A. Morrell et al. / Bioorg. Med. Chem. Lett. 16 (2006) 1846–1849
1849
´
´
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In conclusion, a one-pot synthesis of unsubstituted and
substituted indenopyrans was developed and these com-
pounds were utilized as intermediates for the synthesis
of indenoisoquinolines displaying potent Top1 inhibition
and in some instances increased cytotoxicity relative to
previously reported compounds. The initial results of this
study indicate that lactam substitution modulates the bio-
logical activity to a greater degree than modifications to
the isoquinoline aromatic ring. However, the improved
synthesis of indenopyrans represents a new synthetic
strategy toward the development of Top1 anticancer
agents.
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Acknowledgments
This work was supported by Research Grant UO1
CA89566, Training Grant ST32 CA09634-12, and the
American Chemical Society Division of Medicinal
Chemistry and Pfizer Global Research and Develop-
ment for predoctoral support of A.M. This research
was conducted in a facility constructed with support
from Research Facilities Improvement Program Grant
C06-14400 from the National Institutes of Health.
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Supplementary data
Complete experimental procedures for the synthesis and
characterization for all new indenoisoquinolines can be
found in the online version. Supplementary data associ-
ated with this article can be found, in the online version,
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