Heteroaryl compounds for the treatment of pain
Inventors
Miller, Mark Thomas • Hurley, Dennis James • Neubert, Timothy Donald • Arumugam, Vijayalaksmi • Hadida Ruah, Sara Sabina • McCartney, Jason • Zhou, Jinglan • Chau, Jaclyn • Demoret, Robert Martin • Ghirmai, Senait G. • Valiulin, Roman Askatovich • Kintzer, Alexander Fredrick • Slochower, David Robert • Aertgeerts, Kathleen • Beck, Elizabeth Mary • MUI, James Jun Bon • Wright, Miranda Adele • Knegtel, Ronald Marcellus Alphonsus • Chudyk, Ewa Iwona • Pinder, Joanne Louise • Dodd, James • Simpson, Iain
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12503439-B2
Publication Date
2025-12-23
Expiration Date
Abstract
Compounds, and pharmaceutically acceptable salts thereof, useful as inhibitors of sodium channels are provided. Also provided are pharmaceutical compositions comprising the compounds or pharmaceutically acceptable salts and methods of using the compounds, pharmaceutically acceptable salts, and pharmaceutical compositions in the treatment of various disorders, including pain.
Core Innovation
The invention provides compounds of formula (I), or pharmaceutically acceptable salts thereof, useful as voltage-gated sodium channel inhibitors, including selective NaV1.8 inhibitors. The compounds encompass substituted quinolinones, 1,6-naphthyridinones, 1,7-naphthyridinones, quinazolinones, and related fused heteroaromatic scaffolds with defined linker, ring-atom, and substituent alternatives. The background, abstract, and summary sections are omitted from the provided content, so the problem being solved is not explicitly described in patent.
The disclosed structural variations encompass amino, alkoxy, cycloalkyl, carboxamide, difluoroazepanyl, and fluorinated aryl or heteroaryl substituents, supported by synthetic intermediates and analytical characterization data [procedural detail omitted for safety]. Assays demonstrate human NaV1.8 inhibition with IC50 values below 0.5 micromolar for selected compounds. The provided description also encompasses pharmaceutical compositions containing these compounds and their use in treating pain and related neurological or visceral disorders.
Claims Coverage
The relevant claims identify one independent claim, claim 1. Its coverage is summarized across four inventive features defining the formula (I) compound genus, linker alternatives, ring-atom configurations, and substituent and terminal-ring options with conditional limitations.
Compound of formula (I) and salts
Claim 1 covers a compound of formula (I), or a pharmaceutically acceptable salt thereof.
Linker alternatives
The claim defines alternatives for linker L selected from —O—, a single bond, —O—C(R)₂—, —C(R)₂—, —C(R)₂—O—, or —N(R)—.
Ring-atom configurations
Ring positions X₂, Y₁, Y₂, Y₃, X₄, X₅, X₆, and X₇ are selected from defined alternatives, encompassing carbon- and nitrogen-containing arrangements including CR and N.
Substituent and terminal-ring alternatives with conditional limitations
The claim defines permitted alternatives for R groups, variables m, n, p, and q, and terminal group Z₁ selected from 3–7 membered cycloalkenyl, phenyl, 4–10 membered heterocyclyl, and 5–6 membered heteroaryl groups, while imposing conditional structural limitations on L and Z₁ when X₂ is N, and on phenyl substitution or Z₁ when X₂, X₄, X₅, X₆, and X₇ are each CH and L is a single bond.
The independent claim defines a broad genus of formula (I) compounds and pharmaceutically acceptable salts through specified linker, ring-atom, and substituent alternatives, bounded by conditional limitations, with dependent claims covering subgenera, pharmaceutical compositions, channel inhibition, and therapeutic uses.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Inhibiting a voltage-gated sodium channel in a subject or in a biological sample, including selective inhibition of human NaV1.8.
Treating or lessening the severity of chronic pain, gut pain, neuropathic pain, musculoskeletal pain, acute pain, inflammatory pain, cancer pain, idiopathic pain, postsurgical pain, visceral pain, multiple sclerosis, Charcot-Marie-Tooth syndrome, incontinence, pathological cough, or cardiac arrhythmia.
Pharmaceutical compositions comprising a formula (I) compound or pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers or vehicles, including specific dosage forms, routes of administration, and combination therapies.
Heteroaryl and aryl boronate building blocks for assembling the disclosed compound series.
Use of the compounds or compositions as coatings for implantable medical devices.
Use of radiolabeled analogs in assays and for therapeutic use.
Interested in licensing this patent?