DERIVATIVES OF ACID 1H-INDOL-3-IL GLIOXILICO REPLACED WITH ARILO, ARILOXI AND ALQULOXI AS INHIBITORS OF THE PLASMINOGEN-1 ACTIVATOR INHIBITOR (PAI-1).

摘要

Compounds of formula (I): (See formula) in which: R1 is hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, -CH2-C3-C6 cycloalkyl, or C1-C3 perfluoroalkyl, in which the alkyl groups and cycloalkyl may be optionally substituted by halogen, -CN, C1-C6 alkoxy, -OH,, -NH2 or -NO2; R2 is hydrogen, C1-C8 alkyl, C3-C6 cycloalkyl, -CH2-C3-C6 cycloalkyl, thienyl, CH2-thienyl, furanyl, CH2furanyl, oxazoyl, CH2-oxazoyl, phenyl, benzyl, or CH2-naphthyl; in which the alkyl group and the rings of the cycloalkyl, thienyl, furanyl, oxazoyl, phenyl, benzyl and naphthyl groups may be optionally substituted by 1 to 3 groups independently selected from halogen, C1-C3 alkyl, C1-C3 perfluoroalkyl, -O-perfluoroC1-C3 alkyl, -S-perfluoroalkyl C1-C3, C1-C3 alkoxy, -OCHF2, -CN, -COOH, -CH2CO2H, -C (O) CH3, -C (O) OR7, -C (O ) NH2, -S (O) 2CH2, -OH, -NH2 or -NO2; R3 is hydrogen, halogen, C1-C6 alkyl, C1-C3 perfluoroalkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, or -CH2-ci C3-C6 cloalkyl; R4 is C3-C8 alkyl, C3-C6 cycloalkyl, -CH2-C3-C6 cycloalkyl, thienyl, CH2-thienyl, furanyl, oxazoyl, phenyl, benzo [b] furan-2-yl, benzo [b] thien-2- yl, benzo [1,3] dioxol-5-yl, or naphthyl; wherein the alkyl group and the rings of the cycloalkyl, thienyl, furanyl, oxazoyl, phenyl, benzofuranyl, benzothienyl and naphthyl groups may be optionally substituted by 1 to 3 groups independently selected from halogen, C1-C3 alkyl, C1-perfluoroalkyl C3, -O-C1-C3 perfluoroalkyl, -S-C1-C3 perfluoroalkyl, C1-C3 alkoxy, -OCHF2, -C (O) CH3, -C (O) OR7, -C (O) NH2, -S ( O) 2CH3, -OH, -NH2 or -NO2; R5 is C1-C8 alkyl, C3-C6 cycloalkyl, -CH2-C3-C6 cycloalkyl, pyridinyl, -CH2-pyridinyl, thienyl, CH2-thienyl, furanyl, CH2-furanyl, oxazoyl, CH2-oxazoyl, phenyl, benzyl, benzo [b] furan-2-yl, benzo [b] thien-2-yl, benzo [1,3] dioxol-5-yl, naphthyl, CH2-naphthyl, 9H-fluoren-1-yl, 9H-fluoren-4 -yl, 9H-fluoren-9-yl, 9-fluorenone-1-yl, 9-fluorenone-2-yl, 9-fluorenone-4-yl, or CH2-9H-fluoren-9-yl; wherein the alkyl group and the rings of the cycloalkyl, pyridinyl, thienyl, furanyl, oxazoyl, phenyl, benzyl, benzofuranyl, benzothienyl, naphthyl, fluorenyl and fluorenone groups may be optionally substituted by 1 to 3 groups independently selected from halogen, C1-C3 alkyl, C3-C6 cycloalkyl, C1-C3 perfluoroalkyl, -O-C1-C3 perfluoroalkyl, -S-perfluoro C1-C3 alkyl, C1C3 alkoxy, -OCHF2, -CN, -COOH, -CH2CO2H, -C (O ) CH3, -C (O) OR7, -C (O) NH2, -S (O) 2CH3, -OH, -NH2, -NO2, or phenoxy, the phenoxy group being optionally substituted by 1 to 3 independently selected groups from halogen, C1-C3 alkyl, or C1-C3 perfluoroalkyl; R6 is hydrogen, C1-C8 alkyl, C3-C6 cycloalkyl, -CH2-C3-C6 cycloalkyl, pyridyl, thienyl, CH2-thienyl, furanyl, CH2-furanyl, oxazoyl, CH2-oxazoyl, phenyl, benzyl, benzo [b] furan-2-yl, benzo [b] thien-2-yl, benzo [1,3] dioxol-5yl, CH2-1-naphthyl, or CH2-2-naphthyl; in which the alkyl group and the rings of the cycloalkyl, thienyl, furanyl, oxazoyl, phenyl, benzyl, benzofuranyl, benzothienyl and naphthyl groups may be optionally substituted by 1 to 3 groups independently selected from halogen, C1-C3 alkyl, C1 perfluoroalkyl -C3, -O-C1C3 perfluoroalkyl, -S-perfluoroalkyl C1-C3, C1-C3 alkoxy, -OCHF2, -CN, -COOH, -CH2CO2H, -C (O) CH3, -C (O) OR7, -C (O) NH2, -S (O) 2CH3, -OH, -NH2 or -NO2; or R5 and R6 taken together may be C3-C6, 3-indan-1-yl, 1, 2, 3, 4-tetrahydronaphthalen-1-yl, chroman-4-yl, 4H-chromen-4-yl, thiochroman -4-yl, 9H-fluoren-9-yl, 9, 10-dihydroantracen-9-yl, 9H-xanten-9-yl, 9-thioxanten-9-yl, 6, 7, 8, 9-tetrahydro-5H-benzocyclohepten -5-yl, or 10, 11-dihydro-5H-dibenzo [a, d] cyclohepten-5-yl, wherein said groups may be optionally substituted by 1 to 3 groups independently selected from halogen, C1-C3 alkyl , perfluoroalkyl C1-C3, -O-perfluoroalkyl C1-C3, -S-perfluoroalkyl C1-C3, alkoxy C1-C3, -OCHF2, -CN, -COOH, -CH2CO2H, -C (O) CH3, -C (O ) OR7, -C (O) NH2, -S (O) 2CH3, -OH, -NH2 or -NO2; and R7 is C1-C6 alkyl, C3-C6 cycloalkyl, -CH2-C3-C6 cycloalkyl, or benzyl.