Biphenyl and phenylpyridine compounds
Inventors
DONALDSON, Joyann Susan • Gallego, Rebecca Anne • Hoffman, Jacqui Elizabeth • JALAIE, Mehran • Montgomery, Justin Ian • Ninkovic, Sacha • Rescourio, Gwenaella Christine • SPANGLER, Jillian Elyse
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12655105-B2
Publication Date
2026-06-16
Expiration Date
Abstract
The invention relates to compounds of Formula (1):and pharmaceutically acceptable salts thereof to their use in medicine; to compositions containing them; to processes for their preparation; and to intermediates used in such processes. The compounds the present invention may be useful in the treatment, prevention, suppression and amelioration diseases, disorders, and conditions such as cancers.
Core Innovation
The disclosure provides substituted biphenyl and phenylpyridine compounds, biaryl-ether cyclopentyl-amide derivatives, Formula (I), subgenera IA-2 through IA-9, IA-13 through IA-17, IB, and IC, and pharmaceutically acceptable salts thereof. The structural scaffolds link biaryl ethers to cyclic amide moieties, with substituents including cyclobutyl, fluoro, carboxylic acid, sulfonamide, oxadiazolone, and fluorinated azaspiro or piperidine carboxamides. Embodiments encompass KAT2A/KAT2B inhibitors, bifunctional protein degraders linking targeting ligands to E3-ligase degrons, and related pharmaceutical compositions.
The compounds exhibit KAT2A and KAT2B inhibition alongside cellular activity in HT1080 and MM.1S models. Analytical characterization including 1H NMR, LCMS, and optical rotation supports the exemplified series [procedural detail omitted for safety]. Metabolite profiling identifies carboxylic-acid acyl glucuronidation and CYP-mediated oxidation pathways, and a deuterated analog series is proposed to improve metabolic stability and related therapeutic properties.
Claims Coverage
The claim information identifies four independent claims, claims 1, 5, 9, and 13, which encompass two inventive features.
Compound or pharmaceutically acceptable salt
Independent claims 1, 5, 9, and 13 each recite a compound or a pharmaceutically acceptable salt thereof, with dependent claims further specifying depicted chemical structures and salt forms.
Pharmaceutical composition
Dependent claims recite a pharmaceutical composition comprising a claimed compound or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable excipient.
The four independent claims cover compounds and their pharmaceutically acceptable salts. Dependent claims further define depicted chemical structures, salt forms, and pharmaceutical compositions comprising the compound or salt with at least one pharmaceutically acceptable excipient.
Stated Advantages
The deuterated analog series is proposed to improve metabolic stability and related therapeutic properties.
Documented Applications
Pharmaceutical compositions and formulations comprising a claimed compound or its pharmaceutically acceptable salt and at least one pharmaceutically acceptable excipient.
Treatment of cancer, including multiple myeloma, lung cancer, breast cancer, prostate cancer, and acute myeloid leukemia, as well as cancer-treatment combinations involving the described compounds with anticancer therapeutic agents.
Treatment of disorders mediated by KAT2A/KAT2B inhibition.
Targeted protein degradation via bifunctional degrader compounds linking a KAT2A/KAT2B-targeting ligand to a ubiquitin-system degron, such as a CRBN- or VHL-binding ligand.
Interested in licensing this patent?