Structure and Conformation of 1-β-D-Ribo Furanosyl Pyridin-2-one-5-Carboxamide: An Anti-Inflammatory Agent

Abstract

The pyrimidine nucleoside, 1-β-D-ribofuranosyl pyridine-2-one-5-carboxamide, is an anti inflammatory agent used in the treatment of adjuvant-induced arthritis. It is the 2-one isomer of 1-β-D-ribofuranosyl pyridine-4-one 5-carboxamide, an unusual nucleoside isolated from the urine of patients with chronic myelogenic leukemia and an important cancer marker. Crystals of 1-β-D-ribofuranosyl pyridine-2-one-5-carboxamide are monoclinic, space group C2, with the cell dimensions a = 31.7920(13), b = 4.6872 (3), c = 16.1838(11), β = 93.071(3)°, V = 2408.2(2) ų, D_calc = 1.496 mg/m³ and Z = 8 (two molecules in the asymmetric unit). The structure was obtained by the application of direct methods to diffractometric data and refined to a final R value of 0.050 for 1669 reflections with I ≥ 3σ. The nucleoside exhibits an anti conformation across the glycosidic bond (χ_CN = −15.5°, −18.9°), a C3 ′- endo C2 ′ -exo [³ ₂T] ribose pucker and g⁺ across the C(4 ′)-C(5 ′) exocyclic bond. The amino group of the carboxamide group is distal from the 2-one and lacks the intramolecular hydrogen bonding found in the related 2-one molecule. Nuclear magnetic resonance studies shows also an anti conformation across the glycosidic bond but the solution conformation of the furanose ring is not the same as that found in the solid state.

Keywords:

• Anti-inflammatory agents
• pyridine nucleosides
• structure and conformation

Acknowledgments

Our thanks are due to the editor and the referees for their constructive suggestions and comments which were taken into account in revising the manuscript.

Notes

, where n and p denote the number of data and parameters.

, where

.

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^†This is a bifurcated hydrogen bond.^{[ 18 ]}

^a In D₂O at 30˚C unless otherwise indicated.

^b Unpublished results.

^a Resonances move up field with increasing temperature.

^b,c Due to the tentative resonance assignment of HO(2’) and HO(3’), these values may be interchanged.