Synthetic approaches to the guanosine and xanthosine analogues 5-amino-3-beta-D-ribofuranosylpyrazolo[3,4-e][1,3]oxazin-7-one and 3-beta-D-ribofuranosylpyrazolo[3,4-e][1,3]oxazine-5,7-dione and studies of their antitumor potential.
5-Amino-3-beta-D-ribofuranosylpyrazolo[3,4-e][1,3]oxazin-7-o ne has been synthesized via cyclization of the appropriately protected pyrazofurin derivatives and subsequent transformations of the heterocyclic moiety. This guanosine analogue was marginally cytotoxic to L1210 cells in vitro. The xanthosine analogue 3-beta-D-ribofuranosylpyrazolo[3,4-e][1,3]oxazine-5,7-dione was also synthesized, and was found to be highly cytotoxic. It appeared to act as a prodrug of pyrazofurin.
Zou
R M
RM
Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor 48109-1065.
Beylin
V G
VG
Groziak
M P
MP
Wotring
L L
LL
Townsend
L B
LB
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D055598:Chemical Phenomena; D002621:Chemistry; D006151:Guanosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D012263:Ribonucleosides / Q000138:chemical synthesis* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D012263:Ribonucleosides; D006151:Guanosine; C069784:5-amino-3-ribofuranosylpyrazolo(3,4-e)(1,3)oxazine-7-one; C069785:3-ribofuranosylpyrazolo(3,4-e)(1,3)oxazine-5,7-dione