US4276280A
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Radiolabeled derivatives of folic acid
Assignee: Becton Dickinson and Co
•
Filing: 1976-09-29
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Granted: 1981-06-30
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Expires: 1996-09-29
Abstract
Abstract Derivatives of folic acid wherein the α-carboxyl group of the glutamyl moiety is substituted with a radical which is capable of being radioiodinated, such as, substituted and unsubstituted tyrosyl and histidyl. The radioiodinated derivatives can be employed as tracers for the assay of folates.
Inventors
- 👤 Anandrao S. Akerkar
- 👤 Herman Rutner
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-04 19:34
CPC Classifications
C; C07; C07D; C07D475/00; C07D475/02; C07D475/04; A; A61; A61P; A61P3/00; A61P3/02
Claims Analysis
Total Claims: 34
Claim 1
Independent Claim
117 words
A compound having the following structural formula: ##STR3## wherein Y is selected from the group consisting of --H, lower alkyl, or a cation selected from the group consisting of alkali metals, alkaline earth metals, and ammonium; X is selected from the group consisting of radicals having the following structural formula: ##STR4## wherein R 1 and R 2 are each separately selected from the group consisting of hydrogen, fluoro, chloro, bromo-, nitro, lower alkoxy, lower alkyl and radioactive isotopes of iodine, wherein at least one of R 1 and R 2 is a radioactive isotope of iodine, and R 3 is selected from the group consisting of hydrogen, lower alkyl, an alkali metal and an alkaline earth metal.
Claim 2
Dependent Claim
117 words
A compound having the following structural formula: ##STR3## wherein Y is selected from the group consisting of --H, lower alkyl, or a cation selected from the group consisting of alkali metals, alkaline earth metals, and ammonium; X is selected from the group consisting of radicals having the following structural formula: ##STR4## wherein R 1 and R 2 are each separately selected from the group consisting of hydrogen, fluoro, chloro, bromo-, nitro, lower alkoxy, lower alkyl and radioactive isotopes of iodine, wherein at least one of R 1 and R 2 is a radioactive isotope of iodine, and R 3 is selected from the group consisting of hydrogen, lower alkyl, an alkali metal and an alkaline earth metal.
Claim 3
Dependent Claim
11 words
The compound of claim 1 wherein X has structural formula (a).
Claim 4
Dependent Claim
14 words
The compound of claim 2 wherein R 3 is hydrogen and Y is --H.
Claim 5
Dependent Claim
19 words
The compound of claim 3 wherein R 1 is a radioactive isotope of iodine and R 2 is fluoro.
Claim 6
Dependent Claim
13 words
The compound of claim 1 wherein Y is --H, R 3 is hydrogen.
Claim 7
Dependent Claim
11 words
The compound of claim 1 wherein X has structural formula (b).
Claim 8
Dependent Claim
14 words
The compound of claim 6 wherein Y is --H and R 3 is hydrogen.
Claim 9
Dependent Claim
11 words
The compound of claim 1 wherein X has structural formula (c).
Claim 10
Dependent Claim
14 words
The compound of claim 8 wherein Y is --H and R 3 is hydrogen.
Claim 11
Dependent Claim
11 words
The compound of claim 1 wherein X has structural formula (e).
Claim 12
Dependent Claim
14 words
The compound of claim 10 wherein Y is --H and R 3 is hydrogen.
Claim 13
Dependent Claim
14 words
The compound of claim 2 wherein R 3 is methyl and Y is --H.
Claim 14
Dependent Claim
78 words
A process for producing a compound as defined in claim 1, comprising: condensing in solution folic acid with a member selected from the group consisting of the amine and amino acid derivatives defined as X in claim 23; adjusting the pH of the solution from about 8-12 to precipitate and separate the di-substituted derivatives; and thereafter adjusting the pH to from about 2-5 to precipitate and separate an α-mono-substituted derivative of folic acid as defined by claim 1.
Claim 15
Dependent Claim
21 words
The process of claim 13 wherein the condensation is effected with a peptide condensing agent at a pH of from 5-10.
