Abstract
The design of 1,3-diacylaminopropan-2-ols as CNS-directed carrier groups is based on their resemblance to endogenous lipids and the properties of pseudotriglyceride esters to facilitate the brain penetration of therapeutic agents. 2-[S-acetylthiorphan]-l,3-diacylaminopropan-2-ols, differing from the nature of 1,3-acyl chains, were synthesized and evaluated in vivo using the hot-plate jump test. The compounds exhibited naloxone reversible analgesic properties. The effects were superior to those of parent compounds thiorphan and S-acetylthiorphan. The palmitoyl derivative showed also activity at 0.8 mmol/kg after oral administration. Like acetorphan, a thiorphan prodrug, these compounds were poor substrates for brain enkephalinase, suggesting the release of the pharmacological active inhibitor at the site of action in the brain.
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Lambert, D.M., Mergen, F., Berens, C.F. et al. Synthesis and Pharmacological Properties of 2-[S-Acetylthiorphan]-l,3-diacylaminopropan-2-ol Derivatives as Chimeric Lipid Drug Carriers Containing an Enkephalinase Inhibitor. Pharm Res 12, 187–191 (1995). https://doi.org/10.1023/A:1016214506667
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DOI: https://doi.org/10.1023/A:1016214506667