Neuroactive Steroid Compositions for Selective GABA 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 treat CNS-related disorders, as existing therapies like benzodiazepines and barbiturates have limitations and new neuroactive steroids are required to address various neurological conditions.
Innovation Solution
Development of compounds designed as GABA modulators, specifically in the form of Formula (I-Ia) to (I-Ii) or their pharmaceutically acceptable salts, which can be administered to treat CNS-related disorders such as depression, schizophrenia, and other neurological conditions by modulating the GABA A receptor.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing therapies like benzodiazepines and barbiturates are used to treat CNS disorders, then brain excitability can be modulated, but therapeutic limitations and side effects occur
Solution Approach 1:
The patent modifies the chemical structure of neuroactive steroids by introducing specific substitutions at positions 1, 2, and 16 of the steroid nucleus, as well as modifying the A-ring structure. These parameter changes in molecular structure aim to optimize GABA receptor binding affinity and selectivity, thereby improving therapeutic efficacy while reducing unwanted side effects associated with existing benzodiazepines and barbiturates
2Adaptability or versatility
If new neuroactive steroids are developed to treat CNS disorders, then therapeutic benefits can be achieved, but compound specificity and receptor selectivity must be optimized
Solution Approach 1:
The patent introduces specific local modifications at particular positions of the steroid molecule (positions 1, 2, and 16) with specific substituent groups. These localized structural changes are designed to enhance interaction with specific GABA receptor subtypes while maintaining the overall neuroactive steroid framework, thereby achieving both versatility in treating different CNS disorders and precision in receptor selectivity
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 effectively treat a range of CNS-related disorders by modulating brain excitability, providing therapeutic benefits for conditions like depression, schizophrenia, and other neurological disorders through GABA receptor interaction.
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
Data Source
AI summary
Provided herein is a compound of Formula (I-I) or a pharmaceutically acceptable salt thereof, wherein t, R7, R3, R9, R6a, R6b, R11a, R11b, R15a, R15b, R16a, R16b, R17a, R17b, R18a, R18b, R19a, R19b, R5a, R5b, R8 and R13 are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I-I) and methods of using the compounds, e.g., in the treatment of CNS-related disorders.