Synthesis of imidazo[1,5,4-de]quinoxalin-9-ones, benzimidazole analogues of pyrroloiminoquinone marine natural products.
The imidazoquinoxalinones 1 and 2 are benzimidazole analogues of indole-based marine natural products called makaluvamins. The stabilized cation 1 and the zwitterion 2 were prepared in approximately 9 steps from readily available starting materials. Compound 1 is more cytostatic and cytotoxic than 2 and also shows activity in the hollow fiber assay. Unlike the indole-based natural products, 1 and 2 are not potent topoisomerase II inhibitors. Their pattern of cytotoxic and cyostatic activity could be related to inhibition of protein tyrosine kinases.
Labarbera
Daniel V
DV
Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287-1604, USA.
Skibo
Edward B
EB
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis; D001562:Benzimidazoles / Q000138:chemical synthesis*; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008956:Models, Chemical; D015394:Molecular Structure; D011161:Porifera / Q000737:chemistry; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D059005:Topoisomerase II Inhibitors
C500550:7-acetamido-2,8-dimethyl-4,5-dihydroimidazol(1,4,5-de)quinoxalin-9-one; C500549:8-amino-2-methyl-4,5-dihydroimidazol(1,5,4-de)quinoxalin-9-one; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D007093:Imidazoles; D011810:Quinoxalines; D059005:Topoisomerase II Inhibitors