Nlrp3 modulators

A compound of Formula (I):

• or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein:
• W is independently selected from:
• —Y—R6, -Q-R6a, and R6b;
• Q is independently selected from:
• NR5, CHR5, O, and S;
• Y is independently selected from:
• C1-10 alkylene, C2-10 alkenylene, and C2-10 alkynylene, each of which is substituted with 0 to 4 Re and/or each of which is optionally interrupted by one of the following:
• (i) O;
• (ii) N(Rf);
• (iii) C3-6 cycloalkylene substituted with 0 to 4 Rg;
• (iv) phenylene further substituted with 0 to 4 Rd;
• (v) heteroarylene including from 5 to 10 ring atoms, wherein from 1 to 4 ring atoms are each independently selected from N, N(Rf), O, and S, and which is substituted with 0 to 4 Rd;
• or
• (vi) heterocycloalkylene including from 3 to 10 ring atoms, wherein from 1 to 3 ring atoms are each independently selected from N, N(Rf), O and S(O)1-2, and which is substituted with 0 to 4 Rg;
• X1 and X2 are, at each occurrence, independently N or CR1;
• X3 is independently N or CR3;
• X4 is independently N or CR4;
• provided that at least one of X1, X3 and X4 is N and no more than two of X1, X3 and X4 are N;
• R1 and R3 are, at each occurrence, independently selected from:
• H, halogen, cyano, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;
• R2 is independently a heteroaryl including 5 ring atoms, wherein from 1 to 4 ring atoms are each independently selected from N, NH, O, and S, wherein the heteroaryl is substituted with 0 to 3 Rd;
• R4 is independently selected from:
• H, halogen, cyano, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, N(C1-4 alkyl)2, and —(C0-3 alkylene)-heteroaryl including 5 ring atoms, wherein from 1 to 4 ring atoms are each independently selected from N, NH, N(C1-4 alkyl), O, and S, wherein the heteroaryl is substituted with 0 to 3 Rd;
• R5 is independently H or C1-4 alkyl;
• R6 is independently selected from:
• —ORa, C1-4 haloalkoxy, —C(O)Ra, —CO2Ra, —SO1-2(Rh), —CONRiRj, cyano and R6a;
• R6a is independently selected from:
• phenyl substituted with 0 to 4 Rd;
• heteroaryl including from 5 to 10 ring atoms, wherein from 1 to 4 ring atoms are each independently selected from N, N(Rf), O, and S, wherein the heteroaryl is substituted with 0 to 4 Rd;
• C3-10 cycloalkyl substituted with 0 to 4 Rg;
• and heterocyclyl including from 3 to 10 ring atoms, wherein from 1 to 3 ring atoms are each independently selected from N, N(Rf), O and S(O)1-2, wherein the heterocyclyl is substituted with 0 to 4 Rg;
• R6b is independently selected from:
• C1-6 alkoxy, C1-4 haloalkoxy, —C(O)Ra, —CO2Ra, —SO1-2(Rh), —CONRiRj, phenyl substituted with 0 to 4 Rd;
• heteroaryl including from 5 to 10 ring atoms, wherein from 1 to 4 ring atoms are each independently selected from N, N(Rf), O, and S, wherein the heteroaryl is substituted with 0 to 4 Rd;
• C3-10 cycloalkyl substituted with 0 to 4 Rg;
• and heterocyclyl selected from
• wherein the heterocyclyl is substituted with 0 to 2 Rg;
• Ra is independently selected from:
• H;
• C1-8 alkyl substituted with 0 to 2 Re;
• —(C0-3 alkylene)-C3-10 cycloalkyl, wherein the cycloalkyl is substituted with 0 to 4 Rg;
• —(C0-3 alkylene)-heterocyclyl including from 3 to 10 ring atoms, wherein from 1 to 3 ring atoms are each independently selected from N(Rf), O, and S, wherein the heterocyclyl is substituted with 0 to 4 Rg;
• —(C0-3 alkylene)-(C6-10 aryl), wherein the aryl is substituted with 0 to 4 Rd;
• and —(C0-3 alkylene)-heteroaryl including from 5 to 10 ring atoms, wherein from 1 to 4 ring atoms are each independently selected from N, N(Rf), O, and S, wherein the heteroaryl is substituted with 0 to 4 Rd;
• Rb and Rc are, at each occurrence, independently Ra or —C(O)Ra;
• Rd is independently selected from:
• halogen, OH, cyano, C1-4 alkoxy, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, —C(O)O(C1-4 alkyl), NH2, N(C1-4 alkyl)2, —C(O)NH2, —C(O)N(C1-4 alkyl)2, C2-6 alkenyl, C2-6 alkynyl, and C1-6 alkyl substituted with 0 to 2 Re;
• Re is independently selected from:
• F, OH, cyano, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, and C1-4 alkyl substituted with 0 to 1 Rn;
• Rf is independently selected from:
• H, C1-4 alkyl substituted with 0 to 1 OH, —C(O)(C1-4 alkyl), and —C(O)O(C1-4 alkyl);
• Rg is independently oxo or Rd;
• Rh is independently selected from:
• C1-6 alkyl, C1-4 haloalkyl, —(C0-3 alkylene)-phenyl, and —(C0-3 alkylene)-heteroaryl including from 5 to 6 ring atoms, wherein from 1-4 ring atoms are each independently selected from N, N(Rf), O, and S;
• Ri and Rj are, at each occurrence, independently H or Rh;
• or Ri and Rj together with the nitrogen atom to which each is attached forms a ring including from 5 to 6 ring atoms, wherein the ring includes:
• (a) from 3 to 5 ring carbon atoms, each of which is substituted with 1 to 2 substituents independently H and Rm;
• and (b) from 0 to 2 ring heteroatoms (in addition to the nitrogen atom attached to Ri and Rj), which are each independently selected from N(Rf), O, and S;
• Rm is independently oxo or Re;
• and
• Rn is independently selected from:
• OH, CONH2 and C1-4 alkoxy.