28068-33-9Relevant academic research and scientific papers
Structure/activity relationships in lysophosphatidic acid: The 2- hydroxyl moiety
Lynch, Kevin R.,Hopper, Darrin W.,Carlisle, Steven J.,Catalano, John G.,Zhang, Ming,Macdonald, Timothy L.
, p. 75 - 81 (2007/10/03)
Although lipid phosphoric acid mediators such as lysophosphatidic acid (LPA) are now recognized widely as intercellular signaling molecules, the medicinal chemistry of these mediators 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 mobilization 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 proton five bond lengths from the phosphorus atom. That compound, N-oleoyl-2-hydroxyethyl-1-phosphate, was nearly equipotent to 1- oleoyl LPA in both assays. The striking mimicry of LPA by the ethanolamine- based compound and the presence of fatty acid amides in tissue prompts us to propose that phosphorylated N-acyl ethanolamides occur naturally.
Facile synthesis of lysophospholipids containing unsaturated fatty acid chains
Hopper, Darrin W.,Catalano, John G.,Macdonald, Timothy L.
, p. 7871 - 7874 (2007/10/03)
The efficient synthesis of polyunsaturated phospholipids is challenging due to the sensitivity of the unsaturated moiety to the conditions employed in phosphate ester deprotection. We discuss here three independent methods that resolve this issue and enable the synthesis of a series of unsaturated lysophosphatidic acid mimics for the development of a more comprehensive understanding of the structure-activity relationship in this series.
TETRONIC AND THIOTETRONIC ACID DERIVATIVES AS PHOSPHOLIPASE A2 INHIBITORS
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, (2008/06/13)
There are disclosed compounds of the formula: wherein X is ?CH2R; R is and further when Y=S, R may also be ?(CH2)eCH3; Y is ?O?or ?S?; R1 and R2 are each, independently, hydrogen or lower alkyl; R3 is indolyl, furyl, phenyl or phenyl optionally mono- or disubstituted independently by alkyl of 1-7 carbon atoms, ?C(CH3)3, ?C(CH3)2CH2C(CH3), ?C(CH3)2CH2CH3, haloloweralkyl, perfluoroalkyl, lower alkoxy, aryl alkoxy, halo or nitro; R4 and R5 are, independently, ?COCH2R7, ?CO2R7, ?CONHR7, geranyl or CH2R3; R6 is hydrogen or lower alkyl; R7 is geranyl and any moiety selected from R other than AR5 A and B are, independently, ?O?, ?S? or ?NR6 ?; and a is 0-8; b is 1-10 when Y=S, and 2-10 when Y=0; c is 1-3; d is 0-9; and e is 3-18; which by virtue of their ability to inhibit PLA2, are ofuse as antiinflammatory agents and there is also disclosed a method for the treatment of immunoinflammatory conditions, such as allergy, anaphylaxis, asthma and inflammation in mammals
