Synthesis of new 4-aryloxy-N-arylanilines and their inhibitory activities against succinate-cytochrome c reductase.

ABSTRACT

Succinate-cytochrome c reductase (SCR) is composed of a mixture of mitochondrial complex II (succinate-ubiquinone oxidoreductase) and complex III (cytochrome bc1 complex). Meanwhile, complexes II and III are two promising targets of numerous antibiotics and fungicides. With an aim to identify new lead structures for SCR, complex II or III, a new series of 4-aryloxy-N-arylanilines were synthesized by introducing a 4-aryloxy phenyl group as one of the aryl groups in diaryl amines. With the economic Cu(OAc)2·H2O as the optimal copper promoter, a simple and facile protocol was utilized to afford 24 target products in 56-93% yields. Furthermore, extensive screening results suggested variable inhibitory activities of these compounds against SCR. Exceptionally, compounds 7k-7n showed excellent inhibition potency with their IC50 values in the nanomolar range, demonstrating higher potency than the commercial controls (penthiopyrad and azoxystrobin) by over one order of magnitude.