Conformational search for the N6-substituted adenosine analogues and related adenosine A1 receptor antagonists

The search for 3-D requirements for the adenosine A1 receptor affinity is useful to aid in the design of more potent and/or novel ligands as pharmacological tools and therapeutics for the receptor. To emboss 3-D requirements for adenosine A1 receptor affinity among adenosine receptor antagonists, adenosine and xanthine analogs, conformations for the N6-substituted adenosine analogues and related adenosine A1 receptor antagonists were thoroughly searched by semi-empirical quantum mechanics calculations. Newly established global minima for these compounds (C1'-N6-C6-N1 torsion: 10 degrees) are consistent with retrieved structures from the Cambridge Structural Database and previously published NMR data on the solution conformation of N6-substituted adenosine analogues. However, these newly studied global minima for adenosine analogues are found to be different from those previously reported (C1'-N6-C6-N1 torsion: +/-75 degrees).