Sulphonyl urea derivatives as NLRP3 inflammasome modulators
AssigneeNodThera Limited
InventorsDavid Harrison, Alan Paul Watt, Mark G. Bock
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Abstract
The present disclosure relates to compounds of Formula (I): and to their pharmaceutically acceptable salts, pharmaceutical compositions, methods of use, and methods for their preparation. The compounds disclosed herein are useful for inhibiting the maturation of cytokines of the IL-1 family by inhibiting inflammasomes and may be used in the treatment of disorders in which inflammasome activity is implicated, such as inflammatory, autoinflammatory and autoimmune diseases and cancers.
Claims20
A method of treating or preventing a disease or disorder in a subject, comprising administering to the subject a compound of Formula (Iac-1):
- or a prodrug, solvate, or pharmaceutically acceptable salt thereof, wherein:
- R2 is —(CX2X2)n—R2S, wherein n is 0, 1, or 2, and each X2 is independently H, C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl, wherein the C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl is optionally substituted with one or more halo, —CN, —OH, —O(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, or oxo;
- R2S is 4- to 8-membered heterocycloalkyl optionally substituted with one or more C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, halo, —CN, —OH, —O(C1-C6 alkyl), —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, or oxo;
- and
- each R2S is independently C1-C6 alkyl, C1-C6 haloalkyl, C3-C8 cycloalkyl, halo, or C3-C8 heterocycloalkyl, wherein the C1-C6 alkyl, C1-C6 haloalkyl, C3-C8 cycloalkyl, or C3-C8 heterocycloalkyl is optionally substituted with —O(C1-C6 alkyl), —N(C1-C6 alkyl)2, halo, or —CN.
A method of treating or preventing a disease or disorder in a subject, comprising administering to the subject a compound of Formula (Iabc-1):
- or a prodrug, solvate, or pharmaceutically wherein:
- R2S is 4- to 8-membered heterocycloalkyl optionally substituted with one or more C1-C6 alkyl, C1-C6 haloalkyl, or oxo;
- and
- each R2S is independently C1-C6 alkyl, C1-C6 haloalkyl, C3-C8 cycloalkyl, halo, or C3-C8 heterocycloalkyl, wherein the C1-C6 alkyl, C1-C6 haloalkyl, C3-C8 cycloalkyl, or C3-C8 heterocycloalkyl is optionally substituted with —O(C1-C6 alkyl), —N(C1-C6 alkyl)2, halo, or —CN.
A method of treating or preventing a disease or disorder in a subject, comprising administering to the subject a compound selected from:
- or a prodrug, solvate, or pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.