US4925652A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Nitroxyl compounds, and diagnostic media based thereon useful for enhancing NmR imaging
Assignee: Bayer Pharma AG
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Filing: 1984-08-03
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Granted: 1990-05-15
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Expires: 2004-08-03
Abstract
Abstract Diagnostic media suitable for NMR diagnoses contain compounds of Formula I ##STR1## wherein is a single bond or a double bond, X is the grouping --(CH 2 ) n -- or , if is a single bond, also the grouping --NHCO(CH 2 ) n -- wherein n means 0 to 4, m means the numbers 0, 1, or 2, R 1 is an alkyl residue substituted by hydroxy groups, acyloxy groups and/or alkylidenedioxy groups, R 2 has the same meanings as R 1 or is a hydrogen atom or an alkyl residue, R 3 and R 4 are alkyl residues, and R 5 and R 6 are alkyl residues optionally substituted by hydroxy groups.
Inventors
- 👤 Heinz Gries
- 👤 Ulrich Niedballa
- 👤 Hanns-Joachim Weinmann
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-10 01:57
CPC Classifications
C; C07; C07D; C07D405/00; C07D405/02; C07D405/12; A; A61; A61K; A61K49/00; A61K49/06; A61K49/20; C07D207/00; C07D207/02; C07D207/04; C07D207/10; C07D207/16; C07D207/18; C07D207/22; C07D207/46; C07D211/00; C07D211/92; C07D211/94; G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/53; G01N33/531; G01N33/532; G01N33/58; G01N33/60; Y; Y10; Y10T; Y10T436/00; Y10T436/24
Claims Analysis
Total Claims: 31
Claim 1
Independent Claim
155 words
A method of obtaining an MRI image of a patient comprising administering to the patient an amount effective as a contrast agent of a compound of the formula ##STR10## wherein B is a pharmacologically acceptable protein, sugar, or lipid residue, that selectively binds to a biological molecule, ##STR11## is a single or double bond, X is --(CH 2 ) n -- or, when is a single bond, also --NHCO(CH 2 ) n -- wherein n is an integer 0 to 4, m is 0, 1, or 2, R 1 is C 2-8 -alkyl substituted by hydroxy, C 2-6 -alkanoyloxy, 2-hydroxy-1,3-dioxolan-4-ylmethyl, 5-hydroxy-2,2-dimethyl-1,3-dioxepan-6-yl or C 1-6 -alkylidenedioxy, R 2 independently is one of the R 1 groups, hydrogen or C 1-4 -alkyl, R 3 and R 4 independently are C 1-4 -alkyl, and R 5 and R 6 independently are C 1-4 -alkyl or C 1-4 -alkyl substituted by hydroxy, and scanning to obtain an MRI image.
Claim 2
Independent Claim
155 words
A method of obtaining an MRI image of a patient comprising administering to the patient an amount effective as a contrast agent of a compound of the formula ##STR10## wherein B is a pharmacologically acceptable protein, sugar, or lipid residue, that selectively binds to a biological molecule, ##STR11## is a single or double bond, X is --(CH 2 ) n -- or, when is a single bond, also --NHCO(CH 2 ) n -- wherein n is an integer 0 to 4, m is 0, 1, or 2, R 1 is C 2-8 -alkyl substituted by hydroxy, C 2-6 -alkanoyloxy, 2-hydroxy-1,3-dioxolan-4-ylmethyl, 5-hydroxy-2,2-dimethyl-1,3-dioxepan-6-yl or C 1-6 -alkylidenedioxy, R 2 independently is one of the R 1 groups, hydrogen or C 1-4 -alkyl, R 3 and R 4 independently are C 1-4 -alkyl, and R 5 and R 6 independently are C 1-4 -alkyl or C 1-4 -alkyl substituted by hydroxy, and scanning to obtain an MRI image.
Claim 3
Dependent Claim
17 words
A method of claim 1, wherein said compound is administered in admixture with a pharmaceutically acceptable carrier.
Claim 4
Dependent Claim
11 words
A method of claim 2, wherein B is a sugar residue.
Claim 5
Dependent Claim
11 words
A method of claim 2, wherein B is a protein residue.
Claim 6
Dependent Claim
21 words
A method of claim 4, wherein B is NR, R 2 and R 1 is C 2-4 -alkyl substituted by hydroxy.
Claim 7
Dependent Claim
11 words
A method of claim 2, wherein B is a lipid residue.
