Deuterium-Enriched Sulfonamides Modulating Serotonin Receptors
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Solution Overview
Problem
Current treatments for anxiety disorders, depression, and other central nervous system disorders often have limitations such as side effects, poor receptor selectivity, and inadequate efficacy, particularly for patients with treatment-resistant depression and neurodegenerative diseases.
Innovation Solution
Development of deuterium-enriched N-acetylamino-(piperazinyl)-butyl)-alkylsulfonamides that act as 5-HT receptor modulators, partial agonists, antagonists, or inverse agonists, and selective serotonin reuptake inhibitors, offering high binding affinity and functional activity for 5-HT1A receptors, as well as activity on other serotonin and dopamine receptors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional treatments for anxiety disorders and depression are used, then treatment options are available, but side effects and poor receptor selectivity limit effectiveness
Solution Approach 1:
The patent applies parameter changes by incorporating deuterium atoms into the molecular structure of sulfonamide compounds, replacing hydrogen atoms with deuterium to create deuterium-enriched compounds. This isotopic substitution modifies the pharmacokinetic and pharmacodynamic properties of the compounds, potentially improving efficacy and reducing side effects by altering binding affinity and metabolic stability at serotonin and dopamine receptors
Solution Approach 2:
The patent implements local quality by designing compounds with specific deuterium enrichment at particular positions in the molecular structure (such as at the sulfonamide group or aromatic rings). This localized deuteration creates regions of enhanced pharmacological activity or improved metabolic stability, allowing selective modulation of receptor binding while minimizing non-specific interactions that cause side effects
2Reliability
If conventional treatments are used, then anxiety and depression can be treated, but poor receptor selectivity reduces treatment precision
Solution Approach 1:
The patent uses parameter changes by modifying the molecular parameters of existing sulfonamide structures through deuterium substitution. This alters the steric and electronic properties of the compounds, enabling finer tuning of receptor binding selectivity. The deuterium enrichment can enhance affinity for specific serotonin (5-HT1A, 5-HT2A) and dopamine (D2) receptors while reducing off-target binding, thereby improving treatment precision
Solution Approach 2:
The patent applies segmentation by developing a series of deuterium-enriched sulfonamide compounds with varying degrees and patterns of deuteration. This allows systematic exploration of structure-activity relationships, identifying specific deuterium positions that optimize receptor selectivity for different subtypes of serotonin and dopamine receptors,ไป่ achieving precise therapeutic control
3Adaptability or versatility
If existing therapies are used for treatment-resistant depression, then treatment options are limited, but inadequate efficacy persists
Solution Approach 1:
The patent implements universality by designing deuterium-enriched sulfonamide compounds that simultaneously target multiple receptor systems including serotonin (5-HT1A, 5-HT2A, 5-HT2C), dopamine (D2), and potentially other neurotransmitter receptors. This multi-receptor activity allows a single compound class to address diverse pathophysiological mechanisms underlying treatment-resistant depression, anxiety disorders, and related conditions, expanding treatment options with unified therapeutic agents
Solution Approach 2:
The patent applies composite materials by combining deuterium-enriched sulfonamide core structures with various pharmacological moieties and receptor-targeting groups. This creates composite molecular entities that integrate multiple pharmacological activities within a single unified compound, enabling simultaneous modulation of serotonin and dopamine pathways while maintaining optimized binding affinity and pharmacokinetic properties through the deuterium substitution
Data Source
AI summary
The present invention is concerned with deuterium-enriched sulfonamides of formula 1, their pharmaceutically acceptable salts and methods of use thereof for the treatment of anxiety disorders including, General Anxiety Disorder (GAD), Panic Disorder (PD), Post-Traumatic Stress Disorder (PTSD), Social Phobia (SP), Health Anxiety (Hypochondriasis), depression, major depressive disorders, unipolar depression, bipolar I depression disorder, bipolar II depression disorder, treatment-resistant depression, single episodic and recurrent major depressive disorders, depression in the medically ill, attention deficit hyperactivity disorder (ADHD), attention deficit disorder (ADD), Obsessive-Compulsive Disorder (OCD), Obsessive-Compulsive Personality Disorder (OCPD), Autism Spectrum Disorder (ASD), schizophrenia, psychosis, epilepsy, seizures, hot flashes due to menopause, age-related macular degeneration (AMD), premature ejaculation, male erectile dysfunction, sexual dysfunction, obesity, eating disorders, bulimia nervosa, anorexia nervosa, angina, migraine, pain, nociception, sleep disorders, insomnia, fibromyalgia, alcohol withdrawal, autism, Rett's syndrome, cyclothymic disorder, neural injury, neurodegenerative diseases, Parkinson's disease, Parkinson's disease psychosis, Huntington disease, Alzheimer's disease, frontotemporal dementia, cognitive impairment associated with age-related dementia, Alzheimer's disease, schizophrenia, psychosis, depression, pain or discomfort associated with surgery and pain or discomfort associated with medical illness.