Amide derivative and preparation method therefore and use thereof in medicine

A method for inhibiting NLRP3 or treating a disease associated with NLRP3, which comprises:

• contacting a pharmaceutical composition having one or more pharmaceutically acceptable carriers and/or excipients or a compound or a stereoisomer, solvate, deuteride, pharmaceutically acceptable salt, cocrystal or prodrug thereof, with a subject in need thereof or administering to a subject in need thereof the pharmaceutical composition or the compound or the stereoisomer, solvate, deuteride, pharmaceutically acceptable salt, cocrystal or prodrug thereof;
• and
• wherein the composition shown as general formula (I) or a stereoisomer, solvate, prodrug, deuteride, pharmaceutically acceptable salt or cocrystal thereof:
• wherein,
• Q is selected from 6-10 membered aryl and 5-10 membered heteroaryl, wherein the heteroaryl contains 1 to 3 heteroatoms selected from N, O and S, and the aryl or heteroaryl is optionally substituted with 0 to 4 Rq0;
• Rq0 are the same or different and are each independently selected from C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, halogen, OH, cyano, nitro, —NH2, C3-8 cycloalkyl, C3-8 heterocycloalkyl, C6-10 aryl, C5-10 heteroaryl, —C(═O)C1-6 alkyl, —C(═O)OC1-6 alkyl, —OC(═O)C1-6 alkyl, —C(═O)OC3-8 cycloalkyl, —OC(═O)C3-8 cycloalkyl, —OC(═O)C3-8 heterocycloalkyl, —C(═O)OC3-8 heterocycloalkyl, —C(═O)C6-10 aryl, —C(═O)OC6-10 aryl, —OC(═O)C6-10 aryl, —C(═O)C5-10 heteroaryl, —C(═O)OC5-10 heteroaryl, —OC(═O)C5-10 heteroaryl, —NHC1-6 alkyl, —N(C1-6 alkyl)2, —NHC(═O)C1-6 alkyl, —NHC(═O)(C1-6 alkyl)2, —NHC(═O)C6-10 aryl, —NHC(═O)C5-10 heteroaryl, —NHC(═O)C3-8 heterocycloalkyl, —NHC(═O)C3-8 cycloalkyl, —NHC(═O)C2-6 alkynyl, —NHC(═O)C2-6 alkenyl, —NH(C═NRq1)NRq2Rq3, —C(═O)NRq4Rq5, —SH, —SC1-6 alkyl, —S(═O)C1-6 alkyl, —S(═O)2C1-6 alkyl and —S(═O)2NRq2Rq3, wherein the heterocycloalkyl or heteroaryl contains 1 to 3 heteroatoms selected from N, O and S, and the alkyl, alkoxy, —NH2, alkenyl, alkynyl, heterocycloalkyl, cycloalkyl, aryl or heteroaryl is optionally further substituted with 1 or more substituents selected from deuterium, OH, halogen, cyano, ═O, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, —NRq4Rq5, ═NRq6, —C(═O)OC1-6 alkyl, —OC(═O)C1-6 alkyl, —C(═O)NRq4Rq5, C3-8 cycloalkyl, C3-8 heterocycloalkyl, C6-10 aryl, C5-10 heteroaryl, —C(═O)OC6-10 aryl, —OC(═O)C6-10 aryl, —OC(═O)C5-10 heteroaryl, —C(═O)OC5-10 heteroaryl, —OC(═O)C3-8 heterocycloalkyl, —C(═O)OC3-8 heterocycloalkyl, —OC(═O)C3-8 cycloalkyl, —C(═O)OC3-8 cycloalkyl, —NHC(═O)C3-8 heterocycloalkyl, —NHC(═O)C6-10 aryl, —NHC(═O)C5-10 heteroaryl, —NHC(═O)C3-8 cycloalkyl, —NHC(═O)C3-8 heterocycloalkyl, —NHC(═O)C1-6 alkyl, —NHC(═O)C2-6 alkenyl and —NHC(═O)C2-6 alkynyl, wherein the substituent C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C3-8 heterocycloalkyl, C6-10 aryl, C5-10 heteroaryl, —NHC(═O)C6-10 aryl, —NHC(═O)C5-10 heteroaryl, —NHC(═O)C3-8 heterocycloalkyl or —NHC(═O)C3-8 cycloalkyl is optionally further substituted with 1 to 3 substituents selected from OH, halogen, C1-6 alkyl, C1-6 alkoxy, —NRq4Rq5 and ═O;
• or
