Queuine-TGT Pathway Compounds for Autoimmune Disease Treatment
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Solution Overview
Problem
Current treatments for autoimmune diseases such as multiple sclerosis and rheumatoid arthritis are inadequate, as they only manage symptoms and have significant side effects, with no cure available, and there is a need for more effective and tolerable therapies for these conditions, as well as for neurodegenerative diseases like Alzheimer's and Parkinson's.
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, offering enhanced efficacy, bioavailability, and tolerability compared to existing queuine mimetic compounds.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing treatments for autoimmune diseases are used, then symptoms can be managed, but they cannot cure the disease and have significant side effects
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of queuine to create novel compounds with improved therapeutic properties. The compounds of formula (I) and (II) represent structural modifications that enhance efficacy while reducing side effects, directly addressing the contradiction between treatment effectiveness and harmful side effects
Solution Approach 2:
The patent employs composite materials by creating hybrid molecular structures that combine features of queuine with modified functional groups. These composite compounds target multiple pathways simultaneously, achieving better therapeutic outcomes with reduced toxicity compared to existing single-mechanism treatments
2Ease of operation
If existing medications are administered, then some symptom relief is achieved, but they are only moderately effective and poorly tolerated
Solution Approach 1:
The patent modifies chemical parameters of queuine-based compounds to optimize the balance between tolerability and effectiveness. By adjusting molecular weight, functional groups, and structural configuration in compounds of formula (I) and (II), the invention achieves improved pharmacokinetic properties that enhance both patient tolerability and therapeutic effectiveness
3Duration of action of stationary object
If current autoimmune disease treatments are used, then symptom management is provided, but no cure is available and disease progression cannot be reversed
Solution Approach 1:
The patent applies preliminary action by targeting the underlying metabolic deficiency in the TGT pathway before irreversible disease progression occurs. The compounds prevent further depletion of queuine and t6A levels, thereby preventing disease progression and potentially reversing early-stage damage, rather than merely managing established symptoms
Data Source
AI summary
The present invention provides a compound of formula (I), or pharmaceutically acceptable salt or solvate thereof, wherein: Y is selected from C or N; X is O; bond a is a single or double bond; x is 1 when a is a single bond and x is 0 when a is a double bond; R1 is selected from hydrogen and methyl; R2 (when present) is selected from hydrogen and methyl; R3 is selected from hydrogen, (1-6C)alkyl and (1-6C)alkyl-phenyl, wherein said phenyl is optionally substituted by one or more (for example 1 to 3) substituents each independently selected from hydroxy, (1-6C)alkoxy, (1-6C)alkyl and halo (such as chloro and fluoro).