Cyclic Amine Derivatives for Selective 5-HT2A Receptor Antagonism
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current therapeutic agents for neurodegenerative disorders like Parkinson's disease and Alzheimer's disease are ineffective in directly altering disease progression and often cause severe side effects, with no specific drug approved for these conditions, and existing antipsychotics and antidepressants have poor tolerability and adverse effects on the cardiovascular system.
Innovation Solution
Development of a novel compound with serotonin 5-HT2A receptor antagonism and/or inverse agonism, specifically designed to target 5-HT2A and 5-HT2C receptors, reducing adverse effects on the cardiovascular system and improving selectivity for these receptors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing therapeutic agents (antipsychotics, antidepressants, Parkinson's disease agents) are used to treat neuropsychiatric symptoms, then symptom relief is achieved, but tolerability is significantly poor and severe adverse effects occur
Solution Approach 1:
The patent modifies the pharmacological parameters of existing 5-HT2A receptor antagonists by changing their chemical structure (introducing specific substituents at defined positions) to alter their binding characteristics and selectivity, thereby improving the balance between efficacy and tolerability
Solution Approach 2:
The invention focuses on improving selectivity for specific receptor subtypes (5-HT2A and 5-HT2C) over other serotonin receptors and cardiovascular targets, creating local specificity in receptor interaction to reduce off-target adverse effects while maintaining therapeutic effectiveness
2Reliability
If pimavanserin is used as a 5-HT2A receptor inverse agonist, then hallucinations and delusions are treated, but cardiovascular adverse effects are large and use is restricted
Solution Approach 1:
The patent modifies the pharmacological parameters of pimavanserin and related compounds by changing their chemical structure (introducing specific substituents at defined positions) to alter their binding characteristics and selectivity, thereby improving the balance between efficacy and tolerability
Solution Approach 2:
The invention focuses on improving selectivity for specific receptor subtypes (5-HT2A and 5-HT2C) over other serotonin receptors and cardiovascular targets, creating local specificity in receptor interaction to reduce off-target adverse effects while maintaining therapeutic effectiveness
3Adaptability or versatility
If existing antipsychotics and antidepressants are used, then neuropsychiatric symptoms are addressed, but tolerability is significantly poor
Solution Approach 1:
The patent modifies the pharmacological parameters of existing agents by changing their chemical structure to achieve a more favorable side effect profile while maintaining symptom coverage
Solution Approach 2:
The invention focuses on improving selectivity for specific receptor subtypes (5-HT2A and 5-HT2C) over other serotonin receptors and cardiovascular targets, creating local specificity in receptor interaction to reduce off-target adverse effects while maintaining therapeutic effectiveness
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 compound effectively treats and prevents serotonin-related diseases such as Parkinson's disease-related hallucinations and delusions with improved receptor selectivity and reduced cardiovascular side effects, providing a therapeutic option for neurodegenerative disorders.
Implementation Method 1
a compound having serotonin 5-HT2A receptor antagonism and/or inverse agonism
Implementation Method 2
it also has serotonin 5-HT2C receptor inverse agonism
Data Source
AI summary
Provided are a compound having serotonin 5-HT2A receptor antagonism and/or inverse agonism, a pharmaceutically acceptable salt thereof, and a composition for serotonin 5-HT2A receptor antagonism and/or inverse agonism comprising them.A compound represented by Formula (I):wherein R1 is substituted or unsubstituted aromatic heterocyclyl or the like; R2 is each independently a hydrogen atom or the like; R3 is each independently a hydrogen atom or the like; n is 1 or the like; a combination of (L1, L2) is (NH, N) or the like; R4 is a group represented by Formula:wherein p and q are each independently 2 or the like; Ra is substituted or unsubstituted alkyl or the like; Xb is each independently CRbRb′; Rb is each independently a hydrogen atom or the like; Rb′ is each independently a hydrogen atom or the like; Xc is each independently CRcRc′; Rc is each independently a hydrogen atom or the like; Rc′ is each independently a hydrogen atom or the like; Xd is CRd or the like; and Rd is a hydrogen atom or the like; R5 and R6 are each independently a hydrogen atom or the like; and R7 is a group represented by Formula:wherein A is CR11 or the like; R9 is substituted or unsubstituted alkyloxy or the like; R10 is a hydrogen atom or the like; and R11 is each independently a hydrogen atom or the like; or a pharmaceutically acceptable salt thereof.