Halophenyl furanopyrimidines as potent and selective anti-VZV agents.

Bicyclic furano pyrimidines have been previously reported by us to be highly potent and selective inhibitors of varicella zoster virus (VZV). p-Alkyl phenyl analogues are particularly potent with EC50 values below 1 nM. In this article we report the synthesis and anti-VZV activity of a series of halophenyl analogues, with variation in the nature (F, Cl, Br) and location (o, m, p) of the halogen substituent. The compounds show a range of activities from ca. 10 nM to > 50 microM. In most cases, ortho substitution leads to greatest activity, meta substitution is in general poor, and the effect of p-substitution shows a marked dependence on the halogen atom. The p-fluorophenyl compound is unique amongst compounds of this class in being inactive as an antiviral. The possible origins of these marked SARs are discussed.

Upon the intriguing stereoselective formation of organobismuth(V) complexes.

The preparation of triphenylbismuth(V) 3a-k and antimony(V) 4e-k bis-carboxy ester complexes is described. A range of studies in solution suggest that the diastereoselective formation of (RR,SS)-3a-j is governed by the thermodynamic stability of rapidly interconverting epimeric species. Diastereoselectivity is absent in the case of the corresponding Sb complexes, leading to the conclusion that a combination of both ligand-ligand (steric) and metal-ligand (hyperconjugative) interactions govern stereoselectivity. The formation of homochiral complexes (RR,SS)-3a-j is rationalised using a simple model, invoking for the first time a palindromic BiPh3 propeller moiety, which correlates the chirality of the trans axial carboxy-ester ligands. The X-ray crystal structures of both hetero- and homochiral diastereoisomeric antimony complexes (4h and 4i, respectively) are presented in support of this model.