Two targeted sets of novel 1,5-diaryl-1-imidazole-4-carboxylic acids and carbohydrazides were designed and synthesized from their corresponding ester intermediates , which were prepared via cycloaddition of ethyl isocyanoacetate and diarylimidoyl chlorides . Evaluation of these new target scaffolds in the AlphaScreen HIV-1 IN-LEDGF/p75 inhibition assay identified seventeen compounds exceeding the pre-defined 50% inhibitory threshold at 100 µM concentration. Further evaluation of these compounds in the HIV-1 IN strand transfer assay at 100 μM showed that none of the compounds (with the exception of , , and , with marginal inhibitory percentages) were actively bound to the active site, indicating that they are selectively binding to the LEDGF/p75-binding pocket. In a cell-based HIV-1 antiviral assay, compounds , , , and exhibited moderate antiviral percentage inhibition of 33-45% with cytotoxicity (CC) values of >200 µM, 158.4 µM, >200 µM, and 50.4 µM, respectively. The antiviral inhibitory activity displayed by was attributed to its toxicity. Upon further validation of their ability to induce multimerization in a Western blot gel assay, compounds , , and appeared to increase higher-order forms of IN.