Substituted pyrano [2,3-b] pyridinamine compounds as beta-secretase modulators and methods of use

A compound of Formula I:

• or a stereoisomer or pharmaceutically acceptable salt thereof, wherein
• R1 is a cyclobutenyl, a fully unsaturated aryl ring or a fully unsaturated 5-6 membered monocyclic or 8-10 membered bicyclic heteroaryl ring, said heteroaryl ring formed of carbon atoms including 1-3 heteroatoms if monocyclic or 1-6 heteroatoms if bicyclic, said heteroatoms selected from O, N, or S, and wherein said cyclobutenyl, aryl and heteroaryl ring is each optionally substituted independently with 1-5 substituents of oxo, R7, NR7R7, OR7, SR7, C(O)R7, OC(O)R7, COOR7, C(O)NR7R7, NR7C(O)R7, NR7C(O)NR7R7, NR7(COOR7), OC(O)NR7R7, S(O)2NR7R7, NR7S(O)2NR7R7 or NR7S(O)2R7;
• R2 is aryl optionally substituted independently with 1-5 substituents of oxo, R7, NR7R7, OR7, SR7, C(O)R7, OC(O)R7, COOR7, C(O)NR7R7, NR7C(O)R7, NR7C(O)NR7R7, NR7(COOR7), OC(O)NR7R7, S(O)2NR7R7, NR7S(O)2NR7R7 or NR7S(O)2R7;
• each R3, independently, is H, C1-6-alkyl, C2-8-alkenyl or C2-8-alkynyl, each of the C1-6-alkyl, C2-8-alkenyl and C2-8-alkynyl optionally substituted with 1-5 substituents of R7;
• R4 is H, halo or C1-6-alkyl;
• R5 is H, halo, haloalkyl, oxo, C1-6-alkyl, —O—C1-6-alkyl, —S—C1-6-alkyl, —NH—C1-6alkyl, —N-di-C1-6-alkyl, CN, OH or NH2 , wherein the C1-6-alkyl and the C1-6-alkyl portion of —O—C1-6-alkyl, —S—C1-6-alkyl, —NH—C1-6-alkyl and —N-di-C1-6-alkyl are optionally substituted independently with 1-5 substituents of R7;
• each of Al, A2 and A3, independently, is CH or CR6;
• A4 is N;
• X is O;
• Z is a 3-6 membered spirocyclic ring formed of carbon atoms optionally including 1-2 heteroatoms selected from O, and optionally substituted independently with 1-3 substituents of R7;
• each R6, independently, is halo, haloalkyl, C1-6-alkyl, —O—C1-6-alkyl, —S—C1-6-alkyl, —NH—C1-6-alkyl, —N-di-C1-6-alkyl, CN, OH, NH2, C2-6-alkenyl or C2-6-alkynyl, wherein the C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl and the C1-6-alkyl portion of —O—C1-6-alkyl, —S—C1-6-alkyl, —NH—C1-6-alkyl and —N-di-C1-6-alkyl are optionally substituted with 1-5 substituents of R7;
• and
• each R7, independently, is H, halo, haloalkyl, CN, OH, NO2, NH2, acetyl, oxo, C1-10-alkyl, C2-10-alkenyl, C2-10-alkynyl, C3-10-cycloalkyl, C4-10-cycloalkenyl, C1-10-alkylamino-, C1-10-dialkylamino-, C1-10-alkoxyl, C1-10-thioalkoxyl or a fully saturated or partially or fully unsaturated 3-8 membered monocyclic or a 6-12 membered bicyclic ring, said ring formed of carbon atoms optionally including 1-3 heteroatoms if monocyclic or 1-6 heteroatoms if bicyclic, said heteroatoms selected from O, N, or S, wherein each of the C1-10-alkyl, C2-10-alkenyl, C2-10-alkynyl, C3-10-cycloalkyl, C4-10-cycloalkenyl, C1-10-alkylamino-, C1-10-dialkylamino-, C1-10-alkoxyl, C1-10-thioalkoxyl and ring is optionally substituted independently with 1-5 substituents of halo, haloalkyl, CN, NO2, NH2, OH, oxo, methyl, methoxyl, ethyl, ethoxyl, propyl, propoxyl, isopropyl, isopropoxyl, cyclopropyl, cyclopropylmethoxyl, butyl, butoxyl, isobutoxyl, tert-butoxyl, isobutyl, sec-butyl, tert-butyl, cyclobutyl, pentyl, cyclopentyl, hexyl, cyclohexyl, C1-10-alkylamino-, C1-10-dialkylamino-, C1-10-thioalkoxyl, benzyl or phenyl.