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US 2022/0009936 A1Published application
Rip1k inhibitors
AssigneeRigel Pharmaceuticals, Inc.
InventorsSomasekhar BHMIDIPATI, Simon SHAW, Ihab DARWISH, Jiaxin YU, Rao KOLLURI, Vanessa TAYLOR, Esteban MASUDA, Mark IRVING
Life of this patent
Estimating the term…
Abstract
Disclosed herein are kinase inhibitory compounds, such as a receptor-interacting protein-1 (RIP1) kinase inhibitor compounds, as well as pharmaceutical compositions and combinations comprising such inhibitory compounds. The disclosed compounds, pharmaceutical compositions, and/or combinations may be used to treat or prevent a kinase-associated disease or condition, particularly a RIP1-associated disease or condition.
Claims24
A compound according to the formula
- wherein
- X is selected from CH2, O, S, S(O), S(O)2 and NRa;
- Ra is for each occurrence selected from hydrogen, C1-6alkyl and C1-6acyl;
- Y1, Y2 and Y3 are independently selected from the group consisting of N, N(Ra), O, C(Rb)1-2 and C═O;
- Rb is selected from hydrogen, C1-6alkyl and halo;
- Z is C(Rc) or NRc;
- Rc is a C1-4 unsaturated carbon chain optionally substituted with one or more R1 groups, optionally interrupted by 1 or 2 heteroatoms selected from O, N and S;
- Rz is N, CH or C(R′) and together with ZRc and the carbon to which they are bound form a 5 or 6 membered heteroaryl or 6-membered aryl ring substituted with m R1 groups;
- R1 is a linker-R6 group, wherein the linker is a bond, (C1-C4) alkanyl, (C1-C4) alkenyl or (C1-C4) alkynyl, optionally substituted by one or more Rb and R6 is Re, —C(Rf)3, or —C(Rf)═C(Rf)2;
- R2 is Ra;
- ring B is 5-10-membered heteroaryl;
- R3 is, for each occurrence, independently selected from Rb and ORa;
- L is O, NRa or alkylene;
- W is 5-10 membered aryl or heteroaryl optionally substituted by p R4;
- R4 is for each occurrence selected from Rb and ORa;
- Rd is for each occurrence independently selected from hydrogen, C1-6alkyl, aralkyl, C5-10 aryl or heteroaryl, or two Rd together with a nitrogen to which they are both attached form a C3-10heterocyclic group optionally substituted by one or more Re;
- Re is independently for each occurrence halo, —ORd, —SRd, —S(O)2Rd, —NRdRd, —Si(Ra)3, —C(O)OH, —C(O)ORa, or —C(O)NRdRd;
- Rf is independently for each occurrence Ra, Rb, or Re, or two Rf groups together with the carbon atom bound thereto provide a C3-6cycloalkyl group or a C3-10heterocyclic group each optionally substituted with one or more Re;
- m is 1, 2, 3, or 4;
- n is 0, 1 or 2;
- and
- p is 0, 1, 2, 3, 4, or 5.
19 more elements
A compound according to the formula
- wherein
- X is selected from CH2, O, S, S(O), S(O)2 and NRa;
- Ra is for each occurrence selected from hydrogen, C1-6alkyl and C1-6acyl;
- Y1, Y2 and Y3 are independently selected from the group consisting of N, N(Ra), O, C(Rb)1-2 and C═O;
- Rb is selected from hydrogen, C1-6alkyl and halo;
- Z is C(Rc) or NRc;
- Rc is a C1-4 unsaturated carbon chain optionally substituted with one or more R1 groups, optionally interrupted by 1 or 2 heteroatoms selected from O, N and S;
- Rz is N, CH or C(R′) and together with ZRc and the carbon to which they are bound form a 5 or 6 membered heteroaryl or 6-membered aryl ring optionally substituted with m R1 groups;
- R1 is halo or a linker-R6 group, wherein the linker is a bond, (C1-C4) alkanyl, (C1-C4) alkenyl or (C1-C4) alkynyl, optionally substituted by one or more Rb and R6 is Re, —C(Rf)3, or —C(Rf)═C(Rf)2;
- R2 is Ra;
- ring B is 5-10-membered heteroaryl;
- R3 is, for each occurrence, independently selected from Rb and ORa;
- L is O, NRa or alkylene;
- W is 5-10 membered aryl or heteroaryl optionally substituted by p R4;
- R4 is for each occurrence selected from Rb and ORa;
- Rd is for each occurrence independently selected from hydrogen, C1-6alkyl, aralkyl, C5-10 aryl or heteroaryl, or two Rd together with a nitrogen to which they are both attached form a C3-10heterocyclic group optionally substituted by one or more Re;
- Re is independently for each occurrence halo, —ORd, —SRd, —S(O)2Rd, —NRdRd, —Si(Ra)3, —C(O)OH, —C(O)ORa, or —C(O)NRdRd;
- Rf is independently for each occurrence Ra, Rb, or Re, or two Rf groups together with the carbon atom bound thereto provide a C3-6cycloalkyl group or a C3-10heterocyclic group each optionally substituted with one or more Re;
- m is 1, 2, 3, or 4;
- n is 0, 1 or 2;
- and
- p is 0, 1, 2, 3, 4, or 5.
19 more elements
A compound according to the formula
- wherein
- X is selected from CH2, O, S, S(O), S(O)2 and NRa;
- Ra is for each occurrence selected from hydrogen, C1-6alkyl and C1-6acyl;
- Y1, Y2 and Y3 are independently selected from the group consisting of N, N(Ra), O, C(Rb)1-2 and C═O;
- Rb is selected from hydrogen, C1-6alkyl and halo;
- Z is C(Rc) or NRc;
- Rc is a C1-4 unsaturated carbon chain optionally substituted with one or more R1 groups, optionally interrupted by 1 or 2 heteroatoms selected from O, N and S;
- Rz is N, CH or C(R′) and together with ZRc and the carbon to which they are bound form a 5 or 6 membered heteroaryl or 6-membered aryl ring optionally substituted with m R1 groups;
- R1 is halo or a linker-R6 group, wherein the linker is a bond, (C1-C4) alkanyl, (C1-C4) alkenyl or (C1-C4) alkynyl, optionally substituted by one or more Rb and R6 is Re, —C(Rf)3, or —C(Rf)═C(Rf)2;
- R2 is Ra;
- ring B is 5-10-membered heteroaryl;
- R3 is, for each occurrence, independently selected from Rb and ORa;
- L is O, NRa or alkylene;
- W is 5-10 membered aryl or heteroaryl optionally substituted by p R4;
- R4 is for each occurrence selected from Rb and ORa;
- Rd is for each occurrence independently selected from hydrogen, C1-6alkyl, aralkyl, C5-10 aryl or heteroaryl, or two Rd together with a nitrogen to which they are both attached form a C3-10heterocyclic group optionally substituted by one or more Re;
- Re is independently for each occurrence halo, —ORd, —SRd, —S(O)2Rd, —NRdRd, —Si(Ra)3, —C(O)OH, —C(O)ORa, or —C(O)NRdRd;
- Rf is independently for each occurrence Ra, Rb, or Re, or two Rf groups together with the carbon atom bound thereto provide a C3-6cycloalkyl group or a C3-10heterocyclic group each optionally substituted with one or more Re;
- m is 1, 2, 3, or 4;
- n is 0, 1 or 2;
- and
- p is 0, 1, 2, 3, 4, or 5.
19 more elements
Dependencies are inferred from the claim text.