US3928319A
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4 -Fluoro nucleosides, novel intermediates and methods of preparing same
Assignee: Syntex USA LLC
•
Filing: 1972-05-31
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Granted: 1975-12-23
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Expires: 1992-05-31
Abstract
Abstract 4''-fluoro nucleosides, 4''-fluoro nucleoside analogs of Nucleocidin, 2''-deoxy-4''-fluoro pyrimidine nucleosides and novel intermediates produced in the process of preparing such compounds. The process for preparing the 4''-fluoro nucleosides of the present invention comprises treating a 4'',5''-unsaturated nucleoside with iodine monofluoride to form the corresponding 5''deoxy-4''-fluoro-5''-iodo nucleoside. The latter product is transformed to corresponding 5''-azido-5''-deoxy-4''-fluoro nucleosides, 5''-amino-5''-deoxy-4''-fluoro nucleosides,5''-deoxy-4''fluoro nucleosides, 4''-fluoro nucleosides, 5''-O-phosphoryl-4''fluoro nucleosides, and 5''-sulfamoyl-4''-fluoro nucleosides. The 2''-deoxy-4''-fluoro pyrimidine nucleosides are prepared in an analogous manner from the 4'',5''-unsaturated-2''-deoxy nucleosides. The nucleosides of this invention exhibit general antimetabolite activity and/or are intermediates for compounds exhibiting such activity.
Inventors
- 👤 Ian Jenkins
- 👤 John G Moffatt
- 👤 Julien P H Verheyden
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-06 09:43
CPC Classifications
C; C07; C07H; C07H19/00; C07H19/02; C07H19/04; C07H19/06; C07H19/16
Claims Analysis
Total Claims: 38
Claim 1
Independent Claim
11 words
A COMPOUND SELECTED FROM THE GROUP OF COMPOUNDS HAVING THE FORMULAS:
Claim 2
Dependent Claim
11 words
A COMPOUND SELECTED FROM THE GROUP OF COMPOUNDS HAVING THE FORMULAS:
Claim 3
Dependent Claim
14 words
The compound of claim 1 having the Formula I, and pharmaceutically acceptable salts thereof.
Claim 4
Dependent Claim
68 words
The compound of claim 2 wherein R1 and R2 are independently hydroxy or benzoyloxy or together form an isopropylidene group, and B1 is selected from the group of purine and pyrimidine bases consisting of 6-(1-adamantylamino)-purine, 6-mercaptopurine, adenine, 2-fluoroadenine, 8-aza-9-deazaadenine, 7-deaza-7-cyanoadenine, 8-azaadenine, cytosine, 5-fluorocytosine, 5-iodocytosine, 5-lower alkyl cytosine, 5-trifluoromethylcytosine, 5-hydroxymethylcytosine, 5-azacytosine, 6-azacytosine, 2-thiocytosine, uracil, 5-fluorouracil, 5-iodouracil, 5-lower alkyluracil, 5-azauracil, 6-azauracil, 4-hydroxylamino-5-fluoro-pyrimidin-2-one, 4-hydroxylamino-5-lower alkylpyrimidin-2-one, 4-hydroxylamino-5-trifluoromethyl-pyrimidin-2-one, 4-hydroxylamino-5-aza-pyrimidin-2-one, 4-hydroxylamino-6-aza-pyrimidin-2-one, 4-hydroxylamino-pyrimidin-2-one, and 4-hydroxylamino-pyrimidin-2-thione.
Claim 5
Dependent Claim
13 words
The compound of claim 2 wherein said compound is a Beta -D-ribo isomer.
Claim 6
Dependent Claim
13 words
The compound of claim 3 wherein said compound is a Beta -D-ribo isomer.
Claim 7
Dependent Claim
11 words
The compound of claim 2 wherein A1 has the formula -CH2OH.
Claim 8
Dependent Claim
11 words
The compound of claim 3 wherein A1 has the formula -CH2OH.
Claim 9
Dependent Claim
11 words
The compound of claim 2 wherein A1 has the formula -CH2I.
Claim 10
Dependent Claim
11 words
The compound of claim 3 wherein A1 has the formula -CH2I.
Claim 11
Dependent Claim
11 words
THe compound of claim 2 wherein A1 has the formula -CH2OPO(OH)2.
Claim 12
Dependent Claim
11 words
The compound of claim 3 wherein A1 has the formula -CH2OPO(OH)2.
Claim 13
Dependent Claim
11 words
The compound of claim 2 wherein A1 has the formula -CH2N3.
Claim 14
Dependent Claim
11 words
The compound of claim 3 wherein A1 has the formula -CH2N3.
Claim 15
Dependent Claim
14 words
The compound of claim 1 having the Formula II, and pharmaceutically acceptable salts thereof.
Claim 16
Dependent Claim
67 words
The compound of claim 14 wherein R1 and R2 are independently hydroxy or benzoyloxy or together form an isopropylidene group, and B2 is selected from the group of purine and pyrimidine bases consisting of 6-(1-adamantylamino) purine, adenine, 2-fluoroadenine, 8-aza-9-deaza-adenine, 7-deaza-7-cyanoadenine, 8-azaadenine, cytosine, 5-fluorocytosine, 5-chlorocytosine, 5-lower alkyl cytosine, 5-trifluoromethylcytosine, 5-hydroxymethylcytosine, 5-azacytosine, 6-azacytosine, uracil, 5-fluorouracil, 5-chlorouracil, 5-lower alkyl uracil, 5-azauracil, 6-azauracil, 4-hydroxylamino-5-fluoro-pyrimidin-2-one, 4-hydroxylamino-5-lower alkyl-pyrimidin-2-one, 4-hydroxylamino-5-trifluoromethyl-pyrimidin-2-one, 4-hydroxylamino-5-aza-pyrimidin-2-one, 4-hydroxylamino-6-aza-pyrimidin-2-one, and 4-hydroxylamino-pyrimidin-2-one.
