Compounds and their use as BACE1 inhibitors

A compound according to Formula (VI):

• Wherein
• X is selected from the group consisting of C(O) and S(O)2;
• Y is (CR7R8)n;
• Z is absent;
• W is absent or present and when present is selected from the group consisting of alkyl, haloalkyl, heteroalkyl, alkenyl, alkynyl, OR9, O, NR9R10, NR9, C(O)R9, C(O)NR9, NR9C(O), C(O)OR9, OC(O)R9 and heterocycloalkyl;
• Q is selected from NR1, (CR14R15)t;
• is selected from
• wherein each of Ri, Rii, Riii, Riv, Rv, Rvi, Rvii, and Rviii, independently, is hydrogen, halogen, cyano group, amino group, amido group, C1-6 alkyl, C1-6 alkoxyl, C2-6 alkenyl, or C2-6 alkynyl, or is a moiety selected from C3-10 cycloalkyl, C1-10 heterocycloalkyl, aryl, and heteroaryl, each of which is optionally mono-, di-, or tri-substituted with halogen, nitro group, cyano group, amino group, amido group, C1-6 alkyl, C1-6 alkoxyl, C2-6 alkenyl, C2-6 alkynyl, aryl, or heteroaryl, or optionally fused with C3-10 cycloalkyl, C1-10 heterocycloalkyl, aryl, or heteroaryl;
• Gi is selected from CH2, O, and SO2;
• Gii is selected from CH2 and O;
• the bond between Gi and Gii is a single bond;
• R1 is selected from hydrogen, alkyl, cycloalkyl, haloalkyl, heteroalkyl, heterohaloalkyl and heteroalkynyl;
• R2 is selected from CN, alkyl, cycloalkyl, and aryl;
• R4 is independently selected from the group consisting of:
• hydrogen, deuterium, halogen, hydroxyl, CN, alkyl, haloalkyl, heteroalkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, cycloalkyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl and heterocycloalkyl;
• R5 is selected from hydrogen, C1-5 alkyl, C(O)R14 and CR17R16OC(O)R18;
• R7 is independently selected from hydrogen, fluorine, and trifluoromethyl;
• R8 is independently selected from hydrogen, fluorine, and trifluoromethyl;
• R9 is independently selected from hydrogen, deuterium, halogen, C1-5 alkyl or alkynyl;
• R10 is independently selected from hydrogen, deuterium, halogen and C1-5 alkyl;
• R14 is a straight chain or branched alkyl group of 1 to 28 carbons, heterocycloalkyl, cycloalkyl, monocyclic aryl, multicyclic aryl, monocyclic heteroaryl, multicyclic heteroaryl, haloalkyl or heteroalkyl;
• R15 is independently selected from hydrogen, deuterium, halogen and C1-5 alkyl;
• or
• R14 and R15 are optionally taken together with the carbon atom they are attached to form a cycloalkyl or heterocycloalkyl ring structure;
• R16 is independently selected from hydrogen, deuterium, halogen and C1-5 alkyl;
• R17 is independently selected from hydrogen, deuterium, halogen and C1-5 alkyl;
• R18 is a straight chain or branched alkyl group of 1 to 28 carbons, heterocycloalkyl and cycloalkyl, monocyclic aryl, multicyclic aryl, monocyclic heteroaryl, multicyclic heteroaryl, haloalkyl or heteroalkyl;
• n is 1 or 2;
• m is 0 or more;
• t is 1;
• or a stereoisomer, tautomer, prodrug, pharmaceutically acceptable salt, solvate, or solvate of a salt thereof.

A compound according to Formula (VI):

• wherein
• X is selected from the group consisting of C(O) and S(O)2;
• Y is CH2;
• Z is absent;
• W is absent or present and when present is selected from the group consisting of alkyl, haloalkyl, heteroalkyl, alkenyl, alkynyl, OR9, O, NR9R10, NR9, C(O)R9, C(O)NR9, NR9C(O), C(O)OR9, OC(O)R9 and heterocycloalkyl;
• Q is selected from NR1, or (CR14R15)t;
• is selected from
• wherein each of Ri, Rii, Riii, Riv, Rv, Rvi, Rvii, and Rviii, independently, is hydrogen, halogen, cyano group, amino group, amido group, C1-6 alkyl, C1-6 alkoxyl, C2-6 alkenyl, or C2-6 alkynyl, or is a moiety selected from C3-10 cycloalkyl, C1-10 heterocycloalkyl, aryl, and heteroaryl, each of which is optionally mono-, di-, or tri-substituted with halogen, nitro group, cyano group, amino group, amido group, C1-6 alkyl, C1-6 alkoxyl, C2-6 alkenyl, C2-6 alkynyl, aryl, or heteroaryl, or optionally fused with C3-10 cycloalkyl, C1-10 heterocycloalkyl, aryl, or heteroaryl;
• Gi is selected from CH2, O, and SO2;
• Gii is selected from CH2 and O;
• the bond between Gi and Gii is a single bond;
• R1 is selected from hydrogen, alkyl, cycloalkyl, haloalkyl, heteroalkyl, heterohaloalkyl and heteroalkynyl;
• R2 is alkyl;
• R4 is independently selected from the group consisting of:
• hydrogen, deuterium, halogen, hydroxyl, CN, alkyl, haloalkyl, heteroalkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, cycloalkyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl and heterocycloalkyl;
• R5 is selected from hydrogen, C1-5 alkyl, C(O)R14 and CR17R16OC(O)R18;
• R9 is independently selected from hydrogen, deuterium, halogen, C1-5 alkyl and alkynyl;
• R10 is independently selected from hydrogen, deuterium, halogen and C1-5 alkyl;
• R14 is a straight chain or branched alkyl group of 3 to 28 carbons, heterocycloalkyl, or cycloalkyl;
• R15 is independently selected from hydrogen, deuterium, halogen and C1-5 alkyl;
• or
• R14 and R15 are optionally taken together with the carbon atom they are attached to form a cycloalkyl or heterocycloalkyl ring structure;
• R16 is independently selected from hydrogen, deuterium, halogen and C1-5 alkyl;
• R17 is independently selected from hydrogen and C1-5 alkyl;
• R18 is a straight chain or branched alkyl group of 3 to 28 carbons, heterocycloalkyl or cycloalkyl;
• m is 0 or more;
• t is 1;
• or a stereoisomer, tautomer, prodrug, pharmaceutically acceptable salt, solvate, or solvate of a salt thereof.