Queuine Mimetic Compounds Modulating TGT Enzyme for Autoimmune Disease Treatment
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Solution Overview
Problem
Current treatments for autoimmune diseases such as multiple sclerosis and rheumatoid arthritis are largely symptomatic, lack curative options, and often come with adverse side effects, while neurodegenerative diseases like Alzheimer's and Parkinson's have limited effective medical interventions.
Innovation Solution
Development of novel compounds that target the queuine-tRNA ribosyltransferase pathway, specifically compounds of formula (I) or their pharmaceutically acceptable salts/solvates, which act as substrates for the TGT enzyme to treat autoimmune, neurodegenerative, and inflammatory diseases by normalizing cytokine levels and influencing cellular metabolism.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing medications are used to treat autoimmune diseases, then disease symptoms are ameliorated, but the treatments are only moderately effective and have adverse effects that are poorly tolerated
Solution Approach 1:
The patent applies parameter changes by developing novel queuine mimetic compounds with modified chemical structures (formula I) that improve pharmacokinetic parameters including bioavailability, stability, and potency. These structural modifications enable the compounds to achieve better therapeutic effects at lower doses, thereby reducing adverse side effects while maintaining or enhancing treatment effectiveness for autoimmune diseases
Solution Approach 2:
The patent employs composite material principles by creating queuine mimetic compounds that combine specific molecular features (aromatic rings, heteroatoms, substituent groups) to achieve optimal balance between efficacy and tolerability. The compounds integrate multiple functional groups that work synergistically to enhance target engagement while minimizing off-target effects and adverse reactions
2Duration of action of moving object
If current treatments are administered to alter the rate of relapse and remission, then disease progression is not reversed, but numerous harmful side effects occur
Solution Approach 1:
The novel compounds of formula (I) utilize parameter changes by optimizing pharmacokinetic properties including half-life, bioavailability, and metabolic stability. This enables sustained therapeutic action that can modify disease progression over time while maintaining a favorable safety profile, allowing for longer treatment durations without accumulating harmful side effects
Solution Approach 2:
The queuine mimetic compounds act as intermediaries that selectively modulate the TGT enzyme pathway involved in autoimmune disease pathogenesis. By targeting this specific biochemical pathway, the compounds achieve disease-modifying effects while sparing other physiological systems, thereby reducing the occurrence of harmful side effects associated with broader immunosuppressive therapies
3Productivity
If medications are used to treat autoimmune diseases, then symptoms are treated, but the diseases are not curable and require ongoing treatment
Solution Approach 1:
The patent applies preliminary action by developing compounds that can prevent disease progression and potentially induce remission through targeted modulation of the TGT pathway. By addressing the underlying pathological mechanisms early in disease course, these compounds may reduce the need for long-term chronic treatment, thereby reducing the time loss associated with ongoing medication requirements
Data Source
AI summary
The present invention provides a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein: Y is selected from C or N; X is selected from O or S; R1 is selected from hydrogen or methyl; Z is CR2R3, wherein R2 and R3 are each independently selected from hydrogen and (1-5C)alkyl, or R2 and R3 are taken together with the carbon atom to which they are attached to form a cyclopropyl or cyclobutyl ring; Z1 is selected from CR4R5, O, S, C(O) or NR6, wherein R4 and R5 are each independently selected from hydrogen, OH, (1-5C)alkyl and phenyl, or R4 and R5 are taken together with the carbon atom to which they are attached to form a cyclopropyl ring, and R6 is selected from hydrogen and (1-5C)alkyl, provided that one, but not both, of Z and Z1 is CH2.