Claim 17
Dependent Claim
13 words
The compound of claim 14 wherein said compound is a Beta -D-ribo isomer.
Claim 18
Dependent Claim
13 words
The compound of claim 15 wherein said compound is a Beta -D-ribo isomer.
Claim 19
Dependent Claim
11 words
The compound of claim 14 wherein A2 has the formula -CH3.
Claim 20
Dependent Claim
11 words
The compound of claim 15 wherein A2 has the formula -CH3.
Claim 21
Dependent Claim
11 words
The compound of claim 14 wherein A2 has the formula -CH2NH2.
Claim 22
Dependent Claim
11 words
The compound of claim 15 wherein A2 has the formula -CH2NH2.
Claim 23
Dependent Claim
14 words
The compound of claim 1 having the Formula III, and pharmaceutically acceptable salts thereof.
Claim 24
Dependent Claim
68 words
The compound of claim 22 wherein R1 and R2 are independently hydroxy or benzoyloxy or together form an isopropylidene group, and B3 is selected from the group of purine and pyrimidine bases consisting of 6-(1-adamantylamino)purine, 6-mercaptopurine, 2-fluoroadenine, 8-aza-9-deazaadenine, 7-deaza-7-cyanoadenine, 8-azaadenine, cytosine, 5-fluorocytosine, 5-iodocytosine, 5-lower alkyl cytosine, 5-trifluoromethylcytosine, 5-hydroxymethylcytosine, 5-azacytosine, 6-azacytosine, 2-thiocytosine, uracil, 5-fluorouracil, 5-iodouracil, 5-lower alkyl uracil, 5-azauracil, 6-azauracil, 4-hydroxylamino-5-fluoro-pyrimidin-2-one, 4-hydroxylamino-5-lower alkylpyrimidin-2-one, 4-hydroxylamino-5-trifluoromethyl-pyrimidin-2-one, 4-hydroxylamino-5-aza-pyrimidin-2-one, 4-hydroxylamino-6-aza-pyrimidin-2-one, 4-hydroxylamino-pyrimidin-2-one, and 4-hydroxylamino-pyrimidine-2-thione.
Claim 25
Dependent Claim
13 words
The compound of claim 22 wherein said compound is a Beta -D-ribo isomer.
Claim 26
Dependent Claim
13 words
The compound of claim 23 wherein said compound is a Beta -D-ribo isomer.
Claim 27
Dependent Claim
14 words
The compound of claim 1 having the Formula XV, and pharmaceutically acceptable salts thereof.
Claim 28
Dependent Claim
9 words
The compound of claim 26, wherein A4 is -CH2OH.
Claim 29
Dependent Claim
9 words
The compound of claim 26 wherein A4 is -CH2I.
Claim 30
Dependent Claim
9 words
The compound of claim 26 wherein A4 is -CH2N3.
Claim 31
Dependent Claim
9 words
The compound of claim 26 wherein A4 is -CH2OPO(OH)2.
Claim 32
Dependent Claim
8 words
The compound of claim 26 wherein A4 is
Claim 33
Dependent Claim
14 words
The compound of claim 1 having the formula XVI, and pharmaceutically acceptable salts thereof.
Claim 34
Dependent Claim
9 words
The compound of claim 32 wherein A2 is -CH3.
Claim 35
Dependent Claim
9 words
The compound of claim 32 wherein A2 is -CH2NH2.
Claim 36
Dependent Claim
26 words
The process of preparing the compounds of claim 1 having the Formula I wherein A1 is -CH2I, said process comprising treating a compound having the formula:
Claim 37
Dependent Claim
74 words
A process for preparing the compounds of claim 1 of formulas I and XV wherein A1 and A4 are each -CH2OH, which comprises treating the corresponding intermediate of formula I or XV, wherein A1 or A4 is -CH2N3, and wherein said intermediate does not have an amino function on the base moiety, with NOBF4, under reactive conditions thereby affording the corresponding 4''-fluoro nucleoside of formula I or XV wherein A1 or A4 is -CH2OH.
Claim 38
Dependent Claim
99 words
A process for preparing the compounds of claim 1 of formulas I and XV wherein A1 and A4 are each -CH2OH which comprises treating the corresponding intermediate of formula I or XV wherein A1 and A4 is -CH2N3, and wherein the base moiety of said intermediate is not 4-thiouracil or 2,4-thiouracil, by photolysis, in an inert organic solvent, at a wave length of about from 290 m Mu to about 330 m Mu to afford the corresponding 5''-aldehyde nucleoside and reducing said 5''-aldehyde nucleoside to the corresponding compound of formula I or XV wherein A1 or A4 is -CH2OH.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1978-12-22 | 1979-06-23 | 1979-12-23 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1982-12-22 | 1983-06-23 | 1983-12-23 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1986-12-22 | 1987-06-23 | 1987-12-23 | $7700.00 | Window Closed / Lapsed |