Journal of Medicinal Chemistry 2003-11-06

Synthesis, in vitro evaluation, and intraocular pressure effects of water-soluble prodrugs of endocannabinoid noladin ether.

Juha Juntunen, Jouko Vepsäläinen, Riku Niemi, Krista Laine, Tomi Järvinen

Index: J. Med. Chem. 46(23) , 5083-86, (2003)

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Abstract

The poor aqueous solubility of 2-arachidonyl glyceryl ether (noladin ether) 2 hinders both pharmacological studies and pharmaceutical development. The synthesized mono- and diphosphate esters of noladin ether (4 and 6) considerably increased the aqueous solubility of noladin ether (>40000-fold), showed high stability against chemical hydrolysis in buffer solutions, and were rapidly converted to the parent drug via enzymatic hydrolysis. The monophosphate ester of noladin ether reduced intraocular pressure in normotensive rabbits.