Synthesis of benz[d]indeno[1,2-b]pyran-5,11-diones: versatile intermediates for the design and synthesis of topoisomerase I inhibitors.
A method has been developed that relies on a two-step, one-pot condensation between phthalide and 2-carboxybenzaldehydes to provide benz[d]indeno[1,2-b]pyran-5,11-diones in a multi-gram fashion. Treatment of these compounds with a primary amine allows rapid access to various N-substituted indenoisoquinolines, whose in vitro anticancer activity and topoisomerase I inhibition have been evaluated.
Morrell
Andrew
A
Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Purdue University, West Lafayette, IN 47907, USA.
Antony
Smitha
S
Kohlhagen
Glenda
G
Pommier
Yves
Y
Cushman
Mark
M
D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011714:Pyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D059004:Topoisomerase I Inhibitors
D004791:Enzyme Inhibitors; D011714:Pyrans; D059004:Topoisomerase I Inhibitors