Vinyl fluoride cyclopropyl fused thiazin-2-amine compounds as beta-secretase inhibitors and methods of use

A compound of Formula I

• or a stereoisomer, tautomer, hydrate, solvate or a pharmaceutically acceptable salt thereof, wherein
• A4 is CR4 or N;
• A5 is CR5 or N;
• A6 is CR6 or N;
• A7 is CR7 or N, provided that no more than two of A4, A5, A6, and A7 are N;
• each of Ra and Rb, independently, is H, F, Cl, C1-6-alkyl, C2-4-alkenyl, C2-4-alkynyl, CN, —CH2OC1-6-alkyl, —OC1-6-alkyl, —S(O)oC1-6-alkyl, —NHC1-6-alkyl or —C(O)C1-6-alkyl, wherein each of the C1-6-alkyl, C2-4-alkenyl, C2-4-alkynyl, 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 independently selected from F, oxo, or OH;
• R1 is H, F, Cl, C1-6-alkyl, C2-4-alkenyl, C2-4-alkynyl, CN, —CH2OC1-6-alkyl, —OC1-6-alkyl, —S(O)oC1-6-alkyl, —NHC1-6-alkyl, —C(O)NH2, —CH═CHC(O)NH2, —CH═CHC(O)NHC1-6-alkyl, —CH═CHC(O)N(C1-6-alkyl)2, —CH═CHC(O)NHC1-6-alkyl-OC1-6-alkyl, —CH═CHC(O)-heterocyclyl, —CH═C(CH3)C(O)-heterocyclyl, —CH═CHC(O)2H, —CH═CHC(O)OC1-6-alkyl, —CH═CHCH2OH, C1-6-alkyl-C(O)NHC1-6-alkyl, C1-6-alkyl-C(O)N(C1-6-alkyl)2, —C(O)C1-6-alkyl, —C(O)C2-6-alkenyl, —C(O)OH, —C(O)OC1-6-alkyl, —C(O)NHC1-6-alkyl, —C(O)N(C1-6-alkyl)2, —C(O)NHC3-6-cycloalkyl, —C(O)NH-aryl, —C(O)NH-heterocyclyl, —C(O)NHOC1-6-alkyl, —C(O)N(C1-6-alkyl)OC1-6-alkyl, —C(O)-heterocyclyl, —CH2-heteroaryl, or heteroaryl, wherein the heterocyclyl groups of the —CH═CHC(O)-heterocyclyl, —CH═C(CH3)C(O)-heterocyclyl, —C(O)— heterocyclyl, and —C(O)NH-heterocyclyl groups are fully or partially saturated 3-, 4-, 5-, or 7-membered monocyclic rings or 6-, 7-, 8-, 9-, or 10-membered bicyclic rings that include 1 heteroatom selected from N, O, or S if the ring is a 3-membered ring, that include 1 or 2 heteroatoms independently selected from N, O, or S if the ring is a 4- or 5-membered ring, and include 1, 2, or 3 heteroatoms independently selected from N, O, or S if the ring is a 6-, 7-, 8-, 9-, or 10-membered ring, wherein the heteroaryl groups of the —CH2-heteroaryl and heteroaryl groups is a 5- or 6-membered ring that includes 1, 2, 3, or 4 heteroatoms independently selected from N, O, or S, wherein the aryl group of the —C(O)NH-aryl group is a phenyl or naphthyl group, wherein each of the C1-6-alkyl, C2-4-alkenyl, C2-4-alkynyl, and C1-6-alkyl and C2-6-alkenyl portions of —CH2OC1-6-alkyl, —OC1-6-alkyl, —S(O)oC1-6-alkyl, —NHC1-6-alkyl, C(O)C1-6-alkyl, —C(O)C2-6-alkenyl, —CH═CHC(O)NHC1-6-alkyl, —C(O)NHC1-6-alkyl, —C(O)N(C1-6-alkyl)2, and C1-6-alkyl-C(O)NHC1-6-alkyl groups is optionally substituted with 1-4 substituents independently selected from F, CN, oxo, or OH, and further wherein each of the heterocyclyl groups of the —CH═CHC(O)-heterocyclyl, —CH═C(CH3)C(O)-heterocyclyl, —C(O)heterocyclyl, and —C(O)NH-heterocyclyl groups is optionally substituted with 1-4 substituents independently selected from methyl, F, OH, oxo, —CN, OCH3, —CH2OC1-6-alkyl, —C(O)C1-6-alkyl, —C(O)OC1-6-alkyl, —CH2OH, —NH2, —NHC1-6-alkyl, —N(C1-6-alkyl)2, —CF3, phenyl, or —CH2—C3-6-cycloalkyl and further wherein each of the heteroaryl groups of the —CH2-heteroaryl and heteroaryl groups and the aryl group of the —C(O)NH-aryl group is optionally substituted with 1-3 substituents independently selected from halo, methyl, or OH;
