Cytochrome P-450 (CYPIIB1 isoform) ligands were constructed de novo on the basis of QSAR models derived using the frontal polygon (FP) method. The following compounds were designed and synthesized: 2-phenyl-6-benzyl-2,4,6,8- tetraazabicyclo[3.3.0]octane-3,7-dione, N-acetyl-N′-(1-phenylethyl)urea, and (1-phenyl-3-methylbutyl)urea. Their interaction with phenobarbital-induced microsomes isolated from rat liver was studied spectrophotometrically. The dissociation constants K s of the enzyme - substrate complexes measured are in good agreement with the values predicted using the QSAR models. The results show that the FP method has a high potential for designing biologically active compounds.
ASJC Scopus subject areas
- Molecular Medicine
- Pharmacology, Toxicology and Pharmaceutics(all)