Amides from Piper capense with CNS activity - a preliminary SAR analysis.
Piper capense L.f. (Piperaceae) is used traditionally in South Africa as a sleep inducing remedy. Bioassay-guided fractionation of the roots of P. capense led to the isolation of piperine (1) and 4,5-dihydropiperine (2), which showed moderate affinity for the benzodiazepine site on the GABA(A) receptor (IC(50) values of 1.2 mM and 1.0 mM, respectively). The present study suggests that strict structural properties of the amides are essential for affinity. Taken together, these observations suggest that the carbon chain must contain not less than four carbons, and that a conjugated double bond, adjacent to the amide group, is necessary for binding to the receptor and that the amine part should be bulky.
Pedersen
Mikael E
ME
Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark. hbr@farma.ku.dk
Metzler
Bjørn
B
Stafford
Gary I
GI
van Staden
Johannes
J
Jäger
Anna K
AK
Rasmussen
Hasse B
HB
D000577:Amides / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects*; D031701:Piper / Q000737:chemistry*; D051381:Rats; D013329:Structure-Activity Relationship
D000577:Amides