Synthesis and structure-activity relationships of heterocyclic compounds containing a trimethoxyarene function

Pyrazole-, isoxazole-, and pyrazolone-containing systems were prepared from 3,4-dihydro-5,6,7-trimethoxy-1(2H)-naphthalenone, 3,4-dihydro-6,7,8-trimethoxy-1(2H)-naphthalenone, and 3,4-dihydro-6,7,8-trimethoxy-1(2H)-phenanthrone. Primarily, the pyrazoles displayed inhibition of growth in the microbial screens and in tissue culture. Correlation of the heteroatom distances between the oxygen atoms of two methoxy groups and a nitrogen atom in the pyrazole function with the percent plating efficiency on KB cell growth suggests increased inhibition as the (OA-N)/(OB-N) ratio deviates from one. No trend was observed in relating the OA-N-OB angle and activity for the examples studied.