title: [Development of nonsteroidal antiandrogens: 4-nitro-3-trifluoromethyldiphenylamines].
abstract: For the development of new nonsteroidal antiandrogens a series of 4-nitro-3-trifluoromethyldiphenylamines was synthesized and compounds were tested for their affinities to steroid hormone receptors and for antiandrogenic activities. These compounds were synthesized by reacting 4-nitro-3-trifluoromethylphenylsulfocyanamide-sodium (4) with the corresponding aromatic amines to give the N-(4-nitro-3-trifluoromethylphenylsulfonyl)-N'-phenylguanidines . The crude products were then converted to the desired diphenylamines by Smiles rearrangement and hydrolysis. 2-Hydroxy-4'-nitro-3'-trifluoromethyldiphenylamine (13), which shows a relative binding affinity (RBA) to the androgen receptor (AR) of 6.5% of that of testosterone, exerts a higher affinity than hydroxyflutamide (RBA = 4.5). Shift of the hydroxy-function to position 3 or 4 as well as N-methylation caused a decrease in AR-affinity. Compounds exerting AR-affinity were tested for antiandrogenic activity. Compound 13 showed the best antiandrogenic effect, though less than the well-known antiandrogen flutamide.
authors.affiliation: Institut für Pharmazie, Lehrstuhl Pharmazeutische Chemie II, Universität Regensburg.
authors.forename: A W
authors.initials: AW
authors.lastname: Humm
authors.forename: M R
authors.initials: MR
authors.lastname: Schneider
mesh_terms: D000726:Androgen Antagonists / Q000138:chemical synthesis* / Q000378:metabolism; D000814:Aniline Compounds; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004159:Diphenylamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D008297:Male; D051379:Mice; D009574:Nitro Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism
chemical_list: D000726:Androgen Antagonists; D000814:Aniline Compounds; D009574:Nitro Compounds; D011956:Receptors, Cell Surface; D004159:Diphenylamine
vernacular_title: Entwicklung nichtsteroidaler Antiandrogene: 4-Nitro-3-trifluormethyldiphenylamine.