkylenediamine-N,N'-diacetic acids, and N,N'-bis-(pyridoxal-5-phosphate)-1,2-arylenediamine-N,N'-diacetic acids, the corresponding monophosphate compounds and monoacetic acid compounds, and their salts and esters form stable, highly soluble chelates with paramagnetic metal ions, and are highly effective NMRI contrast agents. Preferred contrast agents are paramagnetic ion chelates of N,N'-bis-(pyridoxal-5-phosphate)ethylene-diamine-N,N'-diacetic acid, N,N'-bis-(pyridoxal-5-phosphate)trans-1,2-cyclohexylenediamine-N,N'-diacetic acid, N,N'-bis-(pyridoxal-5-phosphate)trans-1,2-arylenediamine-N,N'-diacetic acid, and the soluble calcium salts thereof. Novel intermediates for forming these compounds are N,N'-bis(pyridoxal-5-phosphate)alkylenediimines, N,N'-bis(pyridoxal-5-phosphate)alkylenediamines, N,N'-bis(pyridoxal-5-phosphate)-1,2-cycloalkylenediimines, N,N'-bis(pyridoxal-5-phosphate)-1,2-cycloalkylenediamines, N,N'-bis(pyridoxal-5-phosphate(-1,2-arylenediamines, and the corresponding monophosphate compounds.
Inventors
- 👤 Scott M. Rocklage
- 👤 Steven C. Quay
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-03 05:09
CPC Classifications
G; G01; G01R; G01R33/00; G01R33/20; G01R33/44; G01R33/48; G01R33/54; G01R33/56; G01R33/5601; A; A61; A61K; A61K49/00; A61K49/06; C; C07; C07F; C07F13/00; C07F13/005; C07F9/00; C07F9/02; C07F9/547; C07F9/553; C07F9/576; C07F9/58
Claims Analysis
Total Claims: 22
Claim 1
Independent Claim
177 words
A metal ion chelate of a chelating compound of the formula: ##STR9## wherein: R is hydrogen or ##STR10## R 1 is hydrogen or ##STR11## with the proviso that at least one of R and R 1 is other than hydrogen; R 5 and R 6 are each, independently, hydroxy, alkoxy having from 1 to 18 carbons, hydroxy-substituted alkoxy having from 1 to 18 carbons, amino, or alkylamido having from 1 to 10 carbons; R 3 is alkylene having from 1 to 8 carbons, 1,2-cycloalkylene having from 5 to 8 carbons, or 1,2-arylene having from 6 to 10 carbons; R 4 is hydrogen, hydroxymethyl, alkyl having from 1 to 6 carbons, or ##STR12## each R 7 is, independently, hydrogen, hydroxy-substituted alkyl having from 1 to 18 carbons, or aminoalkyl having from 1 to 18 carbons; and the chelated metal ion is a paramagnetic ion of a metal having an atomic number of from 21 to 29, inclusive, 42, 44, or from 58 to 70, inclusive, or a physiologically biocompatible inorganic or organic salt of said metal ion chelate.
Claim 2
Dependent Claim
177 words
A metal ion chelate of a chelating compound of the formula: ##STR9## wherein: R is hydrogen or ##STR10## R 1 is hydrogen or ##STR11## with the proviso that at least one of R and R 1 is other than hydrogen; R 5 and R 6 are each, independently, hydroxy, alkoxy having from 1 to 18 carbons, hydroxy-substituted alkoxy having from 1 to 18 carbons, amino, or alkylamido having from 1 to 10 carbons; R 3 is alkylene having from 1 to 8 carbons, 1,2-cycloalkylene having from 5 to 8 carbons, or 1,2-arylene having from 6 to 10 carbons; R 4 is hydrogen, hydroxymethyl, alkyl having from 1 to 6 carbons, or ##STR12## each R 7 is, independently, hydrogen, hydroxy-substituted alkyl having from 1 to 18 carbons, or aminoalkyl having from 1 to 18 carbons; and the chelated metal ion is a paramagnetic ion of a metal having an atomic number of from 21 to 29, inclusive, 42, 44, or from 58 to 70, inclusive, or a physiologically biocompatible inorganic or organic salt of said metal ion chelate.
