METAPRINT: a metabolic fingerprint. Application to cassette design for high-throughput ADME screening

METAPRINT, a metabolic fingerprint, has been developed by predicting metabolic pathways and corresponding potential metabolites. Calculated drug-likeness parameters (log P and MW) have been incorporated into METAPRINT to allow the encoding of metabolic diversity within a chemical library. The application of METAPRINT in the design of cassette dosing experiments is demonstrated using a library of alpha-1a antagonists synthesized at Glaxo Wellcome. Results obtained by Ward's clustering algorithm suggest that METAPRINTs are able to discriminate between low- and high-clearance compounds. Cassette design was performed by maximizing the intracassette Euclidean distances between compounds in METAPRINT space, using simulated annealing. Calculated distances in METAPRINT space were in accordance with experimental data.     

Association of Molybdenum Ionic Species with Alumina Surface

The adsorption isotherms at 25, 45, and 65 degrees C of molybdenum solutions of concentration ranges between 10(-3) and 3x10(-2) M(Mo) (pH 4-5) on different alumina samples are investigated. The analysis is conducted using a modified Frumkin isotherm which takes a more realistic account of the lateral interaction between adsorbed species and considers that the adsorption takes place on the most basic OH groups on the surface of alumina. The results are discussed in view of the difference in solutions speciation, and the changes in the pH of the remaining supernatant solutions. The solution temperature, PZC of the used aluminas, the configuration of the basic OH groups on their surface, and the pore structure have been shown to intervene effectively. Copyright 2000 Academic Press.