Structure activity relationship (c log p), synthesis and biological activity of some novel syslooxygenase -ii inhibitors.
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Date
2005
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Abstract
Classical QSAR(Quantitative Structure Activity Relationship) analysis play an important role in drug design, despite the progress in protein crystallography, QSAR methods are simple and efficient tools to derive and prove hypothesis on SAR in a quantitative manner. The quantitative description of transport distribution, metabolism and elimination of drugs still remain the domain of classical QSAR methods.
The biological activity of a compound is most often a combination of several known and unknown subeffects, (physico-chemical parameters) QSAR will contribute directly or indirectly to development of new drug, this is further justified with the increasing evident of importance of dissociation, polarazability, electron and hydrogen bond interaction, steric fit on drug action and lipophilicity, one of the important contributor for selectivity, transport and the distribution of the COX-2 selective drugs. In the present study, we aimed to correlate the different physico-chemical parameters, mainly lipophilicity (logP) of various classes of selective COX-2 inhibitors using various types of regression analysis like Genetic Function Approximation (GFA), Genetic Partial Least Square (GPLS), Partial Least Square (PLS) and Linear regression equation using Cerius2 molecular modeling software running on SGI work station. The synthesis of some novel of the imidazo[2,1-b]1,3,4-thiadiazole (GVSK 1-3) derivatives by reacting 5(benzo(a)(1,3,) dioxol-5-yl)- 1,3,4-thiadiazole-2-amine with the various α-haloketones, The synthesized compounds were assessed for anti-inflammatory activity in carrageenan induced rat paw edema model. The results showed that compounds GVSK2 and GVSK1 exhibited good to moderate activity with percentage inhibition 57.08 and 32.57 respectively.
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COX-2, QSAR, liphophilicity, (log P) GFA, GPLS, imidazo[2,1-b]-1,3,4-thiadiazoles