The electron density and electronic energy densities in ethyl 4,6-dimethyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate have been studied from accurate X-ray diffraction measurements at 110 K and theoretical single-molecule and periodic crystal calculations. The Quantum Theory of Atoms in Molecules and Crystals (QTAMC) was applied to analyze the electron-density and electronic energy-density features to estimate their reproducibility in molecules and crystals. It was found that the local electron-density values at the bond critical points derived by different methods are in reasonable agreement, while the Laplacian of the electron density computed from wavefunctions, and electron densities derived from experimental or theoretical structure factors in terms of the Hansen-Coppens multipole model differ significantly. This disagreement results from insufficient flexibility of the multipole model to describe the longitudinal electron-density curvature in the case of shared atomic interactions. This deficiency runs through all the existing QTAMC bonding descriptors which contain the Laplacian term. The integrated atomic characteristics, however, suffer noticeably less from the aforementioned shortcoming. We conclude that the electron-density and electronic energy QTAMC characteristics derived from wavefunctions, especially the integrated quantities, are nowadays the most suitable candidates for analysis of the transferability of atoms and atomic groups in similar compounds.

A high yield preparation of 9-(2-O-~-~-ribofbranosyl-~-~-ribofUranosyl)adenine, guanine-and the pyrimidine analogs (cytosine, thymine and uracil base moiety) has been achieved, and the conformational properties of the ring systems were investigated using NMR spectroscopy and X-ray.

Non-nucleoside reverse transcriptase inhibitors (NNRTI) are key components in highly active antiretroviral therapy for treating HIV-1. Herein we present the synthesis for a series of N1-alkylated uracil derivatives bearing ω-(2-benzyl- and 2-benzoylphenoxy)alkyl substituents as novel NNRTIs. These compounds displayed anti-HIV activity similar to that of nevirapine and several of them exhibited activity against the K103N/Y181C RT mutant HIV-1 strain. Further evaluation revealed that the inhibitors were active against most nevirapine-resistant mono- and di-substituted RTs with the exception of the V106A RT. Thus, the candidate compounds can be regarded as potential lead compounds against the wild-type virus and drug-resistant forms.

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