Compound for inhibiting nlrp3, preparation method, and use

A compound represented by Formula I, or an enantiomer, diastereomer, racemate, tautomer, stereoisomer, geometric isomer, nitrogen oxide, metabolite thereof, or a pharmaceutically acceptable salt, ester, solvate, hydrate, isotope-labeled (preferably deuterated) compound or prodrug thereof,

• wherein,
• is connected to ring A,
• is connected to ring B;
• ring A and ring B are each independently selected from:
• 5-6 membered heteroaryl, 5-6 membered heterocyclyl, and phenyl;
• ring C is selected from:
• 6-10 membered aryl, 5-10 membered heteroaryl, phenyl fused 4-7 membered cycloalkyl, phenyl fused 4-7 membered heterocyclyl, 5-6 membered heteroaryl fused 4-7 membered cycloalkyl, 5-6 membered heteroaryl fused 4-7 membered heterocyclyl, 4-7 membered cycloalkyl, and 4-7 membered heterocyclyl;
• each Rc is independently selected from:
• H, deuterium, halogen, —OH, —NH2, —CN, C1-6 alkoxy, C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, hydroxyl C1-6 alkyl, C1-6 alkoxy-C1-6 alkyl, Rc1S(O)2—, —(CH2)s—N(Rc1)(Rc2), 3-6 membered cycloalkyl, 3-6 membered heterocyclyl, phenyl, and 5-6 membered heteroaryl;
• the 3-6 membered cycloalkyl, 3-6 membered heterocyclyl, phenyl, and 5-6 membered heteroaryl are optionally substituted with 1, 2, or 3 substituents selected from:
• deuterium, halogen, —OH, —NH2, —CN, C1-6 alkyl, C1-6 haloalkyl, and C1-6 alkoxy;
• alternatively, two Rc together with the C atom to which they are attached may form a 3-6 membered cycloalkyl, 4-7 membered heterocyclyl, 6 membered aryl, or 5-6 membered heteroaryl, the 3-6 membered cycloalkyl, 4-7 membered heterocyclyl, 6 membered aryl, and 5-6 membered heteroaryl may be optionally substituted with 1, 2, or 3 substituents selected from:
• deuterium, halogen, —OH, —NH2, —CN, C1-6 alkoxy, C1-6 alkyl, and C1-6 haloalkyl;
• each Ra and Rb are independently selected from:
• H, deuterium, halogen, —OH, —NH2, —CN, oxo, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 alkoxy-C1-6 alkyl, C1-6 haloalkoxy, hydroxyl C1-6 alkyl, —NH(C1-6 alkyl), —N(C1-6 alkyl)(C1-6 alkyl), —C(═O)—(C1-6 alkyl), and 3-6 membered heterocyclyl optionally substituted by hydroxyl;
• L1 is selected from:
• bond, C3-6 cycloalkylene, —NR2—, —O—, —S—, —C(═O)—, —(CR3R4)a—, —NR2—(CR3R4)a—, —(CR3R4)a—NR2—, —O—(CR3R4)a—, —(CR3R4)a—O—, —S—(CR3R4)a—, —(CR3R4)a—S—, —C(═O)—(CR3R4)a—, —(CR3R4)a—C(═O)—, —(CR3R4)a—(CR9═CR10)—, —(CR9═CR10)—(CR3R4)a—, —C(═O)—O—, —O—C(═O)—, —C(═O)—NR2—, —(CR3R4)a—C(═O)—NR2—, —NR2—C(═O)—, —(CR3R4)a—NR2—C(═O)—, —S(═O)2—NR2—, —NR2—S(═O)2—, —NR2—(CR3R4)a—C(═O)—, —C(═O)—(CR3R4)a—NR2—, —NR2—(CR3R4)a—C(═O)—NR5—, —NR2—C(═O)—(CR3R4)a—NR5—, —C(═S)—NR2—, and —NR2—C(═S)—;
• L2 is selected from:
• bond, —NR6—, —O—, —S—, —NR6—(CR7R8)b—, —(CR7R8)b—NR6—, —O—(CR7R8)b—, —(CR7R8)b—O—, —S—(CR7R8)b—, and —(CR7R8)b—S—;
• each R2, R5, R6, R9 and R10 are each independently selected from:
