QSAR of Adenosine Receptor Antagonists II:

Abstract

Considering potential of selective adenosine receptor subtype ligands in the development of prospective drug candidates, A₁ and A₃ receptor binding affinity data of 2-arylpyrazolo[3,4-c]quinoline derivatives have been subjected to QSAR analyses to explore the physicochemical requirements for selective binding. The study has been carried out with Wang-Ford charges of the common atoms of the molecules calculated from their energy minimized conformations using AM1 technique. Apart from the charge parameters, physicochemical variables like partition coefficient and molar refractivity of the whole molecules have been used along with suitable indicator variables. The study shows that substituents on the appended 2-phenyl ring and 4-amino or 4-keto substitution on the pyrazolo[3,4-c]quinoline nucleus modulate the selectivity pattern. Further, negative charge on the quinoline nitrogen and volume and lipophilicity of the whole molecules are important contributors to the selectivity.