• at least one pair of Rq0 and an atom to which they are attached form a 4-10 membered carbocycle or a 5-10 membered heterocycle, wherein the heterocycle contains 1 to 2 heteroatoms selected from N, O and S, the carbocycle or the heterocycle is optionally further substituted with 1 or more substituents selected from OH, halogen, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, —NRq4Rq5, ═NRq6, —C(═O)OC1-6 alkyl and —C(═O)NRq4Rq5, and the substituent C1-6 alkyl or C1-6 alkoxy is optionally further substituted with a substituent selected from OH, halogen, ═O, —NRq4Rq5, ═NRq6, —C(═O)OC1-6 alkyl, C3-8 cycloalkyl, C3-8 heterocycloalkyl, C6-10 aryl, C5-10 heteroaryl and —C(═O)NRq4Rq5;
• Rq1 is selected from C1-6 alkyl, C1-6 alkoxy and C6-10 aryl;
• Rq2 and Rq3 are selected from H and C1-6 alkyl;
• Rq4 and Rq5 are selected from H, C1-6 alkyl, —NH(C═NRq1)NRq2Rq3, —S(═O)2NRq2Rq3, —C(═O)Rq1 and —C(═O)NRq2Rq3, wherein the C1-6 alkyl is optionally further substituted with 1 or more substituents selected from OH, halogen, C1-6 alkyl, C1-6 alkoxy, C6-10 aryl, C5-10 heteroaryl, C3-8 cycloalkyl and C3-8 heterocycloalkyl;
• or Rq4 and Rq5 form a 3-8 membered heterocycle with an N atom, the heterocycle containing 1 to 3 heteroatoms selected from N, O and S;
• Rq6 is C1-6 alkyl;
• W is selected from O and NH;
• W1 is O;
• X is NH;
• Y is CRbRc;
• Rb and Rc are each independently selected from H, C1-6 alkyl and 3-10 membered carbocyclyl, wherein the C1-6 alkyl is optionally further substituted with 1 to 4 substituents selected from F, Cl, Br, I, C1-6 alkyl, C1-6 alkoxy, 3-10 membered carbocyclyl and 3-10 membered heterocyclyl, the heterocyclyl optionally containing 1 to 3 heteroatoms selected from N, O and S;
• or
• Rb and Rc form a double bond;
• R and R1 are each independently selected from deuterium, H, F, Cl, Br, I, CN, NH2, OH, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, —(C═O)—C1-6 alkyl, —(C═O)O—C1-6 alkyl, —O(C═O)—C1-6 alkyl, —O(C═O)-3-10 membered carbocyclyl, —O(C═O)-3-10 membered heterocyclyl, —(C═O)O-3-10 membered carbocyclyl, —O(C═O)O—C1-6 alkyl, 3-10 membered carbocyclyl, 4-10 membered heterocyclyl, —NHC1-6 alkyl, —N(C1-6 alkyl)2 and (C═O)NRa1Ra2, wherein the heterocyclyl contains 1 to 3 heteroatoms selected from N, O and S, and the alkyl, alkenyl, alkoxy, carbocycle or heterocycle is optionally further substituted with 1 to 4 substituents selected from OH, F, Cl, Br, I, CN, NRa1Ra2, ═O, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, —(C═O)—C1-6 alkyl, —(C═O)O—C1-6 alkyl, —O(C═O)—C1-6 alkyl, —(C═O)O-3-10 membered carbocyclyl, —O(C═O)-3-10 membered carbocyclyl, —O(C═O)-3-10 membered heterocyclyl, —O(C═O)O—C1-6 alkyl, 3-10 membered carbocyclyl, 5-10-membered heterocyclyl, —NHCOC1-6 alkyl, —NH(C═O)-3-10 membered carbocyclyl, —NH(C═O)-3-10 membered heterocyclyl and —(C═O)NRa1Ra2;
• or
• R and R1, together with an atom to which they are attached, form a 4-8 membered ring, wherein the 4-8 membered ring contains 0 to 4 heteroatoms selected from N, O and S, and is optionally further substituted with 0 to 4 substituents selected from H, F, Cl, Br, I, OH, —NRa1Ra2, ═O, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, —(C═O)OC1-6 alkyl, 3-10 membered carbocyclyl and 5-10 membered heterocyclyl;
• C is 3-10 membered cycloalkyl;
• R2 is selected from H, F, Cl, Br, I, OH, —NRa1Ra2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C1-6 alkoxy;
• G1, G2 and G3 are each independently selected from N and CH;
• q and r are selected from 0, 1 and 2;
• n is selected from 0, 1, 2 and 3.