Phthalazine derivatives as P2X3 inhibitors
Inventors
FIORELLI, Claudio • BRUNO, PAOLO • Biagetti, Matteo • Baker-Glenn, Charles • Van De Poöel, Hervè
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12534455-B2
Publication Date
2026-01-27
Expiration Date
Abstract
The present invention relates to compounds of formula (I) inhibiting P2X purinoceptor 3; particularly the invention relates to compounds that are phthalazine derivatives, methods of preparing such compounds, pharmaceutical compositions containing them and therapeutic use thereof. The compounds of the invention may be useful in the treatment of many disorders associated with P2X3 receptors mechanisms, such as respiratory diseases including cough, asthma, idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD).
Core Innovation
The invention provides phthalazin-1-amine derivatives as compounds of formula (I), where Z is selected from (5-6 membered)-heteroaryl and aryl, with optional substitution by (C1-C3) alkyl and halo, and where R1, R2, R3, and Y are defined by selectable groups and ranges. The scope includes stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate forms of the compounds.
The problem addressed is the treatment of disease associated with one or more P2X3 receptors, particularly respiratory diseases such as cough, asthma, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, bronchospasm, and chronic cough. The claimed compound scaffold and substituent patterning are directed to providing P2X3-receptor-associated respiratory disease treatment agents.
The document also provides analytical characterization, including 1H NMR and LCMS, and chiral analysis using chiral SFC and chiral analysis times. It further includes patch-clamp electrophysiology assay results using IC50 and pIC50 measures, along with reported P2X3/P2X2/3 activity and selectivity classifications, including comparative example references.
Claims Coverage
The claim coverage centers on one main compound claim and dependent claims that refine structure, formulation, and use. Across the claims shown, six inventive features are identified: two related to the formula (I) scaffold, one to a structural limitation with Y and R1 as H, one to a pharmaceutical composition, and two to treatment of P2X3-receptor-associated respiratory disease including chronic cough.
Phthalazin-1-amine compound of formula (I)
A compound of formula (I) having defined selectable groups Z, R1, R2, R3, and Y, wherein Z is selected from (5-6 membered)-heteroaryl and aryl with optional (C1-C3) alkyl and halo substitution, and wherein the compound includes stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate forms.
Phthalazin-1-amine derivatives with defined substituent and stereochemical variants
A compound of formula (I), including stereoisomers, tautomers, pharmaceutically acceptable salts, or solvates, specifically selected from listed phthalazin-1-amine derivatives with specified substituents and stereochemistry.
Phthalazin-1-amine compound with Y and R1 as H
A compound of formula (I) or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, with Y and R1 equal to H and represented by formula (Ia), with Z, R2, and R3 defined by the stated substituent selections and ranges.
Pharmaceutical composition containing the formula (I) compound
A pharmaceutical composition includes the compound of formula (I) or its stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate, mixed with one or more pharmaceutically acceptable carriers or excipients, optionally together with one or more other active ingredients.
Method for treating P2X3-receptor-associated respiratory disease
A method for treating a disease associated with one or more P2X3 receptors includes administering the pharmaceutical composition to a subject in need, where the disease is a selected respiratory condition listed in the claim.
Method for treating chronic cough
The method further specifies that the disease being treated is chronic cough.
Overall, the claims coverage centers on a phthalazin-1-amine scaffold defined by formula (I) with selectable substituents, optionally constrained to Y and R1 as H, and extends to a pharmaceutical composition and an administration method aimed at treating P2X3-receptor-associated respiratory diseases, particularly chronic cough.
Stated Advantages
Provides selective P2X3 inhibition for respiratory diseases, framed as selective activity for P2X3 homomeric versus P2X2/3 heteromeric, with selective P2X3 over P2X2/3 by ≥10–50-fold.
Documented Applications
Treatment of respiratory diseases associated with one or more P2X3 receptors, including cough, asthma, idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), bronchospasm, and chronic cough.
Use of the disclosed pharmaceutical composition for treating chronic cough.
Interested in licensing this patent?