Pyridazine derivatives as modulators of NLRP3 inflammasome and related methods
AssigneeNeumora Therapeutics, Inc.
InventorsAnne-Marie Beausoleil, Ryan Hudson
Life of this patent
Estimating the term…
Abstract
Compounds are provided for modulating NLRP3 inflammasome generally, or for treating a NLRP3 inflammasome dependent condition more specifically, by contacting the NLRP3 inflammasome or administering to a subject in need thereof, respectively, an effective amount of a compound having structure (I): or a pharmaceutically acceptable salt, isomer, hydrate, solvate or isotope thereof, wherein R1, R2, R3, R4, R5, R8, R9, R10, R11, R12, and R13 are as defined herein. Pharmaceutical compositions containing such compounds, as well as the compounds themselves, are also provided.
Claims15
A compound having structure (A):
- or a pharmaceutically acceptable salt, isomer, hydrate, solvate or isotope thereof, wherein:
- X is O or NR15;
- R1 is H, OH, CF3, CHF2, C1-6 alkyl, C3-5 cycloalkyl, CN, C1-6 cyanoalkyl, F, Cl, C(O)OH, OC1-6 alkyl or OCF3;
- R2, R3, R4, and R5 are independently H, CF3, CHF2, C1-6 alkyl, CN, C1-6 cyanoalkyl, F, Cl, C(O)OH, OCF3, OC1-6 alkyl or C3-5 cycloalkyl;
- R8 is H or halo;
- R9 is H, C3-5 cycloalkyl, or C1-6 alkyl optionally substituted with one or more R9′;
- R9′ is OH, F, CHF2, CF3 or C3-5 cycloalkyl;
- R10 and R13 are independently H or halo;
- R11 and R12 are each, independently, H, halo, CF3, C1-6 alkyl, CN, OH or OC1-6 alkyl;
- R15 is H, C1-6 alkyl or C3-5 cycloalkyl;
- n is 1 or 2;
- wherein if R1 is F, X is NR15, and R2, R3, R4, R5, R8, R11 and R12 are each H, then R9 is not ethyl;
- and
- wherein if R1 is H or CH3, then R9 is not H.
A compound having structure (II):
- or a pharmaceutically acceptable salt, isomer, hydrate, solvate or isotope thereof, wherein:
- X is O or NR15;
- R1 is OH, CF3, CHF2, C1-6 alkyl, C3-5 cycloalkyl, CN, F, Cl, OC1-6 alkyl or OCF3;
- R2, R3, R4, and R5 are independently H, CF3, CHF2, C1-6 alkyl, CN, F, Cl, OCF3 or OC1-6 alkyl;
- R8 is H or halo;
- R9 is C3-5 cycloalkyl, or C1-6 alkyl optionally substituted with one or more R9′;
- R9′ is OH, F, CHF2, CF3 or C3-5 cycloalkyl;
- R10 and R13 are independently H or halo;
- R11 and R12 are each, independently, is H, halo, CF3, C1-6 alkyl, CN, OH or OC1-6 alkyl;
- and
- R15 is H or C1-6 alkyl;
- wherein if R1 is F and R2, R3, R4, R5, R8, R11 and R12 are each H, then R9 is not tert-butyl.
Dependencies are inferred from the claim text.