Several 'second-generation' click inhibitors of the multi-species biofilm propagated by the adherence of the oral pathogen <i>Porphyromonas gingivalis</i> to <i>Streptococcus gordonii</i> were synthesized and evaluated. The design of the structures was based on the results obtained with the first-generation diphenyloxazole 'click' inhibitors which bear suitable hydrophobic and polar groups within a dual scaffold molecule bearing a 1,2,3-triazole spacer. The structures of the synthetic targets reported herein now consist of a triazolyl(phenylsulfonylmethyl) and a triazolyl(phenylsulfinylmethyl) spacer which joins a 4,5-diphenyloxazole with both phenyl rings bearing lipophilic substituents. The triazolyl "linker" group is formed by a click reaction between the 4-azido(phenylsulfonyl/sulfinylmethyl) oxazoles and acetylenic components having aryl groups bearing hydrophobic substituents. The 1,3,5-trisubstituted-2,4,6-triazine scaffold of the most active click compounds were modeled after the structural motif termed the VXXLL nuclear receptor (NR) box. When substituted at the 3- and 5-positions with 2- and 4-fluorophenylamino and <i>N</i>,<i>N</i>-diethylamino units, the candidates bearing the 1,3,5-trisubstituted-2,4,6-triazine scaffold formed a substantial subset of the second-generation click candidates. Four of the click products, compounds <b>95</b>, <b>111</b>, <b>115</b> and <b>122</b> showed inhibition of the adherence of <i>P. gingivalis</i> to <i>S. gordonii</i> with an IC<sub>50</sub> range of 2.3-4.3 μM and only <b>111</b> exhibited cytotoxic activity against telomerase immortalized gingival keratinocytes at 60 μM. These results suggest that compounds <b>95</b>, <b>115</b>, <b>122</b>, and possibly <b>111</b> represent the most suitable compounds to evaluate for activity <i>in vivo</i>.