Design and synthesis of sustain-acting melatonin prodrugs

Twelve melatonin amide prodrugs aiming at prolonging the action of melatonin in vivo by improving its half-life were designed and synthesized. using an 80% human plasma model,it was found that the aliphatic amide derivatives were relatively stable and melatonin release from these compounds was not sufficient with melatonin release percentage. after 4-hour incubation with 80% human plasma,the melatonin release percentage achieved only approximately less than 20%. in contrast,the n 1 -succinyl and n 1 -glutaroylmelatonin derivatives (compounds 11 and 12,resp.) were found to release melatonin in much higher rates. after 3-hour incubation in 80% human plasma,the melatonin release rates from 11 and 12 were found to be 67.3 and 75.6%,respectively. from these results,the n 1 -succinyl and n 1 -glutaroylmelatonin derivatives (compounds 11 and 12) could be promising as sustained release prodrugs of melatonin. © 2013 phm vǎn thoi and nguyen hai nam.