Substituted lactams as inhibitors of Aβ protein production

A compound of Formula (I):

• or a pharmaceutically acceptable salt thereof, wherein:
• Q is —(CR7R7a)m—R4, —(CR7R7a)n—S—R4, —(CR7R7a)n—O—R4, —(CR7R7a)m—N(R7b)—R4, —(CR7R7a)n—S(═O)—R4, —(CR7R7a)n—S(═O)2—R4, or
• —(CR7R7a)n—C(═O)—R4;
• provided when n is 0, then R4 is not H;
• m is 1, 2, or 3;
• n is 0, 1, or 2;
• R4 is H,
• C1-C8 alkyl substituted with 0-3 R4a,
• C2-C8 alkenyl substituted with 0-3 R4a,
• C2-C8 alkynyl substituted with 0-3 R4a,
• C3-C10 carbocycle substituted with 0-3 R4b,
• aryl substituted with 0-3 R4b, or
• 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and
• sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R4b;
• R4a, at each occurrence, is independently selected from is
• H, Cl, F, Br, I, CN, NO2, NR15R16, CF3, OR14a, OR22,
• SR22, C(═O)OR22, NR21R22, S(═O)R22, S(═O)2R22,
• C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl,
• C1-C4 haloalkoxy, C1-C4 haloalkyl-S—,
• C3-C10 carbocycle substituted with 0-3 R4b,
• aryl substituted with 0-3 R4b, and
• 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R4b;
• R4b, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(═O)CH3, S(═O)2CH3,
• C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-S—;
• R5 is H;
• C1-C6 alkyl substituted with 0-3 R5b;
• C2-C6 alkenyl substituted with 0-3 R5b;
• C2-C6 alkynyl substituted with 0-3 R5b;
• C3-C10 carbocycle substituted with 0-3 R5c;
• aryl substituted with 0-3 R5c;
• and
• 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R5c;
• R5b, at each occurrence, is independently selected from:
• H, C1-C6 alkyl, CF3, Cl, F, Br, I, ═O, CN, NO2, NR15R16;
• C3-C10 carbocycle substituted with 0-3 R5c;
• aryl substituted with 0-3 R5c;
• or
• 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R5c;
• R5c, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(═O)CH3, S(═O)2CH3,
• C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, and
• C1-C4 haloalkoxy, and C1-C4 haloalkyl-S—;
• R6 is H;
• C1-C6 alkyl substituted with 0-3 R6a;
• C3-C10 carbocycle substituted with 0-3 R6b;
• or
• aryl substituted with 0-3 R6b;
• R6a, at each occurrence, is independently selected from H, C1-C6 alkyl, OR14, Cl, F, Br, I, ═O, CN, NO2, NR15R16, aryl or CF3;
• R6b, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, and C1-C4 haloalkoxy;
• R7, at each occurrence, is independently H or C1-C4 alkyl;
• R7a, at each occurrence, is independently H or C1-C4 alkyl;
• R7b is H or C1-C4 alkyl;
• Ring B is
• R11 at each occurrence, is independently selected from
• H, C1-C4 alkoxy, Cl, F, Br, I, ═O, CN, NO2, NR18R19,
• C(═O)R17, C(═O)OR17, C(═O)NR18R19, S(═O)2NR18R19, CF3;
• C1-C6 alkyl optionally substituted with 0-3 R11a;
• aryl substituted with 0-3 R11b;
• C3-C10 carbocycle substituted with 0-3 R11b;
• or
• 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R11b;
• R11a, at each occurrence, is independently selected from
• H, C1-C6 alkyl, OR14, Cl, F, Br, I, ═O, CN, NO2, NR15R16, CF3;
• phenyl substituted with 0-3 R11b;
• C3-C6 cycloalkyl substituted with 0-3 R11b;
• and
• 5 to 6 membered heterocycle containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R11b;
• R11b, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(═O)CH3, S(═O)2CH3,
