Synthesis, Antitumor Activity, and Tolerability of Phospholipids Containing Nitrogen Homologues

摘要

Edelfosir.e (2-0-methyl-1-O-octadecyl-rac-glyceryl-3-phos-phocholine. 2-N) and miltcfosine (hexadecylphosphoeholine) are prototypes of new antineoplnsticallv active phospholipids that have been already used clinically. However, oral administration ofthese drugs to cancer patients was seriously hampered by side effects in the digestive tract (nausea, vomiting, diarrhea, loss of body weight). Corresponding animal experiments led us to assume that during the metabolism of these phospholipids. choline esters are formed which imitatf the effects of the parasympathetie nervous system on the intestine: such com-pounds might be responsible at least in pan. for the symptoms observed in patients and animals. This hypothesis has been supported by the findingthat a heterocyclic phospholipid in which choline is replaced by N-(2-hydroxyethyl)-N-methylpiperidine is tolerated much better.