Use of hydroxyguanidines for treatment and prevention of ischemic disease in particular hydroxyguanidine substituted with 4-methoxy-phenyl group

摘要

Hydroxyguanidines shown as Formula (I) are useful in the treatment or prevention of an ischemic disease condition including an ischemic condition caused by surgery or other therapy and being associated with the production of oxygen derived radicals. The disease condition being a xanthine oxidase/xanthine dehydrogenase mediated ischemic condition selected from heart infarction, angina pectoris, cerebrovascular infarction, circulatory shock, transient ischemic attacks of the cerebrovascular system, arterial occlusion, arterial thromboembolism, bowel torsion with strangulation, testicular torsion, lung embolus, cardiac surgery including by-pass grafting, and localised organ surgery involving reduced blood flow, organ transplantation, circulatory shock, and general hypoxia. Preferred hydroxyguanidines are carbimino hydroxyguanidines, in particular aryl carbimino hydroxyguanidines. Wherein; R1 is -N=CR3R4; R2 is selected from hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloalkenyl, cycloheteroalkenyl, alkynyl, aryl, heteroaryl, a carbon atom or heteroatom connected to R3, and a single bond of R3; R3 and R4 are selected independently of each other from the group consisting of H, alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, alkynyl, aryl, heteroaryl, and a bridge of from 4 to 5 carbon or heteroatoms forming a 5- or 6-membered ring which is optionally fused with cycloalkyl, cycloheteroalkyl, cycloalkenyl, cycloheteroalkenyl, aryl or heteroaryl, and wherein R3, in addition, is selected from a single bond of R2 and a carbon or hetero atom connected to R2 such as to form a 6-or 5-membered ring which is optionally fused with cycloalkyl, cycloheteroalkyl, cycloalkenyl, cycloheteroalkenyl, aryl or heteroaryl; and wherein optionally one or several hydrogen(s) in R2, R3, R4 are independently exchanged for alkyl, alkenyl, cycloalkyl, cycloheteroalkyl, cycloalkenyl, cycloheteroalkenyl, alkynyl, aryl, heteroaryl, halogen or functional group, and wherein one or more hydrogen(s) in alkyl, alkenyl, cycloalkyl, cycloheteroalkyl, cycloalkenyl, cycloheteroalkenyl, alkynyl, aryl, heteroaryl, functional group are optionally independently exchanged for halogen or functional group.