C5-c6-oxacyclic fused iminopyrimidinone compounds as bace inhibitors, compositions, and their use

A compound, or a pharmaceutically acceptable salt thereof, said compound having the structural Formula (I):

• or a tautomer thereof having the structural Formula (I′):
• or pharmaceutically acceptable salt thereof, wherein:
• ring C is selected from the group consisting of tetrahydrofuranyl and tetrahydropyranyl, wherein 1 or 2 of the ring carbon atoms having two available substitutable hydrogen atoms of said tetrahydrofuranyl and tetrahydropyranyl rings are optionally independently replaced with a —C(RC1RC2)— group,
• wherein RC1 and RC2 are each independently selected from the group consisting of H, halogen, —CO2-(lower alkyl), alkyl, cycloalkyl, -alkyl-cycloalkyl, -heterocycloalkyl, -alkyl-heterocycloalkyl, aryl, -alkyl-aryl, heteroaryl, and -alkyl-heteroaryl,
• wherein said alkyl, cycloalkyl, -alkyl-cycloalkyl, -heterocycloalkyl, -alkyl-heterocycloalkyl, aryl, -alkyl-aryl, heteroaryl, and -alkyl-heteroaryl of RC1 and RC2 are optionally substituted with one or more R3, and
• wherein 1 to 2 non-adjacent, non-terminal carbon atoms in each said alkyl of RC1 and RC2 are optionally independently replaced with —O—, —NH—, —N(alkyl)-, —S—, —S(O)—, or —S(O)2—,
• or, alternatively, wherein said RC1 and RC2 of one said —C(RC1RC2)— group are taken together with the carbon to which they are attached form a spirocyclic ring consisting of from 3 to 6 carbon atoms, wherein 1 of said carbon atoms may be replaced with —O—, —NH—, —N(lower alkyl)-, —N(lower haloalkyl)-, —S—, —S(O)—, or —S(O)2—, and
• wherein each of the carbon atoms of said spirocyclic ring may be optionally independently substituted with 1 to 4 fluorine, lower alkyl, lower haloalkyl, or —CH2O-(lower alkyl).
• RN is selected from the group consisting of H, alkyl, cycloalkyl, and -alkyl-cycloalkyl,
• wherein said alkyl, cycloalkyl, and -alkyl-cycloalkyl are optionally substituted with one or more fluorine, and
• wherein 1 to 2 non-adjacent, non-terminal carbon atoms in said alkyl are optionally independently replaced with —O—, —NH—, —N(alkyl)-, —S—, —S(O)—, or —S(O)2—;
• R1 is selected from the group consisting of H, halogen, and alkyl,
• wherein said alkyl is optionally substituted with one or more fluorine, and
• wherein 1 to 2 non-adjacent, non-terminal carbon atoms in said alkyl are optionally independently replaced with —O—, —NH—, —N(alkyl)-, —S—, —S(O)—, or —S(O)2—;
• ring A is selected from the group consisting of aryl and heteroaryl;
• m is 0 or more, with the proviso that the value of m does not exceed the number of available substitutable hydrogen atoms on ring A;
• each RA (when present) is independently selected from the group consisting of halogen, oxo, —OH, —CN, lower alkyl, —O-(lower alkyl), lower alkenyl, —O-(lower alkenyl), and -(lower alkyl)-(lower cycloalkyl).
• wherein said lower alkyl, —O-(lower alkyl), lower alkenyl, —O-(lower alkenyl), and -(lower alkyl)-(lower cycloalkyl) of RA are each optionally independently unsubstituted or substituted with one or more fluorine, and
• wherein 1 to 2 non-adjacent, non-terminal carbon atoms in said lower alkyl and are optionally independently replaced with —O—, —NH—, —N(alkyl)-, —S—, —S(O)—, or —S(O)2—;
• n is 0 or 1;
• -L1- (when present) independently represents a bond or a divalent moiety selected from the group consisting of —O—, —CH2—O—, —CH(CH3)—O—, —CH(CF3)—O—, and —CH(CHF2)—O—;
• ring B is selected from the group consisting of aryl, heteroaryl, cycloalkyl, and heterocycloalkyl;
• p is 0 or more, with the proviso that the value of p does not exceed the number of available substitutable hydrogen atoms on ring B;
• and
• each RB (when present) is independently selected from the group consisting of halogen, oxo, —OH, —CN, —SF5, —OSF5, —OR2B, —SR2B, alkyl, alkenyl, alkynyl, cycloalkyl, -alkyl-cycloalkyl, heterocycloalkyl, -alkyl-heterocycloalkyl, aryl, and heteroaryl,
• wherein said alkyl, alkenyl, alkynyl, cycloalkyl, -alkyl-cycloalkyl, heterocycloalkyl, -alkyl-heterocycloalkyl, aryl, and heteroaryl of RB are each optionally independently unsubstituted or substituted with one or more groups independently selected from R3, and wherein 1 to 2 non-adjacent, non-terminal carbon atoms in said alkyl are optionally independently replaced with —O—, —NH—, —N(alkyl)-, —S—, —S(O)—, or —S(O)2—;
• each R2B is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, cycloalkyl, -alkyl-cycloalkyl, heterocycloalkyl, and -alkyl-heterocycloalkyl,
• wherein each said alkyl, alkenyl, alkynyl, cycloalkyl, -alkyl-cycloalkyl, heterocycloalkyl, and -alkyl-heterocycloalkyl of R2B is unsubstituted or optionally substituted with one or more fluorine, and
• wherein 1 to 2 non-adjacent, non-terminal carbon atoms in said alkyl are optionally independently replaced with —O—, —NH—, —N(alkyl)-, —S—, —S(O)—, or —S(O)2—;
• each R3 (when present) is independently selected from the group consisting of halogen, —OH, —CN, alkyl, -alkyl-OH, —O-alkyl, cycloalkyl, -alkyl-cycloalkyl, —O-cycloalkyl, —O-alkyl-cycloalkyl, -heterocycloalkyl, -alkyl-heterocycloalkyl, —O-heterocycloalkyl and —O-alkyl-heterocycloalkyl,
• wherein each said alkyl, -alkyl-OH, —O-alkyl, cycloalkyl, -alkyl-cycloalkyl, —O-cycloalkyl, —O-alkyl-cycloalkyl, -heterocycloalkyl, -alkyl-heterocycloalkyl, —O-heterocycloalkyl and —O-alkyl-heterocycloalkyl, are optionally substituted with one or more halogen,
• and wherein 1 to 2 non-adjacent, non-terminal carbon atoms in said alkyl and —O-alkyl, are optionally independently replaced with —O—, —NH—, —N(alkyl)-, —S—, —S(O)—, or —S(O)2—.