Claim 3
Dependent Claim
26 words
A metal ion chelate according to claim 1 wherein R and R 1 are each other than hydrogen, or a salt of said metal ion chelate.
Claim 4
Dependent Claim
22 words
A metal ion chelate according to claim 1 wherein each R 7 is hydrogen, or a salt of said metal ion chelate.
Claim 5
Dependent Claim
53 words
A metal ion chelate according to claim 1 wherein R and R 1 are each other than hydrogen, R 5 and R 6 are each, independently, hydroxy, alkoxy having from 1 to 8 carbons, hydroxyethyl, dihydroxypropyl, amino, or alkylamido having from 1 to 8 carbons, or a salt of said metal ion chelate.
Claim 6
Dependent Claim
27 words
A metal ion chelate according to claim 4 wherein R 3 is alkylene having from 2 to 6 carbons, or a salt of said metal ion chelate.
Claim 7
Dependent Claim
29 words
A metal ion chelate of N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid or a salt thereof, wherein the metal ion is as recited in claim 1, or a salt of said metal ion chelate.
Claim 8
Dependent Claim
21 words
A metal ion chelate according to claim 4 wherein R 3 is cyclohexyl, or a salt of said metal ion chelate.
Claim 9
Dependent Claim
29 words
A metal ion chelate of N,N'-bis(pyridoxal-5-phosphate)-trans-1,2-cyclohexyldiamine-N,N'-diacetic acid or a salt thereof, wherein the metal ion is as recited in claim 1, or a salt of said metal ion chelate.
Claim 10
Dependent Claim
24 words
A metal ion chelate according to claim 1 wherein the metal ion is divalent or trivalent, or a salt of said metal ion chelate.
Claim 11
Dependent Claim
54 words
A metal ion chelate according to claim 1 wherein the metal ion is chromium (III), manganese (II), iron (III), iron (II), cobalt (II), nickel (II), copper (II), praseodymium (III), neodymium (III), samarium (III), ytterbium (III), gadolinium (III), terbium (III), dysprosium (III), holmium (III), or erbium (III), or a salt of said metal ion chelate.
Claim 12
Dependent Claim
23 words
A metal ion chelate according to claim 1 wherein the metal ion is manganese (II), or a salt of said metal ion chelate.
Claim 13
Dependent Claim
19 words
A manganese (II) chelate of N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid or a salt thereof, or a salt of said manganese (II) chelate.
Claim 14
Dependent Claim
19 words
A manganese (II) chelate of N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid or a salt thereof, or a salt of said manganese (II) chelate.
Claim 15
Dependent Claim
19 words
A manganese (II) chelate of N,N'-bis(pyridoxal-5-phosphate)-trans-1,2-cyclohexyldiamine-N,N'-diacetic acid or a salt thereof, or a salt of said manganese (II) chelate.
Claim 16
Dependent Claim
19 words
A manganese (II) chelate of N,N'-bis(pyridoxal-5-phosphate)-trans-1,2-cyclohexyldiamine-N,N'-diacetic acid or a salt thereof, or a salt of said manganese (II) chelate.
Claim 17
Dependent Claim
40 words
A metal ion chelate according to claim 1 in the form of a calcium salt of an anionic chelate complex of a paramagnetic metal ion and a chelating compound of formula I, or a salt of said metal ion chelate.
Claim 18
Dependent Claim
24 words
A metal ion chelate or salt according to claim 14 wherein the molar ratio of calcium to chelating compound is from 0.05 to 1.0.
Claim 19
Dependent Claim
23 words
A metal ion chelate in the form of a calcium salt of the manganese (II) chelate of claim 12 or a salt thereof.
Claim 20
Dependent Claim
24 words
A metal ion chelate or salt according to claim 16 wherein the molar ratio of calcium to chelating compound is from 0.05 to 1.0.
Claim 21
Dependent Claim
15 words
A sodium-calcium salt of a manganese (II) chelate of N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid or a salt thereof.
Claim 22
Dependent Claim
15 words
A sodium-calcium salt of a manganese (II) chelate of N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid or a salt thereof.
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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) | 1993-06-11 | 1993-12-11 | 1994-06-12 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1997-06-11 | 1997-12-11 | 1998-06-12 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2001-06-11 | 2001-12-11 | 2002-06-12 | $7700.00 | Window Closed / Lapsed |