Hoffmann-la Roche Inc.

Balraj K Handa

Peter J Machin

Gareth J Thomas

Sally Redshaw

Joseph A Martin

William H Johnson

Michael John Broadhurst

Geoffrey Lawton

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

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, 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.

The invention relates compounds of the formula ##STR1## wherein R.sup.1 -R.sup.5 and X have the significance given in the description, and their pharmaceutically acceptable salts. The compounds of formula I inhibit the enzyme collagenase and can be used in the form of medicaments for the control or prevention of degenerative joint diseases such as rheumatoid arthritis and osteoarthritis.

Phosphinic acid derivatives

Compounds of the formula ##STR1## wherein A is a group of the formula HN(OH)--CO-- or HCO--N(OH)--; R.sup.1 is a C.sub.2 -C.sub.5 -alkyl; R.sup.2 is the characterizing group of a natural .alpha.-amino acid in which any functional group present may be protected, any amino group present may be acylated and any carboxyl group present may be amidated, with the proviso that R.sup.2 is not hydrogen or methyl; R.sup.3 is hydrogen, amino, hydroxy, mercapto, C.sub.1 -C.sub.6 -alkyl, C.sub.1 -C.sub.4 -alkoxy, C.sub.1 -C.sub.6 -alkylamino, C.sub.1 -C.sub.6 -alkylthio or aryl-(C.sub.1 -C.sub.6 -alkyl), or amino-(C.sub.1 -C.sub.6 -alkyl), hydroxy-(C.sub.1 -C.sub.6 -alkyl), mercapto-(C.sub.1 -C.sub.6 -alkyl) or carboxy-(C.sub.1 -C.sub.6 -alkyl) in which the amino, hydroxy, mercapto or carboxyl group may be protected, the amino group may be acylated or the carboxyl group may be amidated; R.sup.4 is hydrogen or methyl; R.sup.5 is hydrogen or a C.sub.1 -C.sub.6 -alkyl, C.sub.1 -C.sub.6 -alkoxy-C.sub.1 -C.sub.6 -alkyl, di(C.sub.1 -C.sub.6 -alkoxy)-methylene, carboxyl, (C.sub.1 -C.sub.6 -alkyl)-carbonyl, (C.sub.1 -C.sub.6 -alkoxy)carbonyl, arylmethoxycarbonyl, (C.sub.1 -C.sub.6 -alkyl)aminocarbonyl or arylaminocarbonyl; and R.sup.6 is hydrogen or methyl; or R.sup.2 and R.sup.4 taken together are a group of the formula --(CH.sub.2).sub.n -- in which n is a number from 4 to 11; or R.sup.4 and R.sup.6 taken together are a trimethylene; and pharmaceutically acceptable salts of those compounds which are acidic or basic are described. The compounds of formula I possess collagenase inhibitory activity and can be used in the control or prevention of degenerative joint diseases.

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Welwyn Garden City, United Kingdom

Balraj K Handa