Synthesis and antitumor activity of ribavirin imidates. A new facile synthesis of ribavirin amidine (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamidine hydrochloride).
Methyl 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboximidate (4) and ethyl 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamidate (6) were synthesized and tested for antitumor and antiviral activity. A new facile synthesis of 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamidine hydrochloride (5), starting with imidate 4, was also developed. The imidates 4 and 6 differed greatly in solubility and dosing requirements. Even so, both compounds exhibited significant activity in vivo against murine leukemia L1210. Nontoxic dosing with 4 also significantly diminished Friend leukemia induced splenomegaly. In contrast, neither imidate was active in vitro.
Kini
G D
GD
Department of Tumor Biology, ICN-Nucleic Acid Research Institute, Costa Mesa, California 92626.
Robins
R K
RK
Avery
T L
TL
D000818:Animals; D000970:Antineoplastic Agents; D055598:Chemical Phenomena; D002621:Chemistry; D005622:Friend murine leukemia virus; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy; D051379:Mice; D012254:Ribavirin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D012263:Ribonucleosides / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D012263:Ribonucleosides; C060144:methyl 1-ribofuranosyl-1,2,4-triazole-3-carboxamidate; C060143:ethyl 1-ribofuranosyl-1,2,4-triazole-3-carboximidate; D012254:Ribavirin; C026956:taribavirin