ao0c01879_si_001.pdf (2.01 MB)
Derivatives of a PARP Inhibitor TIQ‑A through the Synthesis of 8‑Alkoxythieno[2,3‑c]isoquinolin-5(4H)‑ones
journal contribution
posted on 2020-05-28, 13:42 authored by Mirko
M. Maksimainen, Antti Nurmesjärvi, Reima A. Terho, Michael D. Threadgill, Lari Lehtiö, Juha P. HeiskanenThieno[2,3-c]isoquinolin-5(4H)-one is known for its potential as an anti-ischemic agent
through
the inhibition of poly(ADP-ribose) polymerase 1 (PARP1). However,
the compound also inhibits many other enzymes of the PARP family,
potentially limiting its usability. The broad inhibition profile,
on the other hand, indicates that this molecule backbone could be
potentially used as a scaffold for the development of specific inhibitors
for certain PARP enzymes. These efforts call for novel synthetic strategies
for substituted thieno[2,3-c]isoquinolin-5(4H)-one that could provide the needed selectivity. In this
article, an efficient synthetic strategy for 8-alkoxythieno[2,3-c]isoquinolin-5(4H)-ones through eight
steps is presented and other tested synthetic pathways are discussed
in detail. Synthesis of 7-methoxythieno[2,3-c]isoquinolin-5(4H)-one is also demonstrated to show that the strategy can
be applied widely in the syntheses of substituted alkoxythieno[2,3-c]isoquinolin-5(4H)-ones.