Claim 16
Dependent Claim
11 words
The process of claim 13 wherein X has structural formula (a).
Claim 17
Dependent Claim
10 words
The process of claim 15 wherein R 2 is hydrogen.
Claim 18
Dependent Claim
19 words
In the radioassay of folates, the improvement comprising: employing a compound as defined in claim 1 as the tracer.
Claim 19
Dependent Claim
22 words
In the radioassay of folates, the improvement comprising: employing a compound as defined in claim 2 as the tracer in said assay.
Claim 20
Dependent Claim
22 words
In the radioassay of folates, the improvement comprising: employing a compound as defined in claim 3 as the tracer in said assay.
Claim 21
Dependent Claim
22 words
In the radioassay of folates, the improvement comprising: employing a compound as defined in claim 4 as the tracer in said assay.
Claim 22
Dependent Claim
22 words
In the radioassay of folates, the improvement comprising: employing a compound as defined in claim 6 as the tracer in said assay.
Claim 23
Dependent Claim
109 words
A compound having the following structural formula: ##STR5## wherein y is selected from the group consisting of --H, lower alkyl, or a cation selected from the group consisting of alkali metals, alkaline earth metals and ammonium; X is selected from the group consisting of radicals having the following structural formula: ##STR6## wherein R 1 and R 2 are each separately selected from the group consisting of hydrogen, fluoro, chloro, bromo-, nitro, lower alkoxy and lower alkyl, wherein at least one of R 1 and R 2 is hydrogen, and R 3 is selected from the group consisting of hydrogen, lower alkyl, an alkali metal and an alkaline earth metal.
Claim 24
Dependent Claim
109 words
A compound having the following structural formula: ##STR5## wherein y is selected from the group consisting of --H, lower alkyl, or a cation selected from the group consisting of alkali metals, alkaline earth metals and ammonium; X is selected from the group consisting of radicals having the following structural formula: ##STR6## wherein R 1 and R 2 are each separately selected from the group consisting of hydrogen, fluoro, chloro, bromo-, nitro, lower alkoxy and lower alkyl, wherein at least one of R 1 and R 2 is hydrogen, and R 3 is selected from the group consisting of hydrogen, lower alkyl, an alkali metal and an alkaline earth metal.
Claim 25
Dependent Claim
11 words
The compound of claim 22 wherein X has structural formula (a).
Claim 26
Dependent Claim
15 words
The compound of claim 23 wherein one of R 1 and R 2 is fluoro.
Claim 27
Dependent Claim
11 words
The compound of claim 22 wherein X has structural formula (b).
Claim 28
Dependent Claim
11 words
The compound of claim 22 wherein X has structural formula (c).
Claim 29
Dependent Claim
11 words
The compound of claim 22 wherein X has structural formula (e).
Claim 30
Dependent Claim
79 words
A process for producing a compound as defined in claim 22 comprising: condensing in solution folic acid with a member selected from the group consisting of the amine and amino acid derivatives defined as X in claim 22: adjusting the pH of the solution to from about 8-12 to precipitate and separate the di-substituted derivatives; and thereafter adjusting the pH to from about 2-5 to precipitate and separate an α-mono-substituted derivative of folic acid as defined by claim 22.
Claim 31
Dependent Claim
21 words
The process of claim 28 wherein the condensation is effected with a peptide condensing agent at a pH of from 5-10.
Claim 32
Dependent Claim
20 words
The process of claim 29 wherein X has structural formula (a), and R 1 and R 2 are both hydrogen.
Claim 33
Dependent Claim
11 words
The compound of claim 22 wherein X has structural formula (d).
Claim 34
Dependent Claim
11 words
The compound of claim 1 wherein X has structural formula (d).
References Cited (Backward Citations)
US3989812A
Cited
US3988431A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1984-06-29 | 1984-12-29 | 1985-06-30 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1988-06-29 | 1988-12-29 | 1989-06-30 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1992-06-29 | 1992-12-29 | 1993-06-30 | $7700.00 | Window Closed / Lapsed |