CLEMENT, BERND,WOLTER-REEH, CHRISTIANE,HUNGELING, HELEN
申请号：
EP14155230.7
公开号：
EP2732816A1
申请日:
2009.02.02
申请国别(地区):
EP
年份:
2014
代理人:
摘要：
Die vorliegende Erfindung betrifft ein Verfahren zur Verbesserung der Bioverfügbarkeit und Ermöglichung der Blut-Hirn-Schrankengängigkeit von Arzneistoffen, die wenigstens eine oder mehrere Amidin-, Guanidm-, N-Hydroxyamidin- (Amidoxim) bzw. N-Hydroxyguanidin-Funktionen aufweisen und entsprechend modifizierte Arzneistoffe enthaltende Arzneimittel.Use of amidoxime carboxylic acid ester compound (I) or N-hydroxyguanidine carboxylic acid ester compound (II), as substitution of amidine-, N-hydroxyamidine- (amidoxime), guanidine- or N-hydroxyguanidine-functions of an active agent in a medicament to improve the solubility, bioavailability and/or blood-brain-barrier mobility of the medicament, is claimed, where the active agent is protease inhibitor, an inhibitor of factor Xa, factor VII or all protease of the coagulation cascade or a matriptase inhibitor, DNA- and RNA-intercalating compounds, or the N-methyl-D-aspartate-receptor-antagonist. Use of amidoxime carboxylic acid ester compound of formula (CH 3-C(NH 2)=N-O-C(=O)-(CH 2) n-C(=O)-OR 1) (I) or N-hydroxyguanidine carboxylic acid ester compound of formula (CH 3-NH-C(NH 2)=N-O-C(=O)-(CH 2) n-C(=O)-OR 1) (II), as substitution of amidine-, N-hydroxyamidine- (amidoxime), guanidine- or N-hydroxyguanidine-functions of an active agent in a medicament to improve the solubility, bioavailability and/or blood-brain-barrier mobility of the medicament, is claimed, where the active agent is protease inhibitor, preferably a thrombin inhibitor, an inhibitor of a factor Xa, factor VII, all protease of the coagulation cascade or a matriptase inhibitor, DNA- and RNA-intercalating compounds, inhibitor of viral enzyme or the N-methyl-D-aspartate-receptor-antagonist. R 1 : H, alkyl, or aryl or its salt； and n : 0-12. ACTIVITY : Protozoacide； Antiinflammatory； Respiratory-Gen.； Cytostatic； Anticoagulant； Thrombolytic； Hemostatic； Hypertensive； Neuroprotective； Virucide； Anti-HIV. MECHANISM OF ACTION : None given.