• H, deuterium, and C1-6 alkyl;
• each R3, R4, R7, and R8 are each independently selected from:
• H, deuterium, halogen, oxo, —OH, —NH2, C1-6 alkyl;
• R1 is selected from:
• H, —OH, —NH2, —COOH, C1-6 alkyl, C1-6 alkoxy, NHR11—C(═O)—, C1-6 alkyl-C(═O)—O—, C1-6 alkyl-O—C(═O)—, 3-10 membered cycloalkyl, 3-6 membered monocyclic heterocyclyl, 6-11 membered bicyclic heterocyclyl, 6-10 membered aryl, and 5-10 membered heteroaryl;
• wherein the —NH2, C1-6 alkyl, C1-6 alkoxy, NHR11—C(═O)—, C1-6 alkyl-C(═O)—O—, C1-6 alkyl-O—C(═O)—, 3-10 membered cycloalkyl, 3-6 membered monocyclic heterocyclyl, 6-11 membered bicyclic heterocyclyl, 6-10 membered aryl, and 5-10 membered heteroaryl are each independently optionally further substituted with 1, 2, or 3 substituents selected from:
• H, deuterium, halogen, —OH, oxo, —CN, C1-6 alkyl, hydroxyl C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, —(CH2)s—O(Rc1), —(CH2)s—N(Rc1)(Rc2), C3-6 cycloalkyl, 3-6 membered monocyclic heterocyclyl, 5-6 membered heteroaryl, —C(═O)—Rc3, —S(O)—Rc3, —S(O)2—Rc3, —C(═O)O—Rc3, —CH2—C(═O)O—Rc4, —N(Rc4)—C(═O)—Rc3, —CH2—N(Rc4)—C(═O)—Rc4, —C(═O)—N(Rc6)(Rc5), —CH2—C(═O)—N(Rc4)(Rc4), —N(Rc4)—C(═O)—N(R6)(Rc5), —P(═O)Rc5Rc6, —CRc7Rc8-CN, and —(CH2)s—Rc9;
• each Rc1 and Rc2 are independently selected from:
• H, C1-6 alkyl, C1-6 haloalkoxy, C3-6 cycloalkyl, and 4-7 membered heterocyclyl;
• Rc3 is selected from:
• H, deuterium, C1-6 alkyl, C1-6 haloalkyl, and C3-6 cycloalkyl, wherein the C1-6 alkyl and C3-6 cycloalkyl are optionally substituted with 1, 2, or 3 substituents selected from:
• deuterium, halogen, —OH, —NH2, —CN, oxo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkoxy-C1-6 alkyl, —NH(C1-6 alkyl), and —N(C1-6 alkyl)(C1-6 alkyl);
• Rc4 is selected from:
• H, deuterium, and C1-6 alkyl;
• each Rc5 and Rc6 are independently selected from:
• H, deuterium, C1-6 alkyl, and C3-6 cycloalkyl, or Rc°, Rc6 together with the N atom to which they are attached form a 4-6 membered heterocyclyl;
• wherein the C1-6 alkyl, C3-6 cycloalkyl, and 4-6 membered heterocyclyl are optionally substituted with 1-3 substituents selected from:
• deuterium, halogen, —OH, —NH2, —CN, oxo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkoxy-C1-6 alkyl, —NH(C1-6 alkyl), and —N(C1-6 alkyl)(C1-6 alkyl);
• each Rc7 and Rd8 are independently selected from:
• H, deuterium, and C1-6 alkyl, or Rc7, Rc8together with the C atom to which they are attached form a C3-6 cycloalkyl;
• Rc9 is selected from 3-6 membered heterocyclyl, wherein the heterocyclyl is optionally substituted with 1, 2 or 3 substituents selected from:
• H, deuterium, and C1-6 alkyl;
• R11 is selected from:
• H, deuterium, C1-6 alkyl, and 3-6 monocyclic heterocyclyl;
• each a and b are each independently 1, 2, 3, or 4;
• each s, n, m, and p are each independently selected from:
• 0, 1, 2, 3, and 4;
• provided that,
• is not H, C1-6 alkyl.