4-(1-BENZOFURAN-3-YL-METHYLIDENEAMINOXY.PROPOXY))-BENZOIC ACID DERIVATIVES AND RELATED COMPOUNDS AS PAI-1 INHIBITORS FOR THE TREATMENT OF IMPAIRMENT OF THE FIBRINOLYTIC SYSTEM AND OF THROMBOSIS

• Main Author: DOUGLAS JOHN JENKINS
• Format: Patent
• Language: English; Spanish
• Published: 08.06.2006
• Edition: 7
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

The present invention relates to benzofuryl-oximes of formula (I) or a pharmaceutically acceptable salt or ester form thereof wherein R1 is a direct bond to A, C1-C4 alkylene, or -O-C1-C4 alkylene; R2 and R3 are, independently hydrogen, halogen, C1-C4 alkyl, C1-C3 perfluoroalkyl, -O-C1-C3 perfluoroalkyl, C1-C3 alkoxy, -OH, -NH2, -NO2, -O(CH2)p-aryl, -O(CH2)P-heteroaryl, aryl, heteroaryl, -NH(CH2)P-aryl, -NH(CH2)P-heteroaryl, -NH(CO)-aryl, NH(CO)-heteroaryl, -O(CO)-aryl, O(CO)-heteroaryl, -NH(CO)-CH=CH-aryl, or -NH(CO)-CH=CH-heteroaryl; p is an integer from 0-6; R4 is hydrogen, C1-C8 alkyl, or C3-C6 cycloalkyl; A is -COOH or an acid mimic; X is C1-C8 alkylene, C3-C6 cycloalkylene, -(CH2)mO-, or -(CH2)mNH-; m is an integer from 1-6; and R5 is hydrogen, C1-C8 alkyl, C3-C6 alkyl, C3-C6 cycloalkyl, -CH2-C3-C6 cycloalkyl, heteroaryl, -CH2-heteroaryl, aryl or benzyl; R6 and R7 are independently, hydrogen, halogen, C1-C6 alkyl, C1-C6 perfluoroalkyl, -O-C1-C6 perfluoroalkyl, C1-C6 alkoxy, _OH, -NH2, -NO2, -O(CH2)n-aryl, -O(CH2)n-heteroaryl, aryl, or heteroaryl; and n is an integer from 0-6, wherein the alkyl, cycloalkyl, aryl and heteroaryl groups are each optionally substituted by one or more substituents. The present compounds are PAI-1 inhibitors for the treatment e.g of impairment of the fibrinolytic system, thrombosis or cardiovascular diseases. La presente invencion se refiere a oximas de benzofurilo de la formula: (ver formula) forma de sal o ester farmaceuticamente aceptable del mismo en donde: R1 es un enlace directo a A, alquileno C1-C4, o -O-alquileno C1-C4; R2 y R3 son, independientemente hidrogeno, halogeno, alquilo C1-C4, perfluoroalquilo C1-C3, -O-perfluoroalquilo C1-C3, alcoxi C1-C3, -OH, -NH2, -NO2, -O(CH2)p-arilo, -O(CH2)p-heteroarilo, arilo, heteroarilo, -NH(CH2)p-arilo, -NH(CH2)p-heteroarilo, -NH(CO)-arilo, -NH(CO)-heteroarilo, -O(CO)-arilo, -O(CO)-heteroarilo, -NH(CO)-CH=CH-arilo, o -NH(CO)-CH=CH-heteroarilo; p es un entero desde 0-6; R4 es hidrogeno, alquilo C1-C8, o cicloalquilo C3-C6; A es -COOH o un imitador acido; X es alquileno C1-C8, cicloalquileno C3-C6, -(CH2)mO-, o - m es un entero desde 1-6, y R5 es hidrogeno, alquilo C1-C8, cicloalquilo C3-C6, -CH2-cicloalquilo C3-C6, heteroarilo, -CH2-heteroarilo, arilo, o bencilo; R6 y R7, son, independientemente, hidrogeno, halogeno, alquilo C1-C6, perfluoroalquilo C1-C6, -O-perfluoroalquilo C1-C6, alcoxi C1-C6, -OH, -NH2, -NO2, -O(CH2)n-arilo, -O(CH2)n-heteroarilo, arilo, o heteroarilo; y n es un entero desde 0-6, en donde los grupos alquilo, cicloalquilo, arilo y heteroarilo son cada uno opcionalmente substituidos por uno o mas substituyentes. Los presentes compuestos son inhibidores PAI-1 para el tratamiento, por ejemplo de mejora del sistema fibrinolitico, trombosis o enfermedades cardiovasculares.