Patent Evaluation Cardiovascular & Renal: Novel aminoheterocyclic derivatives as inhibitors of factor Xa

Abstract

This patent from Zeneca Ltd. describes compounds which possess antithrombotic or anticoagulant activity. This activity has been attributed to their strong inhibition of the coagulation serine protease known as factor Xa. Thus, factor Xa inhibitors (i.e., anticoagulant compounds) should have application in several medical disorders, such as venous and/or arterial thrombosis, coagulation syndromes, myocardial infarction, atherosclerotic plaque formation, restenosis, stroke, cerebral and/or pulmonary embolism, ischaemia and angina.

Several protein and/or peptidic inhibitors have been previously described in the general and patent literature, but with the exception of DX-9065a there is a paucity of small molecule nonpeptidic factor Xa inhibitors. The compounds disclosed in the present patent are highly selective for factor Xa. efficacious in secondary in vivo and in vivo models and synthetically less challenging than other known factor Xa inhibitors. In addition to the previously described inhibitors of trypsin-like serine proteases such as factor Xa, the compounds described in this patent do not contain a free amidino or guanidino group. Thus, the present disclosure will provide compounds of significant interest as pharmacological tools to further evaluate the importance of factor Xa in the blood coagulation pathway, as well as compounds that may be of further clinical interest.