title: Design, synthesis and biochemical studies of new 7α-allylandrostanes as aromatase inhibitors.
abstract: Two series of derivatives of 7α-allylandrostenedione, namely its 3-deoxo and 1-ene analogs, were designed and synthesised and their biochemical activity towards aromatase evaluated. In each of these series, the C-17 carbonyl group was further replaced by the hydroxyl and acetoxyl groups. The attained data pointed out that the absence of the C-3 carbonyl group led to a slightly decrease in the inhibitory activity and the introduction of an additional double bond in C-1 revealed to be a very beneficial structural change in the studied compounds (compound 12, IC₅₀ = 0.47 μM, K(i) = 45.00 nM). Furthermore, the relevance of the C-17 carbonyl group in the D-ring as a structural feature required to achieve maximum aromatase inhibitory activity is also observed for this set of derivatives.
authors.affiliation: CEF, Center for Pharmaceutical Studies, Pharmaceutical Chemistry Group, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal.
authors.forename: Carla L
authors.initials: CL
authors.lastname: Varela
authors.forename: Cristina
authors.initials: C
authors.lastname: Amaral
authors.forename: Georgina
authors.initials: G
authors.lastname: Correia-da-Silva
authors.forename: Rui A
authors.initials: RA
authors.lastname: Carvalho
authors.forename: Natércia A
authors.initials: NA
authors.lastname: Teixeira
authors.forename: Saul C
authors.initials: SC
authors.lastname: Costa
authors.forename: Fernanda M F
authors.initials: FM
authors.lastname: Roleira
authors.forename: Elisiário J
authors.initials: EJ
authors.lastname: Tavares-da-Silva
mesh_terms: D047072:Aromatase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry*; D006801:Humans; D008861:Microsomes; D013256:Steroids / Q000138:chemical synthesis* / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D047072:Aromatase Inhibitors; D013256:Steroids