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US 2024/0391899 A1Published application
Potent and selective inhibitors of irak4
AssigneeDana-Farber Cancer Institute, Inc.
InventorsJohn M. Hatcher, Nathanael S. Gray
Life of this patent
Estimating the term…
Abstract
The disclosure relates to compounds that act as inhibitors of interleukin 1 (IL-1) receptor-associated kinase 4 (IRAK4); pharmaceutical compositions comprising the compounds; and methods of treating or preventing kinase-mediated disorders, including cancer and other proliferation diseases.
Claims43
A compound of Formula (I):
- or a pharmaceutically acceptable salt thereof, wherein:
- RA1 is C3-10 cycloalkyl or 4- to 10-membered heterocyclyl, wherein the cycloalkyl and heterocyclyl are unsubstituted or substituted with one, two, or three R1;
- RA2 is H;
- or RA1 and RA2 taken together with the atoms to which they are bound form a C3-10 cycloalkyl or a 5- to 10-membered heterocyclyl, wherein the cycloalkyl and heterocyclyl are unsubstituted or substituted with one, two, or three R11;
- B is C6-10 aryl or 5- to 10-membered heteroaryl, wherein the aryl and heteroaryl are unsubstituted or substituted with one, two, or three R2;
- C is pyridinyl that is unsubstituted or substituted with one, two, or three R3;
- R1 and R11, independently for each occurrence, are C1-8 alkyl, C1-8 haloalkyl, C1-8 alkoxy, halo, C3-8 cycloalkyl, or 3- to 8-membered heterocyclyl;
- R2, independently for each occurrence, is C1-6 alkyl, C3-6 cycloalkyl, C1-6 haloalkyl, C1-6 alkoxy, halo, or —CN;
- R3, independently for each occurrence, is —OH, —CN, halo, —C(X)OR5, —C(X)N(R5)(R6), C1-8 alkyl, C2-8 alkenyl, C1-8 haloalkyl, C1-8 alkoxy, C3-10 cycloalkyl, 4- to 10-membered heterocyclyl, C6-10 aryl, 5- to 10-membered heteroaryl, C1-3 alkyl-(4- to 10-membered heterocyclyl), C1-3 alkyl-(5-to 10-membered heteroaryl), —O—C1-3 alkyl-(4- to 10-membered heterocyclyl), or —O—C1-3 alkyl-(5-to 10-membered heteroaryl) wherein the alkyl, alkenyl, haloalkyl, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, alkylheterocyclyl, alkylheteroaryl, —O-alkylheterocyclyl, and —O-alkylheteroaryl are unsubstituted or substituted with one, two, or three R4;
- R4, independently for each occurrence, is oxo, —OH, —CN, halo, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, —C0-3 alkyl-C(X)OR5, —C0-3 alkyl-C(X)N(R5)(R6), or —C0-3 alkyl-(5- to 10-membered heteroaryl), wherein the alkylheteroaryl is unsubstituted or substituted with one, two, or three C1-3 alkyl or halo;
- X is, independently for each occurrence, O or S;
- Y is C or N;
- Z is C or N;
- and
- R5 and R6 are each, independently, hydrogen or C1-4 alkyl;
- provided that when Y is C, then Z is N, and when Y is N, then Z is C;
- and
- provided that when B is unsubstituted, either R1 is not isopropyl or R3 is not
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Dependencies are inferred from the claim text.