N-((1,2,3,5,6,7-hexahydro-S-indacen-4-yl)carbamoyl)-4, 5, 6, 7-tetrahydrobenzofuran-2-sulfonamide derivatives and related compounds as NLPR3 modulators for the treatment of multiple sclerosis (MS)

A compound having the structure of Formula (I):

• wherein:
• X1 is O, S, N(R3), or C(NO2)(R4);
• X2 is —N(R5)— or —C(R5)2—;
• X3 is —N(R5)— or —C(R5)2—;
• X4 is —C(O)— or —CH2—;
• Y1 is O;
• Y2 is N or C(R9);
• Y3 is O or N(R10);
• Z is N or C(R19);
• R1 is
• R2 is
• R3 is —OR14, —CN, —NO2, or —S(═O)2R15;
• R4 is hydrogen, C1-C6alkyl, or C1-C6heteroalkyl;
• each R5 is independently selected from hydrogen, C1-C6alkyl, and C1-C6heteroalkyl;
• R6 is —OH, —C1-C6alkyl-OH, or —NH(R16);
• each R7 is independently selected from C1-C6alkyl, —C1-C6alkyl-CO2R18, C1-C6haloalkyl, and C1-C6heteroalkyl;
• or R6 and R7 are combined to form a 5- or 6-membered heteroaryl ring;
• R9 is hydrogen, halogen, C1-C6alkyl, C1-C6haloalkyl, or C1-C6heteroalkyl;
• R10 is —OH or —O—C1-C6alkyl;
• R11 is C1-C6alkyl;
• R12 is C1-C6alkyl;
• each R13 is independently selected from halogen, C1-C6alkyl, C1-C6haloalkyl, and C1-C6heteroalkyl;
• R14 is hydrogen or C1-C6alkyl;
• R15 is C1-C6alkyl;
• R16 is hydrogen, C1-C6alkyl or —C(O)—C1-C6alkyl;
• R17 is hydrogen or C1-C6alkyl;
• R18 is hydrogen or C1-C6alkyl;
• R19 is hydrogen, halogen, —CN, C1-C6alkyl, C1-C6haloalkyl, or C1-C6heteroalkyl;
• n is 1 or 2;
• p is 0, 1, 2, 3, or 4;
• q is 0, 1, or 2;
• s is 1, 2, or 3;
• and
• t is 1, 2, or 3;
• or a pharmaceutically acceptable salt or solvate thereof.