Synthesis and in vitro cytostatic activity of new beta-D-arabino furan[1',2':4,5]oxazolo- and arabino-pyrimidinone derivatives.
A series of nucleoside derivatives was obtained via heteroatom annulation of the amino oxazoline of D-(-)-arabinose. Unequivocal proofs for the stereostructure of some new arabinosyl pyrimidinone derivatives were obtained by X-ray structure analysis. These newly synthesized compounds were then evaluated for their cytostatic activity against murine leukemia (L1210), and human T-lymphocytes (Molt 4/C8 and CEM). Of all the compounds in the series, the protected silylated tricyclic fused pyrimidinone 10 showed the most significant antitumor activity against murine leukemia L1210 (IC(50)=6 microM), and human T-lymphocytes cells Molt 4/C8 (IC(50)=7.9 microM) and CEM/0 cell lines (IC(50)=7.5 microM). None of the compounds exhibited significant antiviral inhibitory activities.
Bosc
Jean-Jacques
JJ
Université de Bordeaux, Pharmacochimie EA 4138, Bordeaux, France.
Latxague
Laurent
L
Léger
Jean-Michel
JM
Balzarini
Jan
J
Forfar
Isabelle
I
Jarry
Christian
C
Guillon
Jean
J
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D054697:Cytostatic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D010080:Oxazoles / Q000737:chemistry*; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014780:Viruses / Q000187:drug effects
D000970:Antineoplastic Agents; D054697:Cytostatic Agents; D010080:Oxazoles; D011744:Pyrimidinones