13, 17-Substituted Steroids for GABA Receptor Modulation
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Solution Overview
Problem
Current neuroactive steroids for anesthetic and GABA-related disorders have limitations, particularly in understanding the structural features that enable anesthetic activity, and there is a need for new compounds that can effectively act as anesthetics and treat disorders related to GABA function.
Innovation Solution
Development of novel 13, 17-substituted tetracyclic steroid compounds with specific structural features, such as a cyclopenta[a]phenanthrene ring system, that are neuroactive and suitable for use as anesthetics, including pharmaceutically acceptable salts and pharmaceutical compositions for inducing anesthesia and treating GABA-related disorders.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional anesthetics are used, then anesthetic effect is achieved, but bacterial contamination risk increases
Solution Approach 1:
The patent modifies the chemical structure of traditional steroids by introducing specific substituents at positions 13 and 17 of the steroid nucleus, creating novel compounds with improved safety profiles while maintaining anesthetic efficacy. These structural parameter changes result in compounds less susceptible to bacterial contamination.
2Reliability
If traditional steroids are used, then GABAergic activity is achieved, but solubilization properties are insufficient
Solution Approach 1:
The patent introduces specific functional groups and substituents at particular positions (13 and 17) of the steroid molecule, creating local chemical modifications that enhance solubilization properties without compromising the overall GABAergic activity of the compound.
Solution Approach 2:
The novel steroid compounds represent composite molecular structures combining the core steroid nucleus with specific substituent groups that provide both GABAergic activity and improved solubilization characteristics.
3Reliability
If alphaxalone is used, then anesthetic activity is achieved, but structural understanding is incomplete
Solution Approach 1:
The patent systematically varies substituents at specific positions (13 and 17) of the steroid nucleus, segmenting the molecular structure into modifiable components to identify which structural features are critical for anesthetic activity. This structure-activity relationship analysis fills the knowledge gap regarding structural requirements.
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 compounds provide effective anesthesia and treatment for disorders like insomnia, mood disorders, convulsive disorders, anxiety, and ethanol withdrawal, with advantages such as lower bacterial contamination risk and improved solubilization properties compared to existing anesthetics.
Implementation Method 1
Activation of the GABAA receptor induces increased inward chloride ion flux, resulting in membrane hyperpolarization and neuronal inhibition
Implementation Method 2
it allosterically increases chloride currents mediated by GABA acting at GABAA receptors in the brain
Data Source
AI summary
The present disclosure is generally directed to neuroactive 13, 17-substituted steroids as referenced herein, and pharmaceutically acceptable salts thereof, for use as, for example, an anesthetic, and/or in the treatment of disorders relating to GABA function and activity. The present disclosure is further directed to pharmaceutical compositions comprising such compounds.