title: Versatile synthesis and biological evaluation of 1,3-diamino-substituted 1alpha,25-dihydroxyvitamin D3 analogues.
abstract: A concise route to 1alpha,3beta-diamino-25-hydroxy-3-deoxyvitamin D(3) (5) and 1beta,3alpha-diamino-25-hydroxy-3-deoxyvitamin D(3) (6) has been developed starting from (R)- or (S)-carvone for the construction of the modified A-ring fragments. The conversion of the hydroxyl group to amine function with complete inversion of the configuration was efficiently accomplished by Mitsunobu reaction using phthalimide as nucleophile or activation of the hydroxyl group as mesylate followed by reaction with NaN(3). Diamino 5 and 6 as well as monoamino 3, 4, 30, and 31 vitamin D(3) derivatives have shown poor binding to VDR compared with 1alpha,25-dihydroxyvitamin D(3). The most active compound in the inhibition of MCF-7 cell proliferation and HL 60 cell differentiation was 1alpha-amino analogue 3. Also, very low in vivo calcemic effects of derivatives 3 and 4 were found.
authors.affiliation: Departamento de Química Orgánica e Inorgánica, Facultad de Química, Universidad de Oviedo, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Oves
authors.forename: Susana
authors.initials: S
authors.lastname: Fernández
authors.forename: Miguel
authors.initials: M
authors.lastname: Ferrero
authors.forename: Roger
authors.initials: R
authors.lastname: Bouillon
authors.forename: Annemieke
authors.initials: A
authors.lastname: Verstuyf
authors.forename: Vicente
authors.initials: V
authors.lastname: Gotor
mesh_terms: D000586:Amination; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: C118756:dihydroxy-vitamin D3; D014807:Vitamin D