1313740-87-2Relevant academic research and scientific papers
Efficient modulation of γ-aminobutyric acid type a receptors by piperine derivatives
Sch?ffmann, Angela,Wimmer, Laurin,Goldmann, Daria,Khom, Sophia,Hintersteiner, Juliane,Baburin, Igor,Schwarz, Thomas,Hintersteininger, Michael,Pakfeifer, Peter,Oufir, Mouhssin,Hamburger, Matthias,Erker, Thomas,Ecker, Gerhard F.,Mihovilovic, Marko D.,Hering, Steffen
supporting information, p. 5602 - 5619 (2014/08/05)
Piperine activates TRPV1 (transient receptor potential vanilloid type 1 receptor) receptors and modulates γ-aminobutyric acid type A receptors (GABAAR). We have synthesized a library of 76 piperine analogues and analyzed their effects on GABAAR by means of a two-microelectrode voltage-clamp technique. GABAAR were expressed in Xenopus laevis oocytes. Structure-activity relationships (SARs) were established to identify structural elements essential for efficiency and potency. Efficiency of piperine derivatives was significantly increased by exchanging the piperidine moiety with either N,N-dipropyl, N,N-diisopropyl, N,N-dibutyl, p-methylpiperidine, or N,N-bis(trifluoroethyl) groups. Potency was enhanced by replacing the piperidine moiety by N,N-dibutyl, N,N-diisobutyl, or N,N-bistrifluoroethyl groups. Linker modifications did not substantially enhance the effect on GABAAR. Compound 23 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dipropyl-2,4-pentadienamide] induced the strongest modulation of GABAA (maximal GABA-induced chloride current modulation (IGABA-max = 1673% ± 146%, EC 50 = 51.7 ± 9.5 μM), while 25 [(2E,4E)-5-(1,3-benzodioxol- 5-yl)-N,N-dibutyl-2,4-pentadienamide] displayed the highest potency (EC 50 = 13.8 ± 1.8 μM, IGABA-max = 760% ± 47%). Compound 23 induced significantly stronger anxiolysis in mice than piperine and thus may serve as a starting point for developing novel GABA AR modulators.
NOVEL PIPERINE DERIVATIVES AS GABA-A RECEPTORS MODULATORS
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Page/Page column 23; 28, (2011/07/30)
The present invention encompasses novel piperin compounds of general formula (I) wherein R1, R2, R3, m and n are defined as in claim 1, which are suitable for the prevention and/or treatment of diseases mediated by modulation of GABAA receptor and the use thereof for preparing a medicament having the above mentioned properties.
