Crystal structures of some acyclonucleosides with antiviral activity and related compounds

Abstract

The crystal structure of the acyclonucleoside, 9-[4-hydroxy-2-(hydroxymethyl)-butyl]guanine (2HM-HBG), has been compared with related acyclonucleosides, and that of the acyclonucleotide, 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine-3',5'-cyclic phosphate (DHPG-cMP), also with its parent second messenger cGMP and cyclic monophosphate nucleotides. There is considerable conformational flexibility in the acyclic chain of these compounds with several conformations coexisting in the solid state. This flexibility together with the narrow range of the glycosidic torsion angles (from 69 degrees to 94 degrees, with an average of 83(3) degrees for 11 molecules when the aglycon is guanine, and from 92 degrees to 108 degrees with an average of 103(3) degrees for 4 molecules when the aglycon is adenine) may be essential for the antiviral activity of these compounds and their ability to act as substrates. The mechanism of antiviral activity of, 9-[(1,3-dihydroxy-2-propoxy)methyl] guanine-3',5'-cyclic phosphate is different from that of the acyclonucleosides, and is discussed in the light of it being a close structural analogue to the second messenger cGMP.