Pyrrolidine Beta-3 Agonists for Bladder Muscle Relaxation
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Solution Overview
Problem
Current medical therapies for overactive bladder are suboptimal, as many patients do not respond adequately or tolerate side effects, highlighting a need for new treatments that effectively manage urinary frequency, urgency, and incontinence.
Innovation Solution
Development of novel β3-adrenergic receptor (β3AR) agonists, specifically compounds of Formula I, which are designed to relax bladder smooth muscle and treat disorders mediated through β3AR activation, including overactive bladder and urinary incontinence.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current medical therapies for overactive bladder are used, then treatment is provided, but patient response is inadequate or side effects occur
Solution Approach 1:
The patent modifies the chemical structure of β3-adrenergic receptor agonists by changing molecular parameters (introducing pyrrolidine ring, adjusting substituent groups at positions R1-R6) to optimize the balance between efficacy and side effect profile. This structural parameter change enables improved treatment response while reducing adverse effects such as dry mouth associated with anticholinergic therapy.
2Reliability
If β3AR agonists are developed to relax bladder smooth muscle, then detrusor relaxation is achieved, but new compounds must be synthesized and tested
Solution Approach 1:
The patent divides the complex molecule into functional segments: a core pyrrolidine ring structure (positions 1-5) with specific substituent groups (R1-R6) that can be independently optimized. This segmentation allows systematic modification of specific regions to achieve desired pharmacological effects while maintaining overall molecular integrity and functionality.
3Reliability
If novel β3AR agonists are created, then improved treatment options are provided, but development time and complexity increase
Solution Approach 1:
The patent performs preliminary structural optimization by establishing the core pyrrolidine framework and identifying key substituent positions (R1-R6) before conducting extensive pharmacological testing. This preliminary design phase allows virtual screening and prediction of pharmacological properties, reducing the time required for iterative optimization and clinical development.
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 β3AR agonists provide effective relaxation of the detrusor muscle, potentially offering improved treatment options for overactive bladder and urinary incontinence with enhanced tolerability and efficacy compared to existing therapies.
Implementation Method 1
β Adrenergic receptors (βAR) are present in detrusor smooth muscle of various species, including human, rat, guinea pig, rabbit, ferret, dog, cat, pig and non-human primate
Data Source
AI summary
The present invention provides compounds of Formula (I), pharmaceutical compositions thereof, and method of using the same in the treatment or prevention of diseases mediated by the activation of β3-adrenoceptor.