title: Synthesis of 17beta-N-substituted 19-Nor-10-azasteroids as inhibitors of human 5alpha-reductases I and II.
abstract: The synthesis of 17beta-[N-(phenyl)methyl/phenyl-amido] substituted 10-azasteroids has been accomplished by either the TiCl4- or TMSOTf-catalysed reaction of carbamates 11 and 12 with Danishefsky's diene. The reaction provided 5alpha-H isomers 3a-5a and 5beta-H isomers 3b-5b depending on the reaction conditions. Both epimers of each compound were tested against human 5alpha-reductase types I and II. Unexpectedly, 5beta-H compounds were found more active than their 5alpha-H counterparts, the best inhibitors being 3b (IC50=279 and 2000 nM toward isoenzyme I and II, respectively) and 5b (IC50=913 and 247 nM toward isoenzymes I and II, respectively).
authors.affiliation: Dipartimento di Chimica Organica Ugo Schiff, Università di Firenze, Via della Lastruccia 13, Sesto Fiorentino, Florence, Italy.
authors.forename: Dina
authors.initials: D
authors.lastname: Scarpi
authors.forename: Ernesto G
authors.initials: EG
authors.lastname: Occhiato
authors.forename: Giovanna
authors.initials: G
authors.lastname: Danza
authors.forename: Mario
authors.initials: M
authors.lastname: Serio
authors.forename: Antonio
authors.initials: A
authors.lastname: Guarna
mesh_terms: D058891:5-alpha Reductase Inhibitors; D001378:Azasteroids / Q000138:chemical synthesis* / Q000494:pharmacology*; D002384:Catalysis; D002855:Chromatography, Thin Layer; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011994:Recombinant Proteins / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D058891:5-alpha Reductase Inhibitors; D001378:Azasteroids; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D007527:Isoenzymes; D011994:Recombinant Proteins