Synthesis and biological evaluation of -n[4-(2-trans-[([2,6-diamino-4(3H)-oxopyrimidin-5-yl]methyl)thio]cyclobutyl)benzoyl] -l-glutamic acid a novel 5-thiapyrimidinone inhibitor of dihydrofolate reductase

The synthesis and biological evaluation of N-[4-(2-trans-[([2,6-diamino-4(3H)-oxopyrimidin-5-yl]methyl)thio]cyclobutyl)benzoyl]-L-glutamic acid (1) is reported. Compound 1 is a potent dihydrofolate reductase (DHFR) inhibitor (K_j = 12 nM) with excellent in vitro cell culture growth inhibition (L1210, IC₅₀ = 29 nM). Protection experiments showed that the cell growth inhibitory activity was due to DHFR inhibition. The key step in the synthesis was the coupling of a cyclobutylmethylthiol with the 5-bromo-2,6-diamino-4-oxopyrimidine ⁸.     

Separation of the radioelements210Pb−210Bi−210Po by spontaneous deposition onto noble metals and verification by Cherenkov and liquid scintillation counting

A method for the separation of²¹⁰Pb,²¹⁰Bi and²¹⁰Po using spontaneous deposition has been developed. The²¹⁰Bi and²¹⁰Po are simultaneously removed by deposition onto nickel foil (copper and tin could also be used but less effectively) while the²¹⁰Po is separated from²¹⁰Bi, after dissolution of the nickel foil, by deposition onto silver foil. The effectiveness of each separation was evaluated by adding aliquot portions of each solution to a cocktail and counting with a liquid scintillation counter. Water was used as the medium to observe the Cherenkov count of the sample solution.