Beecham Group Plc

Beecham Group P.l.c. of Beecham House

David J Hunter

Roger Edward Markwell

Robert William Ward

Stephen A Smith

Novel compounds of formula (I) and salts, solvates and hydrates thereof, processes for their preparation and their use in the treatment of conditions in which degradation of connective tissue and other proteinaceous components of the body occurs: ##STR1## in which, R is hydrogen, C.sub.1-6 alkyl or optionally substituted benzyl; R.sub.1 is hydrogen or C.sub.1-6 alkyl; R.sub.2 is C.sub.3-6 alkyl; R.sub.3 is hydrogen, alkyl, --CH.sub.2 --Z where Z is optionally substituted phenyl or heteroaryl, or R.sub.3 is a group ##STR2## where R.sub.7 is hydrogen, alkyl or --CH.sub.2 --Ph where Ph is optionally substituted phenyl and R.sub.8 is hydrogen or alkyl; and R.sub.4 is --CH.sub.2 --(CH.sub.2).sub.n OR.sub.5 or --CH.sub.2 --(CH.sub.2).sub.n OCOR.sub.6 or --CH(R.sub.9)COR.sub.10, where n is an integer from 1 to 6; R.sub.5, R.sub.6 and R.sub.9 are hydrogen or C.sub.1-6 alkyl; and R.sub.10 is hydroxy or --O--C.sub.1-6 alkyl or --NR.sub.5 R.sub.6 (where R.sub.5 and R.sub.6 may be linked to form a heterocyclic ring; or R.sub.3 and R.sub.4 are joined together as --(CH.sub.2).sub.m -- where m is an integer from 4 to 12.

Compounds

Novel compounds of the formula (I), a process for their preparation and their use as collagenase inhibitors are described: ##STR1## in which R.sub.1 is hydrogen or hydroxy; R.sub.2 is hydrogen or alkyl; R.sub.3 is C.sub.3-6 alkyl; R.sub.4 is hydrogen, alkyl, --CH.sub.2 --Z where Z is optionally substituted phenyl or heteroaryl, or R.sub.4 is a group ##STR2## where R.sub.8 is hydrogen, alkyl or --CH.sub.2 --Ph where Ph is optionally substituted phenyl, and R.sub.9 is hydrogen or alkyl; and R.sub.5 is hydrogen or alkyl.

Phosphorus containing peptides, pharmaceutical compositions and method

Compounds of the general formula I ##STR1## in which: R.sub.1 and R.sub.2 are independently hydrogen, C.sub.1-6 alkyl or together are a group X which is C.sub.3-6 polymethylene optionally in which one carbon atom is replaced by O, S or NR.sub.6 wherein R.sub.6 is hydrogen or C.sub.1-6 alkyl;

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Harlow, United Kingdom

David J Hunter