Chemically stable homocinnamyl analogues of the leukotrienes: synthesis and preliminary biological evaluation.
Basic Information
ID: ALA1123519
Journal: J Med Chem
Title: Chemically stable homocinnamyl analogues of the leukotrienes: synthesis and preliminary biological evaluation.
Authors: Bernstein PR, Snyder DW, Adams EJ, Krell RD, Vacek EP, Willard AK.
Abstract: The synthesis and biological characterization of a series of stable leukotriene analogues (2) are reported. They are derivatives of (5S,6R,7Z)-6-peptidyl-5-hydroxy-9-phenyl-7-nonenoic acid, in which the phenyl group is variously substituted with a heptanyl, 2-heptenyl, or hexanyloxy chain (R1) and the peptide is either glutathionyl, cysteinylglycinyl, or cysteinyl. The most potent agonist is (5S,6R,7Z)-6-S-glutathionyl-5-hydroxy-9-(4-heptanylphenyl)-7 -nonenoic acid. This analogue has an EC50 value of 74.5 nM, in the presence of 1-serine borate (45 mM), on guinea pig tracheal spirals. The agonist activity of the cysteinylglycinyl- and the cysteinyl-substituted analogues was inhibited by FPL-55712. Three of the analogues were weak leukotriene antagonists in vitro on guinea pig tracheal spirals. The most potent of these was (5S,6R,7Z)-6-S-cysteinyl-5-hydroxy-9-(2-heptanylphenyl)-7-++ +nonenoic acid. At 10 microM, this analogue inhibited by 28% the contraction induced by 8 nM LTE4.
CiteXplore: 2878081
DOI: 10.1021/jm00162a010
Patent ID: ┄