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US3968101A
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8-Substituted cyclic nucleotides by free radical alkylation and acylation
Assignee: Viratek Inc
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Filing: 1974-12-20
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Granted: 1976-07-06
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Expires: 1994-12-20
Abstract
Abstract Novel compounds of the general formula ##SPC1## Wherein X is H or NH 2 ; R' is C 1 to C 8 alkyl, C 1 to C 8 substituted alkyl, benzyl, C 1 to C 8 acyl, benzoyl, carbamoyl, are disclosed as well as a novel free radial alkylation and acylation process for making such compounds. The compounds of the invention display activity comparable to or superior to their naturally occurring analogue while resisting phosphodiesterase degradation. In some cases the compounds of this invention actually inhibit enzymatic degradation of the natural analogue.
Inventors
- 👤 Leon F. Christensen
- 👤 Roland K. Robins
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-04 22:11
CPC Classifications
C; C07; C07H; C07H19/00; C07H19/02; C07H19/04; C07H19/16; C07H19/20
Claims Analysis
Total Claims: 29
Claim 1
Independent Claim
63 words
The compound of the structure: ##SPC4## wherein X is H or NH 2 ; and R' is iso-propyl; neo-pentyl; C 1 to C 8 substituted alkyl wherein the alkyl is substituted at the 1-alkyl position and the substituents are selected from the group consisting of hydroxyl, phenyl, semicarbazone, thiosemicarbazone, 4-phenyl semicarbazone, and phenyl hydrazone; benzyl; C 1 to C 8 acyl; or carbamoyl.
Claim 2
Dependent Claim
63 words
The compound of the structure: ##SPC4## wherein X is H or NH 2 ; and R' is iso-propyl; neo-pentyl; C 1 to C 8 substituted alkyl wherein the alkyl is substituted at the 1-alkyl position and the substituents are selected from the group consisting of hydroxyl, phenyl, semicarbazone, thiosemicarbazone, 4-phenyl semicarbazone, and phenyl hydrazone; benzyl; C 1 to C 8 acyl; or carbamoyl.
Claim 3
Dependent Claim
55 words
The compound of the structure: ##SPC5## wherein R' is iso-propyl; neo-pentyl; C 1 to C 8 substituted alkyl wherein the alkyl is substituted at the 1-alkyl position and the substituents are selected from the group consisting of hydroxyl, phenyl, semicarbazone, thiosemicarbazone, 4-phenyl semicarbazone, and phenyl hydrazone; benzyl; C 1 to C 8 acyl; or carbamoyl.
Claim 4
Dependent Claim
55 words
The compound of the structure: ##SPC5## wherein R' is iso-propyl; neo-pentyl; C 1 to C 8 substituted alkyl wherein the alkyl is substituted at the 1-alkyl position and the substituents are selected from the group consisting of hydroxyl, phenyl, semicarbazone, thiosemicarbazone, 4-phenyl semicarbazone, and phenyl hydrazone; benzyl; C 1 to C 8 acyl; or carbamoyl.
Claim 5
Dependent Claim
5 words
The compound 8-butyrylguanosine 3',5'-cyclic phosphate.
Claim 6
Dependent Claim
5 words
The compound 8-butyrylguanosine 3',5'-cyclic phosphate.
Claim 7
Dependent Claim
5 words
The compound 8-benzoylguanosine 3',5'-cyclic phosphate.
Claim 8
Dependent Claim
5 words
The compound 8-benzoylguanosine 3',5'-cyclic phosphate.
Claim 9
Dependent Claim
5 words
The compound 8-carbamoylguanosine 3',5'-cyclic phosphate.
Claim 10
Dependent Claim
5 words
The compound 8-carbamoylguanosine 3',5'-cyclic phosphate.
Claim 11
Dependent Claim
5 words
The compound 8-(1-hydroxyethyl)guanosine 3',5'-cyclic phosphate.
Claim 12
Dependent Claim
5 words
The compound 8-(1-hydroxyethyl)guanosine 3',5'-cyclic phosphate.
Claim 13
Dependent Claim
5 words
The compound 8-(α-hydroxybenzyl)guanosine 3',5'-cyclic phosphate.
Claim 14
Dependent Claim
5 words
The compound 8-(α-hydroxybenzyl)guanosine 3',5'-cyclic phosphate.
Claim 15
Dependent Claim
59 words
The compound of the structure: ##SPC6## wherein R' is C 1 to C 8 alkyl; C 1 to C 8 substituted alkyl wherein the alkyl is substituted at the 1-alkyl position and the substituents are selected from the group consisting of hydroxyl, phenyl, semicarbazone, thiosemicarbazone, 4-phenyl semicarbazone and phenyl hydrazone; benzyl; C 1 to C 8 acyl; or carbamoyl.
Claim 16
Dependent Claim
59 words
The compound of the structure: ##SPC6## wherein R' is C 1 to C 8 alkyl; C 1 to C 8 substituted alkyl wherein the alkyl is substituted at the 1-alkyl position and the substituents are selected from the group consisting of hydroxyl, phenyl, semicarbazone, thiosemicarbazone, 4-phenyl semicarbazone and phenyl hydrazone; benzyl; C 1 to C 8 acyl; or carbamoyl.
