Substituted Purine Compounds for CB1 Metabolic Disorder Therapy
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Solution Overview
Problem
Existing CB1 receptor inhibitors for treating metabolic syndrome, such as Rimonabant, cause neuropsychiatric side effects, necessitating the development of alternative compounds that effectively target the CB1 receptor without these adverse effects.
Innovation Solution
Development of purine compounds and their pharmaceutically acceptable salts, which can be formulated into pharmaceutical compositions to treat or prevent disorders associated with the CB1 receptor, including obesity and metabolic syndrome, by modulating appetite, glucose regulation, fibrosis, and inflammation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CB1 receptor inhibitors (e.g., Rimonabant) are used to treat metabolic syndrome, then effectiveness in treating obesity and metabolic disorders is improved, but neuropsychiatric side effects occur
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of CB1 receptor inhibitors through various substitutions on the purine core (different R groups including aryl, heteroaryl, alkyl, and heterocycloalkyl groups). These structural parameter changes aim to alter the pharmacological profile to reduce neuropsychiatric side effects while maintaining metabolic benefits. The detailed specification describes multiple compounds with varying substituents designed to optimize the therapeutic window.
2Object-affected harmful factors
If alternative compounds targeting CB1 receptor are developed, then neuropsychiatric side effects are reduced, but the challenge remains to maintain effectiveness
Solution Approach 1:
The patent applies local quality by introducing specific functional groups at different positions on the purine molecule (R1, R2, R3, R4 positions with various substituents). Each local modification affects different aspects of the compound's interaction with the CB1 receptor, allowing selective optimization of therapeutic effects versus side effect profile. The patent describes compounds with hydroxyl groups, heterocycloalkyl groups, and other functional groups at specific positions to achieve this local differentiation.
Solution Approach 2:
The patent employs composite molecular structures combining a purine core with various substituent groups (aryl, heteroaryl, heterocycloalkyl, alkyl groups with hydroxyl substitutions). These composite structures integrate multiple functional elements that work together to achieve both CB1 receptor modulation and reduced neuropsychiatric side effects. The specification describes compounds combining nitrogen-containing heterocycles with hydroxyl-substituted alkyl groups attached to the purine core.
Data Source
AI summary
The present document relates to purine compounds, pharmaceutical compositions comprising the same and their use in the treatment or prevention of diseases and disorders associated with the cannabinoid CB1 receptor. For example, the purine compounds, or a tautomeric form and/or salt thereof, are of the formula (I): wherein R1 to R4 are as defined herein.