Bis-14-membered ring diketal diamines: synthesis and evaluation of their anti-HIV and anti-tumoral activities.
Chiral and achiral macrocyclic bis-diketal diamines, analogs of bicyclam AMD 3100, were synthesized in three steps from the previously obtained 14-membered ring diketal dilactams. Their monoreduction with lithium aluminium hydride gave the corresponding diketal aminolactams. Coupling these with dibromo-p-xylene led to xylyl dimer compounds. A second reduction step yielded the expected bis-diketal diamines in the methyl and unsubstituted series. Biological tests on the unreduced and reduced dimers showed both weak anti-HIV and anti-proliferative activities for the bis-diphenyl diketal aminolactam 13b, with a mode of action probably different from that of AMD 3100.
Laboratoire Synthèse Et Etude de Systèmes à Intérêt Biologique, UMR CNRS 6504, Université Blaise Pascal de Clermont-Ferrand, Aubière, France.
Radouane
R
Affani
Franck
F
Pélissier
Anne-Marie
AM
Aubertin
Denise
D
Dugat
D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001596:Benzylamines; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000080027:Cyclams; D003959:Diamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D047029:Lactams, Macrocyclic / Q000737:chemistry; D008968:Molecular Conformation; D010100:Oxygen / Q000737:chemistry
D019380:Anti-HIV Agents; D000970:Antineoplastic Agents; D001596:Benzylamines; D000080027:Cyclams; D003959:Diamines; D006571:Heterocyclic Compounds; D047029:Lactams, Macrocyclic; D010100:Oxygen; C088327:plerixafor