Claim 17
Dependent Claim
5 words
The compound 8-acetylinosine 3',5'-cyclic phosphate.
Claim 18
Dependent Claim
5 words
The compound 8-acetylinosine 3',5'-cyclic phosphate.
Claim 19
Dependent Claim
5 words
The compound 8-Benzoylinosine 3',5'-cyclic phosphate.
Claim 20
Dependent Claim
5 words
The compound 8-Benzoylinosine 3',5'-cyclic phosphate.
Claim 21
Dependent Claim
104 words
A process of synthesizing 8-substituted 3',5'-cyclic phosphate nucleotides of the general formula: ##SPC7## wherein X is H or NH 2 and R' is iso-propyl, neo-pentyl, benzyl, C 1 to C 8 acyl or carbamoyl comprising reacting the corresponding 8 unsubstituted nucleotide with a free radical corresponding to R' generated in situ from an alkyl peroxide, an aldehyde, formamide or toluene in the presence of Fe + + and either a persulfate or alkyl peroxide free radical initiator with the proviso that when R' is generated from the alkyl peroxide the alkyl peroxide can serve as both the R' source and the free radical initiator.
Claim 22
Dependent Claim
104 words
A process of synthesizing 8-substituted 3',5'-cyclic phosphate nucleotides of the general formula: ##SPC7## wherein X is H or NH 2 and R' is iso-propyl, neo-pentyl, benzyl, C 1 to C 8 acyl or carbamoyl comprising reacting the corresponding 8 unsubstituted nucleotide with a free radical corresponding to R' generated in situ from an alkyl peroxide, an aldehyde, formamide or toluene in the presence of Fe + + and either a persulfate or alkyl peroxide free radical initiator with the proviso that when R' is generated from the alkyl peroxide the alkyl peroxide can serve as both the R' source and the free radical initiator.
Claim 23
Dependent Claim
30 words
The process of claim 11 wherein the iso-propyl and neo-pentyl free radicals are generated in situ with the nucleotide via reaction between Fe + + and the corresponding alkyl peroxide.
Claim 24
Dependent Claim
14 words
The process of claim 12 wherein the alkyl peroxide is t-butyl peroxide or trimethylhydroperoxypentane.
Claim 25
Dependent Claim
30 words
The process of claim 11 wherein the benzyl free radical is generated in situ with the nucleotide via reaction between Fe + + , toluene and a free radical initiator.
Claim 26
Dependent Claim
37 words
The process of claim 11 wherein the C 1 to C 8 acyl free radical is generated in situ with the nucleotide via hydrogen abstraction of the carbonyl carbon of an aldehyde by a free radical source.
Claim 27
Dependent Claim
35 words
The process of claim 15 wherein the free radical source is generated via the reaction between Fe + + and a free radical initiator selected from the group consisting of t-butyl peroxide and ammonium persulfate.
Claim 28
Dependent Claim
97 words
A process of synthesizing 8-(1-substituted)purine of the general formula: ##SPC8## wherein X is H or NH 2 ; Z is selected from the group consisting of 9-β-D-ribofuranosyl, 9-β-D-ribofuranosyl 3',5'-cyclic phosphate, and 9-β-D-ribofuranosyl 5'-phosphate; R is selected from the group consisting of C 1 to C 8 alkyl, phenyl, and benzyl; and Y is selected from the group consisting of hydroxy, semicarbazone, thiosemicarbazome, 4-phenyl semicarbazone, and phenyl hydrazone comprising reacting a compound of the structure: ##SPC9## wherein X, Z, and R are the same as above with NaBH 4 , hydrazine, semicarbazide, thiosemicarbazide, 4-phenyl semicarbazide, or phenyl hydrazine.
Claim 29
Dependent Claim
97 words
A process of synthesizing 8-(1-substituted)purine of the general formula: ##SPC8## wherein X is H or NH 2 ; Z is selected from the group consisting of 9-β-D-ribofuranosyl, 9-β-D-ribofuranosyl 3',5'-cyclic phosphate, and 9-β-D-ribofuranosyl 5'-phosphate; R is selected from the group consisting of C 1 to C 8 alkyl, phenyl, and benzyl; and Y is selected from the group consisting of hydroxy, semicarbazone, thiosemicarbazome, 4-phenyl semicarbazone, and phenyl hydrazone comprising reacting a compound of the structure: ##SPC9## wherein X, Z, and R are the same as above with NaBH 4 , hydrazine, semicarbazide, thiosemicarbazide, 4-phenyl semicarbazide, or phenyl hydrazine.
References Cited (Backward Citations)
No citation records indexed.
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1979-07-06 | 1980-01-05 | 1980-07-06 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1983-07-06 | 1984-01-05 | 1984-07-06 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1987-07-06 | 1988-01-05 | 1988-07-06 | $7700.00 | Window Closed / Lapsed |