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Two targeted sets of novel 1,5-diaryl-1<i>H</i>-imidazole-4-carboxylic acids <b>10</b> and carbohydrazides <b>11</b> were designed and synthesized from their corresponding ester intermediates <b>17</b>, which were prepared via cycloaddition of ethyl isocyanoacetate <b>16</b> and diarylimidoyl chlorides <b>15</b>. Evaluation of these new target scaffolds in the AlphaScreen^TM 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 <b>10a</b>, <b>10l</b>, and <b>11k</b>, 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 <b>11a</b>, <b>11b</b>, <b>11g</b>, and <b>11h</b> exhibited moderate antiviral percentage inhibition of 33–45% with cytotoxicity (CC₅₀) values of >200 µM, 158.4 µM, >200 µM, and 50.4 µM, respectively. The antiviral inhibitory activity displayed by <b>11h</b> was attributed to its toxicity. Upon further validation of their ability to induce multimerization in a Western blot gel assay, compounds <b>11a</b>, <b>11b</b>, and <b>11h</b> appeared to increase higher-order forms of IN.