US5508270A
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Nucleoside phosphinate compounds and compositions
Assignee: Novartis Corp
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Filing: 1994-02-28
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Granted: 1996-04-16
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Expires: 2014-02-28
Abstract
Abstract A compound of formula ##STR1## where R 1 is hydrogen or a protecting group Q; R 2 is hydrogen, a C 1 -C 8 aliphatic radical, a C 6 -C 15 aromatic radical, a C 3 -C 8 cycloaliphatic radical, a C 7 -C 13 araliphatic radical, an alkali metal ion or an ammonium ion; R 3 and R 4 are independently hydrogen, halogen or hydroxy; R 5 is C 6 -C 10 aryloxythiocarbonyloxy, the C 6 -C 10 aryl group being unsubstituted or substituted, or R 5 a ; R 5 a is hydrogen, fluorine, chlorine, hydroxy, --OR 8 , --OCOR 8 or silyloxy substituted by three C 1 -C 15 hydrocarbyl groups; R 6 is hydrogen, a C 1 -C 10 aliphatic radical, a C 6 -C 15 aromatic radical, a C 7 -C 16 araliphatic radical, --COR 9 , --SO 2 R 9 or silyl substituted by three C 1 -C 15 hydrocarbyl groups; R 7 is a monovalent nucleoside base radical, hydroxyl, --OR 8 or --OCOR 8 , and R 9 are independently a C 1 -C 10 aliphatic radical, a C 3 -C 8 cycloaliphatic radical, a C 6 -C 15 aromatic radical or a C 7 -C 16 araliphatic radical; or R 5 and the indicated R 6 O-together denote an isopropylidenedioxy group or R 5 and R 7 together denote an isopropylidenedioxy group, provided that when R 5 and R 7 together denote isopropylidenedioxy, R 1 R 2 , R 3 R 4 and R 6 are not all hydrogen. The disclosure further relates to a method of preparing the compounds of formula I by reacting a olefinic acetonide with a phosphinate compound and to the use of the compounds of formula I as pharmaceutical agents.
Inventors
- 👤 Anthony D. Baxter
- 👤 Eric K. Baylis
- 👤 Stephen P. Collingwood
- 👤 Roger J. Taylor
- 👤 Alain Mesmaeker
- 👤 Chantal Schmit
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-05 00:23
CPC Classifications
C; C07; C07H; C07H19/00; C07H19/02; C07H19/04; C07H19/06; C07H19/10; C07H19/16; C07H19/20; C07H21/00; Y; Y02; Y02P; Y02P20/00; Y02P20/50; Y02P20/55
Claims Analysis
Total Claims: 11
Claim 1
Independent Claim
267 words
A compound of formula ##STR107## where R 1 is hydrogen or Q, wherein Q is a protecting group; R 2 is hydrogen, a C 1 -C 8 aliphatic radical, a C 6 -C 15 aromatic radical, a C 3 -C 8 cycloaliphatic radical, a C 7 -C 13 araliphatic radical, an alkali metal ion or an ammonium ion; R 3 and R 4 are independently hydrogen, halogen or hydroxy; R 5 is C 6 -C 10 aryloxythiocarbonyloxy, the C 6 -C 10 aryl group being unsubstituted substituted, or R 5 a ; R 5 a is hydrogen, fluorine, chlorine, hydroxy. --OR 8 , --OCOR 8 or silyloxy substituted by three C 1 -C 15 hydrocarbyl groups;. R 6 is hydrogen, a C 1 -C 10 aliphatic radical. a C 6 -C 15 aromatic radical, a C 7 -C 16 araliphatic radical, --COR 9 , --SO 2 R 9 or silyl substituted by three C 1 -C 15 hydrocarbyl groups; R 7 is a monovalent nucleoside base radical, hydroxyl, --OR 8 or --OCOR 8 , and R 8 and R 9 are independently a C 1 -C 10 aliphatic radical, a C 3 -C 8 cycloaliphatic radical, a C 6 -C 15 aromatic radical or a C 7 -C 16 araliphatic radical; or R 5 and the indicated R 6 O-- together denote an isopropylidenedioxy group or R 5 and R 7 together denote an isopropylidenedioxy group, provided that when R 5 and R 7 together denote an isopropylidenedioxy group, R 1 , R 2 , R 3 , R 4 and R 6 are not all hydrogen.
Claim 2
Dependent Claim
267 words
A compound of formula ##STR107## where R 1 is hydrogen or Q, wherein Q is a protecting group; R 2 is hydrogen, a C 1 -C 8 aliphatic radical, a C 6 -C 15 aromatic radical, a C 3 -C 8 cycloaliphatic radical, a C 7 -C 13 araliphatic radical, an alkali metal ion or an ammonium ion; R 3 and R 4 are independently hydrogen, halogen or hydroxy; R 5 is C 6 -C 10 aryloxythiocarbonyloxy, the C 6 -C 10 aryl group being unsubstituted substituted, or R 5 a ; R 5 a is hydrogen, fluorine, chlorine, hydroxy. --OR 8 , --OCOR 8 or silyloxy substituted by three C 1 -C 15 hydrocarbyl groups;. R 6 is hydrogen, a C 1 -C 10 aliphatic radical. a C 6 -C 15 aromatic radical, a C 7 -C 16 araliphatic radical, --COR 9 , --SO 2 R 9 or silyl substituted by three C 1 -C 15 hydrocarbyl groups; R 7 is a monovalent nucleoside base radical, hydroxyl, --OR 8 or --OCOR 8 , and R 8 and R 9 are independently a C 1 -C 10 aliphatic radical, a C 3 -C 8 cycloaliphatic radical, a C 6 -C 15 aromatic radical or a C 7 -C 16 araliphatic radical; or R 5 and the indicated R 6 O-- together denote an isopropylidenedioxy group or R 5 and R 7 together denote an isopropylidenedioxy group, provided that when R 5 and R 7 together denote an isopropylidenedioxy group, R 1 , R 2 , R 3 , R 4 and R 6 are not all hydrogen.
