Picolinic-2-carboxamide hybridized with anthraquinone derivatives, methods of preparation, and a pharmaceutical composition comprising the same
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Solution Overview
Problem
Current pharmacological treatments for hyperlipidemia, such as statins, bile acid sequestrants, and nicotinic acid, have limitations including adverse side effects and inefficacy in certain patient populations, and there is a need for alternative antihyperlipidemic agents that effectively reduce lipid levels without significant side effects.
Innovation Solution
Development of picolinic-2-carboxime compounds hybridized with anthraquinone derivatives, which are synthesized through a specific method involving picolinic acid, thionyl chloride, and anthraquinone derivatives, and can be administered in various forms to treat hyperlipidemia.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If statins are used to treat hyperlipidemia, then lipid levels are reduced, but patients with high liver transaminase and myopathy experience adverse side effects including rhabdomyolysis and kidney failure
Solution Approach 1:
The invention segments the therapeutic approach by developing a hybrid molecule that combines the lipid-lowering picolinic acid component with the antioxidant anthraquinone component. This segmentation allows the compound to address multiple pathological mechanisms (hyperlipidemia and oxidative stress) simultaneously while potentially reducing the toxic effects associated with conventional statin monotherapy
Solution Approach 2:
The invention applies composite material principles by creating a hybrid molecule that integrates two distinct pharmacological components: picolinic acid derivatives (for lipid metabolism modulation) and anthraquinone derivatives (for antioxidant activity). This composite structure aims to achieve synergistic therapeutic effects while mitigating the harmful side effects of conventional treatments
2Reliability
If bile acid sequestrants are used to inhibit LDL-C levels, then serum cholesterol is reduced, but triglyceride levels are raised
Solution Approach 1:
The hybrid compound performs multiple functions simultaneously: it modulates lipid metabolism (affecting both cholesterol and triglycerides) and provides antioxidant protection. This multi-functionality allows the single agent to address both the LDL-C reduction goal and the triglyceride elevation problem that occurs with bile acid sequestrant therapy
3Reliability
If nicotinic acid is used to reduce TGs synthesis and LDL-C levels, then lipid profiles improve, but patients experience flushing, headache, dizziness, blurred vision and gastrointestinal problems
Solution Approach 1:
The invention segments the therapeutic mechanism into two distinct components within a single molecule: the picolinic acid moiety responsible for lipid metabolism regulation and the anthraquinone moiety providing antioxidant activity. This segmentation may allow for more selective action on lipid pathways while reducing off-target effects that cause flushing and gastrointestinal symptoms
Solution Approach 2:
The invention changes the chemical parameters of the therapeutic agent by modifying the molecular structure from conventional nicotinic acid to a hybrid picolinic-anthraquinone structure. This structural parameter change alters the pharmacological profile, potentially maintaining lipid-lowering efficacy while reducing the incidence of adverse effects through different receptor interactions or metabolic pathways
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
The compounds significantly reduce triglycerides, LDL-C, and LDL-C levels while increasing HDL-C levels, offering a therapeutic option with potential cardiovascular benefits and minimal side effects.
Implementation Method 1
Adding picolinoyl chloride to an anthraquinone derivative, pyridine, and trimethylamine to produce a third mixture; Heating the third mixture at a temperature of about 100° C. to produce a solid mixture
Implementation Method 2
Mixing picolinic acid and thionyl chloride in toluene to produce a first mixture; Refluxing the first mixture for about 24 hours at a temperature of about 80° C. till completion of reaction
Implementation Method 3
nicotinic acid reduces the synthesis of TGs in the liver through inhibiting both the synthesis and esterification of fatty acids
Implementation Method 4
enhances apo B degradation
Data Source
AI summary
A picolinic-2-carboxime compound hybridized with anthraquinone derivative(s), may have formula (I), optionally in salt form:wherein R may be an alkane (e.g., C1-C12), O alkane (e.g., O-C1-C6), OH, NH2, NHR4 with R4 being C1-C6, or halogen; R1 may be an alkane (e.g., C1-C12), O alkane (e.g., O-C1-C6), OH, NH2, NHR4, or halogen; and R2 may be a halogen (F, Cl, I, Br), alkane (C1-12), OH, NH2, NHR4, CN, COOH, NO2, COOR4, or CONHR4. Such a picoline derivative can be made, provided in a pharmaceutical composition, and/or used for treating hyperlipidemia.