Inventors:
Bruce E. Tomczuk - Collegeville PA
Richard M. Soll - Lawrenceville NJ
Tianbao Lu - Exton PA
Cynthia L Fedde - Warrington PA
Carl R Illig - Phoenixville PA
Thomas P. Markotan - Pottstown PA
Thomas P Stagnaro - St. David PA
Assignee:
3-Dimensional Pharmaceuticals, Inc. - Exton PA
International Classification:
A61K 31255
US Classification:
514613, 5142382, 51425502, 514307, 514311, 514327, 514357, 514426, 514459, 514467, 514517, 514518, 514614, 514617, 514618, 514620, 514626, 514628, 514629, 514630, 514633, 544158, 544384, 546145, 546172, 546221, 546332, 548558, 548561, 549426, 558 48, 558 50, 564123, 564148, 564149, 564150, 564182, 564186, 564217, 564221, 564223, 564163, 564164, 564165, 564167, 564168, 564229
Abstract:
Aminoguanidine and alkoxyguanidine compounds, including compounds of the formula: wherein X is O or NR and R -R , R -R , R , R , R , R , R , 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.