Small Molecule IL-17 Modulators for Oral Autoimmune Therapy
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Solution Overview
Problem
Current treatments for autoimmune diseases and inflammatory conditions often rely on monoclonal antibodies, which are not orally available, limiting patient convenience and potential safety due to long half-lives and systemic modulation effects.
Innovation Solution
Development of novel small molecule IL-17 modulators with high metabolic stability, membrane permeability, and solubility, suitable for oral administration, to modulate the IL-17 signaling pathway, addressing various autoimmune and inflammatory diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If monoclonal antibodies are used to treat autoimmune diseases, then therapeutic efficacy is improved, but patient convenience deteriorates due to lack of oral availability and long half-lives
Solution Approach 1:
The patent replaces the mechanical/biological system of monoclonal antibodies (which require injection and have long half-lives) with small molecule compounds that can be administered orally. This substitution transitions from a complex biological therapy to a simpler chemical therapy that patients can self-administer, thereby improving convenience while maintaining therapeutic efficacy through oral bioavailability
Solution Approach 2:
The patent changes key pharmacokinetic parameters by developing small molecules with appropriate absorption, distribution, metabolism, and excretion (ADME) properties for oral administration. The compounds are designed to achieve suitable half-lives, metabolic stability, and membrane permeability, transforming the therapeutic from one requiring frequent injections to one suitable for convenient oral dosing
2Adaptability or versatility
If monoclonal antibodies are used for systemic modulation, then therapeutic coverage is improved, but safety deteriorates due to long half-lives and systemic effects
Solution Approach 1:
The patent introduces dynamic control over drug exposure by designing small molecules with shorter, more controllable half-lives compared to monoclonal antibodies. This allows the therapeutic effect to be turned on and off more rapidly, enabling better control of systemic modulation and reducing prolonged exposure-related side effects while maintaining adequate therapeutic coverage
Solution Approach 2:
The patent modifies pharmacokinetic parameters including half-life, metabolic stability, and tissue distribution to achieve optimal therapeutic coverage with reduced systemic accumulation. By adjusting these parameters, the compounds provide sufficient target engagement while minimizing off-target effects and systemic toxicity associated with long-acting antibodies
3Ease of operation
If small molecule modulators are developed for oral administration, then patient convenience is improved, but metabolic stability and membrane permeability requirements increase
Solution Approach 1:
The patent applies local quality optimization by modifying specific regions of the small molecule structure to enhance oral bioavailability. This includes optimizing functional groups, molecular weight, lipophilicity, and hydrogen bonding capacity at specific locations within the molecule to improve membrane permeability and metabolic stability without requiring complete structural redesign
Solution Approach 2:
The patent systematically adjusts molecular parameters including logP, molecular weight, polar surface area, and hydrogen bond donors/acceptors to achieve the optimal balance for oral absorption. By controlling these physicochemical parameters, the compounds attain suitable metabolic stability and membrane permeability characteristics necessary for successful oral delivery
Data Source
AI summary
The present invention relates to a compound according to formula (I)and pharmaceutically acceptable salts, hydrates, or solvates thereof. The invention further relates to said compounds for use in therapy, to pharmaceutical compositions comprising said compounds, to methods of treating diseases, e.g., dermal diseases, with said compounds, and to the use of said compounds in the manufacture of medicaments.