Amino acid amidinohydrazones, alkoxyguanidines and...

A - Human Necessities – 61 – K

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A61K 38/00 (2006.01) C07D 207/16 (2006.01) C07D 223/16 (2006.01) C07F 9/06 (2006.01) C07K 5/02 (2006.01) C07K 5/065 (2006.01)

Patent

CA 2329929

The present invention is directed to aminoguanidine and alkoxyguanidine compounds, including compounds of Formula (I) wherein X is O or NR19 and A1, A2, R7-R10, R18, Ra, Rb, Rc, 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.

L'invention concerne des composés d'aminoguanidine et d'alcoxyguanidine, y compris des composés de la formule (I) dans laquelle X est O ou NR?19¿ et A?1¿, A?2¿, R?7¿-R?10¿, R?18¿, R?a¿, R?b¿, R?c¿, n et m sont tels que décrits dans le mémorandum descriptif. L'invention concerne également des hydrates, des solvates ou des sels pharmaceutiquement acceptables desdits composés, qui inhibent des enzymes protéolytiques, telles que la thrombine. On décrit des procédés de préparation des composés de la formule (I), dont certains présentent une activité antithrombotique par le biais d'une inhibition directe sélective de la thrombine, ou sont des intermédiaires utiles pour la préparation de composés ayant une activité antithrombotique. L'invention inclut une composition destinée à inhiber la perte de plaquettes sanguines, l'agrégation plaquettaire, la formation de fibrine, de thrombus ou d'embolus chez un mammifère. Dans d'autres modes d'utilisation, les composés de l'invention, en tant qu'agents anticoagulants, sont intégrés ou physiquement liés à des matériels entrant dans la fabrication de dispositifs employés pour le prélèvement, la circulation et l'entreposage du sang.

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