Steroid Compounds for Extrasynaptic GABA(A) Modulation
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Solution Overview
Problem
Current treatments for neuropsychiatric diseases such as anxiety, depression, and schizophrenia lack effective steroid compounds that can modulate GABA(A) receptors outside the synapses, particularly the α4β3δ subtype, and suffer from issues like anesthesia and sedation.
Innovation Solution
Development of steroid compounds with specific structures that can modulate GABA(A) receptors, including the α4β3δ subtype, offering improved pharmacokinetic properties, oral bioavailability, formulatability, stability, safety, and reduced side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing treatments for neuropsychiatric diseases are used, then they can bind to GABA(A) receptors, but they cause side effects like anesthesia and sedation
Solution Approach 1:
The patent applies local quality by designing steroid compounds with specific structural modifications at particular positions (R1, R2, R3, R4 substituents) to achieve selective binding to GABA(A) receptor subtypes. This localized structural differentiation enables the compound to interact specifically with certain receptor subtypes while avoiding non-specific binding that causes anesthesia and sedation, thus providing therapeutic effect with reduced side effects.
Solution Approach 2:
The patent employs parameter changes by systematically varying the chemical structure parameters of steroid compounds (different substituents at R1, R2, R3, R4 positions, different ring structures) to optimize the balance between therapeutic efficacy and side effect profile. By adjusting these structural parameters, the invention achieves compounds with improved potency and selectivity that maintain therapeutic effect while reducing harmful side effects like anesthesia and sedation.
2Reliability
If steroid compounds are developed to modulate GABA(A) receptors outside synapses, then they can treat neuropsychiatric diseases more effectively, but their pharmacokinetic properties and oral bioavailability need improvement
Solution Approach 1:
The patent applies parameter changes by optimizing the pharmacokinetic parameters of steroid compounds through systematic structural modifications. By adjusting substituents at different positions and modifying the steroid core structure, the invention improves oral bioavailability, metabolic stability, and other pharmacokinetic properties while maintaining the ability to modulate GABA(A) receptors outside synapses for effective treatment of neuropsychiatric diseases.
Solution Approach 2:
The patent uses local quality by introducing specific functional groups and substituents at particular positions on the steroid molecule to enhance pharmacokinetic properties. These localized structural features improve solubility, membrane permeability, and metabolic stability without compromising the compound's ability to reach and modulate extrasynaptic GABA(A) receptors, thereby resolving the contradiction between therapeutic effectiveness and pharmacokinetic performance.
Data Source
AI summary
The present invention relates to a steroid compound, a use thereof and a preparation method therefor. It is expected that such compound can effectively treat mental and neurological diseases, and has good active efficacy, pharmacokinetic (PK) performance, oral bioavailability, stability, safety, clearance rate, and/or metabolic performance and the like.