Conformation and structure of 2-amino-8-(β- d-ribofuranosyl)imidazo [1,2-a]-s-triazin-4-one (5-aza-7-deaza guanosine), a potent antiviral nucleoside

Abstract

The crystal and molecular structure of one imidazo[1,2-a]-s-triazine nucleoside and its antiviral activity are described. The crystal structure of 2-amino-8-(β- d-ribofuranosyl)imidazo-[1,2-a]-s-triazin-4-one monohydrate (C 10H 13N 5O 5·H 2O) was solved by X-ray counter data. The compound crystallizes in the monoclinic space group P2 1 with cell dimensions a = 7.353 (1), b = 6.465 (1), c = 13.701 (1) Å, β = 104.64 (1)°. The structure was solved by direct methods and refined by full matrix least-squares technique to a final value of the conventional R-factor of 0.049 using 1998 observed intensities. The orientation of the base relative to the sugar ring defined in terms of rotation about the C(1′)-N(8) glycosyl bond is anti (47.8°). The ribose moiety exhibits C(2′)- endo, 2E conformation. The conformation around C(4′)-C(5′) is gauche −. Molecular packing is dominated by hydrogen bonds. Base stacking occurs long the b axis. 5-Aza-7-deazaguanosine has shown a marked antiviral activity in vitro against herpes simplex virus despite the fact that N(3) is effective as the hydrogen acceptor only.