Dinucleoside phosphinates and their pharmaceutical compositions
First Claim
1. A dinucleotide analogue of formula ##STR128## where B1 and B2 are each independently a monovalent nucleoside base radical;
- R1 is R1a or Z;
R1a, R2, R3 and R4 are each independently hydrogen, halogen or hydroxy;
R5 is R5a or Z;
R6 is hydrogen or R6a ;
R7 is hydrogen, alkyl-N,N-dialkylphosphoramidyl or R7a, R8 is R8a or Z, or the indicated R7 O and R8 together denote an isopropylidenedioxy group;
R5a and R8a are each independently hydrogen, halogen, hydroxy, --OR10, --OCOR10 or silyloxy substituted by three C1 -C15 hydrocarbyl groups;
R6a and R7a are each independently a C1 -C10 aliphatic radical, a C6 -C15 aromatic radical, a C7 -C30 araliphatic radical, --COR11, --SO2 R11 or silyl substituted by three C1 -C15 hydrocarbyl groups;
R9 is hydrogen, a C1 -C8 aliphatic radical, a C3 -C8 cycloaliphatic radical, a C6 -C15 aromatic radical, a C7 -C13 araliphatic radical, an alkali metal ion or an ammonium ion;
R10 and R11 are each independently a C1 -C10 aliphatic radical, a C3 -C8 cycloaliphatic radical, a C6 -C15 aromatic radical or a C7 -C16 araliphatic radical;
Rx and Ry are independently hydrogen, halogen, hydroxy, a C1 -C10 alkyl, C2 -C10 alkenyl, C3 -C8 cycloalkyl, C6 -C15 aryl, C7 -C16 aralkyl, C1 -C10 alkoxy, C2 -C10 alkenoxy, C6 -C10 aryloxy or C7 -C16 aralkyloxy group, which is substituted or unsubstituted, or --OCORZ ;
Rz is a substituted or unsubstituted C1 -C10 alkyl, C2 -C10 alkenyl, C3 -C8 cycloalkyl, C6 -C15 aryl or C7 -C16 aralkyl group; and
Z is C6 -C10 aryloxythiocarbonyloxy, the C6 -C10 aryl group being substituted or unsubstituted.
1 Assignment
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Accused Products
Abstract
A dinucleotide analogue of formula ##STR1## where B1 and B2 are each independently a monovalent nucleoside base radical;
R1 is R1a or Z;
R1a, R2, R3 and R4 are each independently hydrogen, halogen or hydroxy;
R5 is R5a or Z;
R6 is hydrogen or R6a ;
R7 is hydrogen, alkyl-N,N-dialkylphosphoramidyl or R7a, R8 is R8a or Z, or the indicated R7 O and R8 together denote an isopropylidenedioxy group;
R5a and R8a are each independently hydrogen, halogen, hydroxy, --OR10, --OCOR10 or silyloxy substituted by three C1 -C15 hydrocarbyl groups;
R6a and R7a are each independently a C1 -C10 aliphatic radical, a C6 -C15 aromatic radical, a C7 -C30 araliphatic radical, --COR11, --SO2 R11 or silyl substituted by three C1 -C15 hydrocarbyl groups;
R9 is hydrogen, a C1 -C8 aliphatic radical, a C3 -C8 cycloaliphatic radical, a C6 -C15 aromatic radical, a C7 -C13 araliphatic radical, an alkali metal ion or an ammonium ion;
R10 and R11 are each independently a C1 -C10 aliphatic radical, a C3 -C8 cycloaliphatic radical, a C6 -C15 aromatic radical or a C7 -C16 araliphatic radical;
Rx and Ry are independently hydrogen, halogen, hydroxy, a C1 -C10 alkyl, C2 -C10 alkenyl, C3 -C8 cycloalkyl, C6 -C15 aryl, C7 -C16 aralkyl, C1 -C10 alkoxy, C2 -C10 alkenoxy, C6 -C10 aryloxy or C7 -C16 aralkyloxy group, which is substituted or unsubstituted, or --OCORz ;
Rz is a substituted or unsubstituted C1 -C10 alkyl, C2 -C10 alkenyl, C3 -C8 cycloalkyl, C6 -C15 aryl or C7 -C16 aralkyl group; and
Z is C6 -C10 aryloxythiocarbonyloxy, the C6 -C10 aryl group being substituted or unsubstituted.
