TYK2 inhibitors and uses thereof

A compound of Formula (I):

• or a pharmaceutically acceptable salt, tautomer, or solvate thereof, wherein:
• Ring A is an unsubstituted or substituted 6-membered heterocyclic ring wherein A1 and A2 are independently N or C, wherein if Ring A is substituted then Ring A is substituted with p instances of R8;
• each R8 is independently hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C1-C6 deuteroalkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted carbocycle, unsubstituted or substituted heterocycle, —CN, —OH, —OR17, —C(═O)R16, —CO2R16, —C(═O)N(R16)2, —N(R16)2, —NR16C(═O)R17, —SR16, —S(═O)R17, —SO2R17, or —SO2N(R16)2;
• wherein if R8 is attached to a nitrogen atom, then R8 is hydrogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C1-C6 deuteroalkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted carbocycle, unsubstituted or substituted heterocycle, —C(═O)R16, —CO2R16, —C(═O)N(R16)2, —S(═O)R17, —SO2R17, or —SO2N(R16)2;
• or two R8 attached to the same carbon atom are taken together to form ═O, ═S, or ═NH;
• Z is —NR10—, —O—, —S—, —S(═O)—, or —SO2—;
• R10 is hydrogen, C1-C6 alkyl, C1-C6 deuteroalkyl, C1-C6 fluoroalkyl, C3-C6 cycloalkyl, or monocyclic heterocycle;
• X1, X2, and X3 are each independently CR11 or N;
• each R11 is independently hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted carbocycle, unsubstituted or substituted heterocycle, —CN, —OH, —OR17, —C(═O)R16, —CO2R16, —C(═O)N(R16)2, —N(R16)2, —NR16C(═O)R17, —SR16, —S(═O)R17, —SO2R17, or —SO2N(R16)2;
• B1 is N or CR12a;
• B2 is N or CR12b;
• R12a and R12b are each independently hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted carbocycle, unsubstituted or substituted heterocycle, —CN, —OH, —OR17, —C(═O)R16, —CO2R16, —C(═O)N(R16)2, —N(R16)2, —NR16C(═O)R17, —SR16, —S(═O)R17, —SO2R17, or —SO2N(R16)2;
• R1 is hydrogen, C1-C6 alkyl, or C1-C6 fluoroalkyl;
• R2 is a Ring B that is an unsubstituted or substituted heterocycle or unsubstituted or substituted carbocycle, wherein if Ring B is substituted then Ring B is substituted with q instances of R13;
• each R13 is independently halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted carbocycle, unsubstituted or substituted heterocycle, —CN, —OH, —OR17, —C(═O)R16, —CO2R16, —C(═O)N(R16)2, —N(R16)2, —NR16C(═O)R17, —SR16, —S(═O)R17, —SO2R17, or —SO2N(R16)2;
• or two R13 groups on adjacent atoms of Ring B are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic carbocycle or an unsubstituted or substituted 5- or 6-membered monocyclic heterocycle;
• or R2 is —C(═O)R14, —C(═O)NR14R15, or —C(═O)OR14,
• R14 is hydrogen, unsubstituted or substituted C1-C6 alkyl, C1-C6 deuteroalkyl unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted monocyclic carbocycle, unsubstituted or substituted bicyclic carbocycle, unsubstituted or substituted monocyclic heterocycle, or unsubstituted or substituted bicyclic heterocycle;
• R15 is hydrogen, C1-C6 alkyl, or C1-C6 fluoroalkyl;
• or R14 and R15 are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 4- to 6-membered monocyclic heterocycle;
• or R1 and R15 are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic heterocycle;
• W is —NR3— or —O—;
• R3 is hydrogen, C1-C6 alkyl, C1-C6 deuteroalkyl, C1-C6 fluoroalkyl, C3-C6 cycloalkyl, or monocyclic heterocycle;
• R4 is hydrogen, C1-C6 alkyl, C1-C6 deuteroalkyl, C1-C6 fluoroalkyl, C3-C6 cycloalkyl, or monocyclic heterocycle;
• or R3 and R4 are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycle;
• or R3 and R12a are taken together with the intervening atoms to which they are attached to form a substituted or unsubstituted 5- or 6-membered heterocycle;
• R5 is hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, C3-C6 cycloalkyl, or monocyclic heterocycle;
• each R6 and R7 is independently hydrogen, deuterium, halogen, C1-C6 alkyl, C1-C6 deuteroalkyl, C1-C6 fluoroalkyl, C3-C6 cycloalkyl, or monocyclic heterocycle, —CN, —OH, —OR17, —C(═O)R16, —CO2R16, —C(═O)N(R16)2, —N(R16)2, —NR16C(═O)R17, —SR16, —S(═O)R17, —SO2R17, or —SO2N(R16)2;
• or one R6 and one R7 attached to the same carbon atom are taken together with the carbon atom to which they are attached to form C═O or C3-C4 cycloalkyl;
• each R16 is independently hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C7 cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl;
• or two R16 on the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycle;
• and
• each R17 is independently substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C7 cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl;
• wherein each substituted alkyl, substituted fluoroalkyl, substituted deuteroalkyl, substituted alkoxy, substituted fluoroalkoxy, substituted heteroalkyl, substituted carbocycle, and substituted heterocycle is substituted with one or more Rs groups independently selected from the group consisting of deuterium, halogen, C1-C6 alkyl, monocyclic carbocycle, monocyclic heterocycle, —CN, —CH2CN, —OR18, —CH2OR18, —CO2R18, —CH2CO2R18, —C(═O)N(R18)2, —CH2C(═O)N(R18)2, —N(R18)2, —CH2N(R18)2, —NR18C(═O)R18, —CH2NR18C(═O)R18, —NR18SO2R19, —CH2NR18SO2R19, —SR18, —CH2SR18, —S(═O)R19, —CH2S(═O)R19, —SO2R19, —CH2SO2R19, —SO2N(R18)2, or —CH2SO2N(R18)2;
• each R18 is independently selected from hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C2-C6 heterocycloalkyl, phenyl, benzyl, 5-membered heteroaryl and 6-membered heteroaryl;
• or two R18 groups are taken together with the N atom to which they are attached to form a N-containing heterocycle;
• each R19 is independently selected from C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C2-C6 heterocycloalkyl, phenyl, benzyl, 5-membered heteroaryl, and 6-membered heteroaryl;
• n is 1, 2, or 3;
• p is 0, 1, 2, 3, or 4;
• and
• q is 0, 1, 2, 3, or 4.