• C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl,
• C1-C4 haloalkoxy, and C1-C4 haloalkyl-S—;
• W is a bond or —(CR8R8a)p—;
• p is 0, 1, 2, 3, or 4;
• R8 and R8a, at each occurrence, are independently selected from H, F, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl and C3-C8 cycloalkyl;
• X is a bond;
• aryl substituted with 0-3 RXb;
• C3-C10 carbocycle substituted with 0-3 RXb;
• or
• 5 to 10 menibered heterocycle substituted with 0-2 RXb;
• RXb, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(═O)CH3, S(═O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 halothioalkoxy;
• Y is a bond or —(CR9R9a)t—V—(CR9R9a)u—;
• t is 0, 1, or 2;
• u is 0, 1, or 2;
• R9 and R9a, at each occurrence, are independently selected from H, F, C1-C6 alkyl or C3-C8 cycloalkyl;
• V is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)2—, —N(R19)—, —C(═O)NR19b—, —NR19bC(═O)—, —NR19bS(═O)2—, —S(═O)2NR19b—, —NR19bS(═O)—, —S(═O)NR19b—, —C(═O)O—, or —OC(═O)—;
• Z is H;
• C1-C8 alkyl substituted with 0-3 R12a;
• C2-C6 alkenyl substituted with 0-3 R12a;
• C2-C6 alkynyl substituted with 0-3 R12a;
• aryl substituted with 0-4 R12b;
• C3-C10 carbocycle substituted with 0-4 R12b;
• or
• 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R12b;
• R12a, at each occurrence, is independently selected from
• H, OH, Cl, F, Br, I, CN, NO2, NR15R16, —C(═O)NR15R16,
• CF3, acetyl, SCH3, S(═O)CH3, S(═O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 haloalkyl-S—, aryl substituted with 0-4 R12b;
• C3-C10 carbocycle substituted with 0-4 R12b;
• or
• 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R12b;
• R12b, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(═O)CH3, S(═O)2CH3, aryl, C3-C6 cycloalkyl, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-S—;
• R13, at each occurrence, is independently selected from H, OH, C1-C6 alkyl, C1-C4 alkoxy, Cl, F, Br, I, CN, NO2, NR15R16, and CF3;
• R14 is H, phenyl, benzyl, C1-C6 alkyl, C2-C6 alkoxyalkyl, or C3-C6 cycloalkyl;
• R14a is H, phenyl, benzyl, or C1-C4 alkyl;
• R15, at each occurrence, is independently selected from H, C1-C6 alkyl, benzyl, phenethyl, (C1-C6 alkyl)-C(═O)—, and (C1-C6 alkyl)-S(═O)2—;
• R16, at each occurrence, is independently selected from H, OH, C1-C6 alkyl, benzyl, phenethyl, (C1-C6 alkyl)-C(═O)—, and (C1-C6 alkyl)-S(═O)2—;
• alternatively, R15 and R16, together with the nitrogen to which they are attached, may combine to form a 4-7 membered ring wherein said 4-7 membered ring optionally contains an additional heteroatom selected from O or NH;
• R17 is H, C1-C6 alkyl, C2-C6 alkoxyalkyl, aryl substituted by 0-4 R17a, or —CH2-aryl substituted by 0-4 R17a;
• R17a is H, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, butoxy, —OH, F, Cl, Br, I, CF3, OCF3, SCH3, S(O)CH3, SO2CH3, —NH2, —N(CH3)2, or C1-C4 haloalkyl;
• R18, at each occurrence, is independently selected from H, C1-C6 alkyl, phenyl, benzyl, phenethyl, (C1-C6 alkyl)-C(═O)—, and (C1-C6 alkyl)-S(═O)2—;
• R19, at each occurrence, is independently selected from H, OH, C1-C6 alkyl, phenyl, benzyl, phenethyl, (C1-C6 alkyl)-C(═O)—, and (C1-C6 alkyl)-S(═O)2—;
• R19b, at each occurrence, is independently is H or C1-C4 alkyl;
• R21 is H, phenyl, benzyl, or C1-C4 alkyl;
• and
• R22 is C1-C4 alkyl, C2-C4 alkenyl, or C3-C4 alkynyl.