In a continuation of our efforts to simplify the structure of our neurokinin antagonists, a series of substituted biphenyl derivatives has been prepared. Several compounds exhibit potent affinities for both the NK(1) receptor (<10nM) and for the NK(2) receptor (<50 nM). Details on the design, synthesis, biological activities, SAR and conformational analysis of this new class of dual NK(1)/NK(2) receptor antagonists are presented.