Hoffmann-la Roche Inc.

Joseph A Martin

Gareth J Thomas

Sally Redshaw

Peter J Machin

Robert W Lambert

Balraj K Handa

Gareth Mark Taylor

Bradley Stuart Sherborne

The invention relates to new and known tricyclic dione derivatives of the general formula ##STR1## and to their salts which are inhibitors of herpes simplex virus thymidine kinase in the treatment and prophylaxis of infections caused by herpes simplex virus.

Xanthene and acridine derivatives

The invention relates to new and known tricyclic dione derivatives of the general formula ##STR1## wherein W represents hydrogen or lower alkyl;

Acridine derivatives

Pyrimidine nucleoside derivatives of formula ##STR1## wherein R.sup.1 represents aryl, R.sup.2 represents lower alkyl, R.sup.3 represents an acyl group derived from an amino acid and R.sup.4 represents hydrogen or fluorine and the asterisk denotes that the configuration at the carbon atom indicated thereby is (S) or (R), are disclosed. These compounds, as well as their salts, are useful as antiviral agents.

3'-O-aminoacyl ARA uridines, method of making, and antiviral activity

This invention is directed to the novel pyrimidine derivative 1-�5-�2(S)-(2,4-dichloro-5-methoxyphenoxy) propionamido!-2,5-dideoxy-2-fluoro-.beta.-D-arabinofuranosly!-5-ethyluraci l and its use as an antiviral agent, as well as to intermediates useful in the synthesis of this compound.

Pyrimidine nucleosides and methods for treating viral infections with

Compounds of the formula ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, and --N(R.sup.7)--CH(R.sup.8)(R.sup.9) are as claimed herein or their pharmaceutically acceptable acid addition salts inhibit proteases of viral origin and can be used as medicaments for the treatment of viral infections. They can be manufactured according to generally known procedures.

Amino acid derivatives

Compounds of the formula: ##STR1## wherein R.sup.1 is alkoxycarbonyl, aralkoxycarbonyl, alkanoyl, aralkanoyl, heterocyclylcarbonyl or a group of the formula: ##STR2## R.sup.2 is alkyl, cycloalkylalkyl or aralkyl; R.sup.3 is hydrogen and R.sup.4 is hydroxy or R.sup.3 and R.sup.4 together are oxo; R.sup.5 is alkoxycarbonyl or alkylcarbamoyl; R.sup.6 and R.sup.7 together are trimethylene or tetramethylene optionally substituted by alkyl or on adjacent carbon atoms by tetramethylene; R.sup.8 is alkoxycarbonyl, aralkoxycarbonyl, alkanoyl, aroyl, aralkanoyl or heteroeyelylearbonyl; and R.sup.9 is alkyl, cycloalkyl, cycloalkylalkyl, aralkyl, cyanoalkyl, carbamoyl-alkyl, alkylthioalkyl, alkoxyalkyl or alkoxycarbonylalkyl: and pharmaceutically acceptable acid addition salts of those compounds of formula I which are basic, inhibit aspartyl proteases of viral origin and can be used in the form of medicaments for the prophylaxis or treatment of viral infections. They can be manufactured according to generally known methods.

Amino acid derivatives having antiviral activity

Compositions containing compounds ##STR1## and their pharmaceutically acceptable acid addition salts inhibit proteases of viral origin and can be used as medicaments for the treatment or prophylaxis of viral infections. They can be manufactured according to generally known procedures.

Compounds of the formula ##STR1## wherein and their pharmaceutically acceptable acid addition salts inhibit proteases of vital origin and can be used as medicaments for the treatment or prophylaxis of viral infections. They can be manufactured according to generally known procedures.

