Pro-drugs of isoniazid: synthesis and diffusion characteristics of acyl derivatives

The attachment of various acyl groups to the NH2 function of isoniazid afforded in good yields pro-drugs which were characterized by spectroscopic and analytical methods. The in vitro diffusion of pro-drugs was studied; the transfer rate constants from simulated gastro-intestinal juices to simulated plasma, through artificial wall lipid membranes were defined and compared with those of an equivalent dose of pure isoniazid. The diffusion rate constants were not greatly affected by the length of the substituent chain. All compounds were treated with artificial gastric or intestinal juices. No significant hydrolysis was observed.