434 Citations
11 Claims
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1. A dinucleotide analogue of formula ##STR128## where B1 and B2 are each independently a monovalent nucleoside base radical;
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R1 is R1a or Z; R1a, R2, R3 and R4 are each independently hydrogen, halogen or hydroxy; R5 is R5a or Z; R6 is hydrogen or R6a ; R7 is hydrogen, alkyl-N,N-dialkylphosphoramidyl or R7a, R8 is R8a or Z, or the indicated R7 O and R8 together denote an isopropylidenedioxy group; R5a and R8a are each independently hydrogen, halogen, hydroxy, --OR10, --OCOR10 or silyloxy substituted by three C1 -C15 hydrocarbyl groups; R6a and R7a are each independently a C1 -C10 aliphatic radical, a C6 -C15 aromatic radical, a C7 -C30 araliphatic radical, --COR11, --SO2 R11 or silyl substituted by three C1 -C15 hydrocarbyl groups; R9 is hydrogen, a C1 -C8 aliphatic radical, a C3 -C8 cycloaliphatic radical, a C6 -C15 aromatic radical, a C7 -C13 araliphatic radical, an alkali metal ion or an ammonium ion; R10 and R11 are each independently a C1 -C10 aliphatic radical, a C3 -C8 cycloaliphatic radical, a C6 -C15 aromatic radical or a C7 -C16 araliphatic radical; Rx and Ry are independently hydrogen, halogen, hydroxy, a C1 -C10 alkyl, C2 -C10 alkenyl, C3 -C8 cycloalkyl, C6 -C15 aryl, C7 -C16 aralkyl, C1 -C10 alkoxy, C2 -C10 alkenoxy, C6 -C10 aryloxy or C7 -C16 aralkyloxy group, which is substituted or unsubstituted, or --OCORZ ; Rz is a substituted or unsubstituted C1 -C10 alkyl, C2 -C10 alkenyl, C3 -C8 cycloalkyl, C6 -C15 aryl or C7 -C16 aralkyl group; and Z is C6 -C10 aryloxythiocarbonyloxy, the C6 -C10 aryl group being substituted or unsubstituted. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10)
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11. A pharmaceutical composition comprising an effective amount of a dinucleotide analog of formula ##STR130## where B1 and B2 are each independently a monovalent nucleoside base radical;
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R1 is R1a or Z; R1a ;
R2, R3 and R4 are each independently hydrogen, halogen or hydroxy;R5 is R5a or Z; R6 is hydrogen or R6a ; R7 is hydrogen, alkyl-N,N-dialkylphosphoramidyl or R7a, R8 is R8a or Z, or the indicated R7 O and R8 together denote an isopropylidenedioxy group; R5a and R8a are each independently hydrogen, halogen, hydroxy, --OR10, --OCOR10 or silyloxy substituted by three C1 -C15 hydrocarbyl groups; R6a and R7a, are each independently a C1 -C10 aliphatic radical, a C6 -C15 aromatic radical, a C7 -C30 araliphatic radical, --COR11, --SO2 R11 or silyl substituted by three C1 -C15 hydrocarbyl groups; R9 is hydrogen, a C1 -C8 aliphatic radical, a C3 -C8 cycloaliphatic radical, a C6 -C15 aromatic radical, a C7 -C13 araliphatic radical, an alkali metal ion or an ammonium ion; R10 and R11 are each independently a C1 -C10 aliphatic radical, a C3 -C8 cycloaliphatic radical, a C6 -C15 aromatic radical or a C7 -C16 araliphatic radical; Rx and Ry are independently hydrogen, halogen, hydroxy, a C1 -C10 alkyl, C2 -C10 alkenyl, C3 -C8 cycloalkyl, C6 -C15 aryl, C7 -C16 aralkyl, C1 -C10 alkoxy, C2 -C10 alkenoxy, C6 -C10 aryloxy or C7 -C16 aralkyloxy group, which is substituted or unsubstituted, or --OCORz, Rz is a substituted or unsubstituted C1 -C10 alkyl, C2 -C10 alkenyl, C3 -C8 cycloalkyl, C6 -C15 aryl or C7 -C16 aralkyl group; and Z is C6 -C10 aryloxythiocarbonyloxy, the C6 -C10 aryl group being substituted or unsubstituted; and
a pharmaceutically acceptable carrier.
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Specification
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- Resources
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Current AssigneeCiba-Geigy Corporation (Novartis Ag)
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Original AssigneeCiba-Geigy Corporation (Novartis Ag)
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InventorsDe Mesmaeker, Alain, Collingwood, Stephen P., Baxter, Anthony D., Schmit, Chantal, Taylor, Roger J., Baylis, Eric K.
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Primary Examiner(s)Robinson, Douglas W.
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Assistant Examiner(s)Crane, L. Eric
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Application NumberUS08/204,020Time in Patent Office624 DaysField of Search536/23.1, 536/26.5, 536/26.2, 536/24.5, 514/44US Class Current514/44.00RCPC Class CodesA61P 31/12 AntiviralsA61P 31/16 for influenza or rhinovirusesC07H 19/04 Heterocyclic radicals conta...C07H 21/00 Compounds containing two or...
