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US 11,690,850 B2Granted
Inhibitors of receptor interacting protein kinase I for the treatment of disease
AssigneeBoard of Regents, The University of Texas System
InventorsRichard T. Lewis, Matthew Hamilton, William J. Ray, Fernando Alvarez, Naphtali Reyna, Jason Cross, Suyambu Kesava Vijayan Ramaswamy
Life of this patent
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Abstract
Disclosed herein are compounds which inhibit RIPK1, pharmaceutical compositions, and methods of treatment of RIPK1-mediated diseases, such as neurodegenerative disorders, inflammatory disorders, and cancer.
Claims24
A compound of structural Formula I:
- or a salt thereof, wherein:
- R1 is chosen from alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, (cycloalkyl)alkyl, (heterocycloalkyl)alkyl, (aryl)alkyl, and (heteroaryl)alkyl, any one of which is optionally substituted with one or more R5;
- R2 is chosen from H, alkyl, haloalkyl, and (alkoxy)alkyl;
- R3 is chosen from H, CN, halo, alkyl, and alkoxy;
- or R2 and R3, together with the intervening atoms, combine to form a 5-, 6-, or 7-membered cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
- R4a is H;
- R4b is chosen from
- each R5 is independently chosen from CN, halo, hydroxy, oxo, alkyl, and (alkyl)oxy;
- and
- each R6a is independently chosen from H, CN, halo, hydroxy, oxo, C1-6alkyl, haloC1-6alkyl, C3-7 cycloalkyl, 4- to 11-membered heterocycloalkyl, C6-10aryl, 5- to 10-membered heteroaryl, (C2-6alkenyl)C1-6alkyl, (C2-6alkynyl)C1-6alkyl, (C3-7cycloalkyl)C1-6alkyl, (4- to 11-membered heterocycloalkyl)C1-6alkyl, (C6-10aryl)C1-6alkyl, (5- to 10-membered heteroaryl)C1-6 alkyl, (C1-6 alkyl)oxy, (C3-7cycloalkyl)oxy, (4- to 11-membered heterocycloalkyl)oxy, (C6-10aryl)oxy, and (5- to 10-membered heteroaryl)oxy;
- and
- R6b is chosen from H and C1-6alkyl.
9 more elements
A compound of structural Formula IV:
- or a salt thereof, wherein:
- R1 is chosen from alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, (cycloalkyl)alkyl, (heterocycloalkyl)alkyl, (aryl)alkyl, and (heteroaryl)alkyl, any one of which is optionally substituted with one or more R5;
- R2 is chosen from H, alkyl, haloalkyl, and (alkoxy)alkyl;
- R3 is chosen from H, CN, halo, alkyl, and alkoxy;
- or R2 and R3, together with the intervening atoms, combine to form a 5-, 6-, or 7-membered cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
- V1 is chosen from a bond, CR6g, N, NR6g, O, and S;
- V2, V3, and V4 are independently chosen from CR6g, N, NR6g, O, and S;
- V1, V2, V3, and V4, together with the intervening two carbons, combine to form a 5- or 6-membered aryl or heteroaryl;
- W2 is chosen from a bond and CHR6g;
- W3 is chosen from a bond, CHR6g, NR6g, O, and S;
- if W2 is a bond, then W3 is CHR6g;
- each R5 is independently chosen from CN, halo, hydroxy, oxo, alkyl, and (alkyl)oxy;
- R6e is chosen from H, alkyl, and cycloalkyl;
- and
- each R6g is independently chosen from H, CN, halo, hydroxy, oxo, alkyl, cycloalkyl, heterocycloalkyl, (cycloalkyl)alkyl, (heterocycloalkyl)alkyl, aryl, and heteroaryl.
12 more elements
Dependencies are inferred from the claim text.