Crystal structure of ammonium 3'-azido-3'-de-oxy-thymidine-5'-amino-carbonyl-phospho-nate hemi-hydrate: an anti-HIV agent.

The asymmetric unit of the title compound, NH4 (+)·C11H14N6O7P(-)·0.5H2O, contains one 3'-azido-3'-de-oxy-thymidine-5'amino-carbonyl-phospho-nate (ACP-AZT) anion, half of an NH4 (+) cation lying on a twofold rotation axis and in another position, occupied with equal probabilities of 0.5, an NH4 (+) cation and a water mol-ecule. The amide group of the ACP-AZT anion is disordered (occupancy ratio 0.5:0.5), with one part forming an N-H⋯O (involving C=O⋯H4N(+)) hydrogen bond and the other an O-H⋯N (involving C-NH2⋯OH2) hydrogen bond with the components of the split NH4 (+)/H2O position. The pseudorotation parameters of ACP-AZT set it apart from previously studied AZT and thymidine. In the crystal, the various components are linked by N-H⋯O, O-H⋯O, N-H⋯N, C-H⋯O and C-H⋯N hydrogen bonds, forming a three-dimensional framework.

1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents.

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.