Nlrp3 inflammasome inhibitor and uses thereof

A compound of general formula (A) or a pharmacologically acceptable salt, stereoisomer or tautomer thereof:

• Y—W—R3 (A)
• wherein,
• W is selected from
• X1 and X2 are each independently selected from C or N;
• R1 is selected from hydrogen, hydroxyl, amino, carboxyl, cyano, nitro, halogen, carbonyl, C1-6 alkyl, halo C1-6alkyl, C1-6 alkoxy, halo C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, 3-7 membered heterocyclyl, 3-7 membered cycloalkyl, aryl, 5-7 membered heteroaryl, —N(C1-6 alkyl)2, —S—C1-6 alkyl, or absent;
• R2 is selected from hydrogen, hydroxyl, amino, carboxyl, cyano, nitro, halogen, carbonyl, C1-6 alkyl, halo C1-6alkyl, C1-6 alkoxy, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, 3-7 membered heterocyclyl, 3-7 membered cycloalkyl, aryl, 5-7 membered heteroaryl, —N(C1-6 alkyl)2, —S—C1-6 alkyl, or absent;
• R1 and R2 are each optionally substituted by 1-3 substituents selected from hydroxyl, amino, carboxyl, cyano, nitro, halogen, carbonyl, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, 3-7 membered heterocyclyl, 3-7 membered cycloalkyl, aryl, and 5-7 membered heteroaryl;
• or
• R1 and R2, together with the carbon or nitrogen atom to which they are attached, form a 5-12 membered ring A, the 5-12 membered ring A is optionally substituted by 1-4 substituents selected from the group consisting of hydroxyl, amino, carboxyl, cyano, nitro, halogen, carbonyl, C1-6 alkyl, —NH—C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, 3-7 membered heterocyclyl, 3-7 membered cycloalkyl, aryl, 5-7 membered heteroaryl, C1-6 alkylsulfonyl, and —N(C1-6 alkyl)2;
• R3 is selected from the group consisting of —(C1-6 alkylene)0-2-NR4R5, —(C1-6 alkylene)0-2-NR4—COR5, —(C1-6 alkylene)0-2-CO—NR4—R5, and —(C1-6 alkylene)0-2-NR4—C1-6 alkylene-R5;
• R4 is selected from hydrogen or C1-6 alkyl;
• R5 is selected from the group consisting of 3-7 membered heterocyclyl, 3-7 membered cycloalkyl, aryl, and 5-7 membered heteroaryl;
• R5 is optionally substituted by 1-4 substituents selected from the group consisting of halogen, cyano, amino, hydroxyl, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, 3-7 membered heterocyclyl, 3-7 membered cycloalkyl, aryl, 5-7 membered heteroaryl, C2-6 alkenylcarbonyl, sulfonyl, and C1-6 alkylcarbonyl;
• when R5 is substituted, the substituent on R5, which is C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, 3-7 membered heterocyclyl, 3-7 membered cycloalkyl, aryl, 5-7 membered heteroaryl, or sulfonyl, is optionally substituted by 1-3 substituents selected from the group consisting of halogen, cyano, amino, hydroxy, carbonyl, C1-6 alkyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclyl, carboxyl, and C1-6 alkylsulfonyl;
• Y is selected from the group consisting of aryl, 5-14 membered heteroaryl, 3-14 membered heterocyclyl, and 3-12 membered cycloalkyl;
• (1) when X1 and X2 are each selected from C,
• Y is substituted by C2-6 alkenyl or C2-6 alkynyl, and is optionally substituted by 1-2 substituents selected from the group consisting of halogen, cyano, amino, hydroxy, carbonyl, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, 3-7 membered heterocyclyl, 3-7 membered cycloalkyl, aryl, 5-7 membered heteroaryl, C1-6 alkylamino, C1-6 alkylcarbonylamino, C1-6 alkylsulfonyl, aminocarbonyl, C1-6 alkylaminocarbonyl, and sulfonyl;
• (2) when either one or two of X1 and X2 is/are selected from N,
• Y is optionally substituted by 1-3 substituents selected from the group consisting of C2-6 alkenyl, C2-6 alkynyl, halogen, cyano, amino, hydroxy, carbonyl, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, 3-7 membered heterocyclyl, 3-7 membered cycloalkyl, aryl, 5-7 membered heteroaryl, C1-6 alkylamino, C1-6 alkylcarbonylamino, C1-6 alkylsulfonyl, aminocarbonyl, C1-6 alkylaminocarbonyl, sulfonyl, —N(C1-6 alkyl)2, and —S—C1-6 alkyl;
• in (1) and (2) above, when Y is substituted,
• the substituent on Y, which is C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, 3-7 membered heterocyclyl, 3-7 membered cycloalkyl, aryl, 5-7 membered heteroaryl, or sulfonyl, is optionally substituted by 1-3 substituents selected from the group consisting of halogen, cyano, amino, hydroxy, carbonyl, C1-6 alkyl, and 3-6 membered cycloalkyl;
• or
• the substituent on Y, which is C2-6 alkenyl or C2-6 alkynyl, is optionally substituted by 1-3 substituents selected from the group consisting of halogen, cyano, amino, hydroxy, carbonyl, unsubstituted or hydroxy-substituted C1-6 alkyl, unsubstituted or hydroxy-substituted 3-6 membered cycloalkyl, and C1-6 haloalkyl.