Pyrazolyl-quinazoline SK Channel Modulators
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Solution Overview
Problem
Current treatments for various diseases and disorders associated with potassium channel activity, such as respiratory diseases, epilepsy, and cardiovascular conditions, lack effective therapeutic agents that selectively modulate SK channels.
Innovation Solution
Development of novel pyrazolyl-quinazoline derivatives that selectively modulate SK channels, which can be used in pharmaceutical compositions to treat a range of diseases and disorders by regulating potassium channel activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments are used for diseases associated with potassium channel activity, then existing therapeutic options are available, but effective selective modulation of SK channels is lacking
Solution Approach 1:
The patent applies parameter changes by developing compounds with specific molecular structures (pyrazolyl-quinazoline derivatives) that have been optimized to achieve selective binding to SK channels. The chemical parameters including substituent groups at specific positions (R1-R6, X, Y, Z) are systematically varied to tune the affinity and selectivity for different SK channel subtypes, thereby resolving the contradiction between therapeutic effectiveness and selective modulation capability
Solution Approach 2:
The patent segments the broad category of potassium channel modulators into specific subclasses targeting SK channels. By focusing on a defined chemical series (quinazoline derivatives with specific heterocyclic substituents) and identifying distinct binding interactions with SK1, SK2, and SK3 channels, the invention creates selective therapeutic agents that differentiate between channel subtypes, thus achieving both reliability and adaptability
2Adaptability or versatility
If novel pyrazolyl-quinazoline derivatives are developed to selectively modulate SK channels, then selective therapeutic modulation is achieved, but development complexity increases
Solution Approach 1:
The patent achieves universality by creating a core molecular scaffold (quinazoline derivative structure) that can selectively target multiple SK channel subtypes (SK1, SK2, SK3) through systematic substitution patterns. This multi-functional approach allows a single chemical series to address various diseases associated with different SK channel expressions, reducing the need for entirely separate drug development programs for each channel subtype while maintaining selectivity
Data Source
AI summary
This invention relates to novel potassium channel modulating agents, and their use in the preparation of pharmaceutical compositions.Moreover the invention is directed to pharmaceutical compositions useful for the treatment or alleviation of diseases or disorders associated with the activity of potassium channels, in particular respiratory diseases, epilepsy, convulsions, vascular spasms, coronary artery spasms, renal disorders, polycystic kidney disease, bladder spasms, urinary incontinence, bladder outflow obstruction, irritable bowel syndrome, gastrointestinal dysfunction, secretory diarrhoea, ischaemia, cerebral ischaemia, ischaemic heart disease, angina pectoris, coronary heart disease, traumatic brain injury, psychosis, schizophrenia, anxiety, depression, dementia, memory and attention deficits, Alzheimer's disease, dysmenorrhea, narcolepsy, Reynaud's disease, intermittent claudication, Sjorgren's syndrome, migraine, arrhythmia, hypertension, absence seizures, myotonic muscle dystrophia, xerostomi, diabetes type II, hyperinsulinemia, premature labour, baldness, cancer, immune suppression or pain.