Compounds of the formula: ##STR1## wherein R.sup.1 is alkoxycarbonyl, aralkoxycarbonyl, alkanoyl, aralkanoyl, heterocyclylcarbonyl or a group of the formula: ##STR2## R.sup.2 is alkyl, cycloalkylalkyl or aralkyl; R.sup.3 is hydrogen and R.sup.4 is hydroxy or R.sup.3 and R.sup.4 together are oxo; R.sup.5 is alkoxycarbonyl or alkylcarbamoyl; R.sup.6 and R.sup.7 together are trimethylene or tetramethylene optionally substituted by alkyl or on adjacent carbon atoms by tetramethylene; R.sup.8 is alkoxycarbonyl, aralkoxycarbonyl, alkanoyl, aroyl, aralkanoyl or heterocyclylcarbonyl; and R.sup.9 is alkyl, cycloalkyl, cycloalkylalkyl, aralkyl, cyanoalkyl, carbamoyl-alkyl, alkylthioalkyl, alkoxyalkyl or alkoxycarbonylalkyl: and pharmaceutically acceptable acid addition salts of those compounds of formula I which are basic, inhibit aspartyl proteases of viral origin and can be used in the form of medicaments for the prophylaxis or treatment of viral infections. They can be manufactured according to generally known methods.

Compounds having the formula ##STR1## wherein R is benzyloxycarbonyl or 2-quinolylcarbonyl, and their pharmaceutically acceptable acid addition salts inhibit proteases of viral origin and can be used as medicaments for the treatment of prophylaxis of viral infections in mammals, humans or non-humans.

Compounds of the formula ##STR1## wherein R.sup.1 is alkoxycarbonyl, aralkoxycarbonyl, alkanoyl, cycloalkylcarbonyl, aralkanoyl, aroyl, heterocyclylcarbonyl, alkylsulphonyl, arylsulphonyl, monoaralkylcarbamoyl, cinnamoyl or .alpha.-aralkoxycarbonylaminoalkanoyl and R.sup.2 is hydrogen or R.sup.1 and R.sup.2 together with the nitrogen atom to which they are attached represent a cyclic imide group of the formula ##STR2## in which P and Q together represent an aromatic system; R.sup.3 is alkyl, cycloalkyl, aryl, aralkyl, heterocyclylalkyl, cyanoalkyl, alkyl- sulphinylalkyl, carbamoylalkyl or alkoxycarbonylalkyl or, when n stands for zero, R.sup.3 can also represent alkylthioalkyl or, when n stands for 1, R.sup.3 can also represent alkylsulphonylalkyl; R.sup.4 is alkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl; R.sup.5 is hydrogen and R.sup.6 is hydroxy or R.sup.5 and R.sup.6 together represent oxo; R.sup.7 and R.sup.8 together represent a trimethylene or tetramethylene group which is optionally substituted by hydroxy, alkoxycarbonylamino or acylamino or in which one --CH.sub.2 -- group is replaced by --NH--, --N(alkoxycar- bonyl)--, --N(alkyl)-- or --S-- or which carries a fused cycloalkane, aromatic or heteroaromatic ring; and R.sup.9 is alkoxycarbonyl, monoalkylcarbamoyl, monoaralkylcarbamoyl, monoarylcarbamoyl or a group of the formula ##STR3## in which R.sup.10 and R.sup.11 each represent alkyl; and their pharmaceutically acceptable acid addition salts inhibit proteases of viral origin and can be used as medicaments for the treatment or prophylaxis of viral infections. They can be manufactured according to generally known procedures.

Compounds of the formula ##STR1## wherein R.sup.1 is halogen, C.sub.1-4 -alkyl, halo-(C.sub.1-4 -alkyl) or C.sub.2-4 -alkanoyl,

Method of treating herpes simplex viral infection employing pyrimidine

Compounds of the formula ##STR1## wherein A is C.sub.1-8 -alkylene, R.sup.1 is halogen, C.sub.1-4 -alkyl or halo-(C.sub.1-4 -alkyl), R.sup.2 is hydrogen, hydroxy or acyloxy, R.sup.3 is hydrogen or C.sub.1-4 -alkyl, R.sup.4 is aryl or aryloxy and X is O or NH,

Pyrimidine derivatives as an antiviral agent

Compounds of the formula ##STR1## wherein A is C.sub.1-8 -alkylene, R.sup.1 is halogen, C.sub.1-4 -alkyl or halo-(C.sub.1-4 -alkyl), R.sup.2 is hydrogen, hydroxy or acyloxy, R.sup.3 is hydrogen or C.sub.1-4 -alkyl, R.sup.4 is aryl or aryloxy and X is O or NH, and tautomers thereof are described. The compounds of formula I and their tautomers possess antiviral activity and can be used in the form of medicaments for the control and prevention of viral infections.

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Harpenden, United Kingdom

Joseph A Martin