Fused multi-cyclic sulfone compounds as inhibitors of beta-secretase and methods of use thereof

A compound of Formula I

• or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein
• A5 is CR5 or N;
• A6 is CR6 or N;
• A8 is CR8 or N, provided that no more than one of A5, A6 and A8 is N;
• each R1, independently, is H, F, Cl, C1-6-alkyl, C2-4alkenyl, C2-4alkynyl, CN, —CH2OC1-6-alkyl, —OC1-6-alkyl, —S(O)oC1-6-alkyl, —NHC1-6-alkyl, —C(O)C1-6-alkyl or C3-6cycloalkyl, wherein each of the C1-6-alkyl, C2-4alkenyl, C2-4alkynyl, C3-6cycloalkyl and C1-6-alkyl portion of —CH2OC1-6-alkyl, —OC1-6-alkyl, —S(O)oC1-6-alkyl, —NHC1-6-alkyl and —C(O)C1-6-alkyl are optionally substituted with 1-4 substituents of F, oxo or OH;
• alternatively, each R1 taken together with the carbon atom to which they are attached form a C3-6 spirocarbocyclic ring optionally including one heteroatom selected from O and N and optionally substituted, independently, with 1-4 substituents of F, OH, C1-3alkyl, C1-3alkoxyl, CH2OC1-2alkyl or C1-3haloalkyl;
• R2 is C1-4alkyl, CH2OC1-4alkyl, CH2OH, CH2CN, C3-6cycloalkyl or CN, wherein each of the C1-4alkyl, CH2OC1-4alkyl and C3-6cycloalkyl is optionally substituted with 1-4 F atoms;
• each R3, independently, is halo, C1-4alkyl, OC1-4alkyl, CH2OC1-4alkyl, CH2OH, C1-4haloalkyl, cyclopropyl or CN, wherein each of the OC1-4alkyl, CH2OC1-4alkyl and cyclopropyl is optionally substituted with 1-4 F atoms;
• each of R5, R6 and R8, independently, is H, halo, haloalkyl, haloalkoxyl, C1-4-alkyl, CN, OH, OC1-4-alkyl, S(O)oC1-4-alkyl, NHC1-4-alkyl or C(O)C1-4-alkyl;
• R7 is —NH—R9, —NHC(═O)—R9, —C(═O)NH—R9, —O—R9 or —S—R9;
• R9 is acetyl, C1-6-alkyl, C2-4alkenyl, C2-4alkynyl or a fully or partially unsaturated 5-, 6- or 7-membered monocyclic or 8-, 9- or 10-membered bicyclic ring formed of carbon atoms, said ring optionally including 1-4 heteroatoms if monocyclic or 1-5 heteroatoms if bicyclic, said heteroatoms selected from O, N or S, wherein the C1-6-alkyl, C2-4alkenyl, C2-4alkynyl and ring are optionally substituted, independently, with 1-5 substituents of R10;
• each R10, independently, is H, halo, haloalkyl, CN, OH, NO2, NH2, SF5, acetyl, —C(O)NHCH3, oxo, C1-6 alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6alkylamino-, C1-6dialkylamino-, C1-6alkoxyl, C1-6thioalkoxyl, 2-propyn-1-yloxy, 2-butyn-1-yloxy, morpholinyl, pyrazolyl, isoxazolyl, dihydropyranyl, pyrrolyl, pyrrolidinyl, piperazinyl, oxetan-3-yl, dioxolyl, —NHC(O)R11— or —C(O)NHR11—, wherein each of the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6alkylamino-, C1-6dialkylamino-, C1-6alkoxyl, C1-6thioalkoxyl, 2-propyn-1-yloxy, 2-butyn-1-yloxy, morpholinyl, pyrazolyl, isoxazolyl, dihydropyranyl, pyrrolidinyl, oxetan-3-yl or dioxolyl, is optionally substituted independently with 1-5 substituents of F, Cl, CN, NO2, NH2, OH, oxo, methyl, methoxy, ethyl, ethoxy, propyl, propoxy, isopropyl, isopropoxy, cyclopropyl, cyclopropylmethoxy, butyl, butoxyl, isobutoxy, tert-butoxy, 2-butynyloxy, isobutyl, sec-butyl, tert-butyl, C1-3alkylamino-, C1-3dialkylamino, C1-3thioalkoxyl, oxetan-3yl, oxazolyl, isoxazolyl, imidazolyl or pyrazolyl, wherein each of the oxazolyl, isoxazolyl, imidazolyl or pyrazolyl is optionally substituted with 1-3 substituents of F or CH3;
• R11 is C1-6alkyl, C1-6alkoxyl or C3-6cycloalkyl;
• X is H, F, CH3, CH2CH3, cyclopropyl or CN;
• Y is —SCR4R4—, —CR4R4S—, —S(O)2CR4R4—, —OCR4R4—, —CR4R4O— or —CR4R4CR4R4—, wherein each R4, independently, is H, F, OH, C1-6alkyl, OC1-6alkyl or C1-6haloalkyl;
• n is 0, 1 or 2;
• and
• o is 0, 1 or 2.