Allosteric Hemoglobin Modulators for Sickle Cell Oxygenation
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Solution Overview
Problem
Current treatments for disorders mediated by hemoglobin, such as sickle cell disease, are inadequate, and there is a need for additional therapeutics that can effectively address abnormalities in hemoglobin like sickle hemoglobin (HbS) to improve tissue and cellular oxygenation.
Innovation Solution
Development of compounds and pharmaceutical compositions that act as allosteric modulators of hemoglobin, specifically designed to increase oxygen affinity and treat oxygen deficiency associated with sickle cell anemia, which can be administered to subjects in need to provide a therapeutically effective amount.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for sickle cell disease are used, then existing therapeutic options are available, but the treatments are inadequate and do not effectively address abnormalities in hemoglobin
Solution Approach 1:
The patent applies parameter changes by developing compounds that modify the oxygen affinity parameter of hemoglobin S. The allosteric modulators change the binding characteristics of hemoglobin to oxygen, thereby altering the physiological behavior of HbS to prevent sickling and improve treatment effectiveness.
2Reliability
If additional therapeutics are developed to address HbS abnormalities, then treatment effectiveness improves, but the complexity of developing new compounds increases
Solution Approach 1:
The patent uses intermediary compounds (allosteric modulators) that mediate between the hemoglobin molecule and oxygen binding. These intermediary substances bind to hemoglobin at allosteric sites and modify its conformational changes, providing a mechanism to treat HbS abnormalities without directly altering the hemoglobin structure.
3Reliability
If compounds are designed to increase oxygen affinity of HbS, then tissue and cellular oxygenation improves, but the complexity of designing and synthesizing these compounds increases
Solution Approach 1:
The patent applies segmentation by dividing the complex hemoglobin molecule into distinct functional regions (heme groups, globin chains, allosteric sites). The compounds are designed to interact with specific segmented regions (allosteric sites) rather than the entire molecule, simplifying the design and synthesis process while achieving the desired effect on oxygen affinity.
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
These compounds and compositions effectively increase oxygen affinity of hemoglobin S and treat oxygen deficiency, potentially alleviating symptoms of sickle cell anemia and other disorders by enhancing tissue and cellular oxygenation.
Implementation Method 1
compounds and pharmaceutical compositions suitable as allosteric modulators of hemoglobin
Data Source
AI summary
Provide herein are compounds containing an aldehyde group and pharmaceutical compositions suitable as modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation.