No abstract

Purine-β-lactam chimera were prepared as a novel class of hybrid systems through N-alkylation of 6-benzylamino- or 6-benzyloxypurine with (ω-haloalkyl)-β-lactams, followed by reductive ring opening of the β-lactam ring by LiEt(3)BH to provide an entry into the class of purine-aminopropanol hybrids. Both new types of hybrid systems were assessed for their antiviral activity and cytotoxicity, resulting in the identification of eight purine-β-lactam hybrids and two purine-aminopropanol hybrids as promising lead structures.

A variety of novel syn-2-alkoxy-3-amino-3-arylpropan-1-ols was prepared through LiAlH(4)-promoted reductive ring-opening of cis-3-alkoxy-4-aryl-beta-lactams in Et(2)O. The latter gamma-aminoalcohols were easily converted into cis-5-alkoxy-4-aryl-1,3-oxazinanes using formaldehyde in THF. Both series of compounds were evaluated against a chloroquine sensitive strain of Plasmodium falciparum (D10), revealing micromolar potency for almost all representatives. Eleven compounds exhibited antimalarial activity with IC(50) values of