N1-(3,4-dichlorophenyl)maleamide Derivatives and the Use Thereof in the Treatment of Inflammatory Disorders

Simple SummaryContent extracted from patent full text and abstract with AI.

This patent discloses a novel class of small molecule compounds based on N1-(3,4-dichlorophenyl)maleamide derivatives that inhibit the interaction between thymic stromal lymphopoietin (TSLP) and its receptor (TSLPR). By disrupting this protein-protein interaction, these compounds block the downstream activation of pro-inflammatory pathways linked to allergies and inflammatory diseases, particularly those mediated by Th2 cytokines such as IL-4 and IL-13. The lead compounds are suitable for topical application, efficiently absorbed through the skin, and have been shown to suppress key inflammatory markers in human-derived disease models.

Use CasesContent extracted from patent full text and abstract with AI.

• Treatment of atopic dermatitis and other inflammatory skin diseases, including urticaria, skin granulomas, and nonthrombocytopenic palpable purpura.
• Management of allergic diseases such as allergic asthma, allergic rhinitis, drug allergies, and food allergies.
• Therapy for chronic obstructive pulmonary disease (COPD), chronic rhinosinusitis, atopic kerato-conjunctivitis, non-celiac gluten sensitivity, eosinophilic granulomatosis with polyangiitis (EGPA), and eosinophilic esophagitis (EoE).
• Development of topical, non-invasive treatments for allergic inflammation, reducing the need for systemic immunosuppressants or expensive biologics.
• Use in combination with other therapies for treating severe, therapy-resistant cases of atopic and allergic diseases.

BenefitsContent extracted from patent full text and abstract with AI.

• Provides a first-in-class small molecule inhibitor targeting the TSLP-TSLPR interaction, a key driver of allergic and atopic disorders.
• Enables topical administration, minimizing systemic side effects and improving patient convenience, especially for skin-related diseases.
• Offers cost-effective alternatives to biological therapies such as monoclonal antibodies, which are expensive and require injections.
• Shows strong safety and efficacy in preclinical human-based models, indicating good translational potential and reduced risk of interspecies differences encountered in animal models.
• Demonstrates broad anti-inflammatory effects by downregulating multiple key cytokines (IL-4, IL-13, TSLP, periostin) implicated in disease pathogenesis.
• Potential to halt or prevent the progression of atopic diseases (e.g., preventing the so-called 'atopic march' from skin to respiratory tract).
• Low cytotoxicity and good compatibility with human keratinocytes, fibroblasts, and T cells in vitro.

Technical Classifications (CPCs)

Inventors & Applicants

Patent Abstract

Provided herein are compounds of Formula I which are thymic stromal lymphopoietin (TSLP) or thymic stromal lymphopoietin receptor (TSLPR) inhibitory compounds, capable of disrupting the protein-protein interaction between TSLP and TSLPR. Compounds of Formula I and compositions thereof modulate activity or inhibit TSLP and TSLPR binding, and are useful for downregulating atopy-relevant pro-inflammatory cytokines. In particular, compounds of Formula I as described herein are useful in the treatment of skin disease, allergic asthma, allergic rhinitis, drug allergies, and food allergies. Furthermore, the compounds described herein are absorbed by the skin. (I)