Claim 8
Dependent Claim
13 words
A method of claim 2, wherein B is --NR 1 R 2 .
Claim 9
Dependent Claim
13 words
A method of claim 7, wherein R 1 is alkyl substituted by hydroxy.
Claim 10
Dependent Claim
16 words
A method of claim 7, wherein R 1 is C 2-6 -alkanoyloxy or C 1-6 -alkylidenedioxy.
Claim 11
Dependent Claim
21 words
A method of claim 2, wherein B is NR, R 2 and R 1 is C 2-4 -alkyl substituted by hydroxy.
Claim 12
Dependent Claim
17 words
A method of claim 10, wherein X is --(CH 2 ) n -- and n is 0.
Claim 13
Dependent Claim
11 words
A method of claim 2, wherein m is 0 or 1.
Claim 14
Dependent Claim
9 words
A method of claim 2, wherein m is 2.
Claim 15
Dependent Claim
19 words
A method of claim 2, wherein when X is --(CH 2 ) n --, n is 0 or 1.
Claim 16
Dependent Claim
20 words
A method of claim 2, wherein when X is --NHCO(CH 2 ) n --, n is 2, 3 or 4.
Claim 17
Dependent Claim
12 words
A method of claim 2, wherein said compound is 2,2,5,5-tetramethyl-3-pyrroline-1-oxyl-3-carboxylic acid (2-hydroxyethyl)amide.
Claim 18
Dependent Claim
12 words
A method of claim 2, wherein said compound is 2,2,5,5-tetramethyl-3-pyrroline-1-oxyl-3-carboxylic acid (2,3-dihydroxypropyl)amide.
Claim 19
Dependent Claim
203 words
A method of claim 2, wherein said compound is of the formula ##STR12## wherein B is a pharmacologically acceptable, selectively binding protein, sugar, or lipid residue, or ##STR13## is a single or double bond, X is --(CH 2 ) n -- or when is a single bond, also --NHCO(CH 2 ) n wherein n is an integer 0 to 4, m is 0, 1, or 2, R 1 is C 2-8 -alkyl substituted by hydroxy, C 2-6 -alkanoyloxy, 2-hydroxy-2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethyl, 2,2-dimethyl-1,3-dioxolan-4-ylmethyl, 5-hydroxy-2,2-dimethyl-1,3-dioxepan-6-yl, or C 2-6 -alkylidenedioxy, R 2 independently is one of the R 1 groups, hydrogen or C 1-4 -alkyl, R 3 and R 4 independently are C 1-4 -alkyl, and R 5 and R 6 independently are C 1-4 -alkyl or C 1-4 -alkyl substituted by hydroxy, with the provisos that when R 3 -R 6 are each methyl, is a double bond, m is 0, X is --(CH 2 ) n --, n is 0, B is --NR 1 R 2 and R 2 is H, then R 1 is not 2-hydroxyethyl, 2,3-dihydroxypropyl or 1,1-dimethyl-2-hydroxyethyl; and when R 5 and R 6 are each alkyl, is a double bond and m and are 0, then B is not a sugar residue.
Claim 20
Dependent Claim
11 words
A method of claim 18, wherein B is a sugar residue.
Claim 21
Dependent Claim
11 words
A method of claim 18, wherein B is a protein residue.
Claim 22
Dependent Claim
12 words
A method of claim 18, wherein B is albumin or an antibody.
Claim 23
Dependent Claim
11 words
A method of claim 21, wherein B is a monoclonal antibody.
Claim 24
Dependent Claim
11 words
A method of claim 18, wherein B is a lipid residue.
Claim 25
Dependent Claim
13 words
A method of claim 18, wherein B is --NR 1 R 2 .
Claim 26
Dependent Claim
13 words
A method of claim 24, wherein R 1 is alkyl substituted by hydroxy.
Claim 27
Dependent Claim
11 words
A method of claim 18, wherein m is 0 or 1.
Claim 28
Dependent Claim
19 words
A method of claim 18, wherein when X is --(CH 2 ) n --, n is 0 or 1.
Claim 29
Dependent Claim
20 words
A method of claim 18, wherein when X is --NHCO(CH 2 ) n --, n is 2, 3 or 4.
