Heat shock protein modulators and anti-Huntington disease therapeutic agents

A thiadiazine compound having a structure according to Formula I-A,

• wherein
• R1 is selected from aryl or heteroaryl, wherein R1 is substituted with two or more halogens;
• R2 is selected from H, —R′CO2H, —R′CO2R″, —R′CONH2, —R′CONHR″, —R′CONR′″R″″, —R′CONHOH, —and —R′NHSO2R″, wherein R′ is selected from C1-C6 alkyl and alkylaryl, and R″, and R′″ are independently selected from C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 haloalkyl, cycloalkyl, alkylcycloalkyl, cycloalkenyl, cycloheteroalkyl, alkylcycloheteroalkyl, cycloheteroalkenyl, aryl, and heteroaryl, wherein R′, R″, and R′″ are independently optionally substituted with one or more groups selected from halogen, hydroxyl, amino, or alkyl;
• R3 is selected from H, alkyl, alkylcycloalkyl, alkylaryl, alkylheteroaryl, —R′CO2H, —R′CO2R″, —R′CONH2, —R′CONHR″, —R′CONR″R′″, and —R′CONHOH, wherein R′ is selected from C1-C6 alkyl, C2-C6 alkenyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, C1-C6 alkyl cycloalkyl, C1-C6 alkyl cycloheteroalkyl, C1-C6 alkylcycloalkenyl, aryl, C1-C6 alkylaryl, heteroaryl, and C1-C6 alkyl heteroaryl, and R″, and R′″ are independently selected from hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 haloalkyl, cycloalkyl, cycloalkenyl, alkylcycloalkenyl, cycloheteroalkyl, aryl, and heteroaryl, wherein R′, R″, and R′″ are independently optionally substituted with one or more groups selected from halogen, hydroxyl, carboxyl, amino, or alkyl;
• R4 is selected from —CO2H, or —CO2R″, wherein R″ is selected from hydrogen, C1-C6 alkyl, aryl, and alkylaryl;
• and
• R5 is H;
• wherein when R2 is H, R3 is not H.