α5 GABAA Benzodiazepine Modulators for Cognitive Impairment
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Solution Overview
Problem
There is a need for effective treatments to improve cognitive function and treat cognitive impairment associated with central nervous system disorders such as Alzheimer's Disease, PTSD, schizophrenia, and Parkinson's disease, as existing therapies are inadequate.
Innovation Solution
Development of benzodiazepine derivatives that act as positive allosteric modulators of the α5-containing GABA A receptors, enhancing their function to improve cognitive performance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing therapies are used for cognitive impairment, then treatment coverage is provided, but therapeutic effectiveness is inadequate
Solution Approach 1:
The patent develops novel benzodiazepine derivative compounds with modified chemical structures (formula I) that specifically target α5-containing GABA A receptors. By changing the pharmacological parameters through structural modification and selective receptor targeting, the invention achieves enhanced therapeutic effectiveness for cognitive impairment while maintaining broad applicability across multiple CNS disorders.
2Ease of operation
If GABA signaling is enhanced through α5-containing GABA A receptor modulation, then cognitive function improves, but selectivity among GABA A receptor subtypes must be maintained
Solution Approach 1:
The patent employs local quality by designing compounds with specific structural features that confer selective affinity for α5-containing GABA A receptors versus other GABA A receptor subtypes. The molecular structure contains specific substituents and functional groups (R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, R26, R27, R28, R29, R30, R31, R32, R33, R34, R35, R36, R37, R38, R39, R40, R41, R42, R43, R44, R45, R46, R47, R48, R49, R50, R51, R52, R53, R54, R55, R56, R57, R58, R59, R60, R61, R62, R63, R64, R65, R66, R67, R68, R69, R70, R71, R72, R73, R74, R75, R76, R77, R78, R79, R80, R81, R82, R83, R84, R85, R86, R87, R88, R89, R90, R91, R92, R93, R94, R95, R96, R97, R98, R99, R100) that provide selective binding to the α5 subtype, enabling cognitive enhancement without affecting other GABA A receptor-mediated functions.
Data Source
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AI summary
This invention relates to benzodiazepine derivatives, compositions comprising therapeutically effective amounts of those benzodiazepine derivatives and methods of using those derivatives or compositions in treating cognitive impairment associated with central nervous system (CNS) disorders. In particular, it relates to the use of a α5-containing GABAA receptor agonist (e.g., a α5-containing GABAA receptor positive allosteric modulator) as described herein in treating cognitive impairment associated with central nervous system (CNS) disorders in a subject in need or at risk thereof, including, without limitation, subjects having or at risk for age-related cognitive impairment, Mild Cognitive Impairment (MCI), amnestic MCI (aMCI), Age-Associated Memory Impairment (AAMI), Age Related Cognitive Decline (ARCD), dementia, Alzheimer's Disease(AD), prodromal AD, post traumatic stress disorder (PTSD), schizophrenia, bipolar disorder, amyotrophic lateral sclerosis (ALS), cancer-therapy-related cognitive impairment, mental retardation, Parkinson's disease (PD), autism spectrum disorders, fragile X disorder, Rett syndrome, compulsive behavior, and substance addiction.