19-Nor Neuroactive Steroid Composition for Consistent Sedation
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Solution Overview
Problem
Existing neuroactive steroids, such as progesterone and deoxycorticosterone, are not consistently effective in treating conditions associated with reduced levels, such as premenstrual syndrome, postnatal depression, and catamenial epilepsy, due to lack of dose-response relationship and potential side effects.
Innovation Solution
Development of 19-nor compounds with C3 disubstitution and a hydrogen at the C19 position, enhancing solubility and pharmacokinetic properties, allowing for oral administration and chronic use as GABA modulators to regulate brain excitability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If progesterone and deoxycorticosterone are used to treat conditions associated with reduced levels (premenstrual syndrome, postnatal depression, catamenial epilepsy), then treatment effectiveness is improved, but consistency of effect and safety are worsened due to lack of dose-response relationship and potential side effects
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of neuroactive steroids through C3 disubstitution and 19-nor configuration. These structural parameter changes create compounds with improved pharmacokinetic properties, enhanced solubility, and reduced side effects while maintaining treatment effectiveness for conditions like premenstrual syndrome and epilepsy
Solution Approach 2:
The patent applies local quality by introducing specific substituents at the C3 position of the steroid molecule. This localized modification creates distinct pharmacological properties in specific regions of the molecule, enabling differential interaction with GABA receptors and improved therapeutic profile
2Quantity of substance
If 19-nor compounds with C3 disubstitution are developed, then solubility and pharmacokinetic properties are improved, but structural complexity increases
Solution Approach 1:
The patent applies parameter changes by systematically varying the C3 disubstitution patterns and 19-nor configuration to optimize solubility parameters. The structural modifications are designed to improve pharmacokinetic properties while maintaining reasonable structural complexity for synthesis and clinical use
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 19-nor compounds effectively modulate GABA receptors, providing improved treatment options for CNS-related disorders like sleep disorders, mood disorders, and epilepsy, with enhanced solubility and reduced side effects.
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
The 19-nor compounds effectively modulate GABA receptors, providing improved treatment options for CNS-related disorders like sleep disorders, mood disorders, and epilepsy
Data Source
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AI summary
Provided herein are 3,3-disubstituted 19-nor-steroidal compounds according to Formula (I): and pharmaceutical compositions thereof. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, schizophrenia spectrum disorders, disorders of memory and/or cognition, movement disorders, personality disorders, autism spectrum disorders, pain, traumatic brain injury, vascular diseases, substance abuse disorders and/or withdrawal syndromes, tinnitus, and status epilepticus.