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Paper | Regular issue | Vol 63, No. 1, 2004, pp.75-85
Published online, 14th November, 2003
DOI: 10.3987/COM-03-9918
Synthetic Studies on Isoquinoline Derivatives with Multidrug Resistance (MDR) Modulating Activity

Chen Ma,* Su-Dong Cho, J. R. Falck, and Dong-Soo Shin

*School of Chemistry and Chemical Engineering, Shandong University, Jinan, 250100, China

Abstract

Tetrahydropyridazino-1,4-oxazinoisoquinoline derivatives with
multidrug resistance (MDR) modulating activity were designed and synthesized.
A key step for cyclization of 1,4-oxazine ring was developed using K2CO3 and
CH3CN in one-pot. Among prepared compounds, 2-(4-fluorobenzyl)-9,10-
dimethoxy-12-methyl-6,7,11b,12-tetrahydropyridazino[4’,5’,5,6][1,4]oxazine-
[3,4,-a]isoquinolin-1(2H)-one (1f) exhibited significant MDR reversing activity
and low toxicity, which might be as potential MDR agent.