Structure/Activity Relationships in Lysophosphatidic Acid: The

Although lipid phosphoric acid mediators such as lysophos-phatidic acid (LPA) are now recognized widely as intercellular signaling molecules, the medicinal chemistry of these media-tors is poorly developed. With the goal of achieving a better understanding of the structure activity relationships in LPA, we have synthesized and tested a series of LPA analogs that lack the 2-hydroxyl moiety. Our series consisted of compounds with 2, 3, or 4 carbon diol or amino alcohol backbones and oleoyl or palmitoleoyl acyl groups. These molecules cannot be acylated further to form phosphatidic acids, nor do they have chiral centers. The rank order potency of these compounds in mobi-lization of calcium in MDA MB-231 cells suggested a maximum optimal chain length of 24–25 atoms. However, high potency for the inhibition of adenylyl cyclase in these cells was achieved only by one compound that also contained a dissociable proto