Iminothiadiazine Dioxide Compounds as BACE Inhibitors, Compositions and Their Use

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

• wherein:
• -L1- represents a bond or a divalent moiety selected from the group consisting of -alkyl-, -haloalkyl-, -heteroalkyl-, -alkenyl-, and -alkynyl-;
• -L2- represents a bond or a divalent moiety selected from the group consisting of -alkyl-, -haloalkyl-, -heteroalkyl-, -alkenyl-, and -alkynyl-;
• each -L3- independently represents a bond or a divalent moiety independently selected from the group consisting of -alkyl-, -haloalkyl-, -heteroalkyl-, -alkenyl-, -alkynyl-, —N(R7)—, —NHC(O)—, —C(O)NH—, —NHS(O)2—, —S(O)2NH—, —O-alkyl-, -alkyl-O—, —N(R7)-alkyl-, -alkyl-N(R7)—, -haloalkyl-NH—, and —NH-haloalkyl-;
• m, n, and p are each independently selected integers, wherein:
• m is 0 or more;
• n is 0 or more;
• and
• p is 0 or more,
• wherein the maximum value of the sum of m and n is the maximum number of available substitutable hydrogen atoms on ring A, and wherein the maximum value of p is the maximum number of available substitutable hydrogen atoms on ring B;
• R1 is selected from the group consisting of:
• H, alkyl, heteroalkyl, heterohaloalkyl, cycloalkyl, cycloalkylalkyl-, heterocycloalkyl, heterocycloalkylalkyl-, aryl, arylalkyl-, heteroaryl, and heteroarylalkyl-,
• wherein each of said alkyl, heteroalkyl, heterohaloalkyl, cycloalkyl, cycloalkylalkyl-, heterocycloalkyl, heterocycloalkylalkyl-, aryl, arylalkyl-, heteroaryl, and heteroarylalkyl- of R1 is unsubstituted or substituted with one or more independently selected R10 groups;
• R2 is selected from the group consisting of H, halo, alkyl, haloalkyl, and heteroalkyl, wherein each of said alkyl and said haloalkyl of R2 is unsubstituted or substituted with one or more independently selected R10 groups;
• R3 is selected from the group consisting of H, halo, alkyl, haloalkyl, and heteroalkyl, wherein each of said alkyl and said haloalkyl of R2 is unsubstituted or substituted with one or more independently selected R10 groups;
• R4 is selected from the group consisting of alkyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, and heterocycloalkenyl,
• wherein each of said alkyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, and heterocycloalkenyl of R4 is unsubstituted or substituted with one or more independently selected R10 groups;
• ring A is selected from the group consisting of monocyclic aryl, monocyclic heteroaryl, monocyclic cycloalkyl, monocyclic cycloalkenyl, monocyclic heterocycloalkyl, monocyclic heterocycloalkenyl, and a multicyclic group;
• each ring B (when present) is independently selected from the group consisting of monocyclic aryl, monocyclic heteroaryl, monocyclic cycloalkyl, monocyclic cycloalkenyl, monocyclic heterocycloalkyl, monocyclic heterocycloalkenyl, and a multicyclic group;
• each R5 (when present) is independently selected from the group consisting of halo, —CN, —SF5, —OSF5, —NO2, —Si(R6)3, —P(O)(OR7)2, —P(O)(OR7)(R7), —N(R8)2, —NR8C(O)R7, —NR8S(O)2R7, —NR8C(O)N(R8)2, —NR8C(O)OR7, —C(O)R7, —C(O)2R7, —C(O)N(R8)2, —S(O)R7, —S(O)2R7, —S(O)2N(R8)2, —OR7, —SR7, alkyl, haloalkyl, haloalkoxy, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl,
• wherein each said alkyl, haloalkyl, haloalkoxy, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl of R5 (when present) is optionally independently unsubstituted or further substituted with one or more independently selected groups selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, lower heteroalkyl, halo, —CN, —SF5, —OSF5, —NO2, —N(R8)2, —OR7, —C(O)N(R8)2, and cycloalkyl;
• each R6 (when present) is independently selected from the group consisting of alkyl, aryl, arylalkyl-, haloalkyl, cycloalkyl, cycloalkylalkyl-, heteroaryl, and heteroarylalkyl-;
• each R7 (when present) is independently selected from the group consisting of H, alkyl, alkenyl, heteroalkyl, haloalkyl, aryl, arylalkyl-, heteroaryl, heteroarylalkyl-, cycloalkyl, cycloalkylalkyl-, heterocycloalkyl, and heterocycloalkylalkyl-;
• each R8 (when present) is independently selected from the group consisting of H, alkyl, alkenyl, heteroalkyl, haloalkyl, haloalkenyl, aryl, arylalkyl-, heteroaryl, heteroarylalkyl-, cycloalkyl, cycloalkylalkyl-, heterocycloalkyl, and heterocycloalkylalkyl-;
• each R9 (when present) is independently selected from the group consisting of:
• halogen, —CN, —SF5, —OSF5, —NO2, —Si(R6)3, —P(O)(OR7)2, —P(O)(OR7)(R7), —N(R8)2, —NR8C(O)R7, —NR8S(O)2R7, —NR8C(O)N(R8)2, —NR8C(O)OR7, —C(O)R7, —C(O)2R7, —C(O)N(R8)2, —S(O)R7, —S(O)2R7, —S(O)2N(R8)2, —OR7, —SR7, alkyl, haloalkyl, heteroalkyl, alkenyl, alkynyl, aryl, arylalkyl-, cycloalkyl, heteroaryl, heteroarylalkyl-, and heterocycloalkyl;
• each R10 (when present) is independently selected from the group consisting of halo, —CN, —NO2, —Si(R6)3, —P(O)(OR7)2, —P(O)(OR7)(R7), —N(R8)2, —NR8C(O)R7, —NR8S(O)2R7, —NR8C(O)N(R8)2, —NR8C(O)OR7, —C(O)R7, —C(O)2R7, —C(O)N(R8)2, —S(O)R7, —S(O)2R7, —S(O)2N(R8)2, —OR7, —SW, alkyl, haloalkyl, haloalkoxy, heteroalkyl, alkenyl, alkynyl, and cycloalkyl,
• wherein each said alkyl, haloalkyl, haloalkoxy, heteroalkyl, alkenyl, alkynyl, and cycloalkyl of R10 (when present) is optionally independently unsubstituted or further substituted with one or more independently selected groups selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, lower heteroalkyl, halo, —CN, —NO2, —N(R8)2, —OR7, and —C(O)N(R8)2.