title: Developing piperine towards TRPV1 and GABAA receptor ligands--synthesis of piperine analogs via Heck-coupling of conjugated dienes.
abstract: Piperine, the pungent alkaloid of black pepper, and several of its derivatives are modulators of γ-amino butyric acid type A (GABAA) receptors. Concomitantly, this natural product has also been reported to activate transient receptor potential vanilloid type 1 (TRPV1) receptors. We have developed a Heck cross-coupling reaction of conjugated dienamides enabling the rapid assembly of piperine derivatives containing a modified aromatic core. Upon assessment of a focussed compound library, key aromatic substituents were identified selectively affecting either the GABAA or the TRPV1 receptor.
authors.affiliation: Institute of Applied Synthetic Chemistry, Vienna University of Technology, Getreidemarkt 9, 1060 Vienna, Austria. marko.mihovilovic@tuwien.ac.at.
authors.forename: Laurin
authors.initials: L
authors.lastname: Wimmer
authors.forename: David
authors.initials: D
authors.lastname: Schönbauer
authors.forename: Peter
authors.initials: P
authors.lastname: Pakfeifer
authors.forename: Angela
authors.initials: A
authors.lastname: Schöffmann
authors.forename: Sophia
authors.initials: S
authors.lastname: Khom
authors.forename: Steffen
authors.initials: S
authors.lastname: Hering
authors.forename: Marko D
authors.initials: MD
authors.lastname: Mihovilovic
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D000475:Alkenes / Q000737:chemistry*; D052117:Benzodioxoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D060326:Chemistry Techniques, Synthetic; D008024:Ligands; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D053284:Polyunsaturated Alkamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D000470:Alkaloids; D000475:Alkenes; D052117:Benzodioxoles; D008024:Ligands; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011963:Receptors, GABA-A; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; C008922:piperine