Thio Compounds Modulating TNF-α Activity
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Solution Overview
Problem
Current treatments for neurodegenerative disorders and autoimmune diseases often fail to effectively modulate TNF-α activity and angiogenesis, leading to inadequate therapeutic outcomes.
Innovation Solution
Development of compounds with specific structures that modulate TNF-α activity and inhibit angiogenesis, including lenalidomide and pomalidomide derivatives with thiocarbonyl substitutions, which can be used to treat a wide range of pathological conditions associated with TNF-α and angiogenesis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for neurodegenerative disorders and autoimmune diseases are used, then they are administered to patients, but they fail to effectively modulate TNF-α activity and angiogenesis, leading to inadequate therapeutic outcomes
Solution Approach 1:
The patent modifies the chemical structure of existing compounds by introducing thiocarbonyl substitutions at specific positions (C2 or C4) of the phenyl ring in lenalidomide and pomalidomide derivatives. This structural parameter change enhances the compounds' ability to modulate TNF-α activity and inhibit angiogenesis, thereby improving therapeutic outcomes for neurodegenerative disorders and autoimmune diseases
Solution Approach 2:
The patent creates composite chemical structures by combining the core lenalidomide or pomalidomide scaffold with thiocarbonyl functional groups at specific positions. This composite approach generates new derivatives with improved pharmacological properties, including enhanced TNF-α modulation and reduced toxicity compared to parent compounds
2Ease of operation
If thalidomide is used as a sedative hypnotic, then it was introduced onto the market in 1956, but it caused severe congenital abnormalities in babies born to mothers using it for morning sickness
Solution Approach 1:
The patent introduces thiocarbonyl substitutions at specific local positions (C2 or C4) of the phenyl ring in lenalidomide and pomalidomide derivatives. This localized structural modification targets specific biological activities while preserving therapeutic benefits and reducing harmful effects such as teratogenicity, thereby improving the safety profile compared to thalidomide
3Object-generated harmful factors
If thalidomide derivatives with thiocarbonyl substitutions are developed, then they show reduced toxicity and sustained TNF-α inhibitory effects, but their structural complexity increases
Solution Approach 1:
The patent systematically varies the substitution position (C2 or C4) and the R-group parameters at these positions to optimize the balance between toxicity reduction and structural complexity. By changing these chemical parameters, the patent generates derivatives with improved safety profiles while maintaining reasonable structural complexity for drug development
Data Source
AI summary
A compound, or a pharmaceutically acceptable salt or ester thereof, having a structure of:wherein A, B and D are each oxygen or sulfur, provided that least one of A, B and D is sulfur; and R1-R8 are each independently hydrogen, hydroxyl, acyl, substituted acyl, acyloxy, substituted acyloxy, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkoxy, aryl, substituted aryl, amino, substituted amino, halogen, heterocycloalkyl, substituted heterocycloalkyl, heteroaryl, substituted heteroaryl, or a thio-containing group.