title: Novel tail and head group prostamide probes.
abstract: We report the design and synthesis of novel prostaglandin-ethanolamide (PGE2-EA) analogs containing head and tail group modifications to aid in the characterization of a putative prostamide receptor(s). Our synthetic approach utilizes Horner-Wadsworth-Emmons and Wittig reactions to construct the head and the tail moieties of the key PGE2 precursor, which leads to the final products through a peptide coupling, Swern oxidation and HF/pyridine assisted desilylation. The synthesized analogs were shown not to interact significantly with endocannabinoid proteins and recombinant EP1, EP3 and EP4 receptors and suggest a yet to be identified prostamide receptor as their site(s) of action.
authors.affiliation: Center for Drug Discovery and Departments of Chemistry and Chemical Biology and Pharmaceutical Sciences, Northeastern University, 360 Huntington Ave, 116 Mugar Hall, Boston, MA 02115, USA.
authors.forename: David F
authors.initials: DF
authors.lastname: Finnegan
authors.affiliation: Center for Drug Discovery and Departments of Chemistry and Chemical Biology and Pharmaceutical Sciences, Northeastern University, 360 Huntington Ave, 116 Mugar Hall, Boston, MA 02115, USA.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Shelnut
authors.affiliation: Center for Drug Discovery and Departments of Chemistry and Chemical Biology and Pharmaceutical Sciences, Northeastern University, 360 Huntington Ave, 116 Mugar Hall, Boston, MA 02115, USA.
authors.forename: Spyros P
authors.initials: SP
authors.lastname: Nikas
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Institutes of Medicine, 77 Avenue Louis Pasteur (HIM 829), Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Chiang
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Institutes of Medicine, 77 Avenue Louis Pasteur (HIM 829), Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Charles N
authors.initials: CN
authors.lastname: Serhan
authors.affiliation: Center for Drug Discovery and Departments of Chemistry and Chemical Biology and Pharmaceutical Sciences, Northeastern University, 360 Huntington Ave, 116 Mugar Hall, Boston, MA 02115, USA; King Abdulaziz University, Jeddah 22254, Saudi Arabia.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Makriyannis
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D000581:Amidohydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D051379:Mice; D008994:Monoacylglycerol Lipases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis / Q000737:chemistry*; D011485:Protein Binding; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013237:Stereoisomerism; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000577:Amides; D000581:Amidohydrolases; D004791:Enzyme Inhibitors; D008994:Monoacylglycerol Lipases; D011453:Prostaglandins; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D000099252:Fatty Acid Amide Hydrolases; C523108:NAAA protein, human
keywords: Cyclooxygenase-2; Endocannabinoids; Prostamides