INHIBITORS OF BETA-SECRETASE

摘要

594230 Disclosed are spiro condensed benzofuranyl, indanyl or tetrahydronaphthalene compounds of formula I containing two spiro centres with variable X either -O-, -C(RaRb)-C(R3R4)-, -C(R3R4)-C(RaRb)- or -C(R3R4)-; Z is -C(=O)-, -C(=S)-, -C(=NR15)-, -O-, -C(=O)C(R16R17)-, - C(R16R17)C(=O)-, -C(=S)C(R16R17)-, C(R16R17) C(=S)-, -N(R18)-, -(CR16R17)m-, -O-(CR16R17)-, or -(CR16R17)- O--,; and R8 and R9 combine to form a 3-14 membered ring optionally containing 1-3 heteroatoms and the other variables are as defined, for example 3-(spiro[spiro[2,3-dihydro-indene-2,1'-(4-oxacyclohexane)]-1,5'-(3-amino-2-methyl-2H-[1,2,4]oxadiazole)]-6-yl)benzonitrile. Pharmaceutical compositions of the compounds are also disclosed and such compounds are intended for use as BACE inhibitors, for treatment of conditions such as Alzheimer's and glaucoma.