Azabicyclic Carboxamide Derivatives for TRPV1 Receptor Modulation
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Solution Overview
Problem
There is a need for new ligands for TRPV1-like receptors that offer improvements in functional activity, metabolic profile, and safety profile, as existing derivatives may have limitations in these areas.
Innovation Solution
Azabicyclic carboxamide derivatives are developed, which exhibit antagonistic or agonist activity for TRPV1 (or VR1) type receptors, characterized by specific structural formulas and synthesis processes, and are used in medicinal compositions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing bicyclic carboxamide derivatives are used for TRPV1 receptor modulation, then basic pharmacological activity is achieved, but functional activity and safety profile are limited
Solution Approach 1:
The patent applies parameter changes by systematically modifying the bicyclic carboxamide structure through varying substituents at multiple positions (R1-R9 groups, fusion ring configurations, oxidation states of sulfur/nitrogen atoms). These structural parameter changes produce derivatives with improved functional activity and safety profiles while maintaining TRPV1 receptor modulation capability.
2Reliability
If new ligand structures are developed to improve functional activity, then pharmacological performance is enhanced, but development complexity increases
Solution Approach 1:
The patent applies segmentation by dividing the ligand structure into distinct modular components: a core bicyclic carboxamide framework (azetidine, pyrrolidine, piperidine, morpholine rings) with separable substituent positions (R1-R9). This modular segmentation allows systematic optimization of individual components to improve pharmacological performance while managing development complexity through structured variation.
Solution Approach 2:
The patent systematically varies structural parameters including the type of bicyclic ring system, oxidation states of heteroatoms (S(O), S(O)2, N-oxide), and substituent groups at multiple positions. These controlled parameter changes enable methodical improvement of pharmacological performance while maintaining a manageable development framework.
Data Source
AI summary
The invention relates to the compounds of general formula (I) in which X1, X2, X3 and X4 are, independently of one another, a nitrogen atom or a C-Ri group; W is an oxygen or sulphur atom; n is equal to 0, 1, 2 or 3; Y is an optionally substituted aryl or heteroaryl; A is the group of formula: (II), Z1, Z2, Z3 and Z4 are, independently of one another, a nitrogen atom or a C-R2 group; Ra and Rb form, together with the carbon atoms which bear them, either a partially unsaturated cycloalkyl, or an aryl; or a heterocycle, or a heteroaryl with 5 to 7 ring members comprising from one to three heteroatoms selected from O, S or N; it being possible for this cycloalkyl, this aryl, this heterocycle or this heteroaryl to be substituted with one or more substituents R3; in the form of a base or of an addition salt with an acid, and also in the form of a hydrate or of a solvate. Process for the preparation thereof and therapeutic use.