Azacyclic TRPM8 Modulators for Long-Lasting Skin Cooling
Solution Overview
Problem
Existing TRPM8 modulators, such as menthol and its derivatives, provide short-lasting cooling sensations and lack structural diversity, limiting their effectiveness in consumer products.
Innovation Solution
Development of a new class of chemical compounds that significantly differ structurally from known TRPM8 modulators, capable of inducing a long-lasting cooling sensation at very low concentrations by activating TRPM8 ion channels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If existing TRPM8 modulators like menthol and its derivatives are used, then cooling sensation is provided, but the duration of action is short
Solution Approach 1:
The patent applies parameter changes by developing compounds with modified molecular structures (formula I) that differ from traditional menthol derivatives. The invention changes key structural parameters including the core heterocyclic ring system, substituent positions, and functional group arrangements to achieve prolonged TRPM8 channel activation, thereby extending the duration of cooling sensation while maintaining effectiveness
2Adaptability or versatility
If menthol and its derivatives are used as TRPM8 modulators, then cooling sensation is achieved, but structural diversity is limited
Solution Approach 1:
The patent applies segmentation by dividing the molecular structure into distinct functional segments: a core heterocyclic ring system (formula I), various substituent groups (R1, R2, R3), and optional functional moieties. This segmented approach enables systematic variation of each segment to generate structurally diverse compounds with different properties, thereby achieving adaptability while managing structural complexity through modular design
3Temperature
If higher concentrations of cooling agents are used, then stronger cooling sensation is achieved, but the concentration required increases
Solution Approach 1:
The patent applies parameter changes by optimizing the molecular structure of compounds according to formula I to enhance their intrinsic activity at the TRPM8 receptor. The modified heterocyclic core and strategic substituent placement increase the compound's affinity and efficacy, enabling strong cooling sensations at lower concentrations compared to traditional menthol derivatives
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
These compounds provide a prolonged cooling effect on human skin and mucosa, enhancing the sensory appeal of consumer products like foodstuffs, tobacco products, beverages, dentifrices, mouthwashes, toothpastes, and toiletries.
Implementation Method 1
capable of inducing a long-lasting cooling sensation at very low concentrations by activating TRPM8 ion channels
Data Source
AI summary
Disclosed are TRPM8 modulators as defined by formula (I) for achieving a cooling effect on skin and mucousa. The disclosure relates to a particular class of compounds capable to activate TRPM8 ion channels. It further relates to the use of these compounds for inducing a sensation of coldness, and to consumer products comprising these compounds.