title: Synthesis and biological evaluation of thieno[3,2-d]- pyrimidinones, thieno[3,2-d]pyrimidines and quinazolinones: conformationally restricted 17b-hydroxysteroid dehydrogenase type 2 (17b-HSD2) inhibitors.
abstract: In this study, a series of conformationally restricted thieno[3,2-d]pyrimidinones, thieno[3,2-d]pyrimidines and quinazolinones was designed and synthesized with the goal of improving the biological activity as 17b-hydroxysteroid dehydrogenase type 2 inhibitors of the corresponding amidothiophene derivatives. Two moderately active compounds were discovered and this allowed the identification of the biologically active open conformer as well as the extension of the enzyme binding site characterisation.
authors.affiliation: Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C23, D-66123 Saarbrücken, Germany.
authors.forename: Enrico
authors.initials: E
authors.lastname: Perspicace
authors.forename: Sandrine
authors.initials: S
authors.lastname: Marchais-Oberwinkler
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Hartmann
mesh_terms: D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005260:Female; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008968:Molecular Conformation; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000494:pharmacology; D052999:Quinazolinones / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D011743:Pyrimidines; D011744:Pyrimidinones; D052999:Quinazolinones; D006913:Hydroxysteroid Dehydrogenases