Oxytocin (OT) and its receptor (OT-R) are implicated in the aetiology of autism spectrum disorders (ASDs) and OT-R is a potential target for therapeutic intervention. We report here the design and pharmacological activity of a second-generation OT-R agonist that is more potent and selective than OT itself both in vitro and in vivo, in two animal models of autism after peripheral and oral administration. The preclinical potential of this new lead compound, LIT-002, is also evaluated and discussed.

We report the first synthesis of IspH-directed prodrugs targeting the terminal enzyme of the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway, (E)-4-hydroxy-3-methylbut-2-enyl diphosphate reductase (IspH or LytB). A series of alkyne and pyridine monophosphate cycloSaligenyl (cycloSal) prodrugs were prepared to enhance membrane permeability by masking the phosphate group. The effects of electron-withdrawing (Cl, CF₃) and electron-donating (OCH₃, NH₂) substituents were examined, together with amino acid-functionalized and mutual prodrug analogs. Among the synthesized compounds, chlorine-substituted derivatives 5c and 6c displayed the strongest antimycobacterial activity against Mycobacterium smegmatis, surpassing isoniazid in agar diffusion assays. These results indicate that electron-withdrawing substituents accelerate prodrug hydrolysis and facilitate intracellular release of the active inhibitor. This work provides the first experimental evidence of an IspH-targeted prodrug approach, highlighting the cycloSal strategy as a valuable tool for delivering phosphorylated inhibitors and developing novel antimycobacterial agents acting through the MEP pathway.