FIELD: compounds with antagonistic effect.
SUBSTANCE: invention relates to a compound of formula AA, where m=0, 1 or 2; n=0, 1 or 2; o=1 or 2; p=0, 1, 2 or 3, A is a 5-10-membered monocyclic or bicyclic heteroaryl containing at least one heteroatom selected from the group consisting of O, S, N, or monocyclic or bicyclic C6-C10aryl; B is a 5-membered heteroaryl containing at least one heteroatom selected from the group consisting of O, S, N, 7-10-membered monocyclic or bicyclic heteroaryl containing at least one heteroatom selected from the group consisting of O, S, N or monocyclic or bicyclic C6-C10aryl; wherein at least one R6 is in the ortho position relative to the bond connecting ring B to the NH(CO) group of formula AA; each of R1 and R2 is independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, COC1-C6 alkyl, CO2C1-C6 alkyl, C6-C10 aryl, S(O2) C1-C6 alkyl, S(O) C1-C6 alkyl and 3-7 membered heterocycloalkyl containing one heteroatom selected from N, where C1-C6 alkyl, C1-C6 haloalkyl and 3-7 membered heterocycloalkyl are optionally substituted with one or more substituents, each independently selected from hydroxy, C1-C6 alkyl, C1-C6 alkoxy, NR8R9, 3-7 membered heterocycloalkyl containing at least one heteroatom selected from O and N; where each C1-C6 alkyl and each C1-C6 alkoxy representing R1 or R2 substituents representing 3-7 membered heterocycloalkyl are additionally optionally independently substituted with one to three halogen or oxo atoms; or at least one pair of R1 and R2 on adjacent atoms, taken together with the atoms connecting them, independently form one 5-8 membered heterocyclic ring containing 1 or 2 heteroatoms independently selected from O, N, where the heterocyclic ring is optionally independently substituted with one or more substituents independently selected from C1-C6 alkyl; each of R6 and R7 is independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, halo, CN, C6-C10 aryl, C3-C10 cycloalkyl, where each of R6 and R7 is optionally substituted with one or more substituents independently selected from CN, C1-C6 alkyl, or at least one pair consisting of R6 and R7 at adjacent atoms, taken together with the atoms connecting them, independently forms at least one C4-C8 carbocyclic ring or at least one 5-8 -membered heterocyclic ring, containing 1 or 2 heteroatoms independently selected from O, N and S, where the carbocyclic ring or heterocyclic ring is optionally independently substituted with one or more substituents independently selected from hydroxy, hydroxymethyl, halogen, oxo, C1-C6 alkyl, C1-C6 alkoxy; each of R8 and R9 is at each occurrence independently selected from hydrogen, C1-C6 alkyl, COR13, CO2R13; where C1-C6 alkyl is optionally substituted with one or more halogen atoms, C1-C6 alkoxy groups, C3-C7 cycloalkyl groups; R13 is C1-C6 alkyl; R3 is hydrogen; and R14 is hydrogen, C1-C6 alkyl. A pharmaceutical composition and use of a compound of formula AA is also provided.
EFFECT: proposed compounds have an NLRP3 antagonistic effect and are useful in the treatment of a condition, disease or disorder associated with NLRP3 activity.
20 cl, 3 dwg, 38 tbl, 431 ex
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