Inhibitor compounds of 11-beta-hydroxysteroid dehydrogenase type 1
AssigneeLaboratorios Salvat, S.A.
InventorsJuan Lorenzo Catena Ruiz, Carme Serra Comas, Oscar Rey Puiggros, Albert Antolin Hernandez, Esther Monlleo Mas
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Abstract
The compounds of formula (I) are derived from perhydroquinoline and perhydroisoquinoline and are useful as active pharmaceutical ingredients for the prophylaxis or treatment of diseases caused by 11-beta-hydroxysteroid dehydrogenase type 1 (11-beta-HSD1) enzyme-associated disorders, such as glaucoma, elevated ocular pressure, metabolic disorders, obesity, metabolic syndrome, dyslipidemia, hypertension, diabetes, atherosclerosis, Cushing's syndrome, psoriasis, rheumatoid arthritis, cognitive disorders, Alzheimer's disease or neurodegeneration.
Claims20
A compound of formula (I)
- and pharmaceutically acceptable salts thereof, wherein:
- s and p are an integer selected in an opposite manner between 0 and 1, such that when s is 1, p is 0 (to form a perhydroquinoline) and when s is 0, p is 1 (to form a perhydroisoquinoline),
- Y is a biradical selected from CO, CS and SO2,
- W1 and W2 is each independently a bond or a biradical selected from O, S and NR1, wherein R1 is selected from H, C1-4 alkyl and C3-10 cycloalkyl,
- n is an integer selected from 0, 1, 2, 3 and 4,
- V is a radical selected from the group consisting of —CO-T, —CS-T and —SO2-T, or a radical selected from the group consisting of:
- where T is a group selected from the group consisting of NR2R3, R2, OR2 and SR2;
- or a group selected from the group
- consisting of:
- wherein R2 and R3 is each independently H, COR4, SO2R4, C1-4 alkyl, aryl, benzyl, phenethyl, C2-4 alkenyl, C2-4 alkynyl, C3-10 cycloalkyl or a saturated, partially unsaturated or aromatic, 5 to 10 membered heterocycle, containing one or several heteratoms elected from the group consisting of nitrogen, oxygen and sulfur,
- wherein when R2 or R3 is an alkyl, or an alkenyl these can be optionally substituted with one or several substituents independently selected from the group consisting of F, OR4, NR4R5, COOR4, CONR4R5, C3-10 cycloalkyl, aryl and heterocycle;
- and
- wherein when R2 or R3 is an aryl, a benzyl, a phenethyl, a cycloalkyl or a heterocycle, these can be optionally substituted with one or several substituents independently selected from the group consisting of NH2, F, Cl, CN, NO2, COOH, R4, COOR4, OR4, OCF3, SH, SR4, CONR4R5, SO2NR4R5, COR4, NR1COR4, OCOR4, SOR4, SO2R4 and heterocycle;
- and
- wherein when R2 or R3 is a cycloalkyl, this can be optionally substituted with one or several fused benzene rings, the benzene could be optionally substituted with one or several substituents independently selected from the group consisting of alkyl, alkoxide and halogen,
- wherein R4 and R5 is each independently selected from the group consisting of H, C1-4 alkyl, aryl, benzyl, phenethyl, C2-4 alkenyl, C2-4 alkynyl, C3-10 cycloalkyl and heterocycle, or optionally R4 and R5 can be bound to one another forming a 3 to 8 membered cycle,
- wherein R6, R7, R8 and R9 is each independently selected from the group consisting of H, OR4, F and Cl, and
- wherein R10 is independently selected from the group consisting of H, OH, F, C1-4 alkyl, COOR11, COR11, phenyl, benzyl, benzhydryl, C2-4 alkenyl, C2-4 alkynyl, C3-10 cycloalkyl and heterocycle, and wherein the alkyl, phenyl, benzyl, benzhydryl, cycloalkyl or heterocycle can be optionally substituted with one or several substituents independently selected from the group consisting of NH2, F, Cl, NO2, COOH, COOR4, OR4, CF3, SH, SR4, CONR4R5, SO2NR4R5, COR4, NR1COR4, OCOR4, SOR4, SO2R4 and C1-4 alkyl;
- and where R11 is selected from H, C1-4 alkyl and C3-10 cycloalkyl.
Dependencies are inferred from the claim text.