Anti-Sickling Compound Compositions for Restoring Red Blood Cell Shape
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Solution Overview
Problem
Current treatments for sickle cell disease, such as voxelotor, have insufficient activity against clinical endpoints, necessitating the development of more effective therapeutic strategies to manage symptoms and complications like vaso-occlusive crisis and sickle cell-related retinopathy.
Innovation Solution
The use of 1-(thiazol-2-yl)urea, 1-phenyl-1H-pyrrole-2,5-dione, and 1-(9H-carbazol-9-yl)-3-mercaptopropan-2-ol derivatives, either alone or in combination with hydroxyurea, crizanlizumab, arginine, voxelotor, etavopivat, or mitapivat, to treat sickle cell disease and related conditions, including vaso-occlusive crisis and sickle cell-related retinopathy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If voxelotor is used to treat sickle cell disease, then red blood cell transfusion requirements are reduced, but activity against clinical endpoints is insufficient
Solution Approach 1:
The patent modifies the chemical structure of existing anti-sickling compounds by changing molecular parameters - specifically incorporating carbazole moieties with varying substituents (R1-R6) to optimize binding affinity and efficacy against clinical endpoints while maintaining safety profile
Solution Approach 2:
The invention creates composite therapeutic approaches by combining carbazole-based compounds with existing treatments (hydroxyurea, crizanlizumab, voxelotor) to achieve synergistic effects that overcome the limitations of single-agent therapy
2Ease of operation
If current treatments are used, then symptomatic relief is achieved, but disease progression and complications persist
Solution Approach 1:
The patent extracts and targets the specific molecular mechanism of sickle cell pathogenesis by designing compounds that specifically inhibit HbS polymerization and prevent sickling, thereby addressing the root cause rather than merely managing symptoms
Solution Approach 2:
The invention incorporates feedback mechanisms through preclinical and clinical testing that continuously monitor efficacy against clinical endpoints and adjust compound structures to optimize both symptomatic relief and disease control
Data Source
AI summary
This disclosure relates to compounds, pharmaceutical compositions, and methods of treating or preventing sickle cell disease or conditions associated thereto. In certain embodiments, the compounds are 1-(thiazol-2-yl)urea derivatives. In certain embodiments, the compounds are 1-(9H-carbazol-9-yl)-3-mercaptopropan-2-ol derivatives. In certain embodiments, the compounds are 1-phenyl-1H-pyrrole-2,5-dione derivatives. In certain embodiments, this disclosure relates to methods of treating or preventing sickle cell disease or condition associated thereto comprising administering an effective amount of a 1-(thiazol-2-yl)urea derivative, or 1-phenyl-1H-pyrrole-2,5-dione derivative, or a 1-(9H-carbazol-9-yl)-3-mercaptopropan-2-ol derivative as disclosed herein to a subject in need thereof.