Modulators of RAS GTPase
AssigneeTosk, Inc.
InventorsSolomon B. Ungashe, William A. Garland, Stephen D. Yanofsky, Brian D. Frenzel, Philip Liaw, Annie L. Lennek
Life of this patent
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Abstract
RAS modulating compounds and methods of using the same are provided. The compounds find use in modulating the activity of a target RAS in a sample. The target RAS can be a mutant RAS that is implicated in a disease of interest. In some cases, the subject compounds can inhibit the growth of cancer cells whose progression is driven by kRAS or a mutated kRAS. Methods of treating a subject for a RAS driven disease including administering a therapeutically effective amount of the subject compound are provided. Also provided are pharmaceutical compositions and kits which include the subject compounds.
Claims23
A RAS modulating compound of formula (I):
- wherein:
- A is a monocyclic or bicyclic group selected from aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycle, substituted heterocycle, cycloalkyl and substituted cycloalkyl;
- Z0 is N;
- Z1 is CR1;
- Z2 is N or CR2;
- Z3 is N or CR3;
- Z4 is N or CR4;
- Z5 is N or CR5;
- L2 is selected from the group consisting of covalent bond, —NR′—, —(CH2)n—NR′—, —NR′—(CH2)n—, —CO—, —CONR′—, —NR′CO—, —(CH2)m—,
- wherein R′ is H, alkyl or substituted alkyl, m is 1-3 and n is 1 or 2
- R1 is selected from alkyl and substituted alkyl;
- R3 and R4 are independently selected from H, aryl, substituted aryl, heteroaryl and substituted heteroaryl, wherein at least one of R3 and R4 is non-hydrogen and
- R2 and R5 are independently selected from H, alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxy, substituted alkoxy, halogen, nitro, cyano, hydroxy, —NH2, substituted amino, carboxy, sulfoxy, alkylsulfonyl, substituted alkylsulfonyl, alkanoyl, substituted alkanoyl, alkylsulfonamido, substituted alkylsulfonamido, alkylamido, substituted alkylamido, alkylamino and substituted alkylamino;
- or a salt thereof, or a solvate, hydrate or prodrug form thereof.
Dependencies are inferred from the claim text.