Brian S. Freed

The enantioselective synthesis and antiinflammatory activity of novel aryl-sphingolipid PKC inhibitors

Abstract Recently we identified three promising topically active antiinflammatory agents ( 2 , 3 , and 4 ) from a series of racemic aryl-sphingolipids that inhibit protein kinase C (PKC). We now wish to report the enantioselective synthesis of the aforementioned leads and their comparative biological profile. The individual enantiomers examined are equipotent to their racemate in vitro and in vivo .

Aryl-fused sphingolipids as novel PKC inhibitors with topical antiinflammatory activity

Abstract Novel aryl-fused sphingolipids, in which aryl-/heteroaryl-moieties were incorporated into the allylic 4,5,6-positions of sphingosine, were prepared and found to possess good in vitro PKC inhibitory activity. (3-(1-Dodecynyl)phenyl)- and (4- and (5-(1-dodecynyl)-2-thienyl)-2-amino-1,3-propanediols were found to have topical antiinflammatory activity comparable to sphingosine.