Benzamide and sulfonamide substitued aminoguanidines and alkoxyguanidines as protease inhibitors
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United States of America Patent
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Feb 5, 2002
Grant Date -
Oct 18, 2001
app pub date -
Feb 28, 2001
filing date -
Apr 3, 1998
priority date (Note) -
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Abstract
The present invention is directed to aminoguanidine and alkoxyguanidine compounds, including compounds of Formula I: ##STR1## wherein X is O or NH, L is --O-- or --SO.sub.2 --, and R.sup.1 -R.sup.4, R.sup.9 -R.sup.19, R.sup.a, R.sup.b, R.sup.c, Y, Z, n and m are set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof, that inhibit proteolytic enzymes such as thrombin. Also described are methods for preparing the compounds of Formula I. Certain of the compounds exhibit antithrombotic activity via direct, selective inhibition of thrombin, or are intermediates useful for forming compounds having antithrombotic activity. The invention includes a composition for inhibiting loss of blood platelets, inhibiting formation of blood platelet aggregates, inhibiting formation of fibrin, inhibiting thrombus formation, and inhibiting embolus formation in a mammal. Other uses of compounds of the invention are as anticoagulants either embedded in or physically linked to materials used in the manufacture of devices used in blood collection, blood circulation, and blood storage.
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