Neuroactive Steroids for Selective α4β3δ GABAA Receptor Modulation
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Solution Overview
Problem
There is a need for new compounds that can act as modulating agents for brain excitability and agents for the prevention and treatment of CNS-related diseases, as existing therapies like benzodiazepines and barbiturates have limitations.
Innovation Solution
Development of compounds designed as GABA receptor modulators, specifically targeting the GABAA receptor, which can act as positive allosteric modulators and exhibit higher selectivity for the α4β3δ configuration, formulated as pharmaceutical compositions for treating CNS-related disorders.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing therapies like benzodiazepines and barbiturates are used to modulate brain excitability, then therapeutic effects are achieved, but limitations and side effects occur
Solution Approach 1:
The patent applies parameter changes by developing compounds with modified molecular structures (Formula I) that alter the binding characteristics and selectivity profile. The compounds are designed to specifically target the α4β3δ GABAA receptor configuration, changing the pharmacological parameters to achieve therapeutic effects with reduced side effects compared to conventional benzodiazepines and barbiturates
2Adaptability or versatility
If GABA receptor modulators are developed to treat CNS disorders, then therapeutic benefits are provided, but selectivity for specific receptor configurations must be achieved
Solution Approach 1:
The patent applies local quality by designing compounds that specifically interact with particular regions or configurations of the GABAA receptor (α4β3δ). The molecular structure of Formula I is engineered to have specific binding characteristics that target this particular receptor configuration, providing localized and selective modulation rather than broad-spectrum action
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 effectively modulate brain excitability and treat conditions such as depression, schizophrenia, seizures, and other CNS disorders by interacting with the GABAA receptor, providing therapeutic benefits.
Implementation Method 1
GABA interacts with its recognition site on the GRC to facilitate the flow of chloride ions down an electrochemical gradient of the GRC into the cell
Implementation Method 2
compounds designed to act as GABA receptor modulators... act as positive allosteric modulators
Data Source
AI summary
Provided herein is a compound of Formula (I) or a pharmaceutically acceptable salt thereof, wherein R19, R5, R3a, R1a, R1b, R2a, R2b, R4a, R4b, R6a, R6b, R7a, R7b, R11a, R11b, R12a, R12b, R18, RD, and q are defined herein. L is selected from the group consisting of: wherein A indicates the point of attachment at C17 and wherein X is selected from the group consisting of —C(O)N(R55a)(R55b), —N(R55a)(R55b), —N(R55b)C(O)(R55a), and R55C wherein R55c is carbon-bound substituted or unsubstituted heteroaryl or substituted or unsubstituted aryl. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I) and methods of using the compounds, e.g., in the treatment of CNS-related disorders.