Novel Oxazine Derivatives and their use in the Treatment of Disease

摘要

The invention relates to novel oxazine derivatives of formula (I), and pharmaceutically acceptable salts thereof, in which all of the variables are as defined in the specification, pharmaceutical compositions thereof, combinations thereof, and their use as medicaments, particularly for the treatment of Alzheimer's Disease or diabetes via inhibition of BACE-1 or BACE-2.;

主权项

1. A compound of the formula (I), or a pharmaceutically acceptable salt thereof: wherein n represents 0 or 1; X represents CH or N; R1 represents:
phenyl, optionally substituted by 1, 2 or 3 substituents independently selected from R10;a group G1 selected from furan-2-yl, pyridin-2-yl, pyrimidin-2-yl, pyrimidin-4-yl and pyrazin-2-yl, wherein G1 is optionally substituted by 1, 2 or 3 substituents independently selected from R10; ora group G2 selected from isothiazolo[4,5-b]pyridin-3-yl, isothiazolo[4,5-b]pyrazin-3-yl, benzo[d]isothiazol-3-yl, indazol-3-yl, benzo[d]isoxazol-3-yl, pyrido[3,2-d]pyrimidin-4-yl, [1,7]naphthyridin-8-yl and imidazol[1,2-a]pyrazin-8-yl, wherein G2 is optionally substituted by 1, 2 or 3 substituents independently selected from R11; R2, R3 and R4 independently represent hydrogen, halogen or C1-3alkyl; R5 represents C1-3alkyl, halogen-C1-3alkyl or C1-3alkoxy-C1-3alkyl; R6 and R7 independently represent hydrogen or C1-3alkyl; R8 and R9 independently represent hydrogen, C1-3alkyl, halogen-C1-3alkyl or C1-3alkoxy; or R8 and R9 taken together are cyclopropyl; R10 represents halogen, cyano, hydroxy, halogen-C1-3alkoxy, C1-3alkoxy, C1-3alkoxy-C1-3alkoxy, nitro or amino; and R11 represents halogen, cyano, hydroxy, halogen-C1-3alkyl, halogen-C1-3alkoxy, C1-3alkoxy, C1-3alkoxy-C1-3alkyl or C1-3alkoxy-C1-3alkoxy.