Anti-fibrotic NEU3 inhibitor compounds and methods of use
Inventors
Gomer, Richard H. • Meek, Thomas • Karhadkar, Tejas • Pilling, Darrell
Assignees
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Publication Number
US-12616674-B2
Publication Date
2026-05-05
Expiration Date
Abstract
The present disclosure relates to methods of preventing or inhibiting fibrosis using small molecule sialidase inhibitors. The present disclosure also relates to methods treating obesity, liver inflammation, steatosis, and cancer. These methods can involve administering the compounds to a patent at risk of developing fibrosis inflammation, obesity, steatosis, or cancer, in a manner that inhibits NEU3.
Core Innovation
The invention relates to small-molecule NEU3 inhibitors and pharmaceutical formulations comprising a compound of formula (I) or its salt for treating a fibrotic disorder. The compounds are defined by substituent constraints, including R1 selected from CONH2, COCH3, C1-6 alkyl ester, and in another formulation also COOH, with R2, R3, R4, and R5 being hydrogen and X being nitrogen.
The disclosed biological function is inhibition of human NEU3 desialylation activity, with treatment defined functionally by administration sufficient to decrease a level or activity of a sialidase in a human. The claim coverage further ties the inhibition to desialylating specific substrates including LAP and SAP and to decreases in TGF-β1 level or activity.
The invention also connects sialidase-related inhibition to downstream biological responses associated with fibrotic disorder, including inhibiting fibrocyte formation or activation. Representative inhibitors include DANA, oseltamivir, picolinamide, substituted pyridines, and multiple picolinic acid derivatives, together with documented structural motifs for NEU3 inhibitory compounds including nicotinic/picolinic and piperidine/azepane carboxylate motifs.
Claims Coverage
The provided claims include two independent claims directed to methods of treatment of a fibrotic disorder using pharmaceutical formulations comprising a compound of formula (I) or its salt. Across the independent claims, the coverage is defined by structural constraints and by functional therapeutic effects tied to decreasing sialidase level or activity in a human, with one claim also framing NEU3-related desialylation. The main inventive features comprise five merged elements.
Formula (I) compound administration for fibrotic disorder treatment
Administering a pharmaceutical formulation comprising a compound of formula (I) or its salt, wherein R1 is selected from CONH2, COCH3, C1-6 alkyl ester, and in another independent claim also COOH; R2, R3, R4, and R5 are hydrogen; and X is nitrogen.
Sialidase level or activity reduction in a human
Administering the formulation in an amount and for a time sufficient to decrease a level or activity of a sialidase in a human.
NEU3-mediated desialylation of LAP inhibition
Inhibiting the activity of human NEU3 in desialylating LAP, with related substrate/desialylation context identified as LAP and SAP.
Decrease in TGF-β1 level or activity
Administering the formulation in an amount and for a time sufficient to decrease the level or activity of TGF-β1 in a human.
Fibrocyte formation or activation inhibition
Inhibiting the formation or activation of fibrocytes as part of the method.
The claim coverage centers on treating a fibrotic disorder by administering a pharmaceutical formulation containing a compound of formula (I) or its salt under specified structural constraints, with therapeutic dosing defined functionally to decrease sialidase level or activity in a human. Additional disclosed claim refinements connect the NEU3-related mechanism to LAP and SAP, decreased TGF-β1 level or activity, and inhibition of fibrocyte formation or activation.
Stated Advantages
Decreasing a level or activity of TGF-β1 in a human.
Inhibiting fibrocyte formation or activation.
Decreasing a level or activity of a sialidase in a human.
Documented Applications
Treatment of a fibrotic disorder.
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