Matrix metalloprotease inhibitors
AssigneeSyntex (U.S.A.) Inc.
InventorsArlindo Lucas Castelhano, Steven Lee Bender, Judith Gail Deal, Stephen Horne, Teng J. Liak, Zhengyu Yuan
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Abstract
Compounds of formula (I) ##STR1## and their pharmaceutically acceptable salts inhibit matrix metalloproteases, such as stromelysin, gelatinase, matrilysin and collagenase, and are useful in the treatment of mammals having disease-states alleviated by the inhibition of such matrix metalloproteases.
Claims15
A compound of the formula ##STR44## wherein R.sup.1 is mercapto, acetylthio, carboxy, hydroxycarbamoyl, N-hydroxyformamide, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, benzyloxycarbamoyl or a group of the formula ##STR45## where R.sup.6 is aryl, pyridyl or thiazolyl;
- R.sup.2 is biphenyl;
- R.sup.3 is alkyl, cycloalkyl, aralkyl, alkylpyridyl or alkylthiazolyl;
- R.sup.7 is 4-pyridyl or-optionally substituted phenyl;
- X is a group of the formula --(CH.sub.2).sub.m --Y--(CH.sub.2).sub.n --, where:
- Y is O, S, or a single bond,
- m is an integer from 0 to 4,
- n is an integer from 0 to 4, and
- m+n is an integer from 0 to 4;
- and
- p is 0;
- wherein the compound contains pyridyl and optionally thiazolyl as the only heterocyclics in the compound or a pharmaceutically acceptable salt thereof.
A compound of the formula ##STR46## wherein:
- R.sup.1 is carboxy,;
- R.sup.2 is aryl, pyridyl or thiazolyl;
- R.sup.3 is cyclohexyl;
- R.sup.7 is optionally substituted phenyl;
- X is propanyl, and p is 2 or 3;
- and wherein the compound contains pyridyl and optionally thiazolyl as the only heterocyclics in the compound;
- or a pharmaceutically acceptable salt thereof.
A compound for salt of the formula ##STR47## wherein:
- R.sup.1 is mercapto, acetylthio, carboxy, hydroxycarbamoyl, N-hydroxyformamide, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, benzyloxycarbamoyl or a group of the formula ##STR48## where R.sup.6 is aryl, pyridyl or thiazolyl;
- R.sup.2 is a group of the formula:
- ##STR49## where:
- A is CH.sub.2 ;
- R.sup.10 is H or acylamide;
- and
- R.sup.11 is R;
- R.sup.3 is alkyl, cycloalkyl, aralkyl, alkylpyridyl, and alkylthiazolyl;
- R.sup.7 is optionally substituted phenyl;
- X is propanyl;
- and
- p is 0;
- wherein the compound contains pyridyl and optionally thiazolyl as the only heterocyclics in the compound;
- or a pharmaceutically acceptable salt thereof.
A compound of the formula ##STR50## wherein R.sup.1 carboxy;
- R.sup.2 is phenyl, 4-(2-hydroxyethyl)phenyl, 4-(2-hydroxypropyl)phenyl, 4-(2-hydroxybutyl)phenyl, 4-pyridylphenyl, biphenyl, 4'-(aminoethoxy)biphenyl, 4-(cyano)-biphenyl, or 4'-(hydroxy)biphenyl;
- R.sup.3 is alkyl, cycloalkyl, or 2-methylpropyl;
- R.sup.7 is optionally substituted phenyl, or 4-(methoxycarbonyl)phenyl;
- X is a group of the formula --(CH.sub.2).sub.m --Y--(CH.sub.2).sub.n --, where:
- Y is O, S, or a single bond,
- m is-an integer from 0 to 4,
- n is an integer from 0 to 4, and
- m+n is an integer from 0 to 4;
- and
- p is 0;
- wherein the compound contains pyridyl and optionally thiazolyl as the only heterocyclics in the compound;
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.