Claim 30
Dependent Claim
85 words
A method of claim 18, wherein said compound is 2,2,5,5-tetramethylpyrrolidine-1-oxyl-3-carboxylic acid {2-hydroxy-2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethyl}-amide, 2,2,5,5-tetramethylpyrrolidine-1-oxyl-3-carboxylic acid (1,3-dihydroxyprop-2-yl)amide, 2,2,5,5-tetramethyl-3-pyrroline-1-oxyl-3-carboxylic acid (2,2-dimethyl-1,3-dioxolan-4-ylmethyl)amide, 2,2,5,5-tetramethyl-3-pyrroline-1-oxyl-3-carboxylic acid {N-(2,2-dimethyl-1,3-dioxolan-4-ylmethyl)-N-methyl}amide, 2,2,5,5-tetramethyl-3-pyrroline-1-oxyl-3-carboxylic acid N-(2,3-dihydroxypropyl)-N-methylamide, 2,2,5,5-tetramethylpyrrolidine-1-oxyl-3-carboxylic acid (2,3,4-trihydroxybutyl)amide, 2,2,5,5-1-oxyl-3-carboxylic acid {N-(2,3,4,5,6-pentahydroxyhexyl)-N-methyl}-amide, 2,2,5,5-tetramethylpyrrolidine-1-oxyl-3-carboxylic acid (2,3-dihydroxypropyl)amide, 2,2,5,5-tetramethylpyrrolidine-1-oxyl-3-carboxylic acid bis(2-hydroxyethyl)amide, 2,2,5,5-tetramethylpyrrolidine-1-oxyl-3-carboxylic acid [N-(2,2-dimethyl-1,3-dioxolan-4-ylmethyl)-N-methyl]amide, 2,2,5,5-tetramethylpyrrolidine-1-oxyl-3-carboxylic acid N-(2,3-dihydroxypropyl)-N-methylamide, 2,2,5,5-tetramethyl-3-pyrroline-1-oxyl-3-carboxylic acid {2-hydroxy-2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethyl}amide, 2,2,5,5-tetramethyl-3-pyrroline-1-oxyl-3-carboxylic acid (2,3,4-trihydroxybutyl)amide, 2,2,5,5-tetramethyl-3-pyrroline-1-oxyl-3-carboxylic acid (5-hydroxy-2,2-dimethyl-1,3-dioxepan-6-yl)amide, 2,2,5,5-tetramethyl-3-pyrroline-1-oxyl-3-carboxylic acid (1,3,4-trihydroxybut-2-yl)amide, 2,2,5,5-tetramethylpyrrolidine-1-oxyl-3-carboxylic acid (5-hydroxy-2,2-dimethyl-1,3-dioxepan-6-yl)amide, 2,2,5,5-tetramethylpyrrolidine-1-oxyl-3-carboxylic acid (1,3,4-trihydroxybut-2-yl)amide, 2,2,5,5-tetramethyl-3-pyrroline-1-oxyl-3-carboxylic acid {N-(2,3,4,5,6-pentahydroxyhexyl)-N-methyl}-amide, 2,2,5,5-tetramethyl-3-pyrroline-1-oxyl-3-carboxylic acid (1,3-dihydroxyprop-2-yl)amide, 2,2,5,5-tetramethyl-3-pyrroline-1-oxyl-3-carboxylic acid (5hydroxy-2,2-dimethyl-1,3-dioxepan-6-yl)amide, succinic acid N-{2-hydroxy-2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethyl}-N'-(2,2,6,6-tetramethyl-1-oxylpiperidin-4-yl) diamide, succinic acid {N-(2,2,6,6-tetramethyl-1-oxylpiperidin-4-yl)-N'-(2,3,4-trihydroxybutyl)} diamide, (1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl)-acetic acid {N-(2,3,4,5,6-pentahydroxyhexyl)-N-methyl}amide, or succinic acid {N-(1-oxyl-2,2,5,5-tetramethylpyrrolidin-3-yl)-N'-methyl-N'-(2,3,4,5,6-pentahydroxyhexyl(} diamide.
Claim 31
Dependent Claim
16 words
A method of claim 1, wherein said compound is administered as a clathrate in a liposome.
References Cited (Backward Citations)
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FR2235103A1
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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) | 1993-05-14 | 1993-11-13 | 1994-05-15 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1997-05-14 | 1997-11-13 | 1998-05-15 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2001-05-14 | 2001-11-13 | 2002-05-15 | $7700.00 | Window Closed / Lapsed |