Synthesis and in vitro antitumor activity of some amino-deoxy 7-hexofuranosylpyrrolo[2,3-d]pyrimidines.
7-(6-amino-6-deoxy-beta-D-glucofuranosyl)-5-cyanopyrrolo[2,3 -d]pyrimidine (22) and 7-(3-amino-methyl-3-deoxy-beta-D-allofuranosyl)-5- cyanopyrrolo[2,3-d]pyrimidine (28) were synthesized by sequentially coupling silylated 4-amino-6-bromo-5- cyanopyrrolo[2,3-d]pyrimidine with the corresponding protected sugars 9 and 17, followed by deblocking and catalytic hydrogenation. Conversion of the 5-nitrile in 22 and 28 into a carboxamide gave the corresponding sangivamycin derivatives 23 and 29. Whereas 5'-aminomethyl nucleosides 22 and 23 inhibited the growth of four different human tumor cell lines at microM concentrations, the 3'-aminomethyl analogs 28 and 29 were much less active against these cells.
Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
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Bobek
D000903:Antibiotics, Antineoplastic / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019906:Nuclear Magnetic Resonance, Biomolecular; D011741:Pyrimidine Nucleosides / Q000737:chemistry* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D011741:Pyrimidine Nucleosides; C005699:sangivamycin