Substituted Triazole TRPM8 Agonists for Dry Eye Treatment
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Solution Overview
Problem
Current TRPM8 agonists are inadequate for effectively treating dry eye syndrome, vaginal dryness, and burning mouth syndrome, as they fail to provide sufficient activation of TRPM8 channels to alleviate symptoms in humans.
Innovation Solution
Development of substituted triazoles that act as TRPM8 receptor agonists, activating both in vitro and in vivo, specifically designed to treat dry eye syndrome, vaginal dryness, and burning mouth syndrome by increasing tear and mucous secretion.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing TRPM8 agonists are used, then some TRPM8 activation occurs, but the activation is insufficient to effectively treat dry eye syndrome, vaginal dryness, and burning mouth syndrome
Solution Approach 1:
The patent modifies the chemical structure of existing TRPM8 agonists by introducing specific substituents at defined positions on the molecular scaffold. This structural parameter change increases the agonist's potency and efficacy, enabling sufficient TRPM8 channel activation to achieve therapeutic effects for dry eye syndrome, vaginal dryness, and burning mouth syndrome that previous agents could not provide
Solution Approach 2:
The invention creates composite molecular structures by combining specific structural motifs (core scaffold with defined substituents) to generate novel TRPM8 agonists. These composite structures exhibit enhanced pharmacological properties, including improved receptor binding affinity and increased channel activation capability, resolving the insufficiency of existing single-structure agonists
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
The substituted triazoles effectively activate TRPM8 channels, providing therapeutic benefits for dry eye syndrome, vaginal dryness, and burning mouth syndrome by enhancing tear and mucous secretion, offering a novel approach to managing these conditions.
Implementation Method 1
The TRPM8 receptor is an ion channel which, once activated, allows the entry of sodium (Na+) and calcium (Ca2+) into cells
Data Source
Figure 1~2
AI summary
The invention relates to compounds having formula (I) wherein A is selected from the group consisting of: a) optionally substituted (C1-C8) alkyl; b) optionally substituted (C3-C6) cycloalkyl; c) optionally substituted (C6-C14) aryl; d) optionally substituted (C6-C14) heteroaryl; e) C(0)-(C6-C14) aryl, in which group (C6-C14) aryl is optionally substituted; f) C(0)-(C6-C14) heteroaryl, in which group (C6-C14) heteroaryl is optionally substituted; g) CH(OH)-(C6-C14) aryl, in which group (C6-C14) aryl is optionally substituted; and h) CH(OH)-(C6-C14) heteroaryl, in which group (C6-C14) heteroaryl is optionally substituted. The invention also relates to methods for the production of said compounds, to pharmaceutical and veterinary compositions comprising said compounds and to the therapeutic uses thereof, such as for the prevention and/or treatment of dry eye syndrome, vaginal dryness and/or burning mouth syndrome.