Soman is a highly toxic nerve agent with strong inhibition of acetylcholinesterase (AChE), but of the few reactivators showing antidotal efficiency for soman-inhibited AChE presently are all permanently charged cationic oximes with poor penetration of the blood–brain barrier. To overcome this problem, uncharged reactivators have been designed and synthesized, but few of them were efficient for treating soman poisoning. Herein, we used a dual site biding strategy to develop more efficient uncharged reactivators. The ortho-hydroxylbenzaldoximes were chosen as reactivation ligands of AChE to prevent the secondary poisoning of AChE, and simple aromatic groups were used as peripheral site ligands of AChE, which were linked to the oximes in a similar way as that found in the reactivator HI-6. The in vitroexperiment demonstrated that some of the resulting conjugates have robust activity against soman-inhibited AChE, and oxime 8b was highlighted as the most efficient one. Although not good as HI-6 in vitro, these new compounds hold promise for development of more efficient centrally acting reactivators for soman poisoning due to their novel nonquaternary structures, which are predicted to be able to cross the blood–brain barrier.