7-Morpholino-L,6-Naphthyridin-5-yl Derivatives and Pharmaceutical Compositions Thereof Useful as DNA-PK Inhibitor

• Main Authors: Ambler, Martin, Paquette, Jay John, Jaquith, James Brian, Osborne, Simon Andrew, Minchinton, Andrew I, Shidmoossavee, Fahimeh S, Smyth, Elliott, Kyle, Alastair H, Smiljanic-Hurley, Ela, Arns, Stephen Paul, Tan, Jason Samuel, Yee, Leanna, Baker, Jennifer H.E, Hamby, Callum, Hsieh, Tom Han Hsiao
• Format: Patent
• Language: English
• Published: 25.07.2024
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS THEREOF; CULTURE MEDIA; ENZYMOLOGY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SPIRITS; VINEGAR; WINE

The present disclosure provides compounds and methods for inhibiting DNA-dependent protein kinase (DNA-PK). Aspects of the present disclosure also include methods of using the compounds to treat diseases, including, but not limited to, cancer. In certain embodiments, the compounds inhibit DNA-PK and thus sensitize cancers to therapies such as chemotherapy and radiotherapy. Certain compounds of the present disclosure are in the form of prodrugs that release the DNA-PK inhibitor in hypoxic tissue such as is known to occur in cancers. Aspects of the present disclosure also include methods of using the compounds for repairing a DNA break in a target genomic region or for modifying expression of one or more genes or proteins. Compounds provided are of formula.