Aminoguanidine and alkoxyguanidine compounds, including compounds of the formula:wherein X is O or NR<9 >and R<1>-R<4>, R<6>-R<9>, R<11>, R<12>, R, R, R<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 are described. Also described are methods for preparing the compounds of Formula I. The novel compounds of the present invention are potent inhibitors of
proteases, especially
trypsin-like
serine proteases, such as
chymotrypsin,
trypsin,
thrombin,
plasmin and factor Xa. 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, comprising a compound of the invention in a pharmaceutically acceptable carrier. 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, such as catheters, blood
dialysis machines,
blood collection syringes and tubes, blood lines and stents.