As a continuation of the search for antitubercular agents among pyrazole-pyrimidine hybrids, drug-like enamines 7a-i were synthesized using the ligand-based drug design approach. The prototype ylidene compounds had previously demonstrated activity against the Mycobacterium tuberculosis H37Rv strain at a MIC range of 25-50 μg/mL. Microbiological testing showed that enamines 7d and 7e inhibited the strain at significantly lower MICs of 3.1 and 0.35 μg/mL, respectively. To further optimize their structure, in silico identification of a plausible enzyme target was undertaken. Based on several reasonable considerations, undecaprenyl pyrophosphate synthase (UppS) was selected as the target. Subsequent docking of enamines 7a-i into UppS revealed two important aspects. First, they exhibited higher affinities for the enzyme compared to those for the targets for the reference drug isoniazid. Second, the binding of enamines 7a-i occurred in the same enzyme pocket where the natural substrates for UppS were bound. Due to the similarity in binding features between the in vitro active enamines and one of the substrates, farnesyl diphosphate, the former may act as competitive inhibitors of UppS.