• R2 is H, F, Cl, C1-6-alkyl, C2-4-alkenyl, C2-4-alkynyl, CN, —CH2OC1-6-alkyl, —OC1-6-alkyl, —S(O)oC1-6-alkyl, —NHC1-6-alkyl, —C(O)NH2, —CH═CHC(O)NHC1-6-alkyl, —CH═CHC(O)2H, —CH═CHCH2OH, C1-6-alkyl-C(O)NHC1-6-alkyl, —C(O)C1-6-alkyl, or —C(O)C2-6-alkenyl, wherein each of the C1-6-alkyl, C2-4-alkenyl, C2-4-alkynyl, and C1-6-alkyl and C2-6-alkenyl portion of —CH2OC1-6-alkyl, —OC1-6-alkyl, —S(O)oC1-6-alkyl, —NHC1-6-alkyl, C(O)C1-6-alkyl, —C(O)C2-6-alkenyl, —CH═CHC(O)NHC1-6-alkyl, and C1-6-alkyl-C(O)NHC1-6-alkyl, is optionally substituted with 1-4 substituents independently selected from F, CN, oxo, or OH;
• R3 is C1-4-alkyl, CH2OC1-4-alkyl, CH2OH, C1-4haloalkyl or cyclopropyl, wherein each of the C1-4-alkyl, CH2OC1-4-alkyl, C1-4-haloalkyl, and cyclopropyl is optionally substituted with 1-4 F atoms;
• each of R4, R5, R6 and R7, independently, is H, halo, haloalkyl, haloalkoxyl, C1-4-alkyl, CN, OH, OC1-4-alkyl, S(O)oC1-4-alkyl, NHC1-4-alkyl, C(O)C1-4-alkyl, C(O)OC1-4-alkyl, or CH2OH;
• R8 is selected from H, F, Cl, or C1-3-alkyl;
• one of R9 and R10 is selected from F or H and the other of R9 and R10 is a fully or partially unsaturated 3-, 4-, 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 ring is optionally substituted, independently, with 1-5 substituents of R11;
• each R11, independently, is H, halo, haloalkyl, CN, OH, NO2, NH2, SF5, acetyl, —C(O)NHC1-6-alkyl, —OCH2C(O)NHC1-6-alkyl, —OCH2C(O)N(C1-6-alkyl)2, —OCH2CH2-pyrrolidinonyl, oxo, cyclopropylmethoxy, 2-propynyloxy, 2-butynyloxy, 2-pentyloxy, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-6-cycloalkyl, C1-6-alkylamino-, C1-6-dialkylamino-, C1-6-alkoxyl, C1-6-thioalkoxyl, morpholinyl, pyrazolyl, isoxazolyl, dihydropyranyl, pyrrolyl, pyrrolidinyl, piperazinyl, oxetan-3-yl, imidazo-pyridinyl, dioxolyl, or —OCH2-heteroaryl, wherein the heteroaryl group of the —OCH2-heteroaryl group is a 5- or 6-membered ring that includes 1, 2, 3, or 4 heteroatoms selected from N, O, or S, and further wherein each of the cyclopropylmethoxy, 2-propynyloxy, 2-butynyloxy, 2-pentyloxy, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-6-cycloalkyl, C1-6-alkylamino-, C1-6-dialkylamino-, C1-6-alkoxyl, C1-6-thioalkoxyl, morpholinyl, pyrazolyl, isoxazolyl, dihydropyranyl, pyrrolidinyl, oxetan-3-yl, dioxolyl, or —OCH2-heteroaryl is optionally substituted independently with 1-5 substituents of F, Cl, Br, CN, NO2, NH2, OH, oxo, CF3, CHF2, CH2F, methyl, methoxy, ethyl, ethoxy, CH2CF3, CH2CHF2, propyl, propoxy, isopropyl, isopropoxy, cyclopropyl, butyl, butoxyl, cyclobutyl, isobutoxy, tert-butoxy, isobutyl, sec-butyl, tert-butyl, trimethylsilyl, cyclopentyl, cyclohexyl, C1-3alkylamino-, C1-3dialkylamino, C1-3thioalkoxyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiadiazolyl, thienyl, furyl, pyrrolyl, tetrahydropyranyl, pyrrolidinyl, or oxetan-3yl;
• and
• the subscript o is selected from 0, 1, or 2.