Novel tail and head group prostamide probes

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:25

Article

Finnegan, David F.^1,2,3  Shelnut, Erin L.^1,2,3  Nikas, Spyros P.^1,2,3  Chiang, Nan^4,5  Serhan, Charles N.^4,5  Makriyannis, Alexandros^1,2,3,6 

[1] Northeastern Univ, Ctr Drug Discovery, Boston, MA 02115 USA

[2] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA

[3] Northeastern Univ, Dept Pharmaceut Sci, Boston, MA 02115 USA

[4] Brigham & Womens Hosp, Harvard Inst Med, Dept Anesthesiol Perioperat & Pain Med, Ctr Expt Therapeut & Reperfus Injury, Boston, MA 02115 USA

[5] Harvard Univ, Sch Med, Boston, MA 02115 USA

[6] King Abdulaziz Univ, Jeddah 22254, Saudi Arabia

关键词: Prostamides;    Cyclooxygenase-2;    Endocannabinoids;   

DOI  :  10.1016/j.bmcl.2015.01.064

来源: Elsevier

【 摘 要 】

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 PGE(2) 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. (C) 2015 Elsevier Ltd. All rights reserved.

【 授权许可】

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