Claim 3
Dependent Claim
170 words
A compound of claim 1, in which R 2 is hydrogen, substituted or unsubstituted C 1 -C 8 alkyl, C 3 -C 8 cycloalkyl, C 6 -C 15 aryl or C 7 -C 13 aralkyl, an alkali metal ion or an ammonium ion; R 5 as R 5 a is hydrogen, fluorine, chlorine, hydroxy, C 1 -C 10 alkoxy, C 2 -C 10 alkenoxy, C 6 -C 15 aryloxy, C 7 -C 16 aralkyloxy, --OCOR 8 or silyloxy substituted by three C 1 -C 15 hydrocarbyl groups; R 6 is hydrogen, substituted or unsubstituted C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 6 -C 15 aryl or C 7 -C 16 aralkyl, --COR 9 , --SO 2 R 9 or silyl substituted by three C 1 -C 15 hydrocarbyl groups; and R 8 and R 9 are independently substituted or unsubstituted C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 3 -C 8 cycloalkyl, C 6 -C 15 aryl or C 7 -C 16 aralkyl.
Claim 4
Dependent Claim
12 words
A compound of claim 1, which is a stereoisomer of formula ##STR108##
Claim 5
Dependent Claim
94 words
A compound of claim 1, in which the protecting group Q is of formula ##STR109## where R 10 is hydrogen, C 1 -C 10 alkyl, C 3 -C 8 cycloalkyl, C 6 -C 10 aryl or C 7 -C 11 aralkyl and R 11 and R 12 are independently C 1 -C 10 alkyl; or the protecting group Q is of formula ##STR110## where R 13 and R 14 are independently C 1 -C 10 alkyl or R 13 is C 1 -C 10 alkyl and R 14 is C 6 -C 10 aryl.
Claim 6
Dependent Claim
42 words
A compound of claim 4, in which R 10 is hydrogen or C 1 -C 4 alkyl, R 11 and R 12 are each C 1 -C 4 alkyl and R 13 and R 14 are each C 1 -C 4 alkyl.
Claim 7
Dependent Claim
26 words
A compound of claim 1, in which R 2 is hydrogen, unsubstituted or substituted C 1 -C 6 alkyl or an unsubstitued or substituted ammonium ion.
Claim 8
Dependent Claim
15 words
A compound of claim 1, in which R 3 and R 4 are each hydrogen.
Claim 9
Dependent Claim
159 words
A compound of claim 1, in which R 5 is hydrogen, hydroxy, C 1 -C 4 alkoxy, --OCOR 8 where R 8 is C 1 -C 10 alkyl, or C 1 -C 4 alkyl- or halogen-substituted phenyloxythiocarbonyloxy, or R 5 together with R 7 denotes an isopropylidenedioxy group or R 5 together with R 6 O-- denotes an isopropylidenedioxy group; R 6 is hydrogen, C 7 -C 9 aralkyl, --COR 9 or --SO 2 R 9 where R 9 is unsubstituted or substituted C 1 -C 4 alkyl or C 6 -C 10 aryl, C 1 -C 6 alkyldi (C 6 -C 8 aryl) silyl or R 6 together with the attached oxygen atom and R 5 denotes an isopropylidenedioxy group; and R 7 is hydroxy, --COR 8 where R 8 is C 1 -C 10 alkyl or an unsubstituted or substituted thyminyl, cytosinyl, guaninyl or adeninyl group, or R 7 together with R 5 denotes an isopropylidenedioxy group.
Claim 10
Dependent Claim
213 words
A compound of claim 4, in which R 1 is hydrogen or a protecting group Q of formula II as defined in claim 4, in which R 10 is hydrogen, or methyl and R 11 and R 12 are each ethyl; R 2 is hydrogen, methyl or ethyl; R 3 , R 4 and R 5 are each hydrogen; R 6 is hydrogen, --COR 9 where R 9 is phenyl, 4-nitrophenyl or alpha-naphthyl, --SO 2 R 9 where R 9 is methyl or p-tolyl, or tert-butyldiphenylsilyl; and R 7 is thyminyl or N-(4-nitrobenzoyl)thyminyl; or R 5 and R 7 together denote an isopropylidenedioxy group; or R 1 is hydrogen or a protecting group of formula III as defined in claim 4, in which R 13 and R 14 are each methyl; R 2 is hydrogen, methyl, ethyl, isobutyl, ammonium or triethylammonium; R 3 and R 4 are each hydrogen; R 5 is hydrogen, hydroxy, methoxy, --OCOCH 3 or p-tolyloxythiocarbonyloxy, R 6 is hydrogen, benzyl or --COR 9 where R 9 is methyl or 4-nitrophenyl; and R 7 is hydroxy, --OCOCH 3 , thyminyl, N-benzyloxymethylthyminyl, cytosinyl,N-acetylcytosinyl, N-benzoylcytosinyl, guaninyl, adeninyl or N-benzoyladeninyl; or R 8 and R 7 together denote an isopropylidenedioxy group, or R 5 together with R 6 O-- denotes an isopropylidenedioxy group.
Claim 11
Dependent Claim
20 words
A pharmaceutical composition, which comprises an effective antiviral amount of a compound of claim 1 and a pharmaceutically acceptable carrier.
References Cited (Backward Citations)
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