Development of molecules with antiinflammatory and cardioprotective activity: structural modifications, modelling, physicochemical characterization and formulation investigations

The investigations planned include structural modifications of antiinflammatory steroids by esterification C21 position of steroids with [alpha]-alkoxy alkanoic and [alpha]-aryloxy alkanoic acids, in order to obtain prodrugs with decreasing systemic side effects. [Beta]-Hydroxy-[beta]-aryl alkanoic acids with potential systemic antiinflammatory activity will be synthetized by using modified Reformatsky reaction. Physicochemical characterization and impurity degree, as well as some degradation products of drugs applicable in modern pharmacotherapy will be done using spectroscopic and chromatographic methods. The investigations will also include studies of hydrolytic and solvolytic kinetics of de novo synthetised and other therapeutically important prodrugs. The second part of planned investigations includes synthesis and physicochemical characterization of phenylpropiophenone analogs with potential cardioprotective activity and pharmacological activity and potential side effects will be investigated in animal models. The investigations planned include in vivo drug-drug and drug-nutriment interactions for some important cardioprotective drugs (statins, antihypertensive drugs and bioflavonoids). Model pharmaceutical substances with anti-inflammatory action will be the objective of both formulation studies with standard excipents and development of novel carriers in order to achieve satisfactory liberation profiles and overall efficacy of investigated drugs in therapy.